Antiretroviral Analytical Treatment Interruption (ATI) to Assess Immunologic and Virologic Responses in Participants Who Received VRC01 or Placebo and Became HIV-infected During HVTN 704/HPTN 085
Phase: NA
Conditions: HIV Infection
Sponsor: HIV Vaccine Trials Network

  
PROTOCOL 
HVTN 804/HPTN 095 
Antiretroviral analytical treatment interruption (ATI) to 
assess immunologic and virologic responses in 
participants who received VRC01 or placebo and 
became HIV-infected during HVTN 704/HPTN 085 
DAIDS DOCUMENT ID 38632 
Non-IND Protocol 
CLINICAL TRIAL SPONSORED BY 
Division of AIDS (DAIDS) 
National Institute of Allergy and Infectious Diseases (NIAID) 
National Institutes of Health (NIH) 
Department of Health and Human Services (DHHS) 
Bethesda, Maryland, USA 
 
 
March 22, 2022 
Final 
HVTN 804/HPTN 095 
Version 3.0 

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Contents 
1 Protocol summary ..........................................................................................................4 
1.1 
Précis ..............................................................................................................5 
1.2 
Schema ...........................................................................................................7 
1.3 
Protocol team ..................................................................................................8 
2 Background and rationale ............................................................................................10 
2.1 
Antiretroviral therapy ...................................................................................10 
2.2 
Broadly neutralizing antibodies (bnAbs) .....................................................10 
2.3 
bnAbs can mediate virologic control............................................................11 
2.4 
bnAbs modulate the autologous immune response to acute HIV infection .14 
2.5 
bnAbs may limit establishment and decrease the size of the viral reservoir 19 
2.6 
The HVTN 704/HPTN 085 AMP study .......................................................21 
2.7 
Antiretroviral analytical treatment interruption (ATI) .................................22 
2.8 
An AMP ATI ................................................................................................28 
2.9 
Ethical considerations ..................................................................................30 
2.10 The necessity of the AMP placebo control group ........................................31 
2.11 Feasibility .....................................................................................................37 
2.12 Conclusion ....................................................................................................40 
3 Study design .................................................................................................................41 
3.1 
Hypotheses ...................................................................................................41 
3.2 
Objectives and endpoints .............................................................................41 
3.3 
ATI ...............................................................................................................44 
4 Statistical considerations ..............................................................................................47 
4.1 
Accrual and sample size calculations ...........................................................47 
4.2 
Statistical analyses ........................................................................................49 
5 Study population ..........................................................................................................53 
5.1 
Inclusion criteria ...........................................................................................53 
5.2 
Exclusion criteria ..........................................................................................55 
5.3 
Criteria for participant early termination......................................................58 
5.4 
Study termination .........................................................................................58 
6 Study procedures ..........................................................................................................59 
6.1 
Schedule 1: Monitoring ATI ........................................................................59 
6.2 
Schedule 2: Monitoring ATI with viremia ...................................................64 
6.3 
Schedule 3: Follow-up on ART ...................................................................66 
6.4 
Interim visits .................................................................................................67 
6.5 
Early termination visit ..................................................................................68 
6.6 
Contraception status .....................................................................................68 
6.7 
Specific clinical management considerations ..............................................69 
7 Study products .............................................................................................................70 
8 Laboratory ....................................................................................................................71 
8.1 
CRS laboratory procedures ..........................................................................71 
8.2 
Assay timepoints ..........................................................................................71 
8.3 
Endpoint assays: cellular ..............................................................................71 
8.4 
Phenotyping of cell populations ...................................................................72 

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8.5 
Endpoint assays: humoral .............................................................................72 
8.6 
HIV viral reservoir .......................................................................................72 
8.7 
Host genomics ..............................................................................................73 
8.8 
HIV antiretroviral resistance testing.............................................................73 
8.9 
ARV detection ..............................................................................................73 
8.10 Biohazard containment .................................................................................73 
9 Research use of stored human samples and/or data .....................................................74 
9.1 
Specimen storage and other use of specimens .............................................74 
9.2 
Exploratory studies .......................................................................................74 
10 Potential risks and benefits ..........................................................................................75 
10.1 Potential risks ...............................................................................................75 
10.2 Potential benefits ..........................................................................................75 
11 Monitoring of safety ....................................................................................................76 
11.1 Safety monitoring and oversight ..................................................................76 
11.2 Safety reporting ............................................................................................78 
12 Ethics/protection of human subjects ............................................................................80 
12.1 Informed consent process .............................................................................80 
12.2 Participant confidentiality ............................................................................81 
13 Protocol conduct ..........................................................................................................82 
13.1 Emergency communication with study participants ....................................83 
14 Acronyms and abbreviations........................................................................................84 
15 Protocol version history ...............................................................................................86 
16 Document references (other than literature citations) ..................................................89 
17 References ....................................................................................................................91 
Appendix A Sample informed consent form ..................................................................103 
Appendix B Approved contraceptive methods for transgender men (for sample informed 
consent form) ..............................................................................................125 
Appendix C Sample consent form for use of samples and information in other studies 126 
Appendix D Tables of procedures for sample informed consent form ...........................131 
Appendix E Laboratory procedures—Schedule 1: Monitoring ATI ..............................136 
Appendix F Laboratory procedures—Schedule 2: Monitoring ATI with viremia .........140 
Appendix G Laboratory procedures—Schedule 3: Follow-up on ART .........................144 
Appendix H Procedures at CRS—Schedule 1: Monitoring ATI ....................................146 
Appendix I Procedures at CRS—Schedule 2: Monitoring ATI with viremia ...............149 
Appendix J Procedures at CRS—Schedule 3: Follow-up on ART ...............................151 
Appendix K Visit Windows ............................................................................................152 
Appendix L Protocol Signature Page .............................................................................157 

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1 
Protocol summary 
Full title: 
Antiretroviral analytical treatment interruption (ATI) to 
assess immunologic and virologic responses in participants 
who received VRC01 or placebo and became HIV-infected 
during HVTN 704/HPTN 085 
Short title: 
HVTN 804/HPTN 095  
Sponsor: 
NIAID Division of AIDS 
Conducted by: 
HIV Vaccine Trials Network (HVTN) and HIV Prevention 
Trials Network (HPTN) 
Protocol chairs: 
Shelly Karuna, MD, MPH; Katharine Bar, MD 
Sample size: 
16 – 46 
Study population: 
HIV-1–infected HVTN 704/HPTN 085 participants who 
met criteria for transition to Schedule 2 or Schedule 3 in 
that trial  
Study design: 
An exploratory study of HIV-infected participants 
undergoing an analytical treatment interruption after 
receiving VRC01 or placebo infusions in HVTN 
704/HPTN 085 
Study duration: 
Study duration is potentially indefinite for a participant 
maintaining extreme and extended viral control during ATI. 
Study duration for most participants is expected to be 13-18 
months. The maximum anticipated duration for any 
participant is expected to be approximately 2½ to 3 years.  
Study products: 
None. Drugs for anti-retroviral therapy (ART) and for pre-
exposure prophylaxis (PrEP) will not be provided by the 
study or paid for using sponsor funds. Procedures for 
accessing external funding sources for PrEP and ART 
provision are detailed in the HVTN 804/HPTN 095 Study 
Specific Procedures (SSP). 
Primary objectives: 
To evaluate the effect of VRC01 received in the immediate 
pre-HIV acquisition period and/or during early infection on 
the time to meeting ART re-initiation criteria in participants 
undergoing ATI 

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To evaluate the safety of ATI among HVTN 804/HPTN 
095 participants 
Secondary objectives: To evaluate the effect of VRC01 received in the immediate 
pre-HIV acquisition period and/or during early infection on 
the development of anti-HIV immune responses that differ 
from those of placebo recipients, and whether these 
immune responses are associated with time to meeting 
criteria for ART re-initiation in participants undergoing 
ATI 
To evaluate the effect of VRC01 received in the immediate 
pre-HIV acquisition period and/or during early infection on 
viral load in participants undergoing ATI 
To evaluate the effect of VRC01 received in the immediate 
pre-HIV acquisition period and/or during early infection on 
HIV reservoir size before and after ATI, and whether HIV 
reservoir measurements are associated with time to meeting 
criteria for ART re-initiation in participants undergoing 
ATI 
1.1 
Précis 
Mounting preclinical (eg, murine, nonhuman primate [NHP]) and clinical 
evidence suggests that anti-HIV broadly neutralizing antibodies (bnAbs) can 
mediate sustained virologic control of HIV. While the mechanisms responsible 
for this control are not known, studies in both animal models and in humans 
suggest that, in addition to direct viral neutralization, bnAbs can enhance 
autologous cellular and humoral immune responses to HIV. Hence, by a variety of 
mechanisms, including formation of immune complexes, modulation of 
autologous immune responses, dampening HIV replication, exerting a sieve effect 
at acquisition, and immune pressure during early infection, bnAb concentrations 
that are insufficient to prevent HIV acquisition may nevertheless facilitate a more 
effective response to early infection and help set the stage for later durable 
virologic control. In addition, by these same mechanisms, bnAbs may be capable 
of limiting the establishment and decreasing the size of the viral reservoir.  
The Antibody Mediated Prevention (AMP) studies HVTN 704/HPTN 085 and 
HVTN 703/HPTN 081, phase 2b studies assessing the ability of the CD4 binding 
site bnAb VRC01 to prevent HIV-1 infection, provide a unique opportunity to 
assess these hypothesized bnAb effects as they currently have the only cohort of 
individuals who have acquired HIV infection in the presence of a bnAb. HIV-1–
infected AMP participants were diagnosed soon after acquisition, initiated ART 
relatively soon after diagnosis, and those in the VRC01 arms had some level of 
bnAb present at the time of infection. A pause in antiretroviral treatment—that is, 
an analytical treatment interruption (ATI)—is the only way to determine whether 

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the presence of VRC01 at the time of, or shortly after, acquisition of HIV, results 
in blunted, delayed, or absent viral rebound following discontinuation of ART, or 
subsequent immune control of any rebound that may be observed. If such an 
impact is observed, ATI is also the best means of assessing mechanisms and 
predictive biomarkers of that impact through assessment of innate, cellular, and 
humoral markers along with characterization of the viral reservoir. To avoid 
misattribution of extended or sustained virologic control, should such control be 
observed, a comparator group of HIV-1–infected placebo recipients will also be 
enrolled. Extensive virologic, immunologic, and safety monitoring will be 
conducted, and the trial has been formulated for consistency with recent 
consensus guidelines on the design and conduct of ATI studies (1, 2), particularly 
with respect to risk mitigation measures. 
The study schema is shown below. 
 

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1.2 
Schema 
 
 
 
 

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1.3 
Protocol team 
Protocol leadership 
Co-chairs 
Shelly Karuna 
HVTN Core, Fred Hutch 
206-667-4355 
skaruna@fredhutch.org 
Statistician 
Allan DeCamp 
SCHARP, Fred Hutch 
206-667-7892 
adecamp@scharp.org 
 
Katharine Bar 
Univ. of Pennsylvania 
215-573-8497 
bark@pennmedicine.upenn.edu 
Medical officers 
Randall Tressler 
DAIDS Therapeutics Research 
Program 
240-627-3072 
randall.tressler@nih.gov 
Protocol Team 
leaders 
Shelly Karuna 
HVTN Core, Fred Hutch 
206-667-4355 
skaruna@fredhutch.org 
 
Lydia Soto-Torres 
International HIV 
Research\Latin American HIV 
Research Liaison, NIAID 
lsoto-torres@niaid.nih.gov 
301-213-1154 
 
 
 
Phil Andrew 
HPTN LOC, FHI 360 
919.544.7040 x11213 
pandrew@fhi360.org 
 
 
 
Laboratory Leads 
John Hural 
HVTN Laboratory Program, 
Fred Hutch 
206-667-1683 
jhural@fredhutch.org 
 
 
 
Estelle Piwowar-Manning  
HPTN Laboratory Center 
Johns Hopkins University 
410-614-6736 
epiwowa@jhmi.edu 
 
 
 
 
 
 
Other contributors  
Core medical 
monitor 
Shelly Karuna 
HVTN Core, Fred Hutch 
HVTN Regional medical 
liaison, South America 
Robert De La Grecca 
HVTN Core, Fred Hutch 
Consulting 
investigators 
Tae-Wook Chun 
NIAID Laboratory of 
Immunoregulation 
HVTN Clinical safety 
specialist 
Maija Anderson 
HVTN Core, Fred Hutch 
 
Michael Sneller 
NIAID Laboratory of 
Immunoregulation 
HVTN Social behavioral 
scientist 
Michele Andrasik 
HVTN Core, Fred Hutch 
 
Lucio Gama 
NIAID Vaccine Research 
Center 
HVTN Clinical trials 
manager 
Carissa Karg 
HVTN Core, Fred Hutch 
 
Jorge Gallardo Cartagena 
Centro de Investigaciones 
Tecnológicas Biomédicas y 
HPTN Clinical research 
manager 
Phil Andrew 
HPTN LOC, FHI 360 

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Medioambientales, Lima, 
Peru 
HVTN Laboratory 
representatives 
Lisa Sanders 
HVTN Laboratory Program, 
Fred Hutch 
Statistical research 
associate 
Erika Rudnicki 
SCHARP, Fred Hutch 
HPTN Laboratory 
representatives 
Vanessa Cummings 
HPTN Laboratory Center 
Johns Hopkins University 
Clinical data manager 
Alison Ayres 
SCHARP, Fred Hutch 
Regulatory affairs 
associate 
Megan Brandon 
HVTN Core, Fred Hutch 
SDMC Associate director 
of lab science 
April Randhawa 
SCHARP, Fred Hutch 
Clinic 
coordinators 
Debora Dunbar 
Univ. of Pennsylvania CRS 
Philadelphia, PA, USA 
Protocol development 
manager 
Carter Bentley 
HVTN Core, Fred Hutch 
 
Milagros Sabaduche 
Impacta San Miguel CRS  
Lima, Peru 
HVTN Community 
engagement unit 
representative 
Gail Broder  
HVTN Core, Fred Hutch 
Community 
Advisory Board 
(CAB) members 
Mark Hubbard 
Vanderbilt University CAB 
Nashville, TN, USA 
HPTN Community 
program associate 
Jonathan Lucas 
HPTN LOC, FHI 360 
 
Derrick Mapp 
Bridge HIV CAB 
San Francisco, CA, USA 
Community 
educator/recruiter 
DaShawn Usher 
New York Blood Center CRS 
New York, NY, USA 
Prevention 
research specialist 
Michelle Robinson 
HPTN LOC, FHI 360 
 
Hugo Sanchez 
San Marcos CRS 
Lima, Peru 
Ethics 
representative 
Stuart Rennie 
University of North 
Carolina, Chapel Hill, NC, 
USA 
Technical editor 
Richa Chaturvedi 
HVTN Core, Fred Hutch 
 
 
 
 
 
 

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2 
Background and rationale 
2.1 
Antiretroviral therapy 
Antiretroviral therapy (ART) can now achieve prolonged suppression of plasma 
viremia in most HIV-infected individuals. Consequently, ART has dramatically 
improved the mortality, morbidity, quality of life, and overall clinical course of 
infected individuals. However, ART alone has been unable to completely 
eradicate HIV; plasma viremia rapidly rebounds with reactivation of persistent 
viral reservoirs in almost all chronically HIV-infected individuals upon cessation 
of therapy (3-6). Persistence of HIV reservoirs, even with successful suppression 
of plasma viremia by ART, is a major obstacle to HIV eradication.  
Furthermore, clinically successful suppression of HIV comes at a cost: long-term 
toxicity, drug-drug interactions, drug resistance and pill fatigue necessitate a 
continued search for effective alternatives for achieving durable control of HIV 
replication in infected individuals. Thus, one of the highest priorities for the HIV 
field is the search for therapeutic strategies that can eliminate or control HIV 
replication and reservoirs in the absence of ART. One potential strategy is to 
provide passive immunization via broadly neutralizing monoclonal antibodies 
(bnAbs) against HIV. 
2.2 
Broadly neutralizing antibodies (bnAbs) 
Over the past decade, several bnAbs have been discovered and isolated and their 
HIV-1 target sites and mechanisms of neutralization have been elucidated (7-14). 
These efforts have informed the development of recombinant HIV vaccine 
immunogens designed to elicit broadly neutralizing antibodies (11, 15-19) and 
they have set the stage for an evaluation of these antibodies’ potential as tools for 
HIV-1 prevention (ie, passive immunization or antibody-mediated prevention), 
treatment, and possibly cure (20-25). Results from early phase clinical trials using 
different classes of bnAbs such as those targeting the CD4 binding site (VRC01 
and 3BNC117) and the V3 loop (10-1074 and PGT121) have been encouraging, 
demonstrating the potential for—and challenges of—developing anti-HIV-1 
bnAbs as preventive and therapeutic agents (26-29). 
Several early phase trials in HIV-uninfected and HIV-infected individuals 
demonstrated the safety, tolerability, antiviral activity, and pharmacokinetics of 
VRC01 (26, 27, 30-32) and in 2016 VRC01 advanced to the first bnAb prevention 
efficacy trials in HIV-uninfected individuals, the Antibody-Mediated Prevention 
(AMP) trials HVTN 704/HPTN 085 and HVTN 703/HPTN 081. 

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2.3 
bnAbs can mediate virologic control  
Preclinical (eg, murine, NHP) and clinical (ie, human) evidence is mounting in 
support of the premise that anti-HIV bnAbs can mediate sustained virologic 
control of HIV. In a preclinical experiment designed to assess the impact of early 
immunotherapy postacquisition, VRC01 was administered 10 days after 
SHIVSF162P3 inoculation (immediately prior to projected peak viremia) in six 
rhesus macaques, while another six macaques received a combination of VRC07-
523LS + PGT121, and another six macaques received ART alone from day 10. 
Though SHIVSF162P3 is ~10-fold less sensitive to VRC01 than most isolates and 
both VRC07-523LS and PGT121 are more potent than VRC01, suppression of 
viral replication was comparable across all groups prior to the development of 
anti-mAb antibodies, a known limitation of the NHP model for bnAb 
administration (see Figure 2-1) (33). 
 
 
Figure 2-1 Geometric mean plasma SHIV viral loads (pVL) for the untreated group and the 3 
treatment groups (n = 6 per group). The error bars represent the 95% confidence intervals at 
each time point. From (33) Figure 2B. 
In another recent study (34), macaques were infected with SHIVAD8-EO. Three 
days after infection (prior to antibody seroconversion), the animals were 
randomized to receive either a 2-week course of 10-1074 and 3BNC117 or 
standard ART. At 15 weeks postinfection, the ART group discontinued ART. Six 
of the 13 animals treated with 10-1074 and 3BNC117 exhibited prolonged 
suppression of plasma viremia long after serum levels of infused antibodies 
became undetectable; in five of these controller macaques, this period of 
suppression followed an initial rebound of viremia with preservation of CD4+ T 
cells (see Figure 2-2 and Figure 2-3). Although the 7 noncontroller bnAb-treated 
macaques did not fully suppress virus, 4 of those 7 maintained CD4+ T cell 
counts and low levels of viremia (105 – 385 copies/mL) without ART for 2-3 
years postinfection. Thus, 10 of the 13 bnAb-treated macaques appeared to 
benefit from early immunotherapy. In contrast, none of the 3 ART-treated animals 
exhibited sustained suppression of plasma viremia following discontinuation of 

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ART. No significant differences in HIV-specific CD8+ or CD4+ T-cell responses 
or anti-gp120 binding antibody levels were observed in controller and 
noncontroller bnAb-treated macaques, but infusion of a T-cell-depleting anti-
CD8β mAb in the 6 controller animals led to depletion of CD8+ T cells and the 
rapid reappearance of plasma viremia, suggesting that the prolonged suppression 
of viremia observed in these animals resulted from potent antiviral CD8+ T-cell 
immunity induced by the short course bnAb treatment amidst low levels of viral 
replication (34). 
 
Figure 2-2 Establishment of controller status in bnAb-treated animals inoculated with 
SHIVAD8-EO by the intrarectal route (a-f). Plasma viral loads (black) and CD4+ T-cell levels (red) 
are shown in three controller (a-c) and three noncontroller (d-f) macaques. From (34), Figure 2. 

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Figure 2-3 Establishment of controller status in bnAb-treated animals inoculated with 
SHIVAD8-EO by the intravenous route (a-g). Plasma viral loads (black) and CD4+ T-cell levels (red) 
are shown in three controller (a-c) and four noncontroller (d-g) macaques. From (34), Figure 3. 
3BNC117 and 10-1074 in combination, and 3BNC117 alone, have also been 
associated with virologic control in humans. Thirteen individuals with chronic 
HIV who received 2 or 4 3BNC117 infusions, immediately prior to analytical 
treatment interruption and then separated by three or two weeks, respectively, had 
a mean time to virologic rebound of 6.7 weeks (range of 5-9 weeks) after two 
infusions of the antibody or 9.9 weeks (range of 3-19 weeks) after four infusions 
of the antibody. Eleven chronically infected individuals who received 3BNC117 
and 10-1074 immediately prior to and 3 and 6 weeks after analytical treatment 
interruption had a median time to virologic rebound of 21 weeks (range 5 to >30 
weeks) (35, 36) (see Figure 2-4).  
 
Figure 2-4 Kaplan–Meier plots summarizing time to viral rebound for the participants with HIV-
1 RNA < 20 copies per ml two weeks before and at the start of ATI (n = 11, left), for the participants 
sensitive to both antibodies (n = 9, center), and for the participants that showed pre-existing 
resistance to one of the antibodies (n = 2, right). The y axis shows the percentage of participants 
that maintain viral suppression. The x axis shows the time in weeks after start of ATI. Participants 
receiving the combination of 3BNC117 and 10-1074 are indicated by the blue line. Dotted red lines 

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indicate a cohort of individuals receiving 3BNC117 alone during ATI (35) (n = 13) and dotted black 
lines indicate a cohort of participants who underwent ATI without intervention (37) (n = 52). From 
Mendoza, et al. (36), Figure 1c. 
2.4 
bnAbs modulate the autologous immune response to acute HIV 
infection 
The mechanisms underlying bnAb-mediated virologic control are unknown, but 
there are clues in experiments that highlight bnAb-associated enhancement of 
autologous cellular and humoral responses. Adoptive transfer experiments have 
demonstrated that 3BNC117 can accelerate clearance of HIV-infected cells (see 
Figure 2-5) (38).  
 
Figure 2-5 Percentage of Gag+ cells among CD3+CD8- cells in mice treated with 3BNC117 
(600 mcg) or mice treated with isotype control 5 hours after HIV-1YU2–infected cell transfer. 
From (38) Figure 2A. 
Barouch, et al. demonstrated increased CD8+ T cell-mediated virus inhibition and 
decreased CD8+ and CD4+ T cell exhaustion in the presence of PGT121 
compared to control as well as increased titers of autologous neutralizing antibody 
in macaques receiving PGT121, 3BNC117, and b12 (see Figure 2-6 and Figure 
2-7) (39). 
 
Figure 2-6 SHIVSF162P3 and SHIVSF162P4 serum neutralizing antibody titers (ID50) in the 
macaques described in Figure 2-7 after administration of the triple PGT121, 3BNC117, and 
b12 monoclonal antibody cocktail. From (39) Extended Data Figure 2. 
  

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Figure 2-7 Therapeutic efficacy of the triple PGT121, 3BNC117, and b12 monoclonal 
antibody cocktail. LEFT: Log inhibition of viral replication in CD8+ T-lymphocyte-dependent virus 
suppression assays after monoclonal antibody infusion. One animal had no recoverable virus at 
week 2. CENTER and RIGHT: PD-11Ki671 expression on Gag-specific CD8+ (center) and CD4+ 
(right) T lymphocytes after monoclonal antibody infusion. From (39) Figure 1f, 1g, and 1h. 
Enhanced humoral responses—specifically, elevated levels of HIV Env-specific 
antibodies—were also observed in macaques by Bolton, et al. (33). In this study, 
antibody titers in animals that received either VRC01 or VRC07-523LS + 
PGT121 with ART exceeded titers achieved by animals receiving ART alone (see 
Figure 2-8). 
 
Figure 2-8 Geometric mean endpoint titer values for plasma reactivity to HIV-1 SF162 gp120 
(anti-HIV Env) determined by ELISA for each group (n = 6) at the indicated days postinfection. 
Error bars represent the 95% confidence intervals; the dotted lines indicate the limit of detection for 
the assay. From (33) Figure 3B. 
Haigwood, et al. demonstrated accelerated development of autologous 
neutralizing antibodies in macaques. Uninfected macaques were assigned to no 
immunization (n = 4) or passive immunization, 1 and 14 days after challenge, 
with either normal IgG (n = 6) or SIVIG (n = 6), which is a polyclonal IgG 
obtained from a healthy SIV-infected nonprogressor with high-titer neutralizing 
activity. Three of the 6 animals that received SIVIG showed accelerated 
development of neutralizing antibodies, in contrast to the animals that received 
normal IgG or no IgG (see Figure 2-9). These SIVIG-associated antibodies 
contributed to rapid control of post-acute phase viremia, resulting in delayed 
disease onset (40).  

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Figure 2-9 Scatter plot of Env-specific binding and SIVsmE660 nAbs at weeks 2 and 12 in 
macaques that seroconverted. Note that some symbols overlap. Mean ratios are noted for each 
group at weeks 2 and 12, with 95% confidence intervals. From (40), Figure 5. 
Schoofs, et al. also observed significantly increased autologous neutralizing 
antibody breadth and potency in chronically infected viremic individuals who 
received 3BNC117 compared to controls (see Figure 2-10) (41). 

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Figure 2-10 Heterologous antibody responses. (A) The difference in overall AUC (mean AUC 
change) per individual in TZM.bl assays against 13 heterologous viruses for d0 versus week 24 IgG 
obtained from 36 untreated viremic controls (mean sampling interval 26.8 weeks), 15 viremic 
individuals infused with 3BNC117 (mean sampling interval 24.1 weeks), and 12 ART-treated 
individuals receiving 3BNC117 infusion (mean sampling interval 24.0 weeks). (B) The aggregated 
differences in AUC between d0 and week 24 IgG assayed by TZM.bl for all viruses and all 
individuals. Each dot represents a single AUC difference for a single virus from one individual 
displayed in (A). Colored bars represent the mean of all AUCs. (C) 3BNC117 antibody levels 
(ELISA, white) and TZM.bl neutralization titer against tier 2 strain Q769.d22 (green) in patient 2A3. 
(D) Mean AUCs of IgGs of all individuals at d0 (gray) and week 24 (color of respective group) for 
each HIV-1 pseudovirus tested. Changes in neutralization of viremic control individuals without 
3BNC117 infusion are shown in yellow (left). Change in neutralization of 3BNC117-treated 
individuals are shown in dark blue (off ART, middle) and light blue (on ART, right). Red stars 
indicate significant p-values after Bonferroni correction (threshold p < 0.0038). From (41), Figure 2. 
Furthermore, bnAbs appear to render otherwise-ineffective autologous antibodies 
more effective. In a hu-mice model in animals lacking autologous neutralizing 
antibodies, 10-1074 administered in combination with an autologous tier-1 

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neutralizing antibody (either 10-188 or 1-79) was associated with significantly 
greater reduction in viremia than 10-1074 or the autologous bnAbs alone. 
Additional experiments (data not shown) suggested that bnAbs directed viral 
evolution to variants more sensitive to autologous tier-1 nAbs, while the 
autologous nAbs also appeared to limit viral evolution away from the bnAb (see 
Figure 2-11) (42).  
 
Figure 2-11 Changes of log10 viral load (mean and SEM) of mice treated with 10-1074 (gray), 
10-1074 + 10-188 (blue), and 10-1074 + 1-79 (green). Significant differences between treatment 
groups were determined by using repeated measures ANOVA with a Bonferroni pos-hoc test. *, p < 
0.05; **, p < 0.001; ***, p < 0.0001). From (42) Figure 7D.  
The concurrent enhancement of both cellular and humoral responses, and the 
evidence of virologic control in the face of it, calls to mind the immunologic 
responses to tumor antigens in individuals receiving cancer immunotherapy, and 
implicates immune complexes formed by bnAbs bound to circulating virus and 
infected cells (43, 44). Immune complexes act as potent immunogens, as 
evidenced by work in the HIV vaccine field. A trial of an immune complex 
vaccine reported that anti-CD4bs complexes with gp120 led to conformational 
changes in gp120 that stabilized and exposed epitopes in the V3 loop, leading to 
enhanced antigenicity and immunogenicity compared to gp120 alone (45, 46). 
This recapitulates the difference in HIV acquisition without bnAbs present (ie, 
comparable to gp120 alone) compared to acquisition in the presence of bnAbs 
bound to the gp120, forming immune complexes that stimulate a more effective 
autologous immune response.  
Immune complexes with infected cells and with cell-free virions undergo FcγR-
mediated uptake by antigen presenting cells (eg, dendritic cells) and efficient 
antigen processing via proteasomal and endosomal degradation, that exposes 
particularly antigenic epitopes for MHCII presentation, stimulating enhanced 
CD4+ T-cell responses and directing the immunologic response down a Th1 
pathway, with enhanced CD4+ co-stimulation, a more efficient cytokine milieu 
for antiviral control, and enhanced CD8+ T-cell responses. The consequent 
development of pools of precursor T cells, in particular, sets the stage for durable 
virologic control, as these cells proliferate in the presence of antigen later, 
producing large amounts of effector T cells that then clear HIV-infected cells and 
virions (47-49). In fact, this pathway has been demonstrated in the murine FrCasE 
retrovirus model that has many similarities to HIV infection. Treg suppression was 

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also observed in this model after therapeutic bnAb administration and subsequent 
immune complex-mediated induction of an antiviral host response that preserved 
immune function and stymied disease development, demonstrating yet another 
potential contribution to the bnAb-optimized early antiviral responses that may 
ultimately yield long-term virologic control (50, 51).  
Rendering this enhancement of the innate component of the immune response 
even more effective is bnAbs’ binding and neutralization of virus—a direct 
“debulking” of viral particles and of infected cells, thus limiting the number of 
virions capable of direct infection and replication and serving to limit viral factors 
that impair dendritic cell activation and maturation. This “viral debulking” 
function of bnAbs is analogous to surgical debulking (ie, cytoreductive surgery) 
performed for some tumors, which is associated with a survival advantage that is 
attributed in part to improved autologous immune function, with lower levels of 
tumor factors that impair the host immune response to cancer.  
In summary, by forming immune complexes, modulating and enhancing 
autologous immune responses, dampening HIV replication, and exerting a sieve 
effect at acquisition and pressure in early infection, even bnAb concentrations that 
are insufficient to prevent acquisition might nevertheless work in concert with the 
autologous innate and adaptive immune response to facilitate a more effective 
response to early infection and to help set the stage for later durable virologic 
control (52-54).  
2.5 
bnAbs may limit establishment and decrease the size of the viral 
reservoir 
In addition to, and in part likely due to, their enhancement of innate and adaptive 
immune responses, bnAbs appear to be capable of limiting the establishment and 
decreasing the size of the viral reservoir (25, 55). An in-vitro study of cells 
obtained from chronically infected aviremic humans demonstrated bnAb binding 
of cell-free virions produced from the latent reservoir, suppression of entry of 
those virions to activated uninfected CD4+ T cells, and suppression of replication-
competent HIV in autologous CD4+ T cells (56). In a humanized mouse model, 
administration of bnAbs 4 days after infection interfered with the establishment of 
a reservoir through Fc-mediated mechanisms and, when administered with 
latency-reversal agents, decreased the size of an established viral reservoir (20). 
Administration of bnAb with ART to reduce viral load, then of a single bnAb 
alone after ART termination, was followed by functional virologic control, 
demonstrating potential synergy between bnAbs and ART for durable viral 
suppression (57). In macaques, a reduction in cell-associated viral DNA and RNA 
in peripheral blood mononuclear cells (PBMCs) and tissues was also observed 
after administration of single and combination bnAb immunotherapy (39, 58).  
The mechanisms of these impacts on the viral reservoir are likely myriad and 
include direct neutralization of virions from reactivated cells and bnAb binding 

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and Fc-mediated recruitment of cytotoxic immune cells (eg, NK cells) that kill 
reactivated cells, which may be significantly enhanced by immune complex 
formation as described above (20, 25, 49). BnAbs accomplish this work of 
limiting reservoir seeding, and later reducing reservoir size, not only in blood and 
interstitial fluid but also in some of the principal sites of pre-ART virus 
production and persistence, lymph nodes and gut-associated lymphoid tissue, in 
which antiretrovirals have less penetrance (59-61). In one study, a significant 
reduction of cell-associated SHIV DNA was observed in these tissues after 
administration of a single bnAb to infected macaques (39) (see Figure 2-12). 
 
Figure 2-12 Therapeutic efficacy of the single monoclonal antibodies PGT121 and 3BNC117. 
a–c, Plasma viral RNA (log copies/mL) in rhesus monkeys chronically infected with SHIV-SF162P3 
after a single infusion (arrows) of PGT121 (a), 3BNC117 (b), or the control monoclonal antibody 
DEN3 (c). d–f, Proviral DNA (copies/106 cells) in peripheral blood mononuclear cells (PBMCs) (d), 
lymph nodes (e) and gastrointestinal mucosa (f) 14 days after the monoclonal antibody infusion in 

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the animals that received PGT121 or DEN3. Red bars indicate mean values. Assays for one of the 
DEN3-treated controls failed. g, h, PD-1+ Ki671+ expression on Gag-specific CD8+ (g) and CD4+ 
(h) T lymphocytes in the monkeys that received PGT121. From (39), Figure 3. 
2.6 
The HVTN 704/HPTN 085 AMP study 
HVTN 704/HPTN 085 opened in early 2016 and enrolled 2701 men who have sex 
with men (MSM) and transgender (TG) individuals. Participants were randomized 
1:1:1 in a double-blind fashion to receive 10 mg/kg VRC01, 30 mg/kg VRC01, or 
placebo. Participants receive study product via intravenous (IV) infusion every 8 
weeks for a total of 10 infusions over 72 weeks and are then followed every four 
weeks to week 80, and every 8 weeks thereafter to week 104 (62) (see Table 2-1). 
In addition to assessing the prevention efficacy of VRC01 and providing further 
VRC01 safety and PK data, the AMP studies include assessment of functional 
activity (ie, Fc effector functions), sieve analyses, and correlates analyses. Both 
AMP studies completed enrollment in October 2018. 
Table 2-1 HVTN 704/HPTN 085 AMP schema 
 
 
 
Infusion schedule (Weeks) 
[A = VRC01 infusion; C = Control infusion] 
 
Treatment 
N* 
W0 
W8 
W16 
W24 
W32 
W40 
W48 
W56 
W64 
W72 
W80♦ 
W104† 
Group 
1 
VRC01  
10 mg/kg  
900 
A 
A 
A 
A 
A 
A 
A 
A 
A 
A 
 
 
Group 
2 
VRC01  
30 mg/kg  
900 
A 
A 
A 
A 
A 
A 
A 
A 
A 
A 
 
 
Group 
3 
Control 
900 
C 
C 
C 
C 
C 
C 
C 
C 
C 
C 
 
 
* Due to the randomization scheme, the numbers of VRC01 and control recipients may differ 
slightly. 
♦ Week 80 is the last study visit for the primary endpoint analysis of prevention efficacy. 
† Week 104 is the last study visit for the co-primary endpoint analysis of safety and tolerability. 
HIV diagnostic testing is conducted every 4 weeks and is accompanied by 
collection of serum and, at up to four time points, PBMCs for storage. Participants 
who become HIV-infected discontinue further study infusions and are monitored 
(on visit Schedule 2) for 24 weeks with viral loads, CD4+ T-cell counts, and 
VRC01 levels, while providing serum, plasma and PBMCs for storage, functional 
humoral assays and other assessments. HIV-infected participants are linked to 
care for ART initiation and additional clinical follow-up.  
Most HVTN 704/HPTN 085 participants initiate ART within 4 weeks of 
confirmation of HIV infection, a mean of 7 weeks after the first RNA-positive 
HIV diagnostic sample. The vast majority of participants exhibit HIV diagnostic 
patterns of RNA-positive, EIA-positive, and Bio-Rad 
Geenius-negative, -indeterminate, or -positive with p31-negative at the time of 
their confirmatory HIV diagnostic sample, and initiate ART within 4 weeks of 
this time point.  

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2.7 
Antiretroviral analytical treatment interruption (ATI) 
More than 150 studies with ATIs have been conducted since the introduction of 
combination ART over twenty years ago. Nearly 100 of those were conducted in 
the first decade of the 21st century, largely seeking to mitigate the risk of ART 
toxicity, multiresistant virus, and treatment failures (63). Among these was the 
SMART trial, which evaluated standard continuous ART (n = 2,720) vs. episodic, 
CD4+ T cell count-guided ART (n = 2,752). In 2006, the SMART team reported a 
hazard ratio of 2.6 (95% CI 1.9-3.7, p < 0.001) for the combined primary study 
endpoint of opportunistic disease or death from any cause when comparing 
episodic ART with standard continuous ART. Of note, the trial enrolled 
participants with CD4+ counts of > 350 and with any ART history; did not 
exclude participants with chronic HCV or HBV infection; monitored participants 
every two months in the first year and then every 4 months thereafter; and re-
initiated ART in the episodic arm only when CD4+ T-cell counts dipped below 
250 cells/mL. There were no virologic criteria for re-initiating ART, and the 
median duration of the first ATI in the episodic ART group was 16.8 months (64). 
A subset analysis of the SMART data revealed that all SAEs in the trial occurred 
when CD4+ counts were below 300 cells/mL. This subset analysis was restricted 
to 16 weeks of treatment interruption, participants with CD4+ T-cell counts > 400 
cells/mL, ART re-initiation at CD4+ T-cell count of 350, and participants with no 
evidence of hepatitis B, hepatitis C, or diabetes at study entry. In participants 
meeting these criteria, no deaths and no renal or hepatic events were observed; 
two cardiac events were observed, one in each study group; and there was no 
difference in AIDS-related events (0.005% in the continuous ART group and 
0.002% in the episodic treatment group) (65). These findings of no mortality or 
treatment-interruption-associated morbidity in this SMART subset are consistent 
with observations reported for several concurrent and subsequent treatment 
interruptions (all smaller than SMART; approximately half were randomized 
clinical trials like SMART) that similarly limited eligibility for and duration of 
treatment interruption, re-initiated ART at higher CD4+ cell counts, and 
monitored participants more frequently (66-72).  
Treatment interruption designs post-SMART, including the design for HVTN 
804/HPTN 095, reflect lessons learned from SMART to mitigate the risks of 
treatment interruptions. Recent consensus guidelines on the design and conduct of 
analytical treatment interruptions further codify these risk mitigation measures 
and the current concept is aligned with these guidelines (see, eg, Figure 2-13 (1, 
2)) 

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Figure 2-13 Consensus recommendations of the July 9, 2018 forum held at the Ragon 
Institute of MGH, MIT and Harvard, Cambridge, MA, USA. From (2). 

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Specifically, the eligibility criteria recommended in Julg, et al. (2) and proposed 
by the HVTN 804/HPTN 095 team, help ensure that the risks of hepatic, renal, 
and cardiac morbidity and mortality observed in SMART are substantially 
reduced, as individuals are only eligible for treatment interruption if they have no 
active or chronic hepatitis B; no active hepatitis C; no evidence of other 
significant liver disease; no significant or unstable cardiac or cerebrovascular 
disease; and no evidence of HIV-related renal disease or moderate-to-severe 
reduction in eGFR. 
Eligibility and ART re-initiation criteria and the frequency and type of monitoring 
also address the HIV-related morbidity and mortality observed in the SMART 
trial. These safety features include eligibility only after an extended period of 
virologic suppression on ART; requirement that volunteers on Non-nucleoside 
reverse transcriptase inhibitors (NNRTI)-based ART regimens switch to short-
acting antiretrovirals (Protease Inhibitor [PI]- or Integrase Strand Transfer 
Inhibitor [INSTI]-based ART regimens) in order to prevent emergence of ART-
resistant HIV; that volunteers have neither a history of AIDS-defining illness nor 
of specified HIV-associated conditions; eligibility only at higher baseline CD4+ 
T-cell counts (note that Julg, et al. (2) recommends ≥ 500 or ≥ 350 cells/mL, 
depending on a range of factors); ART re-initiation for any symptomatic HIV 
disease, CD4+ T-cell counts < 350 cells/mL, or HIV RNA ≥ 1,000 copies/mL for 
4 weeks; and initial monitoring weekly and then biweekly, including CD4+ T-cell 
counts, viral load, and psychosocial experiences. 
The evidence that post-SMART changes in ATI trial design have, in fact, limited 
the risks of treatment interruption, is growing. For example, Huiting, et al. (73) 
demonstrated that among 22 participants who initiated ART in early HIV 
infection and then underwent a 16-week treatment interruption followed by re-
initiation of ART, there were no significant differences between pre- and 
post-ATI CD4+ or CD8+ T-cell counts or percentage and no significant 
differences in reservoir markers, including HIV DNA, cell-associated RNA, and 
replication-competent HIV (see Figure 2-14).  

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Figure 2-14 Kinetics of HIV reservoirs and immunologic parameters prior to and following 
ATI and reanimation of ART. The frequency of CD4+ T cells carrying HIV DNA and cell-
associated viral RNA was measured prior to (pre-ATI) and following ATI (ATI) and upon re-
initiation of ART (post-ATI). The frequency and cell count of CD4+ and CD8+ T cells are shown at 
the pre-ATI, ATI, and post-ATI timepoints. Statistical significance was tested with Wilcoxon signed 
rank test. *p < 0.05, **p < 0.01, ****p < 0.0001, NS, not significant. Adapted from (73) Figure 1. 
Bar, et al. (27) reported on 24 participants in two cohorts; in one cohort (A5340), 
participants had been taking ART for 3.8-6.0 years (median 4.7) and in the other 
(15-I-0140) participants had been taking ART for 7.7-13.3 years (median 10.0). 
All participants received VRC01, followed by an ATI, which ended upon 
confirmation of viral rebound. Median time to viral rebound was 4 weeks in the 
A5340 trial and 5.6 weeks in the 15-I-0140 trial. VRC01 slightly delayed plasma 
viral rebound compared with historical controls but did not sustain viral 
suppression. No safety issues were observed in either cohort. 
Clarridge, et al. (74) reported on the ten chronically infected participants in the 
15-I-0140 cohort who received VRC01 immediately before and during ATI 
(median of 8 weeks, range 3-17 weeks). The length of the treatment interruption 
was governed by the time to meeting ART re-initiation criteria, which included a 
decrease of > 30% in the baseline CD4+ T-cell count or an absolute CD4+ T-cell 
count < 350 cells/mL, sustained (≥ 4 weeks) plasma viremia > 1,000 copies/mL, 
any HIV-related symptoms or pregnancy (27, 74). During treatment interruption, 
total HIV DNA in CD4+ T cells increased significantly from preinterruption 
levels and all participants rebounded, with median peak viremia of 30,950 
copies/mL observed (range 340 - 273,221). By 6-12 months post-ATI, reservoir 
size, including the proportion of near full-length, genome-intact proviral 
sequences and structurally defective proviral sequences, and immune markers of 

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exhaustion and activation returned to pre-ATI levels; CD4+, CD8+ (including 
activated CD8+), B, and NK cell levels also returned to pre-ATI levels; and there 
was no evidence of emergence of antiretroviral drug resistance mutations in intact 
proviral DNA sequences.  
Similar findings were reported by Salantes, et al., among 14 chronically infected 
individuals who received VRC01 immediately prior to and during treatment 
interruption (median of 6 weeks, range 3-14 weeks) in A5340. The length of the 
treatment interruption was governed by the time to meeting ART re-initiation 
criteria, which included CD4+ T-cell count < 350 cells/mL or a return of HIV 
viremia defined as HIV RNA ≥ 200 copies/mL followed by HIV RNA ≥ 1,000 
copies/mL or three consecutive measurements of ≥ 200 copies/mL. No significant 
changes in pre or postinterruption reservoir size or composition were observed by 
quantitative PCR, cell-associated RNA or quantitative viral outgrowth assay 
(QVOA). Perhaps most relevant to HVTN 804/HPTN 095, these findings 
remained true for participants with very small and relatively less heterologous 
reservoirs pre-ATI (eg, participant 7 in Figure 2-15) (75). 
 
Figure 2-15 Quantitative measures of reservoir change. Pre-ATI and post-ATI values (obtained 
at study entry and more than 6 months after viral suppression following ART re-initiation, 
respectively) of total HIV-1 DNA in CD4+ T cells (A), cell-associated HIV-1 RNA (caRNA) in CD4+ 
T cells (B), and the frequency of resting CD4+ T cells bearing replication-competent virus (IUPM) 
(C) are shown for each A5340 participant. Total DNA is not shown for participant A06, because the 
values were below detectable levels at both timepoints. P-values shown in A–C indicate the 
significance of the within-participant changes and were determined by Wilcoxon signed-rank test. 
From (75), Figure 2. 
Strongin, et al., assessed reservoir measures in 12 early- and chronic-treated 
participants across four ACTG studies that included ATI. Participants had at least 
1 year of suppressive ART prior to treatment interruption that lasted a median of 
12 weeks. No change in integrated HIV DNA was observed between baseline, 
pre-ATI samples and samples six months after ART re-initiation (76). In a 
shorter-term ATI, with a median duration of approximately 4 weeks, Papasavvas, 
et al., demonstrated similar findings among 23 chronically-treated, ART-
suppressed individuals. As expected, treatment interruption was accompanied by 
decreases in CD4+ T cells and increases in HIV viral load, markers of T-cell 
activation (eg, HLA-DR and CD38 co-expression), and levels of cellular HIV 

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DNA (total DNA and 2-LTR [long terminal repeat] circles in PBMCs) and 
cellular RNA (by PCR). However, upon re-initiation of ART, viral re-suppression 
was achieved at a median of 13 weeks and levels of CD4+ T cells, T-cell 
activation markers, and cellular HIV DNA and RNA returned to baseline, pre-
ATI levels (77). 
A recent meta-analysis offers further reassurance of the safety of ART treatment 
interruption with respect to rates of adverse events experienced by participants in 
trials with treatment interruptions. The meta-analysis included 7,104 participants 
across 22 studies with varying ATI designs, allowing for comparisons of 
outcomes across trials with different eligibility criteria, treatment interruption 
duration, follow-up intervals and ART re-initiation criteria. The overall rate of 
adverse experiences (AEs) during ATIs longer than 4 weeks’ duration was 3% 
(95% CI 0%-7%) and was lower in studies with monitoring ≤ every 2 weeks (0%; 
95% CI 0%-1%) than in studies with less frequent follow-up (6%; 95% CI 2%-
13%; p-value for interaction = 0.01). Among the studies reporting new viral 
resistance mutations emerging during ATI, a 3% (95% CI 0%-8%) rate of such 
mutations was observed, with a higher rate in studies with less frequent 
monitoring (9%; 95% CI 3%-16%) compared to the rate observed in trials with 
more frequent (≤ every 2 weeks) monitoring (0%; 95% CI 0%-1%; p = 0.03). Of 
note, the analysis was unable to discern which ART regimens preceded ATI in all 
of these trials, thus limiting their ability to account for trials with NNRTI switch 
periods to reduce the risk of the development of viral drug resistance mutations. 
Baseline CD4+ T-cell count was also associated with outcomes, with baseline 
CD4+ T cells > 500 cells/mcL associated with the fewest AEs (0%; 95% CI 0%-
3%) (78, 79). 
The authors conclude that treatment interruption can be conducted safely—with 
no lasting negative impact on clinical, immunologic, immune activation or 
virologic parameters—when appropriately designed, including frequent 
monitoring and appropriate duration, eligibility and re-initiation criteria. The cited 
authors of the meta-analysis and assessments of ATI impacts described above 
specifically note that appropriate re-initiation criteria should allow for viral spikes 
(ie, without re-initiating ART prematurely) that may be necessary to elicit the 
ART-free, virologic suppression potential of immunomodulatory interventions, 
like bnAbs (73, 78-82). 
The mitigation of risk in treatment interruptions relies on the optimal 
implementation of eligibility assessment, monitoring, timely ART re-initiation, 
and other risk mitigation practices. An assessment of site capacity to implement 
these aspects of the treatment interruption design—for example, capacity for 
weekly and biweekly clinic visits, including retention and adherence metrics thus 
far, and access to ART for timely re-initiation, including metrics of initial ART 
uptake—was completed prior to the determination of participating sites. Ongoing 
monitoring of the implementation of these risk mitigation measures will be in 
place throughout the trial’s conduct. However, even with these measures, 
treatment interruptions do still entail risk and promise no anticipated benefit. 

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These points must be made clear in an informed consent for individuals 
contemplating any interruption in their antiretroviral therapy.  
A pause in antiretroviral therapy—with careful eligibility criteria, frequent 
clinical and laboratory monitoring, and clear criteria for ART re-initiation—is a 
safe and acceptable strategy to evaluate the efficacy of VRC01 in this population 
of antiretroviral-treated HIV-infected adults. Current and prior studies of immune-
based therapy, including a subgroup analysis of the SMART study, support the 
value, safety and acceptability of interruptions in antiretroviral therapy to assess 
virologic efficacy in this context (27, 35, 65, 73, 80, 83-87). In addition, while 
there remains uncertainty regarding how best to measure the latent HIV reservoir, 
several recent studies of participants undergoing similar short-term interruptions 
in antiretroviral therapy have noted no persistent changes in the size of the latent 
reservoir of infected CD4+ T cells following re-suppression by ART, based on the 
measures currently thought to reflect HIV reservoir size (73-80). Specifically, 
ATI with intensive monitoring evaluating time to viral rebound has been 
advanced as a careful approach to utilizing a pause in ART to allow observation 
and insight regarding novel therapeutic approaches to control HIV off ART (61, 
88, 89). 
2.8 
An AMP ATI  
To date, most efforts to explore the potential for bnAbs to facilitate durable 
virologic control have taken place in chronically infected individuals who, in 
some cases, initiated ART before the advent of guidelines directing ART 
initiation immediately upon HIV diagnosis. Even when ART initiation and viral 
suppression are achieved relatively early postacquisition, inflammation and 
impaired immune responses accrue over time in chronic infection, contributing to 
morbidity and mortality and likely facilitating viral persistence through several 
mechanisms, rendering ART-free control or cure more challenging (90-95). 
Consider, for example, the two cohorts described in Bar, Sneller, et al. in which 
VRC01 was administered to chronically HIV-infected individuals prior to 
treatment interruption (27). Only a slight delay in viral rebound compared to 
historical controls was reported (median of 4 weeks in Bar’s A5340 cohort and 
median of 5.6 weeks in Sneller’s NIH 15-I-0140 cohort). The individuals in these 
cohorts had the heterologous viral populations typically observed in individuals 
with chronic infection. In 1 of the cohorts (A5340), most participants had virus 
with preexisting resistance to VRC01; and the prevalence of preexisting resistance 
predicted viral rebound patterns. Analysis of HIV sensitivity to an array of bnAbs 
in the second cohort (15-I-0140) suggested similar results. Evidence of VRC01-
mediated selective pressure on rebounding virus was observed in most 
participants; and of only 2 participants who rebounded with HIV expressing 
VRC01-sensitive envelope glycoproteins, 1 rebounded only after VRC01 
concentrations waned (27). Thus, while there was clearly an effect of VRC01 on 
the virus, it was insufficient to induce meaningful control in the face of 

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heterologous and VRC01-resistant viral populations in hosts with chronic 
infection. 
In distinct contrast, the AMP team is in the singular position of having an 
opportunity to explore the potential for VRC01 to facilitate ART-free durable 
virologic control when present at the time of acquisition—acquisition by an 
immunologically intact host of a relatively homologous virus in the presence of a 
bnAb with considerable breadth. The potential of VRC01, and of bnAbs more 
generally, in this unique immunologic context is explained by the hypothesis 
detailed above that considers the true complexity and interdependencies of the 
autologous immune response to HIV—innate, cellular, and humoral responses all 
modulated by the presence of bnAbs, like VRC01, binding HIV envelope 
proteins—a hypothesis based in extensive preclinical and clinical evidence of the 
potential impact of bnAbs on the earliest moments of HIV infection. 
AMP participants who acquired HIV are unique: they are diagnosed with HIV 
soon after acquisition due to monthly HIV diagnostics on-study; they initiate ART 
soon after diagnosis due to AMP-facilitated linkage to ART; and those 
randomized to receive VRC01 have circulating bnAb at the time of acquisition 
due to the q8-week frequency of infusion and VRC01 pharmacokinetics. This sets 
the stage for formation of immune complexes of VRC01 bound to free virions or 
HIV-infected cells which, as detailed above, can modulate the immune response 
and, thus, the course of infection. This cohort offers a singular opportunity to 
assess the potential impact of very early immunotherapy on the immunologic and 
virologic trajectory of infection, a contribution that recent preclinical and clinical 
data suggests could meaningfully enhance our understanding of HIV pathogenesis 
and illuminate potential host defenses, and means of enhancing them, that 
previous HIV preventive, therapeutic, or curative interventions have heretofore 
not identified or successfully engaged. 
A pause in antiretroviral treatment is the only way to determine if the presence of 
VRC01 at the time of, or shortly after, acquisition of HIV results in a blunted, 
delayed or absent plasma viral rebound off ART, or subsequent control of 
rebound that may be observed. If such an impact on viral rebound is observed, 
ATI is also the best means of assessing mechanisms and predictive biomarkers of 
that impact through a detailed assessment of innate, cellular, and humoral markers 
along with characterization of the viral reservoir. 
Recent research has suggested that viral rebound may be predicted by duration of 
infection, length of ART suppression, CD4+ T-cell nadir, total HIV DNA and 
cell-associated HIV RNA, among others; but samples and validation of these 
potential predictors are limited and there is no consensus biomarker predictive of 
durable viral suppression (37, 59, 96). Identification of reliably predictive 
biomarkers could inform future therapeutic and cure trial design and guide 
allocation of limited resources, advancing promising therapies more efficiently, 
and limiting exposure of trial participants to ineffective interventions. The AMP 
trial has pre and postinfection serum and limited PBMC samples on each 

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participant, including samples obtained ≤ 4 weeks from the time of acquisition 
and pre-ART. Thus, across currently available and proposed samples, ATI among 
AMP participants provides a unique opportunity to contribute to the exploration 
and validation of biomarkers, many observed in the preclinical studies described 
in Section 2.3 through 2.5 above, that may predict the virologic and immunologic 
course of infection among bnAb and placebo recipients. 
2.9 
Ethical considerations 
In the last two decades of treatment interruption conduct, an ethical framework 
for the conduct of such studies has evolved. There is general agreement that the 
risks of treatment interruption must be minimized; the trial must provide valuable 
data to answer an important question; and there must be no other methods 
entailing less risk that could answer that question (97, 98).  
While ethicists have noted that “in general, the risks of the ATI itself, when 
closely monitored, are considered to be low,” risk mitigation is an essential part of 
the design of any treatment interruption. Risk mitigation includes, but is not 
limited to, adoption of appropriate eligibility criteria; efforts to enhance potential 
participant benefits; community engagement in the design and implementation of 
the trial; frequent participant monitoring, balanced with considerations of 
participant burden; and a sound informed consent process. The informed consent 
process should acknowledge the risks and the lack of anticipated individual 
benefits, the fact that treatment interruptions are not recommended in clinical 
care, and the fact that ART guidelines recommend lifelong treatment (97, 98). 
Each of these recommendations has been adopted by the HVTN 804/HPTN 095 
Protocol Team. The HVTN 804/HPTN 095 informed consent process and Sample 
Informed Consent Form (SICF) include all points noted above and include 
elements demonstrated to improve the quality of informed consent in not only 
HIV research but also other fields (see Section 12.1). Trial design, including 
eligibility and ART re-initiation criteria, ATI duration, and monitoring frequency, 
are modeled on the most recent consensus guidelines for treatment interruption 
design (see Figure 2-13 above) (1, 2). The HVTN 804/HPTN 095 Protocol Team 
will implement not only rigorous counseling for participants on reducing HIV 
transmission risk to their partners but also a program for PrEP provision to 
participants’ partners while the participant is enrolled; HIV genotyping (not 
standard of care in many AMP regions, unless first-line ART options have been 
exhausted); and accelerated, physician-led ART (re-initiation) access for 
participants in regions where ART stock-outs, public nurse-led care, and a 
window of several weeks between meeting ART re-initiation criteria and ART 
initiation could pose challenges for participants. 
As all potential participants in HVTN 804/HPTN 095 would come from the 
parent HVTN 704/HPTN 085 study, early engagement of investigators and 
community representatives in several communities where HVTN 704/HPTN 085 

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is being conducted has already been initiated and is ongoing. These consultations 
with community stakeholders and investigators include an overview of the history 
and current context of treatment interruption, including potential risks and region-
specific considerations. They also provide an opportunity for dialogue about the 
immunologic hypotheses and design for HVTN 804/HPTN 095 and began laying 
a foundation of authentic stakeholder engagement in the earliest weeks of 
development of this study. See Section 2.11 below for further details. 
2.10 
The necessity of the AMP placebo control group 
As noted in the recently published Julg, et al., consensus guidelines for ATI 
conduct, “if a placebo group is necessary for the findings of the study to be 
properly interpreted, it could be considered unethical not to include a placebo (ie, 
when a placebo is a scientific necessity, it is arguably an ethical imperative as 
well)” (2). Having reviewed available historical and concurrent controls and 
finding them inadequate to support evaluation of the immune-mediated 
hypotheses described above, it is clear that enrolling a subset of AMP placebo 
participants is necessary for the correct interpretation of the results of HVTN 
804/HPTN 095. Hence, HVTN 804/HPTN 095 clearly appears to meet this 
consensus guideline. Considerations contributing to this conclusion are 
summarized below. 
First, post-treatment control (PTC) appears to be associated with early ART 
initiation, smaller HIV reservoirs, and longer ART duration pre-ATI (see Figure 
2-16; note that follow-up of participants in some of these cohorts continues, hence 
change in duration of virologic control is expected over time). PTCs, who have 
typically initiated ART in Fiebig stages III-V, exhibit sustained virologic control 
in the absence of ART (81, 99-101). The VISCONTI series reported a median 
remission of 9.3 years (range 4.5-12 years) among 20 PTCs (102). PTCs are 
immunologically distinct from elite controllers in that they generally lack 
protective HLA alleles and strong HIV-specific immune responses. While data 
remain limited on this cohort, the PTC phenotype suggests that early ART can 
durably alter the virus/host relationship, leading to possible long-term ART-free 
remission (81, 99-102). 
 

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Figure 2-16 Estimates of the frequency of post-treatment control and remission. Each 
data point represents an individual study, which has measured the frequency of post-treatment 
control or remission following treatment interruption among individuals who commenced ART 
during primary HIV infection (PHI). Included are analyses of the following studies: CASCADE 
(103, 104), ANRS Primo (105), VISCONTI (99, 106), SPARTAC (107, 108), CHAMP (81), 
ZHPI (109), SeaPIP (110) and NCT01859325 (80). Those which define post-treatment control 
(here considered to be > 24 months following treatment interruption) are colored green, those 
defining remission (> 4 months following treatment interruption) are shown in red. In some 
cases, a study explored both phenotypes; where possible these are disaggregated and listed 
twice, otherwise these are shown as remission. The duration of control is the time between 
treatment interruption and viral rebound, or the end of follow-up, and is plotted at the median 
value amongst controllers. The size of the point corresponds to the median duration of ART 
prior to treatment interruption amongst controllers. Where a study did not report either of these 
values, the minimum value for inclusion is used instead. From (111) Figure 1 (references 
added). 
Most AMP participants are estimated to initiate ART in Fiebig stages that may 
contribute to smaller reservoirs (eg, Fiebig III-V), and many AMP participants 
will have been on ART for well over a year by the time of the implementation of 
HVTN 804/HPTN 095. Considerable evidence suggests that these factors are 
likely to promote virologic control independent of, or potentially synergistically 
with, the hypothesized contribution of VRC01 (33, 81, 99-102, 111). However, 
the extent of control due to these non-immunotherapy-based factors cannot be 
predicted—estimates vary widely across studies of post-treatment control. Hence, 
some control group is essential in order to distinguish viral control attributable to 
VRC01 receipt from that caused by early ART initiation. Unfortunately, we have 
been unable to identify any clinical study cohort outside AMP that is sufficiently 
comparable to AMP placebo recipients to provide an adequate control comparator 
(see Table 2-2). In the absence of a placebo control group, the risk of 
misattributing observed control to VRC01 and, thus, misdirecting resources to the 
exploration of that perceived VRC01-mediated control, is high in this cohort. 

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Table 2-2 Potential historical comparator cohorts for AMP ATI 
Cohort Considered 
Key Differences/ Limitations 
References 
Thai RV397  
• 
Different study population: Thai with 80% CRF01_AE 
• 
Substantially different ART re-initiation criteria: confirmed HIV-1 RNA >1,000 copies/mL; single HIV-1 RNA >10,000 copies/mL; 
HIV-1 RNA rise ≥0.5 log10copies/mL/day; confirmed CD4+ T-cell count <350 cells/mm3; CD4+ T-cell count decline >50% from 
baseline prior to ATI; CDC Category B or C disease; acute retroviral syndrome (ARS); pregnancy; or participant request  
(112) 
Thai RV411 
• 
Different study population: Thai with 100% CRF01_AE; ART initiated at Fiebig I  
• 
Substantially different ART re-initiation criteria: 2 viral load measurements >1000 copies/mL 1 to 2 days apart  
(113) 
CHAMP 
• 
Different study population: CHAMP cohort includes participants from 14 studies who initiated ART during early and chronic 
infection; “early-treated participants” identified in 7 study cohorts but how “early-treated participants” is defined varies 
greatly among these (see Supplemental Table 1); post-treatment control defined as off ART ≥24 weeks with viral loads ≤400 
copies/mL at ≥2/3 of timepoints 
(81) 
pDNA-IL-12 Vaccine 
• 
Substantially different ART re-initiation criteria: sustained (≥4 weeks) plasma HIV-1 RNA >50,000 copies/mL; confirmed CD4+ T 
cell decline >30%; absolute CD4+ T cell count <350/mm3; ARS. 
(80) 
ACTG historic cohorts 
• 
Substantially different “viral rebound” criteria: 2 consecutive HIV-1 RNA >200 copies/mL or one HIV-1 RNA >1000 copies/mL 
• 
Time to viral rebound not analyzed for participants for whom ART was initiated during acute or early infection 
(37) 
SeaPIP 
• 
Different study population: post-treatment controllers (HIV-1 RNA <500/mL for >24 months); ART initiated at Fiebig I-VI  
• 
Substantially different “virological failure” criteria: first of two HIV-1 RNA >500 copies/mL or one HIV-1 RNA >500 copies/mL 
followed by ART resumption 
(110) 
VISCONTI 
• 
Different study population: post-treatment controllers (HIV-1 RNA <500/mL for >24 months) 
(99) 
SPARTAC 
• 
Different study population: 40% women 
• 
Short course ART, mixed regimens (48 weeks, 12 weeks, no ART) 
• 
Substantially different endpoints: CD4+ T cell count <350/mm3 or long-term ART initiation (SPARTAC); HIV-1 RNA ≥400 
copies/mL (Stöhr, Martin) 
(67, 99, 107, 
108) 
CASCADE 
• 
Substantially different endpoints: loss of “post-treatment controller” status defined as first of 2 consecutive HIV-1 RNA >50 
copies/mL; alternative endpoints HIV-1 RNA >400 copies/mL and >1000 copies/mL 
(103, 104) 
Primo-SHM  
• 
Different study population: ART initiated at Fiebig I-VI; ART duration 24 or 60 weeks 
• 
Substantially different endpoints: CD4 cell count <350 cells/mm3 on two separate occasions, severe constitutional symptoms, 
or AIDS-defining event 
(114) 
ANRS PRIMO Cohort 
• 
Different study population: 36% women 
• 
Substantially different endpoints: first of two HIV RNA values ≥50 copies/mL or first of two HIV RNA values >500 copies/mL 
(105) 
ZHPI 
• 
Substantially different endpoints: time to VL or ART re-initiation not measured 
(109) 
 

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Second, HVTN 804/HPTN 095 holds promise for identification of mechanisms 
and biomarkers of virologic control that can only be realized with the inclusion of 
a control group for comparison. Early immunotherapy can modulate the host 
immune response to HIV. However, the nature of immunotherapy-induced 
differences in early host-viral dynamics and their impact on later control are 
unknown and preclinical and clinical evidence of bnAb-mediated control suggests 
that these differences may be subtle and challenging to identify (34-36, 38-41). 
Coupled with the fact that the underlying mechanisms of post-treatment control 
are also unknown, a post-AMP treatment interruption without a control group is at 
risk of misperceiving not only the true “cause” of control itself (ie, early ART vs. 
VRC01), but also the immunologic mechanisms underlying and the predictive 
biomarkers of that control. Since the value of understanding and correctly 
attributing underlying immunologic mechanisms, which might efficiently direct 
HIV vaccine and other preventative and curative efforts, and the value of reliable 
identification of biomarker(s) of control, which might ultimately abrogate the 
need for treatment interruptions, is exceptionally high, this would be an immense 
opportunity lost (37, 88, 115). 
To illustrate the hazards of misattribution based on inadequate controls, consider 
the example of a therapeutic HIV vaccine trial in 30 HIV-infected participants 
who, like AMP participants, initiated ART early in infection. Three of fifteen 
placebo participants exhibited evidence of sustained viremic suppression (ie, VL 
< 40 copies/mL throughout treatment interruption), with at least two placebo 
recipients exhibiting control for two or more years. Notably, three placebo 
participants in this trial had spikes in viremia ranging from nearly 30,000 to 
nearly 200,000 copies/mL prior to a period of undetectable viral load (see Figure 
2-17) (80). Based on these results, further investment in this vaccine was 
redirected. In contrast, investigators in a concurrent trial of an HIV therapeutic 
vaccine with romidepsin (116), also conducted among early-treated individuals 
but without a placebo group, reported a high rate of virologic control (38% by 
their definition of control which, if applied to the placebo group in the study by 
Sneller, et al., would yield a comparable 40% rate of control). The initial high 
enthusiasm to credit this observation to the vaccine + romidepsin regimen was 
tempered based on results in the placebo group of the comparable Sneller, et al. 
cohort. In fact, an editorial accompanying the report by Sneller, et al., noted that 
“there is substantial variation in viral rebound dynamics in analytic treatment 
interruption studies, significantly limiting the scientific value of non-placebo-
controlled study designs” (82). 
 

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Figure 2-17 Plasma viremia of individual study participants after discontinuation of ART. 
Participants 04, 30, and 31 received placebo and participant 09 received the studied vaccine. 
Graphs were extracted from (80). 
Control and putative predictors or biomarkers of control have been explored in 
prior treatment interruptions with and without control groups, largely among 
individuals chronically infected with HIV or, more recently, among individuals 
initiating ART in Fiebig I-II (37, 59, 96), including in a cohort initiating ART 
early and receiving VRC01 (112). Both types of cohort have been considered as 
potential historical or concurrent controls for HVTN 804/HPTN 095. However, 
ATIs in these studies used different criteria for re-initiating ART and different 
virologic and immunologic monitoring frequencies than will be used in HVTN 
804/HPTN 095 and the participants in these cohorts differ from the HVTN 
804/HPTN 095 cohort in several ways that render them poor comparators for the 
present study cohort.  
In these other published cohorts, ART was restarted once plasma viremia reached 
a prespecified level (eg, 1,000 copies/ml; (112)) with no additional parameter for 
duration of plasma viremia above this level. ART re-initiation criteria that do not 
allow for duration of viremia will miss a significant proportion of post-treatment 
controllers (eg, Participant 30 and 31 in Figure 2-17 above). Such spikes may be 
necessary to stimulate precursor T cells “primed” in early infection by antigen-
presenting cells whose function may be uniquely enhanced by early 
immunotherapy (see Section 2.3). In addition, these historical trials monitored 
plasma viremia and CD4+ T-cell counts at intervals that differ from those 
proposed in the current study. It would be misleading to compare the efficacy 
endpoint for HVTN 804/HPTN 095 with historical controls from prior studies that 
utilized differing criteria for restarting ART and differing frequencies of 
virologic/immunologic monitoring. 
Furthermore, cohorts of individuals who initiated ART while chronically infected 
or during early acute infection may be less than optimal for identifying control or 
its correlates and are particularly insufficient for comparison to the HVTN 
804/HPTN 095 cohort. By the time infection has progressed in chronically-

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infected individuals, HIV has successfully evolved, outpacing and overwhelming 
the immune system, hiding any HIV “Achilles heel” and suppressing host 
responses potentially capable of exploiting HIV’s vulnerabilities. When ART has 
been initiated and viral replication has been suppressed in acutely infected 
individuals, as with Fiebig I and II ART initiation in the USMHRP/Thai 
SEARCH cohorts, the host immune system has seen so comparatively little HIV 
that its initial (ie, “prime”) or later (“boost”) response may not have been 
successfully or fully triggered. Indeed, individuals who initiated ART in Fiebig I-
II appear to demonstrate much lower rates of post-treatment control than those 
who initiated ART in somewhat later Fiebig stages, possibly because individuals 
who initiate ART earlier in infection have been exposed to insufficient antigen to 
prime an immune response capable of later control (111, 113, 117). Hence, both 
chronic and early acute (ie, Fiebig I-II) cohorts may not sufficiently express some 
immunologic factors capable of facilitating virologic control, or may not express 
them in sufficient quantities, thus limiting the capacity of such cohorts to best 
contribute as comparators to the HVTN 804/HPTN 095 cohort (49, 113).  
Geography, ethnicity, and HIV clade may also play a role. For example, post-
treatment control may be more common among women in sub-Saharan Africa 
with clade C transmitted/founder viruses than among some other populations. The 
SPARTAC trial reported an 18.6% rate of post-treatment control overall. A recent 
SPARTAC sub-study revealed that the African SPARTAC cohort, all females 
infected with non-B (primarily C) subtypes, was more likely than the non-African 
SPARTAC cohort to have a VL < 400 copies/mL by study end (HR 3.9, 95% CI 
1.75-8.81, p < 0.001) (108, 118). And Gossez, et al. reported a 23% rate (5 of 22) 
of post-treatment control (VL < 400 copies/mL for a median of 188 weeks post-
ATI) among Ugandan and South African women who completed 45-50 weeks of 
ART and demonstrated viral suppression prior to treatment interruption (118). 
This Gossez, et al. African cohort is comparable to the HVTN 703/HPTN 081 
(“sister” AMP study to HVTN 704/HPTN 085) cohort. 
Based on the considerations described above, HVTN 804/HPTN 095 meets the 
criteria under which inclusion of placebo recipients is an ethical imperative (2). 
Indeed, the same observation was made by Nelson Michael about the Sneller, et 
al. therapeutic vaccine trial described above in which virologic control and 
significant variability of viral rebound were observed among placebo recipients 
following treatment interruption. As Michael noted, “the use of a placebo control 
was critical to interpreting the results of the study” and was part of “a clinical trial 
design that affords [research teams] and their volunteers the best chance of 
reducing volunteer risk for maximal scientific gain” (82). Michael notes another 
characteristic that strengthened the rigor and scientific contribution of the Sneller 
vaccine trial and that would apply to the timely conduct of HVTN 804/HPTN 
095, as well: reducing observer bias by establishing safeguards such that both the 
investigators and the participants remain blinded to treatment assignment (82). 
AMP is unblinded. 

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Hence, the AMP cohort is in a unique position to overcome the challenges that 
have stymied earlier efforts to identify controllers and potential biomarkers of 
control. HVTN 804/HPTN 095 could illuminate host-virus interactions that only 
immunologically-intact hosts (ie, not chronically infected) exposed to moderate 
viral replication prior to suppression (ie, not treated in Fiebig I-II) and for whom 
some secondary antigen exposure is allowed (ie, with closely monitored, brief 
viral load spikes on treatment interruption) may be able to mount. Furthermore, 
the VRC01-mediated immunomodulation described above could render VRC01-
mediated virologic control and its associated correlates or markers more 
evident—more identifiable by current assays—than control mediated by other 
factors, either because the immunotherapy-induced mechanisms themselves are 
more identifiable, or the magnitude of their enhancement by immunotherapy 
renders them more apparent. No other cohort is in as promising a position to 
illuminate potentially subtle differences in early, and later, immunologic-virologic 
dynamics in order to identify host responses critical to viral control, thus 
highlighting factors we should work to enhance in future strategies for HIV 
prevention, therapy, and cure. Yet the AMP cohort’s ability to do this—to 
accurately identify correlates mediated by immunotherapy in addition to those 
mediated by other factors such as early ART initiation common to both VRC01 
and placebo participants—requires a control group. That is, identification of 
immunotherapy-related correlates requires comparison of mechanisms identified 
in VRC01-recipients to those identified in placebo-recipients. 
We note that inclusion of AMP placebo recipients is operationally feasible. In 
addition to applying the risk mitigation measures described above and throughout 
this protocol, the HVTN 804/HPTN 095 team, informed by our statistical 
colleagues, will appropriately limit the numbers of placebo participants—
appreciating that prevention efficacy of VRC01 in the ongoing, treatment-blinded 
AMP trial could lead to an over-representation of placebo participants among the 
cohort of AMP participants who acquired HIV (see Section 2).  
It is important to note that, while post-treatment control appears to be a real 
phenomenon and, particularly in the AMP cohort, could severely limit 
interpretation of HVTN 804/HPTN 095 control and immunologic profiles without 
placebo participants, the true incidence of this phenotype is unknown and AMP 
participants should not enter ATI with any anticipated benefit of a treatment 
interruption. Furthermore, any AMP placebo participants would not be expected 
to experience bnAb-induced, immune-mediated control, ie, control enhanced by 
early immunotherapy. The HVTN 804/HPTN 095 team is committed to making 
this clear in the informed consent document (see Appendix A) and process, 
developed with our regulatory and community partners. 
2.11 
Feasibility 
 
The HVTN 804/HPTN 095 team has the significant advantage of data and 
experience from the AMP Study to inform an assessment of the feasibility of 

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HVTN 804/HPTN 095, appreciating that while this concept is significantly 
different from the parent AMP Study, all participants for HVTN 804/HPTN 095 
will be from the AMP cohort at sites and in communities now familiar to the 
AMP and HVTN 804/HPTN 095 teams. AMP accrual and retention rates, early 
termination rates, data quality and safety have been excellent by any standard, 
perhaps particularly so considering the demanding nature of the two AMP trials 
(HVTN 704/HPTN 085 and HVTN 703/HPTN 081) that, together, enrolled 4,625 
participants for two years of monthly clinic visits and q8-weekly intravenous 
infusions (119, 120). In over 35,000 IV infusions administered to date, no 
procedural complications (eg, local IV site infection,) have been observed; two 
thirds of participants receive VRC01 and very low rates of infusion reactions have 
been observed, all of which have been medically managed exceptionally well 
(119, 121).  
While overall performance in AMP has been exceptional, the HVTN 804/HPTN 
095 team also considered site-specific performance and other considerations in 
determining which sites will implement HVTN 804/HPTN 095. Considerations 
include: site-specific retention performance; timeliness and accuracy of safety 
data submission; access to potentially eligible participants; site capacity for 
frequent clinic visits and close clinical monitoring of participants; access to and 
capacity for close partnership with primary HIV care, including timely ART re-
initiation; and site willingness to participate, including receptivity of site 
investigators, community representatives, and regulatory authorities.  
Partnership with regional investigator, regulatory, and community representatives 
for the development of HVTN 804/HPTN 095 has already begun in earnest and is 
ongoing.  
A consultation with Peruvian investigators, regulatory and public health 
representatives, and community representatives, including representatives on the 
local Community Advisory Board (CAB), was held in April 2019 in Lima, Peru. 
Attendees were engaged and were universally supportive of HVTN 804/HPTN 
095 moving forward in Peru in their communities, with some participants stating, 
“We need this,” and “Continue with the study development as soon as possible.” 
A postconsultation survey clearly reflected that attendees understood and 
supported the HVTN 804/HPTN 095 concept and design, and their understanding 
and engagement was also evident in attendee questions and dialogue throughout 
the consultation. 
Early in development, the HVTN 804/HPTN 095 team also solicited and received 
input and support from the Martin Delaney Collaboratory Community Advisory 
Board (MDC CAB), whose US-based members reviewed the concept and 
provided positive feedback on the concept’s rationale and design. MDC CAB 
members also contributed to engagement throughout May 2019 with HVTN and 
HPTN community representatives, including the AMP Community Working 
Group (AMP CWG), whose members include community educators, recruiters, 
and CAB members from each AMP site. Several forums also provided 

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opportunities for discussion and feedback regarding HVTN 804/HPTN 095 with 
all AMP Protocol Team and site (eg, investigators, clinic coordinators) 
representatives and AMP CWG members.  
Community engagement and site readiness, as described above, is necessary but 
not sufficient to support the conduct of HVTN 804/HPTN 095. AMP participant 
willingness to participate in the ATI is a crucial additional feasibility 
consideration. Again, interim data from AMP provides some insight here.  
A mixed-methods AMP sub-study enrolled 300 participants—50 AMP 
participants from each of six sites based throughout the US. Upon exiting the 
AMP Study, each participant took part in a brief survey and a 60-minute interview 
regarding their demographics, understanding of bnAbs, and any enrollment or 
retention barriers and facilitators they experienced. In an interim analysis, about a 
quarter of participants expressed concerns about the AMP Study time 
commitment or the experimental nature of the VRC01 product and the associated 
uncertainty regarding its efficacy. All participants expressed a strong sense of 
appreciation for and positive identification with their clinical research site. For 
example, one participant noted: “I’m going to volunteer for clinical research, 
especially if it’s research that’s going to affect the community that I’m part of” 
and another enthused “I’m such a big fan of [the CRS] that any research study 
that they pretty much put forward, I’m like interested in, or definitely highly 
support.” Several participants cited the additional medical care they received at 
the clinic as a facilitator of ongoing study participation: “[staff member name] 
took on this role of like a secondary primary care physician for me. In addition to 
the care I was getting at my doctor’s office, I also felt like I was getting another 
set of eyes on me. I just felt cared for.” Another observed “I liked how I got tested 
so often, and they were there to help me with any concerns I had, whether in 
regard to the infusion or to getting tested for other STDs or STIs.” 
While the scope of the sub-study is limited to the US, anecdotal evidence from 
sites around the world, coupled with the exceptional accrual and retention 
observed in the AMP studies to date (120), suggests that the experience 
participants have with their HVTN and HPTN AMP sites, globally, is a strongly 
positive motivator for continued engagement with their site. Furthermore, many 
sites retain engagement with their participants through various means even post-
AMP and have the ability, prespecified in site-specific AMP consent forms 
approved by their Institutional Review Boards/Ethics Committees (IRBs/ECs), to 
reach out to participants after they’ve exited the trial to inquire about their interest 
in possible future research. 
Thus, the conduct of HVTN 804/HPTN 095 as described herein is thought to be 
highly feasible thanks in large part to the selection of sites for AMP and their 
conduct of the study, including their relationships with site participants and their 
community and regulatory partners. 

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2.12 
Conclusion 
The AMP ATI is uniquely positioned to test for ART-free virologic control 
among individuals who acquired HIV in the presence of circulating bnAb, and to 
enhance understanding of the immunologic (ie, host) and virologic mechanisms 
and biomarkers of control. Here, we have an opportunity to translate the 
intriguing preclinical observations in SHIV-infected primates (34) to humans. 
This trial will extend early clinical observations, explore potential mechanisms, 
validate biomarkers of control, and discern whether AMP participants who 
became HIV-infected while on trial may become “post-bnAb controllers,” capable 
of bnAb-induced immunologic responses that change the course of their infection. 

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3 
Study design 
3.1 
Hypotheses 
3.1.1 
Primary hypotheses 
• VRC01 recipients who became HIV-infected during HVTN 704/HPTN 085 
within 8 weeks of their last study product administration will suppress plasma 
viremia and maintain CD4+ T-cell counts longer during ATI than placebo 
recipients who became HIV-infected during HVTN 704/HPTN 085. 
• ATI will be safe and well-tolerated in individuals who became HIV-infected 
in HVTN 704/HPTN 085. 
3.1.2 
Secondary hypotheses 
• VRC01 recipients who became HIV-infected during HVTN 704/HPTN 085 
within 8 weeks of their last study product administration will have enhanced 
cellular and humoral responses compared to placebo recipients who became 
HIV-infected during HVTN 704/HPTN 085. 
• VRC01 recipients who became HIV-infected during HVTN 704/HPTN 085 
within 8 weeks of their last study product administration will have more 
limited viral reservoirs, before and after ATI, than placebo recipients who 
became HIV-infected during HVTN 704/HPTN 085. 
3.2 
Objectives and endpoints 
3.2.1 
Primary objectives and endpoints 
Primary objective 1 
• To evaluate the effect of VRC01 received in the immediate pre-HIV 
acquisition period and/or during early infection on the time to meeting 
ART re-initiation criteria in participants undergoing ATI 
Primary endpoint 1 
• Time to meeting criteria for ART re-initiation 
• Frequency of sustained post-treatment HIV control, defined as ≥ 24 weeks off 
ART without meeting ART re-initiation criteria 
 
 

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Primary objective 2 
• To evaluate the safety of ATI among HVTN 804/HPTN 095 participants 
Primary endpoint 2 
• Laboratory measures of safety, adverse events (AEs), SAEs (serious AEs), 
and rates of discontinuation 
3.2.2 
Secondary objectives and endpoints 
Secondary objective 1 
• To evaluate the effect of VRC01 received in the immediate pre-HIV 
acquisition period and/or during early infection on the development of 
anti-HIV immune responses that differ from those of placebo recipients, and 
whether these immune responses are associated with time to meeting criteria 
for ART re-initiation in participants undergoing ATI 
Secondary endpoints 1 
• Response rate, magnitude, and polyfunctionality of HIV-specific CD4+ and 
CD8+ T-cell responses as measured by flow cytometry 
• Magnitude and breadth of neutralizing antibody (nAb) responses against 
autologous and heterologous HIV isolates, as measured by TZM-bl 
neutralization assay  
• Non-neutralizing, FcγR-mediated antibody effector functions such as ADCC, 
ADCP, and virion capture 
• Frequency of dendritic cell activation and maturation markers, as measured by 
flow cytometry or other cell phenotyping assays 
• Frequency of T- and B-cell activation and exhaustion markers, as measured by 
flow cytometry or other cell phenotyping assays 
Secondary objective 2 
• To evaluate the effect of VRC01 received in the immediate pre-HIV 
acquisition period and/or during early infection on viral load in participants 
undergoing ATI 
Secondary endpoint 2 
• Cumulative incidence of participants with viral load ≥ 200 at weeks 8, 16, and 
24 

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Secondary objective 3 
• To evaluate the effect of VRC01 received in the immediate pre-HIV 
acquisition period and/or during early infection on HIV reservoir size 
before and after ATI, and whether HIV reservoir measurements are associated 
with time to meeting criteria for ART re-initiation in participants 
undergoing ATI 
Secondary endpoint 3 
• Frequency of CD4+ T cells carrying intact and/or total pro-viral HIV 
DNA, replication competent virus, and/or cell-associated HIV RNA  
3.2.3 
Exploratory objectives 
Exploratory objective 1 
• To assess participant and potential participant motivations, perceptions 
and tolerance for ATIs, for prolonged viremia, and for trial requirements 
(eg, ART switches, barrier protection for all sexual activity) 
Exploratory objective 2 
• To assess social benefits (eg, altruism) and negative social impacts, 
including but not limited to anxiety regarding being off ART and 
becoming viremic again and fear of inadvertent HIV transmission to 
partners 
Exploratory objective 3 
• To assess participant and potential participant decision-making quality, 
including perception of being informed, clarity and support in decision 
making and satisfaction with their choice regarding participation 
Exploratory objective 4 
• To evaluate the effect of VRC01 received in the immediate pre-HIV 
acquisition period and/or during early infection on viral kinetics in 
participants undergoing ATI 
Exploratory objective 5 
• To determine whether characteristics of the transmitted/founder (T/F) 
viruses, rebound virus(es), and/or baseline viral reservoirs, including 
relative VRC01 sensitivity or resistance, are associated with virologic 
control or the development of anti-HIV immunity among individuals who 
became HIV-infected in HVTN 704/HPTN 085 

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Exploratory objective 6 
• To assess whether host genetics (eg, HLA type, CCR5 heterozygosity) 
and sex are associated with time to meeting ART re-initiation criteria 
among VRC01 or placebo recipients who became HIV-infected in 
HVTN 704/HPTN 085 
3.3 
ATI  
For all participants, ATI begins with cessation of ART Schedule 1, Monitoring 
ATI. Participants on ATI (Schedule 1 or 2) who do not meet criteria for moving to 
the next visit schedule (ie, viral rebound or re-initiating ART), or who meet 
criteria for re-initiating ART but decline to do so, should continue with extended 
visits on their current ATI visit schedule until such time as they move to the next 
visit schedule or are terminated from the study. These Schedule 1 and Schedule 2 
extended visits occur quarterly and are designated as Visits Type A and Type B, 
with procedures specified for each visit type, in the laboratory and clinical 
procedures tables (see Appendix E, Appendix F, Appendix H, Appendix I, and 
Appendix K). 
3.3.1 
Transition from Schedule 1, Monitoring ATI to Schedule 2, ATI 
monitoring with viremia  
For participants on Schedule 1, Monitoring ATI, the following virologic criterion 
will trigger a transition to Schedule 2, ATI monitoring with viremia: 
• Confirmed VL ≥ 200 copies/mL (ie, on 2 consecutive samples). 
A confirmatory sample should be drawn at the next visit (within approximately 1-
2 weeks) following the first VL result ≥ 200 copies/mL (see HVTN 804/HPTN 
095 SSP for details).  
3.3.2 
Transition from Schedule 1, Monitoring ATI to Schedule 3, Follow-up 
on ART 
For participants on Schedule 1, Monitoring ATI, any of the following non-
virologic criteria will trigger ART re-initiation and transition to Schedule 3, 
Follow-up on ART: 
• Confirmed CD4+ T-cell count < 350 cells/mm3 (ie, on 2 consecutive samples) 
• Any HIV-related syndrome (eg, acute retroviral syndrome, an opportunistic 
infection) 
• Pregnancy or breastfeeding 

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• ART re-initiation requested by participant 
• ART re-initiation requested by primary HIV care provider or CRS 
Investigator of Record (eg, if deemed medically necessary) 
A confirmatory sample should be drawn at the next visit (within approximately 1-
2 weeks) following the first CD4+ T-cell count < 350 cells/mm3 (see HVTN 
804/HPTN 095 SSP for details).  
3.3.3 
Transition from Schedule 2, ATI monitoring with viremia, to Schedule 
3, Follow-up on ART 
For participants on Schedule 2, Monitoring ATI with viremia, the following 
virologic criteria will trigger ART re-initiation and transition to Schedule 3, 
Follow-up on ART. 
From the Week 0 visit to the Week 24 visit in Schedule 2:  
• Viral load remains ≥ 1,000 copies/mL for ≥ 4 consecutive weeks AND viral 
load has not dropped 0.5 log from the previous week 
This ART re-initiation criterion applies irrespective of missed visits and must take 
account of VL results ≥ 1,000 copies/mL experienced by a participant while on 
Schedule 1. Furthermore, assessing whether participants meet this criterion may 
require additional visits beyond those scheduled from Week 8 (Visit 48) to Week 
24 (Visit 56) in Schedule 2. Ideally, these additional visits will be conducted 
weekly. These additional visits will be treated as interim visits (for more details, 
see the HVTN 804/HPTN 095 SSP).  
After the Week 24 visit, the ART re-initiation criterion is:  
• Confirmed viral load ≥ 200 copies/mL (ie, on 2 consecutive samples). 
A confirmatory sample should be drawn at the next visit (within approximately 1-
2 weeks) following the first VL result ≥ 200 copies/mL (see HVTN 804/HPTN 
095 SSP for details). The above virologic ART re-initiation criteria are shown 
schematically in Figure 3-1. 
 

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Figure 3-1 Virologic criteria for transition from Schedule 2 to Schedule 3 (ie, ART re-
initiation) 
In addition, at any time during Schedule 2, any of the following non-virologic 
criteria will trigger prompt ART re-initiation and transition to Schedule 3, Follow-
up on ART: 
• Confirmed CD4+ T-cell count < 350 cells/mm3 (ie, on 2 consecutive samples) 
• Any HIV-related syndrome (eg, acute retroviral syndrome, an opportunistic 
infection) 
• Pregnancy or breastfeeding 
• ART re-initiation requested by participant 
• ART re-initiation requested by primary HIV care provider or CRS 
Investigator of Record (eg, if deemed medically necessary). 
A confirmatory sample should be drawn at the next visit (within approximately 1-
2 weeks) following the first CD4+ T-cell count < 350 cells/mm3 (see HVTN 
804/HPTN 095 SSP for details).  
3.3.4 
Participants who decline to re-initiate ART 
When ART re-initiation criteria are met, CRS staff will strongly recommend that 
the participant restart ART. Participants who decline to do so should be urged to 
continue clinic visits per Schedule 1 or Schedule 2 (ie, whichever schedule the 
participant is currently on) until such time as the participant re-initiates ART, at 
which time they should transition to Schedule 3. For additional details, see the 
HVTN 804/HPTN 095 Study Specific Procedures (SSP). 

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4 
Statistical considerations 
4.1 
Accrual and sample size calculations 
Recruitment will target participants who received VRC01 or placebo and became 
HIV-infected during participation in HVTN 704/HPTN 085. 
We calculate the expected trial sized under different scenarios for the percentage 
of enrolled participants out of the total number of endpoint infected cases from 
HVTN 704/HPTN 085; scenarios include 25%, 50%, and 75%. Eligible placebo 
recipients will be capped such that the overall placebo to VRC01 recipient ratio of 
enrolled participants is at most approximately 1:1. Given that the parent HVTN 
704/HPTN 085 study was randomized at a 1:2 placebo to VRC01 ratio, we would 
only expect to cap the number of eligible placebo recipients if prevention efficacy 
(PE) exceeds 50%. Given this constraint, along with an assumption of a common 
prevention efficacy at each dose (PE10 and PE30), the expected trial size will 
depend on different levels of PE. Under the null hypothesis (PE10 = PE30 = 0%), 
the total expected number of endpoint infections among placebo recipients is 26 
and VRC01 recipients is 55 (Table 4-3 in the parent protocol HVTN 704/HPTN 
085); therefore, we assume a trial size of 7, 13 or 20 placebo recipients and 14, 
28, or 41 VRC01 recipients depending on the enrollment ratio. Under the 
alternative hypothesis (PE10 = PE30 = 60%), the total expected number of 
endpoint infections among placebo recipients is 37 and VRC01 recipients is 30 
(Table 4-3 in the parent protocol); therefore, under the different enrollment ratio 
scenarios, we assume a trial size of 8, 15, or 23 placebo recipients and an equal 
number of VRC01 recipients so as not to exceed a 1:1 ratio. These six sample size 
scenarios represent estimated upper and lower bounds for sample size given the 
expected number of endpoint infections under the null and alternative hypotheses 
respectively, as well as various scenarios for the percentage of eligible 
participants who will ultimately enroll in HVTN 804/HPTN 095. 
4.1.1 
Sample size considerations for time to ART re-initiation criteria 
Using data from the placebo arm of a therapeutic vaccine study which enrolled 
early treated patients (80), we modeled the time T (in weeks) to meet re-initiation 
criteria as a Weibull distribution with survival function P(T > t) = exp[-(λt)p], 
where λ = exp(-2.932) = 0.053 and p = 2.014. From these parameters, we 
estimated the median time to meet re-initiation criteria as 15.6 weeks in the AMP 
placebo recipients. We can express the treatment effect in terms of either the 
hazard ratio θ or the factor β by which treatment increases the median time to 
meet re-initiation criteria; β and θ are related by β = θ-1/p. 
We model censoring of time to re-initiation criteria using an exponential model 
and a maximum follow-up time of 72 weeks, where follow-up is censored at a 
rate of 20% per year due to either study termination or re-initiation of ART before 
reaching the re-initiation criteria. Simulating 10,000 trials based on these models 

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of time to re-initiation criteria and censoring, we computed power using a log 
rank test with alpha equal to 0.05. Power for a 40%, 50%, 60%, and 70% 
reduction in hazard under different enrollment rate and prevention efficacy 
scenarios are shown in Table 4-1. These hazard reductions correspond to 29%, 
41%, 58%, and 82% increases in the median time to meet re-initiation criteria. 
Therefore, if VRC01 increases the median time to re-initiation criteria 58% and 
the enrollment rate is 50%, then under the parent study null hypothesis power to 
detect a difference in time to re-initiation criteria is 72% while under the 
alternative hypothesis power is 62%. 
Table 4-1 Power under different prevention efficacy results, different enrollment rates and 
different treatment effects, expressed as either reduction in hazard or percent increase in 
median time to meet re-initiation criteria 
Enrollment Rate 
Null hypothesis 
Alternative hypothesis 
25% 
50% 
75% 
25% 
50% 
75% 
Expected number of placebos 
7 
13 
20 
8 
15 
23 
Expected number of VRC01 
14 
28 
41 
8 
15 
23 
Reduction in hazard 
% Increase in 
median time to 
meet re-initiation 
criteria 
 
40% 
29% 
20% 
32% 
44% 
16% 
26% 
37% 
50% 
41% 
31% 
50% 
67% 
24% 
42% 
58% 
60% 
58% 
46% 
72% 
89% 
36% 
62% 
81% 
70% 
82% 
65% 
91% 
98% 
54% 
83% 
96% 
4.1.2 
Sample size considerations for safety 
The goal of the safety evaluation for this study is to identify safety concerns 
associated with ATI. The ability of the study to detect serious adverse events 
(SAEs) (see Section 4.2.4.1) can be expressed by the true event rate above which 
at least 1 SAE would likely be observed and the true event rate below which no 
events would likely be observed. Under the enrollment rate and PE scenarios 
described in Section 4.1, Table 4-2 shows the true event rate such that there is a 
90% chance of observing at least 1 event (or no events) among three groups; 1) 
the placebo recipients only, 2) the VRC01 recipients only, or 3) all enrolled 
participants. 
Table 4-2 True event rates above which at least 1 SAE (or below which no events) would 
likely be observed in a group of size n participants. Event rates are computed separately for 
various values of n given by the range and midpoint for the estimated number of 
participants among 3 groups; 1) the placebo recipients only, 2) the VRC01 recipients only, 
or 3) all enrolled participant based on the enrollment scenarios described in Section 4.1. 
 
Placebo recipients 
VRC01 recipients 
All enrolled 
n 
7 
15 
23 
8 
25 
49 
16 
38 
61 
At least 1 event 
28.0% 
14.2% 
9.5% 
25.0% 
8.8% 
4.6% 
13.4% 
5.9% 
3.7% 
No events 
1.5% 
0.7% 
0.5% 
1.3% 
0.4% 
0.2% 
0.7% 
0.3% 
0.2% 

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4.2 
Statistical analyses 
Analyses for primary endpoints will be performed using SAS and R. All other 
descriptive and inferential statistical analyses will be performed using SAS, 
StatXact, or R statistical software. 
No formal multiple comparison adjustments will be employed for multiple safety 
endpoints or secondary endpoints. However, multiplicity adjustments will be 
made for certain laboratory assays, as discussed below, when the assay endpoint 
is viewed as a collection of hypotheses (eg, testing multiple peptide pools to 
determine a positive response). 
4.2.1 
Analysis variables 
The analysis variables consist of baseline participant characteristics, safety, and 
laboratory outcomes for primary- and secondary-objective analyses. 
4.2.2 
Baseline comparability 
Groups defined by the parent protocol treatment arms will be compared for 
baseline participant characteristics using descriptive statistics. 
4.2.3 
Primary virologic analysis 
In this study we condition on HIV-infection with the intention of comparing 
virologic outcomes by randomized treatment assignment from HVTN 704/HPTN 
085. Since we are conditioning on a postrandomization event, HIV-infection, a 
two-sample test for a difference in outcome is subject to postrandomization 
selection bias. A direct comparison of virologic outcomes between treatment 
groups, which measures the “net treatment effect,” does not have a causal 
interpretation (122). As an example of the type of bias that can occur, suppose 
VRC01 protects against mild viruses but is not effective against virulent viruses. 
If this were true, we might see longer time to re-initiation criteria in VRC01 
recipients than placebo recipients whereas, if we restricted only to those 
participants infected with a virulent HIV strain, we might see shorter time to re-
initiation criteria in the VRC01 group. Therefore, a two‐sample test comparing 
time to re-initiation criteria between treatment groups could give a misleading 
impression that VRC01 shortens viral suppression time during ATI while the 
causal interpretation of this hypothetical example would be that for virulent 
viruses, VRC01 increases viral suppression time during ATI compared to placebo. 
Approaches will be taken to ensure robust and unbiased results. Implementation 
of targeted minimum loss-based estimation (TMLE) methods, used to address the 
objectives in the following sections, will be fully prespecified in the statistical 
analysis plan (SAP) to ensure objective and reproducible inference. 

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Each analysis will be done pooling the VRC01 recipients versus placebo 
recipients with supplemental analyses done separately for each dose group versus 
the placebo recipients.  
4.2.3.1 
Time to ART re-initiation criteria 
The primary outcome is the time from the start of treatment interruption until the 
participant meets criteria to re-initiate ART.  
A Cox proportional hazards model with the indicator of assignment to a mAb 
group versus the control group will be used to estimate the cumulative incidence 
in each of the infected VRC01 and infected placebo groups, as well as the hazard 
ratio, all with 95% confidence intervals and associated 2-sided p-values, where 
the model controls for baseline covariates thought to potentially predict both HIV-
1 infection and the instantaneous hazard of meeting the ART re-initiation criteria. 
This is needed for controlling for potential postrandomization selection bias given 
that analyzed treatment groups are selected postrandomization. Plots of the 
estimated cumulative incidence will be shown by treatment group. 
As a supportive analysis of this hypothesis, targeted minimum loss-based 
estimation (TMLE) may be used to estimate cumulative incidences of the primary 
efficacy endpoint over time for the pooled mAb arm and the control arm. Iterative 
mean-based TMLE is used for this analysis as described by Benkeser et al (123). 
The Super Learner (124) is used to generate initial estimates of the conditional 
censoring distribution and the iterated conditional means. This analysis will use 
TMLE as implemented in the R package survtmle available on CRAN (125). 
4.2.3.2 
Frequency of sustained post-treatment HIV control 
The same covariate adjusted model used to estimate cumulative incidence of 
meeting the re-initiation criteria for ART over time, described in the previous 
section, will be used to compare the rates of failure to maintain HIV control at 24 
weeks between the two treatment groups. 
4.2.3.3 
Time to viral load ≥ 200 
Secondary endpoint 2 is time until the participant has a viral load ≥ 200. The same 
methodology used to assess time to ART re-initiation criteria will be used for this 
endpoint. In this analysis we will compare cumulative incidence at week 8 in each 
of the infected VRC01 and infected placebo groups supplemented by a sensitivity 
analysis based on cumulative incidence at weeks 8, 16, and 24. 
4.2.4 
Primary safety analysis 
4.2.4.1 
AEs and SAEs 
AEs will be summarized using MedDRA System Organ Class and preferred 
terms. Tables will show by treatment arm the number and percentage of 

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participants experiencing an AE within a System Organ Class or within preferred 
term category by severity or by relationship to treatment interruption. For the 
calculations in these tables, a participant with multiple AEs within a category will 
be counted once under the maximum severity or the strongest recorded causal 
relationship to treatment interruption. Formal statistical testing comparing arms is 
not planned since interpretation of differences must rely heavily upon clinical 
judgment. 
4.2.4.2 
Local laboratory values 
Box plots of local laboratory values will be generated for baseline values and for 
values measured during the course of the study by treatment arm and visit. Each 
box plot will show the first quartile, the median, and the third quartile. Outliers 
(values outside the box plot) will also be plotted. If appropriate, horizontal lines 
representing boundaries for abnormal values will be plotted. 
For each local laboratory measure, summary statistics will be presented by 
treatment arm and timepoint, as well as changes from baseline for postenrollment 
values. In addition, the number (percentage) of participants with local laboratory 
values recorded as meeting Grade 2 AE criteria or above as specified in the 
Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events will be tabulated by treatment arm for each timepoint after initiation of 
treatment interruption. Reportable clinical laboratory abnormalities without an 
associated clinical diagnosis will also be included in the tabulation of AEs 
described above. 
4.2.4.3 
Reasons for discontinuation of ATI and early study termination 
The number and percentage of participants who discontinue ATI and who 
terminate the study early will be tabulated by reason and treatment arm. 
4.2.5 
Secondary analyses of immune responses and reservoir 
measurements 
Analyses of immune responses and reservoir measurements will be descriptive 
using appropriate plotting techniques for describing measurements at a fixed time 
point (eg, boxplots and barplots) or longitudinally (eg, spaghetti plots) separately 
by treatment group. In addition, if enough samples are assayed we plan to do 
inferential and descriptive analyses as described in the following sections. 
4.2.5.1 
Evaluate the difference in anti-HIV immune responses or reservoir size 
between VRC01 and placebo recipients 
TMLE will be used to estimate mean endpoints in each of the infected VRC01 
and infected placebo groups, as well as the mean difference, all with 95% 
confidence intervals and associated 2-sided p-values, where the TMLE controls 
for all baseline covariates thought to potentially predict both HIV-1 infection and 
one of the secondary endpoints under study. This is needed for controlling for 

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potential postrandomization selection bias given that analyzed treatment groups 
are selected postrandomization. 
4.2.5.2 
Assess whether anti-HIV immune responses or reservoir size are 
associated with time to meeting ART re-initiation criteria 
Cox regression will be used to estimate cumulative incidence over time for groups 
defined by levels of immune response or reservoir size for each treatment group. 

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5 
Study population  
Participants for this trial will be recruited from among former HVTN 704/HPTN 
085 (NCT02716675) study participants who met criteria for transition to Schedule 
2 or Schedule 3 in that study and who meet the following inclusion/exclusion 
criteria.  
5.1 
Inclusion criteria  
1. Estimated date of HIV-1 acquisition within 8 weeks of participant’s last HVTN 
704/HPTN 085 infusion (see HVTN 804/HPTN 095 SSP). 
2. Initiated ART within 28 weeks of HVTN 704/HPTN 085 HIV-1 date of 
diagnosis.  
3. Receiving continuous ART for at least 1 year  
• ART interruptions of up to 7 days and ≥ 90 days prior to enrollment are 
acceptable.  
• Within- and between-class changes in ART within the previous year are 
acceptable. 
4. If on an NNRTI, willingness and ability to switch to a PI- or INSTI-containing 
regimen for at least 4 weeks prior to ART interruption. 
5. Willingness to interrupt ART for up to 24 weeks or up to the time of meeting 
ART re-initiation criteria (Section 3.3). 
6. Willingness to re-initiate ART upon meeting study ART re-initiation criteria. 
7. Willingness to use barrier protection (ie, male or female condoms) for all 
sexual activity until after confirmation of viral suppression following ART re-
initiation 
8. Willingness for CRS staff to contact primary HIV care provider to exchange 
information regarding HVTN 804/HPTN 095 and participant medical history.  
9. Site investigator anticipates that a fully active alternative ART regimen could 
be constructed and would be available in the event of virologic failure on the 
participant’s current ART regimen.  
10. Access to a participating CRS and willingness to adhere to study visit schedule 
and to be followed for the planned duration of the study. 
11. Ability and willingness to provide informed consent 

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12. Assessment of understanding: volunteer demonstrates understanding of this 
study; completes a questionnaire prior to enrollment with verbal demonstration of 
understanding of all questionnaire items answered incorrectly. 
13. Agrees not to enroll in another study of an investigational research agent for the 
duration of the participant’s trial participation. 
Laboratory Inclusion Values 
Immunology/Virology 
14. HIV-1 infection, with reactive HIV-1 antibody and any Multispot or Geenius 
HIV-1/HIV-2 results, documented by the HVTN 704/HPTN 085 HIV diagnostic 
algorithm. 
15. Plasma HIV-1 RNA ≥ 1,000 copies/mL by any assay, prior to initiating ART. 
16. CD4+ cell count ≥ 450 cells/mm3 obtained within 90 days prior to enrollment. 
17. One plasma HIV-1 RNA below the lower limit of quantitation (LLOQ) 
collected at each of the following: 
• at screening, within 90 days prior to enrollment; and 
• greater than 9 months prior to the screening HIV-1 RNA. 
Note: US volunteers must have results from a CLIA or VQA-approved assay. 
Non-US sites must have results from locally available assays that are approved as 
standard-of-care by their regional governing bodies. 
Hematology 
18. Hemoglobin (Hgb) ≥ 10.0 g/dL for volunteers who were assigned female sex at 
birth, ≥ 11.0 g/dL for volunteers who were assigned male sex at birth. 
19. Absolute neutrophil count (ANC) ≥ 750 cells/mm3 
20. Platelets ≥ 100,000 cells/mm3 
Chemistry 
21. ALT < 2.5 times the institutional upper limit of normal and direct bilirubin 
within the institutional range of normal. 
22. Estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73m2 
Reproductive Status 

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23. Volunteers capable of becoming pregnant: negative serum or urine beta human 
chorionic gonadotropin (β-HCG) pregnancy test performed at the screening visit 
and prior to enrollment. Persons who are NOT capable of becoming pregnant due 
to having reached menopause (no menses for 1 year) or having undergone total 
hysterectomy or bilateral oophorectomy or tubal ligation (verified by medical 
records) are not required to undergo pregnancy testing. 
24. Reproductive status: A volunteer who is capable of becoming pregnant must 
agree to consistently use effective contraception (see Appendix B and HVTN 
804/HPTN 095 SSP) for sexual activity that could lead to pregnancy from at least 
21 days prior to enrollment through confirmation of viral suppression following 
ART re-initiation.  
25. Volunteers capable of becoming pregnant must also agree not to seek 
pregnancy through alternative methods, such as artificial insemination or in 
vitro fertilization, until after confirmation of viral suppression following ART re-
initiation. 
5.2 
Exclusion criteria  
1. Any plasma HIV-1 RNA ≥ LLOQ (LLOQ: 75, 50, 40, or 20 copies/mL) within 
12 months prior to enrollment.  
• 
NOTE: Two “blips” (ie, plasma HIV-1 RNA > LLOQ) < 400 copies/mL are 
allowed if preceded and followed by values < LLOQ and if the blips occur 
more than 6 months prior to enrollment. 
Note: US volunteers must have results from a CLIA or VQA-approved assay. 
Non-US sites must have results from locally available assays that are approved as 
standard-of-care by their regional governing bodies. 
2. History of AIDS-defining illnesses or US Centers for Disease Control (CDC) 
Category C events per the current list on the CDC website (see HVTN 
804/HPTN 095 SSP). 
3. Autoimmune disease, including Type I diabetes mellitus (Not excluded from 
participation: Volunteer with mild, stable and uncomplicated autoimmune disease 
that does not require consistent immunosuppressive medication and that, in the 
judgment of the site investigator, is likely not subject to exacerbation and likely 
not to complicate AE assessments). 
4. Immunosuppressive medications received within 6 months before enrollment 
(Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] 
topical corticosteroids for mild, uncomplicated dermatologic condition; or [4] a 
single course of oral/parenteral prednisone or equivalent at doses < 60 mg/day and 
length of therapy < 11 days with completion at least 30 days prior to enrollment). 

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5. Blood products received within 120 days before planned ART interruption. 
6. Investigational research agents, other than experimental vaccine(s) (See 
Exclusion Criterion #7), received within 30 days before planned ART 
interruption. 
7. HIV or non-HIV experimental vaccine(s) received within the last 1 year. 
Exceptions may be made by the HVTN 804/HPTN 095 PSRT for vaccines that 
have subsequently undergone licensure by the FDA or by the national regulatory 
authority where the volunteer is enrolling. For volunteers who have received 
control/placebo in an experimental vaccine trial, the HVTN 804/HPTN 095 PSRT 
will determine eligibility on a case-by-case basis. For volunteers who have 
received an experimental vaccine(s) greater than 1 year ago, eligibility for 
enrollment will be determined by the HVTN 804/HPTN 095 PSRT on a case-by-
case basis. 
8. Licensed live attenuated vaccines received within 30 days before planned ART 
interruption (eg, measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; 
varicella; yellow fever; live attenuated influenza vaccine). 
9. Licensed vaccines that are not live attenuated vaccines received within 14 days 
before planned ART interruption (eg, tetanus, pneumococcal, hepatitis A or B). 
10. Receipt of any emergency-use authorized, WHO emergency use listed, 
licensed or registered SARS-CoV-2 (severe acute respiratory syndrome 
coronavirus 2) vaccine within 4 weeks before planned ART interruption. Note: 
SARS-CoV-2 vaccination is not required for HVTN 804/HPTN 095 eligibility. 
11. Significant or unstable cardiac or cerebrovascular disease (eg, angina, 
congestive heart failure [CHF], recent cerebrovascular accident [CVA], or 
myocardial infarction [MI]). 
12. Hepatitis B surface antigen (HBsAg) or positive HCV RNA (Not exclusionary: 
positive HCV Ab with negative HCV RNA). 
13. Volunteers who have: 
• 
a SARS-CoV-2 positive test (direct viral detection, eg, viral nucleic acid or 
antigen detection) ≤14 days of enrollment, if asymptomatic 
OR 
• 
unresolved COVID-19 (ie, SARS-CoV-2 positive test AND symptoms) ≤ 14 
days of enrollment (not excluded: individuals with symptoms consistent with 
residual sequelae of resolved COVID19, in the clinical judgement of the 
investigator) 

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14. Pregnant or breastfeeding 
15. Clinically significant medical condition, physical examination findings, 
clinically significant abnormal laboratory results, or past medical history with 
clinically significant implications for current health. A clinically significant 
condition or process includes but is not limited to: 
• A process that would affect the immune response; 
• A process that would require medication that affects the immune response; 
• Any contraindication to repeated blood draws, including inability to establish 
venous access; 
• A condition that requires active medical intervention or monitoring to avert 
grave danger to the volunteer’s health or well-being during the study period; 
or 
• Any condition specifically mentioned among the exclusion criteria. 
16. Any medical, psychiatric, occupational, or other condition that, in the 
judgment of the investigator, would interfere with, or serve as a contraindication 
to, protocol adherence, assessment of safety, or a volunteer’s ability to give 
informed consent. 
17. Any medical, psychiatric, occupational, or other condition that, in the 
judgment of the investigator, could be exacerbated by events associated with 
protocol participation, which include: ATI, low-level viremia, subsequent viral 
rebound, and ART re-initiation. 
18. HIV dementia or other neurologic disease that, in the judgment of the 
investigator, would be a contraindication to study participation. 
19. Psychiatric condition that precludes compliance with the protocol. 
Specifically excluded are persons with psychoses within the past 3 years, ongoing 
risk for suicide, or history of suicide attempt or gesture within the past 3 years. 
20. Malignancy (Not excluded from participation: Volunteer who has had 
malignancy excised surgically and who, in the investigator’s judgment, has a 
reasonable assurance of sustained cure, or who is unlikely to experience 
recurrence of malignancy during the period of the study). 
21. Current untreated or incompletely treated active tuberculosis disease or 
current latent tuberculosis infection (Not excluded from participation: 
Volunteer who has latent tuberculosis infection and is undergoing treatment, with 
at least one month of treatment completed) 
22. Untreated or incompletely treated syphilis, gonorrhea, or chlamydia 
infection 

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5.3 
Criteria for participant early termination 
• Pregnancy or breastfeeding (see Section 6.7.1) 
• Declared intention to become pregnant or begin breastfeeding 
• Request by the participant to withdraw 
• Request of the primary HIV care provider  
• Participant starts ART switch but is not virally suppressed after approximately 
12 weeks (see Section 6.1.3) 
• Participant judged by the investigator to be at significant risk of failing to 
comply with the provisions of the protocol so as to cause to harm to self or 
seriously interfere with the validity of the study results 
• Participant relocates and remote follow-up or transfer to another CRS is not 
possible (Note: Remote follow-up is allowable only after confirmation of viral 
suppression after ART re-initiation; see Ab Manual of Operations (MOP) and 
HVTN 804/HPTN 095 SSP for further detail.) 
• CRS determines that the participant is lost to follow-up 
• Investigator decides, in consultation with Protocol Team leadership, to 
terminate participation (eg, if participant exhibits inappropriate behavior 
toward clinic staff) 
• Any condition where termination from the study is required by applicable 
regulations 
5.4 
Study termination 
This study may be terminated early by the determination of the HVTN 804/HPTN 
095 PSRT, a pertinent national regulatory authority, NIH, or the Office for 
Human Research Protections (OHRP). In addition, the conduct of this study at an 
individual Network CRS may be terminated by the determination of the IRB/EC 
and any applicable RE. 

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6 
Study procedures 
For all study visits, unless otherwise specified, participants will come to their 
assigned Clinical Research Site (CRS).  
6.1 
Schedule 1: Monitoring ATI 
6.1.1 
Screening 
Screening may occur over the course of several contacts/visits. All inclusion and 
exclusion criteria must be assessed within 8 weeks (56 days) prior to enrollment, 
unless otherwise specified in the eligibility criteria (Section 5). 
After signing informed consent, volunteers will undergo the following 
procedures, as shown in Appendix E and Appendix H: 
• Assessment of Understanding 
• Medical history, including: 
o current psychiatric status and history 
o assessment of routine clinically-indicated vaccinations (note: must be 
completed prior to ATI initiation (see Section 5.2) 
• Complete physical examination 
• Assessment of concomitant medications 
• HIV transmission risk behavior assessment and counseling 
• SARS-CoV-2 risk reduction counseling (per clinician judgement based on 
local epidemiology, see HVTN 804/HPTN 095 SSP) 
• Contraception status assessment (for volunteers assigned female sex at birth 
and who are sexually active in a way that could lead to pregnancy; see Section 
6.6 and Appendix B) 
• Decision aid 
• Blood collection for: 
o HIV PCR viral load 
o CD4+ and CD8+ T-cell counts 

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o HBsAg and hepatitis C serology 
o QuantiFERON TB test  
o Hgb, ANC, platelets 
o ALT, direct bilirubin, eGFR 
o Syphilis testing 
• SARS-CoV-2 positive test, (direct viral detection eg, viral nucleic acid or 
antigen detection) for volunteers who have not received a SARS-CoV-2 
vaccine. 
• Urine pregnancy test (for volunteers assigned female sex at birth; persons not 
of reproductive potential due to having reached menopause (no menses for 1 
year), or having undergone hysterectomy or bilateral oophorectomy or tubal 
ligation [verified by medical records], are not required to undergo pregnancy 
testing) 
• Gonorrhea/chlamydia testing by urine, rectal swabs, and oropharyngeal swabs 
• Tuberculin skin test (TST; only if QuantiFERON TB test not available) 
• Confirm volunteer eligibility to enroll 
6.1.2 
Enrollment 
• Participants undergoing an “ART switch” will be considered enrolled on the 
first day of the new ART medication. 
• Participants who do not undergo an “ART switch” will be considered enrolled 
at the initiation of ATI (Day 0). 
6.1.3 
ART Switch 
ART switch 
Participants taking NNRTI-based ART regimens are required to switch to a PI- or 
INSTI-based regimen at least 4 weeks before beginning ATI and must 
demonstrate viral suppression (ie, < LLOQ) on the new regimen before beginning 
ATI. 
At the clinic visit initiating the ART switch, the participant will undergo the 
following procedures (see Appendix E and Appendix H): 

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• Targeted (ie, symptom directed) physical examination, including weight and 
vital signs 
• Assessment of concomitant medications 
• Intercurrent illness/adverse experiences (AEs) 
• HIV transmission risk behavior assessment and counseling 
• SARS-CoV-2 risk reduction counseling (per clinician judgement based on 
local epidemiology, see HVTN 804/HPTN 095 SSP) 
• Contraception status assessment (for participants assigned female sex at birth 
and who are sexually active in a way that could lead to pregnancy; see Section 
6.6 and Appendix B) 
• Decision-making assessment 
• Psychosocial assessment 
• Blood collection for: 
o HIV PCR viral load 
o CD4+ and CD8+ T-cell counts 
o Hgb, ANC, platelets 
o ALT, direct bilirubin, eGFR 
• SARS-CoV-2 testing, (direct viral detection eg, viral nucleic acid or antigen 
detection) per clinician judgement based on local epidemiology and/or 
symptom presentation, see HVTN 804/HPTN 095 SSP. 
• Urine pregnancy test (for volunteers assigned female sex at birth; persons not 
of reproductive potential due to having reached menopause (no menses for 1 
year), or having undergone hysterectomy or bilateral oophorectomy or tubal 
ligation [verified by medical records], are not required to undergo pregnancy 
testing) 
Post-ART switch contact 
The site will make arrangements to contact the participant approximately 2 weeks 
after initiation of the new ART regimen to assess tolerability of the ART switch 
and willingness to continue. This contact may be conducted over the phone or in 
person; see HVTN 804/HPTN 095 SSP for details.  

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ATI qualification visit 
Four weeks or more after initiation of the new ART regimen, participants 
undergoing an ART switch will return for a clinic visit during which they will 
undergo the following procedures (see Appendix E and Appendix H): 
• Targeted (ie, symptom directed) physical examination, including weight and 
vital signs 
• Assessment of concomitant medications 
• Intercurrent illness/adverse experiences (AEs) 
• HIV transmission risk behavior assessment and counseling 
• SARS-CoV-2 risk reduction counseling (per clinician judgement based on 
local epidemiology, see HVTN 804/HPTN 095 SSP) 
• Contraception status assessment (for participants assigned female sex at birth 
and who are sexually active in a way that could lead to pregnancy; see 
Appendix B) 
• Blood collection for: 
o HIV PCR viral load 
o CD4+ and CD8+ T-cell counts 
o Hgb, ANC, platelets 
o ALT, direct bilirubin, eGFR 
• SARS-CoV-2 testing, (direct viral detection eg, viral nucleic acid or antigen 
detection) per clinician judgement based on local epidemiology and/or 
symptom presentation, see HVTN 804/HPTN 095 SSP 
• Urine pregnancy test (for volunteers assigned female sex at birth; persons not 
of reproductive potential due to having reached menopause (no menses for 1 
year), or having undergone hysterectomy or bilateral oophorectomy or tubal 
ligation [verified by medical records], are not required to undergo pregnancy 
testing) 
Any participant who is not virally suppressed at the ATI qualification visit will be 
retested on a weekly basis until virally suppressed. If not virally suppressed by 
approximately 12 weeks after the start of the ART switch, the participant should 
be referred to re-initiate their previous NNRTI-containing regimen, will not 
proceed to the ATI, and will be terminated from the study. 

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ATI should be initiated no more than 2 weeks after the ATI qualification visit at 
which samples are collected that demonstrate viral suppression on the new ART 
regimen. 
6.1.4 
ATI  
For all participants, initiation of ATI is defined as Day 0.  
While on Schedule 1, participants will undergo the following procedures, as 
specified in Appendix E and Appendix H: 
• Complete physical examination OR Targeted (ie, symptom directed) physical 
examination, including weight and vital signs 
• Assessment of concomitant medications 
• Intercurrent illness/adverse experiences (AEs) 
• ART re-initiation assessment 
• HIV transmission risk behavior assessment and counseling 
• SARS-CoV-2 risk reduction counseling (per clinician judgement based on 
local epidemiology, see HVTN 804/HPTN 095 SSP) 
• Contraception status assessment (for participants assigned female sex at birth 
and who are sexually active in a way that could lead to pregnancy; see Section 
6.6 and Appendix B) 
• Decision-making assessment 
• Psychosocial assessment 
• Social impact assessment 
• Social impact assessment questionnaire 
• Blood collection per Appendix E for: 
o HIV PCR viral load 
o CD4+ and CD8+ T-cell counts 
o Hgb, ANC, platelets 
o ALT, direct bilirubin, eGFR 

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o Syphilis testing 
o ARV detection 
o Intracellular cytokine staining (ICS) 
o Immune cell phenotyping 
o Neutralizing antibodies (nAb) 
o FcR-mediated effector functions 
o HIV reservoir assessment 
o Serum, plasma, and PBMC storage 
• SARS-CoV-2 testing, (direct viral detection eg, viral nucleic acid or antigen 
detection) per clinician judgement based on local epidemiology and/or 
symptom presentation, see HVTN 804/HPTN 095 SSP 
• Urine pregnancy test (for volunteers assigned female sex at birth; persons not 
of reproductive potential due to having reached menopause (no menses for 1 
year), or having undergone hysterectomy or bilateral oophorectomy or tubal 
ligation [verified by medical records], are not required to undergo pregnancy 
testing) 
• Gonorrhea/chlamydia testing by urine, rectal swabs, and oropharyngeal swabs 
6.2 
Schedule 2: Monitoring ATI with viremia 
As soon as participants demonstrate viral load ≥ 200 copies/mL, they will 
transition to Schedule 2, during which they will continue ATI while viremia is 
monitored. At Schedule 2 timepoints specified in Appendix F and Appendix I, 
participants will undergo the following procedures: 
• Complete physical examination OR targeted (ie, symptom directed) physical 
examination, including weight and vital signs 
• Assessment of concomitant medications 
• Intercurrent illness/adverse experiences (AEs) 
• ART re-initiation assessment 
• HIV transmission risk behavior assessment and counseling 

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• SARS-CoV-2 risk reduction counseling (per clinician judgement based on 
local epidemiology, see HVTN 804/HPTN 095 SSP) 
• Contraception status assessment (for participants who were assigned female 
sex at birth and who are sexually active in a way that could lead to pregnancy; 
see Section 6.6 and Appendix B). 
• Decision-making assessment 
• Psychosocial assessment 
• Social impact assessment 
• Social impact assessment questionnaire 
• Blood collection for: 
o HIV PCR viral load 
o CD4+ and CD8+ T-cell counts 
o Hgb, ANC, platelets 
o ALT, direct bilirubin, eGFR 
o Syphilis testing 
o ARV detection 
o Intracellular cytokine staining (ICS) 
o Immune cell phenotyping 
o Neutralizing antibodies (nAb) 
o FcR-mediated effector functions 
o Serum, plasma, and PBMC storage 
• SARS-CoV-2 testing, (direct viral detection eg, viral nucleic acid or antigen 
detection) per clinician judgement based on local epidemiology and/or 
symptom presentation, see HVTN 804/HPTN 095 SSP 
• Urine pregnancy test (persons assigned female sex at birth; persons not of 
reproductive potential due to having undergone hysterectomy or bilateral 
oophorectomy [verified by medical records], are not required to undergo 
pregnancy testing). 

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• Gonorrhea/chlamydia testing by urine, rectal swabs, and oropharyngeal swabs 
6.3 
Schedule 3: Follow-up on ART  
After ART re-initiation criteria are met (see Sections 3.3.2 and 3.3.3), participants 
will transition to Schedule 3 (see Appendix G and Appendix J). In Schedule 3, if 
virologic resuppression has not been achieved by Week 12, participants may 
continue with biweekly visits until viral resuppression is achieved. These 
additional visits will be treated as interim visits (see HVTN 804/HPTN 095 SSP).  
At Schedule 3 timepoints specified in Appendix G and Appendix J, participants 
will undergo the following procedures: 
• Complete physical examination OR targeted (ie, symptom directed) physical 
examination, including weight and vital signs 
• Assessment of concomitant medications 
• Intercurrent illness/adverse experiences (AEs) 
• HIV transmission risk behavior assessment and counseling 
• SARS-CoV-2 risk reduction counseling (per clinician judgement based on 
local epidemiology and/or symptom presentation, see HVTN 804/HPTN 095 
SSP) 
• Contraception status assessment (for participants who were assigned female 
sex at birth and who are sexually active in a way that could lead to pregnancy; 
see Section 6.6 and Appendix B). 
• Decision-making assessment 
• Psychosocial assessment 
• Social impact assessment 
• Social impact assessment questionnaire 
• Blood collection for: 
o HIV PCR viral load 
o CD4+ and CD8+ T-cell counts 
o Hgb, ANC, platelets 

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o ALT, direct bilirubin, eGFR 
o Syphilis testing 
o HIV genotypic antiretroviral resistance 
o Viral isolation and sequencing 
o Intracellular cytokine staining (ICS) 
o Immune cell phenotyping 
o Neutralizing antibodies (nAb) 
o FcR-mediated effector functions 
o HIV reservoir assessment 
o Serum, plasma, and PBMC storage 
• SARS-CoV-2 testing, (direct viral detection eg, viral nucleic acid or antigen 
detection) per clinician judgement based on local epidemiology and/or 
symptom presentation, see HVTN 804/HPTN 095 SSP 
• Urine pregnancy test (persons assigned female sex at birth; persons not of 
reproductive potential due to having undergone hysterectomy or bilateral 
oophorectomy [verified by medical records], are not required to undergo 
pregnancy testing). 
• Gonorrhea/chlamydia testing by urine, rectal swabs, and oropharyngeal swabs 
6.4 
Interim visits 
Confirmatory VL samples and confirmatory CD4+ T cell samples may be drawn 
at interim visits (see Sections 3.3.1, 3.3.2, and 3.3.3). At interim visits for this 
purpose, the following clinical procedures will be performed: 
• Targeted physical exam 
• Assessment of concomitant medications 
• Intercurrent illness/adverse experiences (AEs) 
• ART re-initiation assessment 
• HIV transmission risk behavior assessment and counseling 

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• Social impact assessment 
Additional procedures may be performed at the discretion of the clinician.  
For additional information on interim visits, including interim visits for other 
reasons, see the HVTN 804/HPTN 095 SSP. 
6.5 
Early termination visit 
At an early termination visit for a participant on Schedule 1 or 2, CRS staff should 
consider performing procedures specified for Extended Visit Type A (see 
Appendix E, Appendix F, Appendix H, and Appendix I). Such participants will be 
urged to re-initiate ART under the care of their primary HIV care provider (see 
HVTN 804/HPTN 095 SSP for additional details).  
At an early termination visit for a participant on Schedule 3, CRS staff should 
consider performing laboratory procedures specified for Week 40 (Visit 91; 
Appendix G) and clinic procedures specified for Week 52 (Visit 92; Appendix J) 
(see HVTN 804/HPTN 095 SSP for additional details).  
6.6 
Contraception status 
Contraception status is assessed and documented at every scheduled clinic visit 
from screening through confirmation of viral resuppression following ART re-
initiation for a participant who was assigned female sex at birth and who is 
sexually active in a way that could cause that participant to become pregnant. 
Prior to enrollment and until viral resuppression is confirmed following ART re-
initiation, staff will ask participants to verbally confirm their use of adequate 
contraceptive methods (see Appendix B). A participant who was assigned female 
sex at birth and is sexually active in a way that could cause that participant to 
become pregnant should be reminded at all scheduled clinic visits of the 
importance of using contraception and should be referred to specific counseling, 
information, and advice as needed. This reminder should be documented in the 
participant’s study record. 
Self-reported infertility—including having reached menopause (no menses for 1 
year) or having undergone hysterectomy, bilateral oophorectomy, or tubal 
ligation—must be documented in the participant’s study record. 

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6.7 
Specific clinical management considerations 
6.7.1 
Pregnancy or breastfeeding 
Volunteers who are pregnant or breastfeeding are not eligible to participate in this 
study. Participants who become pregnant or are breastfeeding during the ART 
switch will not be allowed to interrupt ART and will be terminated from the study 
immediately. Participants who become pregnant or are breastfeeding during the 
ATI phase will re-initiate ART as soon as possible. Post-ATI follow-up will 
continue per Schedule 3 for up to 24 weeks after viral re-suppression is confirmed 
following ART re-initiation.  
Participants who become pregnant or begin breastfeeding while on Schedule 3 (ie, 
after ART re-initiation) will continue per Schedule 3 for up to 24 weeks after viral 
re-suppression is confirmed. 
If a participant completes the study or chooses to discontinue from the study 
before the pregnancy ends, then CRS staff should request permission to contact 
the participant regarding pregnancy outcomes at the end of the pregnancy. If 
obtained, pregnancy outcomes will be recorded on a CRF at the end of the 
pregnancy. All pregnancies must be reported to the Antiretroviral Pregnancy 
Registry.  
6.7.2 
Acute retroviral syndrome 
Acute retroviral syndrome (ARS) is a rare diagnosis to be made by a CRS clinical 
IoR or designee or a primary HIV care provider. The HVTN 804/HPTN 095 
PSRT is available for consultation on possible ARS, as needed. Participants with 
this diagnosis will re-initiate ART as soon as possible. 
Signs and symptoms that may support a diagnosis of ARS include, but are not 
limited to, unintentional weight loss > 5% of pre-ATI body weight, otherwise 
unexplained persistent fever [> 38⁰C], persistent night sweats, persistent diarrhea, 
oral candidiasis, and generalized lymphadenopathy. 

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7 
Study products 
There are no study products. Drugs for ART and PrEP will not be provided by the 
study or paid for using sponsor funds. Procedures for accessing external funding 
sources for PrEP and ART provision are detailed in the HVTN 804/HPTN 095 
(SSP).  

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8 
Laboratory  
8.1 
CRS laboratory procedures 
The HVTN 804/HPTN 095 Site Lab Instructions and HVTN 804/HPTN 095 SSP 
provide further guidelines for operational issues concerning the clinical and 
processing laboratories. These documents include guidelines for general specimen 
collection, special considerations for phlebotomy, specimen labeling, whole blood 
processing, HIV screening/diagnostic testing, and general screening and safety 
testing. 
Tube types for blood collection are specified in Appendix E, Appendix F, and 
Appendix G. For tests performed locally, the local lab may assign appropriate 
tube types. 
In specific situations, the blood collection tubes may be redirected to another 
laboratory or may require study-specific processing techniques. In these cases, 
laboratory special instructions will be posted on the protocol-specific section of 
the HVTN website. 
Of note, all assays described below with the exception of HIV antiretroviral 
resistance testing are performed as research assays and are not approved for use in 
medical care. Results from these assays are not made available to participants or 
medical professionals to guide treatment decisions. 
8.2 
Assay timepoints 
Endpoint assays for immunologic and virologic responses will be performed on a 
subset of participants to be determined by the outcome of primary objectives and 
endpoints. 
8.3 
Endpoint assays: cellular 
8.3.1 
Intracellular cytokine staining (ICS) assay 
Flow cytometry will be used to examine HIV-specific CD4+ and CD8+ T-cell 
responses following stimulation of PBMCs with synthetic HIV peptides that span 
the HIV-1 viral proteins. ICS parameters will include cytokines such as interferon 
gamma (IFN-γ), interleukin (IL)-2, and TNF-α, and may include other cytokines 
(such as cytokines relevant to Th2 and Th17 responses) to identify T cells of 
specific functionality. Data will be reported as percentages of CD4+ and CD8+ T 
cells responding to a specific peptide pool. Additional cell surface markers, 
cytokines, or functional markers may also be analyzed. 

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8.4 
Phenotyping of cell populations 
Phenotyping of dendritic cells, monocytes, NK cells, B cells, T cells, or other 
leukocytes for lineage, maturation, and activation markers by flow cytometry may 
be performed on PBMCs. Data will be reported as percent of cells positive for 
each marker at the various timepoints. 
8.5 
Endpoint assays: humoral 
8.5.1 
Neutralizing antibody assay 
HIV-1–specific nAb assays will be performed on serum samples from 
study participants. The TZM-bl assay will test neutralization of the autologous 
transmitted/founder virus and a panel of heterologous tier 2 viruses (126, 127). 
Autologous neutralization escape may also be assessed at the discretion of the 
HVTN Laboratory Center, contingent on the results of the nAb assays. 
8.5.2 
Antibody-dependent cellular cytotoxicity (ADCC) 
ADCC activity may be assessed using serum samples from study participants. For 
the Luciferase-based cytotoxicity assay, participant sera are incubated with 
infectious molecular clone (IMC)-infected cells and percent killing is measured 
by evaluating the reduction in the luminescence signal after incubation of 
infected-target and effector cells in presence of serum Ab.  
8.5.3 
Antibody-dependent cellular phagocytosis (ADCP) 
To assess the ability of antibodies to engage cellular FcR for potential antiviral 
function, ADCP may be measured using serum samples from study participants. 
ADCP is measured by assessing the ability of antibodies to mediate monocyte 
phagocytosis of HIV-1 antigen coated fluorescent beads by flow cytometry (128, 
129). An array of antigens or viruses may also be analyzed at the discretion of the 
HVTN Laboratory Center, which may be contingent on the results of the primary 
antigens or viruses. 
8.5.4 
Virion capture  
The ability of purified IgG from participant serum to mediate infectious virion 
capture will be measured by infectious virion capture assay (IVCA). The test uses 
a Protein G column-based capture of Ig-virion immune complexes. 
8.6 
HIV viral reservoir 
Changes in the HIV reservoir will be quantitated in CD4+ T cells purified from 
PBMCs at designated timepoints, using testing methods such as the Intact Proviral 

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DNA Assay (IPDA), Tat/rev Induced Limiting Dilution Assay (TILDA), assays 
detecting replication-competent virus-bearing cells (eg, virus outgrowth assays), 
and/or measures of total proviral DNA. Cell-associated HIV-RNA may be 
quantitated as a measure of the transcriptionally active reservoir. 
8.7 
Host genomics 
Molecular human leukocyte antigen (HLA) and CCR5 genotyping may be 
performed on samples from this study or HVTN 704/HPTN 085 using 
cryopreserved PBMC. Other genes, including those associated with immune 
responses (eg, immunoglobulin or T-cell receptor genes) or HIV-1 disease 
progression may also be assessed. 
8.8 
HIV antiretroviral resistance testing 
HIV antiretroviral resistance testing will be performed by RNA PCR for 
resistance mutations in participants whose plasma viremia shows limited 
suppression after ART re-initiation.  
8.9 
ARV detection  
Blood specimens will be collected during treatment interruption for ARV 
detection and drug level testing. ARV drug levels may be assessed at the 
discretion of the protocol team for participants who have not met virologic and 
non-virologic criteria for transition from monitoring ATI (Schedule 1) to 
monitoring ATI with viremia (Schedule 2) or for ART re-initiation (from 
Schedule 2 to Schedule 3). Assay methods may include HPLC-mass 
spectrometry, reverse-phase HPLC coupled with tandem mass spectrometry, or 
another similar method. 
8.10 
Biohazard containment 
As the transmission of HIV and other blood-borne pathogens can occur through 
contact with contaminated needles, blood, and blood products, appropriate 
precautions will be employed by all personnel in the drawing of blood and 
shipping and handling of all specimens for this study, as currently recommended 
by the CDC and the NIH or other applicable agencies. 
All dangerous goods materials, including Biological Substances, Category A or 
Category B, must be transported according to instructions detailed in the 
International Air Transport Association Dangerous Goods Regulations. 

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9 
Research use of stored human samples and/or data 
9.1 
Specimen storage and other use of specimens 
The HVTN and HPTN store specimens from all study participants indefinitely, 
unless a participant requests that specimens be destroyed or if required by 
IRB/EC, or RA. 
Other use of specimens is defined as studies not covered by the protocol or the 
informed consent form for the main study (see Appendix A and Appendix C). 
This research may relate to HIV, vaccines, antibodies, the immune system, and 
other diseases. This could include genetic testing and, potentially, genome-wide 
studies. This research is done only to the extent authorized in each study site’s 
informed consent form, or as otherwise authorized under applicable law. Other 
research on specimens (“other use”) will occur only after review and approval by 
the Networks, the IRB/EC of the researcher requesting the specimens, and the 
IRBs/ECs/REs of the CRSs if required. 
As part of consenting for the study, participants document their initial decision to 
allow or not allow their specimens to be used in other research, and they may 
change their decision at any time. The participant’s initial decision about other 
use of their specimens, and any later change to that decision, is recorded by their 
CRS in a Web-based tool that documents their current decisions for other use of 
their specimens. The Networks will only allow other research to be done on 
specimens from participants who allow such use. 
CRSs must notify HVTN Regulatory Affairs if institutional or local governmental 
requirements pose a conflict with or impose restrictions on specimen storage or 
other use of specimens. 
9.2 
Exploratory studies 
Samples may be used for other testing and research related to furthering the 
understanding of HIV, immunology, antibodies, or vaccines. In addition, 
cryopreserved samples may be used to perform additional assays to support 
standardization and validation of existing or newly developed methods. 
 

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10 
Potential risks and benefits 
10.1 
Potential risks 
10.1.1 
Risks of ATI 
The risks from a closely monitored ATI are minimal in this study population. 
There is a theoretical risk that such an interruption could lead to the development 
of HIV drug resistance (130). This may be a particular concern for individuals 
taking NNRTIs. However, this potential risk is substantially mitigated by the 
procedures described in Section 6.1.1. Given the study population as restricted by 
the eligibility criteria, the frequency of immunological and virologic monitoring, 
and the criteria for restarting ART, it is extremely unlikely that such an ART 
interruption will lead to the development of any opportunistic infections or AIDS-
defining conditions. The risks of SARS-CoV-2 infection or COVID-19 for people 
living with HIV during a closely monitored ATI are currently unknown.  
Rarely, viremic rebound may be associated with acute retroviral syndrome (see 
Section 6.7.2). 
During the ATI phase, participants may transmit HIV infection if they do not 
adhere to safe sex practices. 
10.1.2 
Phlebotomy 
Drawing blood may be associated with discomfort, bruising, local hematoma 
formation and, on rare occasions, infections, lightheadedness, and fainting. 
The amount of blood drawn for research purposes will be within regulatory limits 
(see 21 CFR 630.15). 
10.2 
Potential benefits 
Study participants should expect no direct health benefits from study 
participation. Knowledge gained in this study may aid in development of better 
interventions against HIV. 
 

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11 
Monitoring of safety 
11.1 
Safety monitoring and oversight 
11.1.1 
HVTN 804/HPTN 095 PSRT 
The HVTN 804/HPTN 095 PSRT is composed of the following members: 
• DAIDS medical officer representatives 
• Protocol chairs 
• Protocol Team leaders 
• Core medical monitor 
• Clinical safety specialist 
• Regional medical liaison 
The Protocol Team clinic coordinator, clinical data manager, clinical trial 
manager, clinical research manager, and others may also be included in HVTN 
804/HPTN 095 PSRT meetings. 
The clinician members of HVTN 804/HPTN 095 PSRT are responsible for 
decisions related to participant safety. 
The PSRT will review laboratory parameters (HIV-RNA, CD4+ T-cell count), 
adverse events, and a summary of the distribution of time to meeting ART re-
initiation criteria twice a month. Once the final participant achieves viral 
resuppression in Schedule 3, the PSRT may consider holding less frequent 
reviews (ie, monthly).  
The PSRT will also review the distribution of time to meeting ART re-initiation 
criteria in the first 20 HVTN 804/HPTN 095 participants and assess whether the 
distribution is comparable to that observed in an NIH intramural therapeutic HIV 
vaccine study that enrolled HIV-infected participants who initiated ART early 
with similar ART re-initiation criteria to those proposed here. Based on the NIH 
intramural therapeutic HIV vaccine study results, we expect that the median time 
to meeting ART re-initiation criteria in HVTN 804/HPTN 095 will be at ATI 
week 15 and that the 75% percentile for time to meeting ART re-initiation criteria 
will be around week 12-18. If the spread in the distribution time to meeting ART 
re-initiation criteria is less than expected, then the HVTN 804/HPTN 095 PSRT, 
in consultation with the NIAID DSMB, will consider strategies for modifying the 
study (eg, to alter the eligibility criteria) with the aim to further enrich for 
potential controllers. 

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The HVTN 804/HPTN 095 PSRT will also monitor specifically for failure to re-
suppress or to demonstrate a 2-log viral load reduction within 12 weeks after ART 
re-initiation. Any such failure and/or any AE ≥ Grade 4 deemed related to the 
study procedures will be reviewed by the HVTN 804/HPTN 095 PSRT promptly 
and, if indicated, by the NIAID DSMB to evaluate whether and how the study 
should be modified. 
11.1.2 
NIAID DSMB 
The NIAID DSMB assesses the study conduct during the trial and may give 
advice to the HVTN 804/HPTN 095 Protocol Team leadership.  
Approximately 6 months after enrollment of the first participant or after the 10th 
participant has completed 12 weeks of ATI (whichever comes first), an interim 
review of the study will occur. The DSMB will review accrual; retention; AE 
summaries, including all reported AEs ≥ Grade 3 and all STIs; summaries of the 
time to meeting ART re-initiation criteria; and longitudinal summaries of HIV-1 
RNA and CD4+ T-cell count. Subsequent DSMB reviews will occur at least 
annually while participants remain on study. A DSMB may also be convened if a 
reason is identified by the DAIDS MO, study Co-chairs, or study statisticians in 
consultation with the HVTN 804/HPTN 095 Protocol Team leadership. 
11.1.3 
Roles and responsibilities in safety monitoring  
The roles and responsibilities of the SDMC in relation to safety monitoring 
include: 
• Maintaining a central database management system for clinical data; 
• Providing reports of clinical data to appropriate groups such as the HVTN 
804/HPTN 095 PSRT and NIAID DSMB (see Section 11.1.2); 
The roles and responsibilities of the HVTN CSS, HVTN RML, or HVTN Core 
designee in relation to safety monitoring include: 
• Daily monitoring of clinical data; 
• Querying CRSs for additional information regarding reported clinical data; 
and 
• Providing support to the HVTN 804/HPTN 095 PSRT. 

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11.2 
Safety reporting 
11.2.1 
Submission of safety forms to SDMC 
CRS staff must submit all safety forms (eg, AEs, local lab results, concomitant 
medications) before the end of the next business day, excluding federal or bank 
holidays. The forms should not be held in anticipation of additional information at 
a later date. If additional information is received at a later date, the forms should 
be updated and resubmitted before the end of the next business day after receiving 
the new information. For the case of a longer CRS holiday closure, CRS staff 
must submit the data by the end of the 5th day (local time) after receiving the 
information even if this day is a holiday.  
For example: If the CRS becomes aware of an AE on Thursday (Day 0), the CRS 
must submit the data by the end of the next business day, on Friday. If there is a 
longer CRS holiday closure, then this AE must be reported no later than the end 
of the fifth day, Monday (Day 4). If Monday is a holiday as well, all safety forms 
still need to be submitted by the end of Monday (Day 4). 
11.2.2 
Serious adverse event (SAE) 
An SAE is an AE that results in one or more of the following outcomes: 
• Death 
• A life-threatening (ie, an immediate threat to life) event 
• Requires in-patient hospitalization or prolongation of an existing 
hospitalization 
• A persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 
• A congenital anomaly/birth defect 
• A medically important event (medical and scientific judgment should be 
exercised in deciding whether expedited reporting is appropriate in such 
situations, such as important medial events that may not be immediately life 
threatening or result in death or hospitalization, but which may jeopardize the 
individual or may require intervention to prevent one of the outcomes listed 
above.) 
11.2.3 
AE reporting 
An AE is any untoward medical occurrence in a clinical investigation participant, 
including an abnormal laboratory finding, symptom, or disease temporally 

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associated with the individual’s participation in the research, whether or not 
related to the research. 
The study intervention for which adverse event attribution reporting is required is 
ATI. 
At designated visits, information regarding AEs will be elicited by appropriate 
questioning and examinations and will be documented in the medical record and 
in the electronic database. 
All AEs are graded according to the Division of AIDS (DAIDS) Table for 
Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 
2.1, July 2017, available on the RSC website at https://rsc.niaid.nih.gov/clinical-
research-sites/daids-adverse-event-grading-tables, except: 
• Unintentional Weight Loss is required to be reported as an AE only if it is 
considered to be potentially deleterious to the participant’s health (see HVTN 
804/HPTN 095 SSP); and 
• Creatinine is required to be reported as an AE only if it is gradable per the 
increase from local lab ULN parameter. Do not grade elevated creatinine 
based on the change from the baseline parameter. 
• eGFR is required to be reported as an AE only if it is gradable per reported 
value or if dialysis is needed. Do not grade decreased eGFR based on the 
change from the baseline parameter (see HVTN 804/HPTN 095 SSP). 
All AEs are reported to the SDMC on the appropriate CRF. 
Sites are expected to notify HVTN clinical safety staff of any serious safety 
concern requiring their attention. Telephone numbers and email addresses are 
found on the protocol home page on the HVTN Members’ site 
(https://members.hvtn.org/protocols/hvtn804-hptn095). Concerns requiring 
immediate attention should be communicated by calling the clinical safety phone. 
In the case of email notification, clinical safety staff will reply within one 
business day. 
In addition, CRS investigators are required to submit AE information in 
accordance with IRB/EC and any applicable RE requirements. 
 
 

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12 
Ethics/protection of human subjects 
12.1 
Informed consent process 
Informed consent is a process where information is presented to enable persons to 
voluntarily decide whether or not to participate in a clinical trial. It is an ongoing 
conversation between the prospective or enrolled research participant and the 
researchers that begins before consent is given and continues through the 
decision-making process and until the end of the participant’s involvement in the 
research. Discussions about the research will provide essential information about 
the study and include: purpose, duration, experimental procedures, alternatives, 
risks, and benefits. Participants will be given the opportunity to ask questions and 
to have them answered.  
The participant will sign the informed consent document prior to undergoing any 
research procedures. The participant may withdraw consent at any time 
throughout the course of the study. A copy of the informed consent document will 
be given to participants for their records. Documentation of the signing of the 
consent form will be retained in the participant’s medical record. The rights and 
welfare of participants will be protected by emphasizing to them that the quality 
of their medical care will not be adversely affected if they decline to participate in 
this study. These rights and responsibilities are further elaborated upon in the 
Participants Bill of Rights and Responsibilities developed by the HVTN and 
HPTN for their jointly conducted trials. 
The HVTN 804/HPTN 095 Sample Informed Consent Form (SICF) is modeled 
on previously-approved treatment interruption consent forms and, specifically, 
emphasizes the cautionary points noted above (see Section 2.9) with respect to the 
uncertainties, risks and lack of anticipated individual benefits; the fact that 
treatment interruptions are not recommended in clinical care; and the fact that 
ART guidelines recommend lifelong treatment. While the SICF is a crucial 
starting point, the quality of informed consent also relies on the process and other 
tools employed to supplement that document. With respect to these 
supplementary measures the team is building upon each Network’s longstanding 
efforts to build rigorous informed consent into trial implementation (131). These 
efforts begin with the community engagement described above (see Section 2.11) 
and go on to include: drafting of the SICF by and with local community 
representatives who reflect the target population and the sites that will be 
conducting the study; review of translated materials by local staff and community 
representatives who are native speakers of each language to help ensure accuracy 
and appropriateness; the provision of a Frequently Asked Questions information 
sheet; the development and use of visual aids to convey some concepts, such as 
blood draw volumes; the development of materials and processes to engage 
sexual partners, if participants and their partners so choose; the use of an 
Assessment of Understanding and re-review of any misunderstandings as part of 

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the initial and ongoing informed consent process; and ongoing community 
engagement throughout the trial, including local education and engagement 
activities, Community Advisory Board (CAB) meetings and study-specific 
stakeholder meetings, among other forums. 
For HVTN 804/HPTN 095, the team will develop additional tools to facilitate 
optimal informed consent and decision-making. Specifically, the team will 
develop decision aids, such as those found to improve the quality of shared 
decision making and consent in preference-sensitive healthcare decisions (132, 
133) and will partner with participant advocates—nonteam members, ideally 
peers, familiar with the AMP Study, treatment interruption, and the HVTN 
804/HPTN 095 study—who could work with the AMP participant to further 
facilitate optimal decision-making regarding potential HVTN 804/HPTN 095 
participation. The latter model has been used, for example, in the setting of organ 
transplantation between HIV-positive donors and recipients (134, 135). Clinic 
staff will also be in consultation with each participant’s primary HIV care 
provider to ensure their understanding and ability to support the participants. Any 
such materials developed for participants will be submitted for review and 
approval to the IRB/EC prior to using with participants.  
12.2 
Participant confidentiality 
All records will be kept confidential to the extent provided by federal, state, and 
local law. Study monitors and other authorized representatives of the Sponsor 
may inspect all documents and records required to be retained by the investigator, 
including but not limited to medical records. Records will be kept locked and all 
computer entry and networking programs will be done with coded numbers only. 
Clinical information will not be released without written permission of the 
participant, except as necessary for monitoring by the developer of VRC01, IRB, 
NIH/NIAID/DAIDS or the sponsor’s designee, OHRP, or another regulatory 
authority. 
In the United States, research participants are protected by a Certificate of 
Confidentiality from the US NIH, which can prevent disclosure of study 
participation even when that information is requested by subpoena. Participants 
are told of the use and limits of the certificate in the study consent form. 
 

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13 
Protocol conduct 
This protocol and all actions and activities connected with it will be conducted in 
compliance with Good Clinical Practice (GCP) (ICHe6), the HVTN and HPTN 
network-specific Manuals of Operations, and DAIDS Clinical Research Policies 
and Standard Procedures Documents, including procedures for the following: 
• Protocol registration, activation, and implementation; 
• Informed consent, screening, and enrollment; 
• Study participant reimbursement; 
• Clinical and safety assessments; 
• Safety monitoring and reporting; 
• Data collection, documentation, transfer, and storage; 
• Participant confidentiality; 
• Study follow-up and close-out; 
• Quality control; 
• Protocol monitoring and compliance; 
• Advocacy and assistance to participants regarding negative social impacts 
associated with the trial; 
• Risk reduction counseling;  
• Specimen collection, processing, and analysis;  
• Exploratory and ancillary studies and sub-studies, and 
• Destruction of specimens. 
Any policies or procedures that vary from DAIDS, HVTN, or HPTN standards or 
require additional instructions will be described in the HVTN 804/HPTN 095 
SSP.  

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13.1 
Emergency communication with study participants 
As in all clinical research, this study may generate a need to reach participants 
quickly to avoid imminent harm, or to report study findings that may otherwise 
concern their health or welfare.  
When such communication is needed, the CRS will request that its IRB/EC and 
any applicable RE expedite review of the message. If this review cannot be 
completed in a timeframe consistent with the urgency of the required 
communication, the site should contact the participant first, and then notify the 
IRB/EC and any applicable RE of the matter as soon as possible. 
 

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14 
Acronyms and abbreviations 
ACTG 
AIDS Clinical Trials Group 
ADCC 
antibody-dependent cellular cytotoxicity 
ADCP 
antibody-dependent cellular phagocytosis 
AE 
adverse experience 
AIDS 
acquired immune deficiency syndrome 
Β-HCG 
beta human chorionic gonadotropin 
AMP 
antibody mediated prevention 
ALT 
alanine transaminase 
ANC 
absolute neutrophil count 
ANOVA 
analysis of variance 
ARS 
acute retroviral syndrome 
ART 
antiretroviral therapy 
ATI 
analytical treatment interruption 
AUC 
area under the curve 
bnAb 
broadly neutralizing antibody 
CAB 
community advisory board 
cART 
combination antiretroviral therapy 
caRNA 
cell-associated HIV-1 RNA 
CBC 
complete blood count 
CDC 
(U.S.) Centers for Disease Control and Prevention 
CHF 
congestive heart failure 
CRF 
case report form 
CVA 
cerebrovascular accident 
DAIDS 
Division of AIDS 
DNA 
deoxyribonucleic acid 
DSMB 
data safety monitoring board 
EAE 
adverse event requiring expedited reporting 
EC 
ethics committee 
eGFR 
estimated glomerular filtration rate 
ELISA 
enzyme-linked immunosorbent assay 
FcγR 
fragment crystallizable gamma receptor 
HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B virus 
HCV 
Hepatitis C virus 
HIV 
human immunodeficiency virus 
HPTN 
HIV Prevention Trials Network 
HVTN 
HIV Vaccine Trials Network 
ICS 
intracellular cytokine staining 
IgG 
immunoglobulin G 
INSTI 
integrase strand transfer inhibitor 
IoR 
investigator of record 
IPDA 
intact proviral DNA assay 
IRB 
institutional review board 
IUPM 
infectious units per million 

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LLOQ 
lower limit of quantitation 
LTR 
long terminal repeat 
mAb 
monoclonal antibody 
MDC CAB 
Martin Delaney Collaboratory Community Advisory Board 
MedDRA 
Medical Dictionary for Regulatory Activities 
nAb 
neutralizing antibody 
NHP 
nonhuman primate 
NIAID 
National Institute of Allergy and Infectious Diseases 
NICD 
National Institute for Communicable Diseases 
NNRTI 
nonnucleoside reverse transcriptase inhibitor 
NIH 
National Institutes of Health 
OHRP 
Office of Human Research Protection 
PBMC 
peripheral blood mononuclear cells 
PCR 
polymerase chain reaction 
PHI 
primary HIV infection 
PI 
protease inhibitor 
PK 
pharmacokinetic 
PML 
progressive multifocal leukoencephalopathy 
PrEP 
pre-exposure prophylaxis 
PSRT 
protocol safety review team 
PTC 
post-treatment controller 
QVOA 
quantitative viral outgrowth assay 
RE 
regulatory entity 
RNA 
ribonucleic acid 
RSC 
Regulatory Support Center 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SDMC 
statistics and data management center 
SHIV 
simian/human immunodeficiency virus 
SICF 
sample informed consent form 
SIVIG 
specific intravenous immunoglobulin 
SMART 
Strategies for Management of Antiretroviral Therapy 
SSP 
study specific procedures 
T/F 
transmitter/founder 
TILDA 
Tat/Rev induced limiting dilution assay 
TMLE 
targeted minimum loss-based estimation 
Treg 
regulatory T cell 
ULN 
upper limit of normal 
VQA 
Virology Quality Assurance 
 
 

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15 
Protocol version history 
Date: March 22, 2022 
Protocol version: Version 3.0 
Protocol modification: Full Protocol Amendment 2 (to incorporate changes from LoA1 and 
CM1 to the protocol version 2.0) 
 
Item 1 
Added in Section 5.2, Exclusion criteria, Section 6.1.1, Screening, Section 
6.1.3, ART switch, Section 6.1.4, ATI, Section 6.2, Schedule 2: Monitoring 
ATI with viremia, Section 6.3, Schedule 3: Follow-up on ART, Section 
10.1.1, Risks of ATI, Section 14, Acronyms and abbreviations, Appendix A: 
Sample informed consent form, and Appendices D through J: monitoring for 
SARS-CoV-2 infection during the study 
 
Item 2 
Updated in Section 2.10, The necessity of the AMP placebo control group 
and Appendix A, Sample Informed Consent Form: AMP participants have 
been unblinded  
 
Item 3 
Deleted in Appendix D, Tables of procedures for sample informed consent 
form; Appendix H, Procedures at CRS—Schedule 1: Monitoring ATI and in 
Appendix I, Procedures at CRS—Schedule 2: Monitoring ATI with Viremia: 
deleted non-relevant footnotes 
 
Item 4 
Corrected in Section 6.1, Schedule 1: Monitoring ATI, and Section 6.3, 
Schedule 3: Follow-up on ART: cross reference to contraception status 
section 
 
Item 5 
Corrected in Appendix J, Procedures at CRS—Schedule 3: Follow-up on 
ART: placement of footnote 5 to visit 92 column  
 
Item 6 
Updated in Section 1.3, Protocol team: protocol leadership members  
 
Item 7 
Corrected in Appendix E, Laboratory Procedures—Schedule 1: Monitoring 
ATI: corrected footnote 9 
 
Item 8 
Updated Section 15, Version History: Modifications to version 2.0 and 
contents of this amendment. 
Date: January 19, 2022 
Protocol version: Version 2.0 
Protocol modification: Clarification memo 1 
 
Item 1 
Corrected in Appendix E, Laboratory Procedures—Schedule 1: Monitoring 
ATI, footnote 9 
Date: August 27, 2021 
Protocol version: 2.0 
Protocol modification: Letter of Amendment 01 
 
Item 1 
Added in Section 5.2, Exclusion criteria, Section 6.1.1, Screening, Section 
6.1.3, ART switch, Section 6.1.4, ATI, Section 6.2, Schedule 2: Monitoring 

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ATI with viremia, Section 6.3, Schedule 3: Follow-up on ART, Section 
10.1.1, Risks of ATI, Section 14, Acronyms and abbreviations, Appendix A: 
Sample informed consent form, and Appendices D through J: monitoring for 
SARS-CoV-2 infection during the study 
 
Item 2 
Updated in Section 2.10, The necessity of the AMP placebo control group 
and Appendix A, Sample Informed Consent Form: AMP participants have 
been unblinded  
 
Item 3 
Deleted in Appendices D, H and I: non-relevant footnotes 
 
Item 4 
Corrected in Section 6.1, Schedule 1: Monitoring ATI, and Section 6.3, 
Schedule 3: Follow-up on ART: cross reference to contraception status 
section Updated in Sections 5.3 and 16: Document reference 
 
Item 5 
Corrected in Appendix J, Procedures at CRS—Schedule 3: Follow-up on 
ART: placement of footnote 4 to visit 92 column  
 
Item 6 
Updated in Section 1.3, Protocol Team: protocol leadership members 
Date: March 16, 2020 
Protocol version: Version 2.0 
Protocol modification: Full Protocol Amendment 1 
Item 1 Clarified in Section 1, Protocol summary: Study population description 
Item 2 Revised in Sections 3.3.1 through 3.3.3 and in footnotes to Appendices E and 
F: Timing for viral load and CD4 count confirmatory testing 
Item 3 Revised in Sections 5.1, Inclusion criteria and 5.2, Exclusion criteria: VL 
assay qualification 
Item 4 Updated in Sections 5.3 and 16: Document reference 
Item 5 Clarified in Section 6.5 and footnote to Appendix J: Procedures at early 
termination visit 
Item 6 Clarified in Section 11.1.1: PSRT meeting frequency 
Item 7 Added in Section 11.2.3, AE reporting: Exception for eGFR reporting 
Item 8 Removed in Section 13, Protocol conduct: Reference to randomization 
Item 9 Updated in Section 15: Protocol version history 
Item 10 Corrected and clarified in Appendix A, Sample informed consent form: Study 
objectives, ATI duration, ATI qualification visit, follow-up for those who 
decline ART restart, data provision to participants, follow-up till viral 
resuppression, lab locations, and potential other studies 
Item 11 Corrected in Appendix C, Sample consent form for use of samples and 
information in other studies: Section 13 checkbox text 
Item 12 Corrected in Appendix D: Table of procedures for Part 2 

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Item 13 Added to HVTN Laboratories in Appendices E, F, and G: Fred Hutchinson 
Cancer Research Center (Seattle, Washington, USA) 
Item 14 Corrected in Appendix G, Laboratory procedures—Schedule 3: Follow-up 
on ART: CT/GC testing by urine at Visits 87, 88, and 90 
Item 15 Corrected in Appendix H footnotes: Visit number reference and 
typographical error 
Item 16 Corrected: Typographical and copy-editing errors 
Item 17 Corrected in Section 3.3.4: Visit schedule references 
Item 18 Corrected in Section 5: Study population description 
 
 
Date: November 13, 2019 
Protocol version: 1.0 
Protocol modification: Original protocol 
 

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16 
Document references (other than literature 
citations) 
Other documents referred to in this protocol, and containing information relevant 
to the conduct of this study, include: 
• Antiretroviral Pregnancy Registry. Available at http://www.apregistry.com/. 
• Assessment of Understanding. Accessible through the HVTN protocol-
specific website. 
• Division of AIDS (DAIDS) Clinical Research Policies and Standard 
Procedures Documents. Available at 
https://www.niaid.nih.gov/research/daids-clinical-research-policies-standard-
procedures  
• Division of AIDS Protocol Registration Manual. Available at 
https://www.niaid.nih.gov/sites/default/files/prmanual.pdf  
• Division of AIDS Table for Grading the Severity of Adult and Pediatric 
Adverse Events. Version 2.1, dated March 2017. Available at 
https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-
tables 
• The Manual for Expedited Reporting of Adverse Events to DAIDS. Version 
2.0, January 2010. Available at https://rsc.niaid.nih.gov/clinical-research-
sites/manual-expedited-reporting-adverse-events-daids  
• HVTN Certificate of Confidentiality. Accessible through the HVTN website. 
• HVTN 804/HPTN 095 Study Specific Procedures. Accessible through the 
HVTN protocol-specific website. 
• Ab Manual of Operations. Accessible through the HVTN website. 
• HVTN Manual of Operations. Accessible through the HVTN website. 
• Dangerous Goods Regulations (updated annually), International Air Transport 
Association. Available for purchase at 
http://www.iata.org/publications/dgr/Pages/index.aspx  
• International Conference on Harmonisation (ICH) E6 (R1), Guideline for 
Good Clinical Practice: Section 4.8, Informed consent of trial subjects. 
Available at http://www.ich.org/products/guidelines/efficacy/article/efficacy-
guidelines.html 

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HVTN804_HPTN095_v3.0_Final / Page 90 of 157 
• HVTN 804/HPTN 095 Participants’ Bill of Rights and Responsibilities. 
Accessible through the HVTN website. 
• NIH Policy on Reporting Race and Ethnicity Data: Subjects in Clinical 
Research. Available at http://grants1.nih.gov/grants/guide/notice-files/NOT-
OD-01-053.html 
• Requirements for Source Documentation in DAIDS Funded and/or Sponsored 
Clinical Trials. Available at  
https://www.niaid.nih.gov/labsandresources/resources/daidsclinrsrch/Pages/Cl
inicalSite.aspx  
• Title 21, Code of Federal Regulations, Part 50. Available at 
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFR
Part=50 
• Title 45, Code of Federal Regulations, Part 46. Available at 
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html 
See Section 17 for literature cited in the background and statistics sections of this 
protocol. 

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17 
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Burton DR, Hangartner L. Broadly Neutralizing Antibodies to HIV and Their Role in 
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Appendix A 
Sample informed consent form 
Title: Antiretroviral analytical treatment interruption (ATI) to assess immunologic 
and virologic responses in participants who received VRC01 or placebo and 
became HIV-infected during HVTN 704/HPTN 085 
Protocol number: HVTN 804/HPTN 095 
Site: [Insert site name] 
Thank you for your interest in our research study. Please read this consent form or 
ask someone to read it to you. If you decide to join the study, we will ask you to 
sign or make your mark on this form. We will offer you a copy to keep. We will 
ask you questions to see if we have explained everything clearly. You can also 
ask us questions about the study. 
Research is not the same as treatment or medical care. The purpose of a research 
study is to answer scientific questions. These answers can help find new 
medicines, treatments, vaccines, and knowledge about how the human body 
works.  
You are being asked to take part in this study because you got HIV while you 
were enrolled in the AMP Study, have been taking HIV medication (also known 
as “ART” or anti-retroviral treatment) and because your HIV has been kept at a 
very low level or “undetectable” for at least the past year. We will enroll people 
who got the study antibody and people who got placebo.  You will know whether 
you got the study antibody or not before joining this study.  
We expect that between 16 and 46 people will join this study. 
Key information 
These are some of the things you should know about this study: 
• One purpose of the study is to learn whether having the AMP Study antibody 
in a person’s body might help the immune system control HIV better if that 
person gets HIV.  
• A second purpose is to learn if it is safe for people to interrupt their HIV 
treatment in a carefully monitored research study. 
• If you are eligible and choose to join, we will ask you to stop taking your HIV 
medication.  
• After you stop taking HIV medication, you will have regular clinic visits to 
carefully track your HIV and your health. If your viral load goes up to 200 or 
higher, you will continue to stay off your HIV medication, and we will check 
on your health more often.  

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• If your viral load goes up to 1,000 or more and stays that high for 4 weeks, or 
if your CD4 count drops below 350, or if you show any symptoms of HIV-
related illness, you will restart taking HIV medication. If your viral load at the 
end of 6 months is 200 or higher, you will restart taking HIV medication. If 
your immune system maintains control of your HIV for the entire 6 months, 
you may choose to keep going without taking HIV medication for as long as 
your viral load remains below 200 and you don’t meet the other restart criteria 
within this study. 
• Once you restart taking HIV medication, you will have follow-up visits for up 
to a year to see how your body responds to restarting HIV medication and to 
make sure that your viral load returns to very low or undetectable levels. 
• At clinic visits we will give you physical exams, ask about your physical and 
mental health, and collect blood for laboratory tests. 
• Stopping your HIV medication is an experimental procedure that is only used 
in carefully monitored research. It is not recommended as part of routine 
healthcare for people living with HIV. Healthcare guidelines recommend that 
people living with HIV take HIV medication for the rest of their lives. Some 
of the risks when you stop taking HIV medication include having a high viral 
load and acute retroviral syndrome, having a low CD4 count, transmitting 
HIV to your partner(s), developing HIV drug resistance, and having to switch 
to a new HIV medication, which could have additional side effects. The study 
is designed to make it unlikely that any of these things will happen. 
• The risks of SARS-CoV-2 infection or having COVID-19 while you are not 
taking HIV medication are currently unknown. 
• There may also be risks we don’t know about, even serious ones, including 
death.  
• There is no direct benefit to you from being in the study. 
• Whether to join this study is your choice. You do not have to join and you are 
free to leave at any time. Your choice will not affect the care you receive at 
this clinic. 
The rest of this form provides a more complete description of this study. Please 
read it carefully and ask questions at any time. 
Why is this study being done? 
Researchers know that when people stop taking their HIV medication, the amount 
of HIV in their blood (known as “viral load”) usually goes up quickly, and they 
must restart taking their medication. This quick increase does not always happen. 

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Very rarely, for only a few people, it stays low, or even undetectable for many 
months.  
We do not expect this study to benefit you directly, even if you received the study 
antibody in the AMP study. You should not expect to control the virus while you 
are off of your HIV medication. 
Researchers think having an anti-HIV antibody like the one used in the AMP 
Study in the body at the time when HIV infection happens may improve how the 
body’s immune system responds to HIV. This could happen even if the antibody 
didn’t prevent HIV acquisition. 
Animal studies suggest that having an anti-HIV antibody in the body at the time 
of HIV infection may help the immune system keep viral load low for a longer 
period of time without taking HIV medication. Researchers want to find out if this 
will happen in people. And if it happens in people, researchers want to know how 
and why this happens. 
1. We are doing this study to answer several questions. 
• Are people who got the study antibody in the AMP Study more likely to keep 
HIV under control longer without taking HIV medication than people who got 
the placebo? 
• Is it safe for people to stop taking their HIV medication in a carefully 
monitored research study? 
• Do people who got the study antibody in the AMP Study and got HIV develop 
and maintain an immune system that is more capable of controlling HIV viral 
load than people who got the placebo and get HIV? 
• Do people who got the study antibody or placebo in the AMP Study and get 
HIV have a difference in the number of cells that are infected with HIV but do 
not reproduce before and after stopping their HIV treatment?  
2. To answer these questions, study participants will stop taking their HIV 
medications. 
Stopping HIV medication is an experimental procedure that is only used in 
carefully monitored research. It is not recommended as part of routine healthcare 
for people living with HIV. Healthcare guidelines recommend that people living 
with HIV take HIV medication for the rest of their lives. We will tell you more 
about the risks of stopping your HIV medication in Section 19 of this form. 
During the time that you do not take your HIV medication we will check your 
health and HIV frequently to minimize the chance of harm to you. If your viral 
load goes up, your CD4 count goes down, you show signs of HIV-related illness, 

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or you and/or your primary HIV care provider decide to, you will restart taking 
HIV medication right away.  
Joining the study 
3. It is completely up to you whether or not to join the study. 
Take your time in deciding. If it helps, talk to people you trust, such as your 
primary HIV care provider, friends or family. We will be happy to help you 
explain this study to anyone you wish. If you decide not to join this study, or if 
you leave it after you have joined, your other care at this clinic and the benefits or 
rights you would normally have will not be affected. 
You cannot be in this study while you are in another study where you get a study 
product. Being in more than one study may not be safe. 
If you choose not to join this study, you may be able to join another study. 
4. If you want to join the study, we will screen you to see if you are eligible. 
Screening involves a physical exam, checking your mental health, an HIV test, 
and asking about your health history. A physical exam may include, but is not 
limited to: 
• Checking your weight, temperature and blood pressure, 
• Looking in your mouth and throat, 
• Listening to your heart and lungs, and 
• Feeling your abdomen (stomach and liver). 
We will also do blood and urine tests. These tests tell us about some aspects of 
your health, such as how healthy your kidneys, liver, and immune system are. We 
will also test you for hepatitis B, hepatitis C, tuberculosis (TB), gonorrhea, 
chlamydia, and syphilis. We will also test you for SARS-CoV-2 and provide you 
with risk reduction counseling (if you have not been vaccinated). We will ask you 
about medications you are taking. If you were assigned female sex at birth and 
can become pregnant, we will test you for pregnancy. If you are pregnant, you 
cannot join the study.  
We will communicate with your primary HIV care provider to coordinate your 
care during this study. We will check to make sure your HIV has been well 
controlled by your HIV medications for at least one year.  

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We will ask if you are willing to use condoms every time you have sex for an 
extended period during the study, until you restart your HIV medications and your 
viral load returns to being very low or undetectable. 
We will review the screening results with you. The screening results may show 
you are not eligible to join the study, even if you want to.  
5. If we find that you have a health problem during screening or during the 
study, we will tell you about the care that we can give here for free. 
For the care that we cannot give, we will explain how we will help you get care 
elsewhere. We will not pay for care for health problems that are unrelated to the 
study. 
Site: Appendix B, Approved contraception methods (for sample informed consent 
form), contains supplemental information. If you want to include Appendix B in this 
consent form, paste it below. 
6. If you were assigned female sex at birth and can become pregnant, you must 
agree to use effective contraception to join this study. 
Current HIV treatment guidelines recommend using HIV medication during 
pregnancy to prevent transmission to the baby. Since you will stop taking your 
HIV medication in this study, you should not become pregnant. In addition to 
using condoms every time you have sex, we will ask you to use another method of 
contraception. These include a diaphragm or cervical cap with a cream or gel that 
kills sperm, IUD, hormone-based contraception, or another method approved by 
the researchers. 
If you become pregnant or start breastfeeding after you stop taking your HIV 
medication, you will have to restart taking it, but you can remain in the study. We 
would like you to come for clinic visits for up to 6 months after your HIV viral 
load returns to very low or undetectable. If you become pregnant or start 
breastfeeding after you have restarted you HIV medication, you will continue 
taking it. We would like you to come for clinic visits for up to 6 months after your 
HIV viral load returns to very low or undetectable. 
The study staff would like to obtain information from you about the outcome of 
the pregnancy (even if it is after your participation in the study ends). If you are 
taking your HIV medication when you become pregnant, your pregnancy will be 
reported to an international database that collects information about pregnancies 
in people using these HIV medications. This report will not use your name or 
other information that could be used to identify you. 
Being in the study 
If you meet the study requirements and want to join, here is what will happen. 

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7. We will make sure you are on the right HIV medication for this study. 
You may have to change some of the HIV medication you are taking. If you are 
taking HIV medications that stay in the blood for a long time even after you stop 
taking them, we will have you switch to a different HIV medication for at least 
one month before you stop taking all of your HIV medication. We will provide 
this new medication to you for free. This is to reduce the already small chance 
that you may develop drug resistance. Drug resistance means the HIV medication 
you have been taking might not control your HIV when you restart it. We will 
check on you after about two weeks to see how you are doing on the new HIV 
medication. If you have any problems after starting the new HIV medication, 
please let us know. 
We will ask you to come to the clinic about 4 weeks after starting the new HIV 
treatment to see if it is controlling your HIV. If it is not, we will ask you to come 
to the clinic weekly for up to 12 weeks (about 3 months) until your HIV is 
controlled. 
If the new HIV medication does not bring your HIV to very low or undetectable 
within about 3 months, you will not able to continue with the rest of the study. 
8. If you join the study, we will collect some basic information. 
We will record your medical history and give you a physical examination, 
including checking your weight and vital signs. We will ask about other 
medications you are taking and about any illnesses you may have. We will also 
collect blood and urine, and if you were assigned female sex at birth and can 
become pregnant, we will give you a pregnancy test. We will test you for 
gonorrhea and chlamydia using urine, rectal swabs, and oral swabs. We will test 
you for syphilis using a blood sample. Testing for SARS-CoV-2 and risk 
reduction counseling will be provided as needed. 
9. In Part 1 of the study, you will stop taking your HIV medication. 
After you stop taking your HIV medication, for the first 8 weeks (about 2 months) 
you will visit the clinic every week (8 visits). For the next 16 weeks (months 2-6), 
you will visit the clinic every 2 weeks (8 visits). For the next 6 months, if you are 
still in Part 1 of the study, you will visit the clinic about every month (7 visits). 
One reason for these frequent clinic visits is to carefully track your HIV and your 
health. 
At these visits we will ask about anything new in your medical history and give 
you a brief physical exam. We will collect blood. When we collect blood the 
amount will depend on the lab tests we need to do. It will be some amount 
between 10 mL and 160 mL (2 teaspoons and 2/3 cup). Your body will make new 
blood to replace the blood we take out. 

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We will check to make sure you are using condoms for all sexual activity. 
If you were assigned female sex at birth and can become pregnant, we will check 
to make sure you are using effective contraception. We will also give you a 
pregnancy test.  
We will test you for gonorrhea and chlamydia at some visits using urine, and oral 
and rectal swabs. 
Some of the blood we collect will be used for lab tests of your general health 
(including syphilis testing) and to check your immune system. We will also check 
to see if you still have any HIV medications in your blood.  
We will review the results of these procedures and tests with you at your next 
visit, or sooner if necessary. If any of the results are important to your health, we 
will tell you. 
Some of the blood collected at each visit will be used to test your viral load and 
your CD4 count. If your viral load goes up to 200 or higher, you will move to Part 
2 of the study.  
If any of the following happens, you will restart your HIV medication as soon as 
possible and move to Part 3 of the study.  
• Your CD4 count drops below 350, 
• You show any symptoms of HIV-related illness, 
• You decide to restart your HIV medication, or  
• Your primary HIV care provider or the doctor at the study clinic decides that 
you should restart your HIV medication. 
If none of these things happens, a person can stay in Part 1 for a year or longer. 
Most people will be in Part 1 of the study for less than 6 months. 
If you meet the restart criteria but decline to restart ART, we will ask you to 
continue Part 1 clinic visits. We may need to see you for additional visits to check 
your safety. If you restart your HIV treatment you will move to Part 3.  
10. Here is what will happen in Part 2 of the study. 
In Part 2, you will continue to stay off your HIV medication. When you start Part 
2, for the first 8 weeks (about 2 months), you will visit the clinic every week (9 
visits). For the next 28 weeks (months 2-8), you will visit the clinic every 2 weeks 
(14 visits). After that, if you still have not met the criteria to restart your HIV 
medication, for the next 4 months, you will visit the clinic once a month (4 visits). 

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One reason for these frequent clinic visits is to carefully track your HIV and your 
health. 
At these visits we will ask about anything new in your medical history. At the first 
visit in Part 2, we will give you a complete physical exam. At all other visits in 
Part 2 we will give you a brief physical exam. We will collect blood. When we 
collect blood the amount will depend on the lab tests we need to do. It will be 
some amount between 10 mL and 130 mL (2 teaspoons and a little more than ½ 
cup). Your body will make new blood to replace the blood we take out. 
We will check to make sure you are using condoms for all sexual activity. 
If you were assigned female sex at birth and can become pregnant, we will check 
to make sure you are using effective contraception. We will also give you a 
pregnancy test.  
We will test you for gonorrhea and chlamydia at some visits using urine, oral 
swabs, and rectal swabs. 
Some of the blood we collect will be used for lab tests of your general health 
(including syphilis testing) and to check your immune system. We will also check 
to see if you have any HIV medications in your blood. 
We will review the results of these procedures and tests with you at your next 
visit, or sooner if necessary. If any of the results are important to your health, we 
will tell you. 
Some of the blood collected at each visit will be used to test your viral load and 
your CD4 count.  
During the first 24 weeks (about 6 months) in Part 2, if any of the following 
happens, you will restart your HIV medication as soon as possible and move to 
Part 3 of the study.  
• Your viral load goes up to 1,000 or higher and stays there for 4 weeks without 
dropping very quickly, 
• Your CD4 count drops below 350, 
• You show any symptoms of HIV-related illness, 
• You decide to restart your HIV medication, or 
• Your primary HIV care provider or the doctor at the study clinic decides that 
you should restart your HIV medication. 

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After 24 weeks (6 months), if any of the following happens, you will restart your 
HIV medication as soon as possible and move to Part 3 of the study. 
• Your viral load is 200 or higher, 
• Your CD4 count drops below 350, 
• You show any symptoms of HIV-related illness, 
• You decide to restart your HIV medication, or 
• Your primary HIV care provider or the doctor at the study clinic decides that 
you should restart your HIV medication. 
If you do not meet these restart criteria, you can stay in Part 2 of the study for as 
long as your viral load stays below 200. Most people will be in Part 2 for a few 
weeks to a few months. Some people may stay in Part 2 for a year or longer. If 
you meet the restart criteria but decline to restart ART, we will ask you to 
continue Part 2 clinic visits. We may need to see you for additional visits to check 
your safety. If you restart your HIV treatment you will move to Part 3. 
11. After you restart taking HIV medication, you will have follow-up clinic visits 
for about another year. This is Part 3 of the study. 
This follow-up period is to see how your body responds to restarting your HIV 
medication and to make sure that your HIV returns to very low or undetectable 
levels. For most people, we expect that your viral load will drop within about 12 
weeks (about 3 months). If it does not, we will ask you to come to the clinic every 
2 weeks until your HIV is controlled. 
Once you restart taking HIV medication, for the first 12 weeks (about 3 months) 
you will have clinic visits every 2 weeks (7 visits). For the next 16 weeks (about 4 
months), you will have clinic visits once a month (4 visits). For the next 24 weeks 
(about 6 months) you will have 2 visits scheduled 3 months apart. At these visits 
we will ask about anything new in your medical history and give you a brief 
physical exam. We will collect blood. When we take blood, the amount will 
depend on the lab tests we need to do. It will be some amount between 10 mL and 
225 mL (2 teaspoons and a little less than 1 cup). 
At some visits, we will test you for gonorrhea and chlamydia using urine, rectal 
swabs, and oral swabs. We will also do a blood test for syphilis. 
Until we have confirmed that your viral load has returned to very low or 
undetectable levels, you will still need to use condoms every time you have sex. 
We will check to make sure you are doing so. 

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Until we have confirmed that your viral load has returned to very low or 
undetectable levels, if you were assigned female sex at birth and can become 
pregnant, we will check to make sure you are using effective contraception. We 
will also give you a pregnancy test at some visits.  
We will review the results of these procedures and tests with you at your next 
visit, or sooner if necessary. If any of the results are important to your health, we 
will tell you. 
12. If you stay in Part 1 or Part 2 of the study for more than a year, you will have 
visits every 3 months. 
At these visits we will ask about anything new in your medical history and give 
you a brief physical exam. We will collect blood. Some of that blood gets used for 
viral load and CD4 testing.  
At some visits, we will test you for gonorrhea and chlamydia using urine, rectal 
swabs, and oral swabs. At these same visits, we will test you for syphilis using 
blood samples. 
We will review the results of these procedures and tests with you at your next 
visit, or sooner if necessary. If any of the results are important to your health, we 
will tell you. 
We will continue to check to make sure you are using condoms every time you 
have sex. 
Also, if you were assigned female sex at birth and can become pregnant, we will 
check to make sure you are using effective contraception. We will also give you a 
pregnancy test at each visit.  
If you meet the restart criteria at any time, you will restart your HIV medication 
and move to Part 3 of the study as described above in Section 11. If you choose to 
not restart your treatment, we will strongly urge you to continue clinic visits on 
the same schedule you have been on. We may need to see you for additional visits 
to check your safety. If you restart your HIV treatment you will move to Part 3. 
13. Most participants will be in the study about 13-18 months. 
This depends on whether you need to switch your HIV medications and how long 
it takes before you meet the criteria to restart your HIV medication. If your 
immune system controls your HIV for a long time without medication, then you 
might be in the study longer. The longest we expect anyone to be in the study is 
about 3 years. 

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14. We will test your samples to see how your immune system is functioning. 
We will send your samples (without your name) to labs approved by the HVTN 
and the HPTN for this study, which are located in the United States. In rare cases, 
some of your samples may be sent to labs approved by the HVTN and HPTN in 
other countries for research related to this study. 
Some of the blood we collected previously in the AMP Study or that we collect in 
this study might be used for limited genetic testing in this study. Your genes are 
passed to you from your birth parents. They affect how you look and how your 
body works. Differences in genes can explain why some people get a disease and 
others don’t. The genetic testing that might be done in this study involves only 
some of your genes related to how your immune system works to fight HIV. The 
testing will not involve all of your genes (your genome). We want to understand 
whether your genes affect your ability to control HIV in combination with 
whether or not you got the AMP Study antibody. 
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that your samples can continue to contribute to this study. 
These tests done on your samples are for research purposes, not to check your 
health. The labs will not give the results to you or this clinic because their tests 
are not approved for use in making health care decisions. These labs are only 
approved to do research tests. 
When your samples are no longer needed for this study, the HVTN will continue 
to store them. 
Site: Delete next section if using separate consent for use of samples and information 
in other studies. 
15. When samples are no longer needed for this study, the HVTN and HPTN 
may want to use them in other studies and share them with other 
researchers.  
These samples are called “extra samples”. The HVTN and HPTN will only allow 
your extra samples to be used in other studies if you agree to this. You will mark 
your decision at the end of this form. If you have any questions, please ask. 
Do I have to agree? No. You are free to say yes or no, or to change your mind 
after you sign this form. At your request, The HVTN and HPTN will destroy all 
extra samples that they have. Your decision will not affect your being in this 
study or have any negative consequences here.  
Where are the samples stored? Extra samples are stored in a secure central place 
called a repository. Your samples will be stored in the HVTN repository in the 
United States. 

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How long will the samples be stored? There is no limit on how long your extra 
samples will be stored. [Site: Revise the previous sentence to insert limits if your 
regulatory authority imposes them.] 
Will I be paid for the use of my samples? No. Also, a researcher may make a new 
scientific discovery or product based on the use of your samples. If this happens, 
there is no plan to share any money with you. The researcher is not likely to ever 
know who you are. 
Will I benefit from allowing my samples to be used in other studies? Probably not. 
Results from these other studies are not given to you, this clinic, or your doctor. 
They are not part of your medical record. The studies are only being done for 
research purposes. 
Will the HVTN or HPTN sell my samples and information? No, but the HVTN 
and HPTN may share your samples with other researchers. Once we share your 
samples and information, we may not be able to get them back. 
How do other researchers get my samples and information? When a researcher 
wants to use your samples and information, their research plan must be approved 
by the HVTN and HPTN. Also, the researcher’s institutional review board (IRB) 
or ethics committee (EC) will review their plan. [Site: If review by your 
institution’s IRB/EC/RE is also required, insert a sentence stating this.] IRBs/ECs 
protect the rights and well-being of people in research. If the research plan is 
approved, the HVTN will send your samples to the researcher’s location.  
What information is shared with HVTN, HPTN, or other researchers? The 
samples and information will be labeled with a code number. The key to the code 
will stay at this clinic. It will not be shared with the HVTN, HPTN, or other 
researchers or with anyone else who does not need to know your name. Your 
name will not be part of the information. However, some information that the 
HVTN and HPTN share may be personal, such as your race, ethnicity, sex, health 
information from the study, and HIV status. The HVTN and HPTN may share 
information about the study product you received and how your body responded 
to the AMP study product.  
What kind of studies might be done with my extra samples and information? The 
studies will be related to HIV, vaccines, monoclonal antibodies, the immune 
system, and other diseases.  
Researchers may also do genetic testing on your samples.  
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that they can continue to do research with them. 
If you agree, your samples could also be used for genome wide studies. In these 
studies, researchers will look at all your genes (your genome). The researchers 

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compare the genomes of many people, looking for common patterns of genes that 
could help them understand diseases. The researchers may put the information 
from the genome-wide studies into a protected database so that other researchers 
can access it. Usually, no one would be able to look at your genome and link it to 
you as a person. However, if another database exists that also has information on 
your genome and your name, someone might be able to compare the databases 
and identify you. If others found out, it could lead to discrimination or other 
problems. The risk of this happening is extremely small. 
Who will have access to my information in studies using my extra samples?  
People who may see your information are: 
• Researchers who use your extra samples and information for other research, 
• Government agencies that fund or monitor the research using your extra 
samples and information, 
• Any regulatory agency that reviews clinical trials, 
• The researcher’s Institutional Review Board or Ethics Committee, or 
• The people who work with the researcher/ 
All these people will do their best to protect your information. The results of any 
new studies that use your extra samples and information may be published. No 
publication will use your name or identify you personally. 
16. We will give you [Site: Insert compensation] for each study visit you 
complete. 
This amount is to cover the costs of [Site: Insert text] 
Site: Insert any costs to participants (eg, contraception costs for participants who 
could become pregnant). 
US sites: Include the following paragraph. You can remove the box around the text. 
Payments you receive for being in the study may be taxable. We may need to ask 
you for your Social Security number for tax reasons. 
You do not have to pay anything to be in this study. 
17. We will do our best to protect your private information. 
US sites: Check HIPAA authorization for conflicts with this section. 

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Your study records and samples will be kept in a secure location. We will label all 
of your samples and most of your records with a code number, not your name or 
other personal information. However, it is possible to identify you, if necessary. 
We will not share your name with the lab that does the tests on your samples, or 
with anyone else who does not need to know your name. 
Clinic staff will have access to your study records. Your records may also be 
reviewed by groups who watch over this study to see that we are protecting your 
rights, keeping you safe, and following the study plan. These groups include: 
• The US National Institutes of Health and its study monitors, 
• The Perú Instituto Nacional de Salud (INS), 
• Any regulatory agency that reviews clinical trials, 
• [Insert name of local IRB/EC] , 
• [Insert name of local and/or national regulatory authority as appropriate], 
• The Dale and Betty Bumpers Vaccine Research Center and people who work 
for them, 
• The HVTN, HPTN and people who work for them,  
• The US National Institute of Allergy and Infectious Diseases Data and Safety 
Monitoring Board, and 
• The US Office for Human Research Protections. 
All reviewers will take steps to keep your records private. 
We cannot guarantee absolute privacy. If you are found to have a medical 
condition that we are required to report by law, then some of your information 
may be shared. At this clinic, we have to report the following information:  
Site: Include any public health or legal reporting requirements. Bulleted examples 
should include all appropriate cases (reportable communicable disease, risk of harm 
to self or others, etc.). If your site does not have public health or legal reporting 
requirements, you may delete the last sentence in the paragraph above, along with 
the bullets below. 
• [Item 1] 
• [Item 2] 
• [Item 3] 

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US sites: Include the following boxed text. You can remove the box. 
We have a Certificate of Confidentiality from the US government, to help protect 
your privacy. With the certificate, we do not have to release information about 
you to someone who is not connected to the study, such as the courts or police. 
Sometimes we can’t use the certificate. Since the US government funds this 
research, we cannot withhold information from it. Also, you can still release 
information about yourself and your study participation to others. 
The results of this study may be published. No publication will use your name or 
identify you personally. 
We may share information from the study with other researchers. We will not 
share your name or information that can identify you. 
A description of this clinical trial will be available on 
http://www.ClinicalTrials.gov. This website will not include information that can 
identify you. At most, the website will include a summary of the results. You can 
search this website at any time. 
18. We may take you out of the study even if you want to stay in the study.  
This may happen if: 
• You move away from the study site and transfer to another study site is not 
possible, 
• Clinic staff cannot contact you, 
• We think, or your primary HIV care provider thinks, that staying in the study 
might harm you, 
• You do not follow study instructions, 
• You enroll in a different research study where you get a study product,  
• You become pregnant or are breastfeeding,  
• You tell us you intend to get pregnant or begin breastfeeding, or 
• The study is stopped for any reason. 

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Risks 
19. There are risks to being in this study. 
This study is designed to minimize the risks of stopping your HIV medication. 
This depends on you following the instructions from the clinic staff and attending 
all your study visits. 
This section describes the risks we know about. There may also be risks we don’t 
know about, even serious ones. The risks of SARS-CoV-2 infection or having 
COVID-19 while you are not taking HIV medication are currently unknown. This 
is why we will monitor you for COVID-19 during the study. We will tell you if 
we learn anything new that may affect your willingness to stay in the study. 
Risks of stopping your HIV medication 
Staying off HIV medication is not recommended for routine healthcare for people 
living with HIV. Stopping your HIV medication is an experimental procedure. It 
can increase the risk of serious health complications, including death.  
High viral load 
At some point after you stop taking your HIV medication, your viral load will 
probably rise. During this time, you probably will not have any symptoms. 
However, it is possible that you could have symptoms of what is called “acute 
retroviral syndrome.” We think that having this syndrome is rare because you 
started taking HIV medication soon after your HIV diagnosis. The symptoms 
could include: 
• Fever, 
• Weight loss, 
• Sore throat, 
• Swollen lymph nodes, 
• Headache, 
• Body or joint aches, 
• Tiredness, 
• Night sweats, 
• Oral yeast infection, 

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• Diarrhea, or 
• Rash. 
If you have any of these symptoms, tell the study staff right away. These 
symptoms should go away or become less severe once you restart your HIV 
medication. 
If your viral load increases, this could lead to inflammation. High levels of 
inflammation over many years are associated with heart disease and other medical 
conditions. Starting your HIV medication again should reduce inflammation. 
Low CD4 count 
If your viral load rises, your CD4 count could drop. This could increase your risk 
for other HIV-related illnesses. In about 60 people studied to date, there has not 
been a significant difference in CD4 counts before and 6-12 months after stopping 
HIV medication. However, it is possible that your CD4 count might not return to 
its original level, even after you restart taking your HIV medication.  
Transmitting HIV to your partner 
While your viral load is controlled, the risk that you could transmit HIV to a 
sexual partner is very low, known as U = U (undetectable = untransmittable). 
Once you stop taking HIV medication that risk gets higher.  
That is why you must use condoms for all sexual activity after you stop taking 
your HIV medication. 
If your sexual partners do not have HIV, they should get regular HIV testing until 
you have restarted your HIV medication and we have confirmed that your viral 
load has returned to very low or undetectable levels. Testing for your partners is 
not part of this study. If your partners are interested, we can tell you about a 
program we have for providing pre-exposure prophylaxis (PrEP) to them during 
the time that you are in the study. You are also welcome to bring partners to the 
clinic for education and risk reduction counseling. 
Transmitting HIV to your baby 
Once you stop taking HIV medication, the risk of transmitting HIV to your baby 
gets higher if you become pregnant. That is why you must keep using 
contraception from when you stop taking HIV medication until you restart and 
your viral load returns to very low or undetectable. If you become pregnant, it is 
extremely important to take your HIV medication throughout the entire 
pregnancy. 
Developing HIV drug resistance 

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As we described in Section 7 above, when you stop taking HIV medication, the 
HIV in your body might mutate in ways that make it resistant to the HIV 
medication you have been taking. This means the HIV medication you were 
taking may not control your HIV when you start taking it again. To make this less 
likely, we may ask you to switch to a different HIV medication before beginning 
the study. 
After you restart your HIV medication, you will have very frequent viral load 
tests. If your viral load is not returning to its original level within 8-12 weeks of 
restarting your HIV medication, we will test to see if the HIV is resistant to your 
HIV medications. If resistance is found, we will recommend more effective HIV 
medications to you and your primary HIV care provider. 
Side effects from new HIV medications or non-study medications: 
If you need to switch your HIV medications, there may be some new side effects 
from the new HIV medications. We or your primary HIV care provider can 
explain those side effects to you. 
There may also be a risk of serious or even life-threatening side effects from non-
study medications taken during the study. For your safety, tell the study doctor or 
nurse about all medications you are taking before you start the study, and also 
before starting any new medications during the study.  
Routine medical procedures: 
In this study, we will take blood. This can cause bruising, pain, fainting, soreness, 
redness, swelling, itching, a sore, bleeding, and (rarely) muscle damage or 
infection where the needle was inserted. In some people, taking blood can cause a 
low blood cell count (anemia), making you feel tired. 
Risks of disclosure of your personal information: 
We will take several steps to protect your personal information. Although the risk 
is very low, it is possible that your personal information could be given to 
someone who should not have it. If that happened, you could face discrimination, 
stress, and embarrassment. We can tell you more about how we will protect your 
personal information if you would like. 
Risks of other people learning your HIV status: 
We will keep your participation in this study and your HIV status confidential. 
However, if others learn that you are in a study for people living with HIV, you 
could face discrimination, stress, embarrassment, or stigma.  
Risk of limitations to research participation: 

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As a result of being in this study, you may not be eligible to participate in other 
HIV treatment or cure studies that require you to have an undetectable viral load 
for a period of time. After you restart taking your HIV medication and your viral 
load becomes undetectable again, this limitation will go away over time. 
Risks of genetic testing: 
It is unlikely, but the genetic tests that might be done on your samples could show 
you may be at risk for certain diseases. If others found out, it could lead to 
discrimination or other problems. However, it is almost impossible for you or 
others to know your test results from the genetic testing. The results are not part 
of your study records and are not given to you. 
US Sites, include the following paragraph In the very unlikely event that your 
genetic information becomes linked to your name, a federal law called the 
Genetic Information Nondiscrimination Act (GINA) helps protect you. GINA 
keeps health insurance companies and employers from seeing results of genetic 
testing when deciding about giving you health insurance or offering you work. 
GINA does not help or protect you against discrimination by companies that sell 
life, disability or long-term care insurance. 
Benefits 
20. We do not expect the study to benefit you directly. 
However, information learned from this study may help others who have HIV and 
being in the study might still help you in some ways. The lab tests and physical 
exams that you get while in this study might detect health problems you don’t yet 
know about. You may also learn whether you are one of the rare people who can 
control HIV without taking HIV medications. This study may help in the search 
for a vaccine or other ways to prevent HIV. 
Your rights and responsibilities 
21. If you join the study, you have rights and responsibilities. 
You have many rights that we will respect. You also have responsibilities. We list 
these in the Participant’s Bill of Rights and Responsibilities. We will give you a 
copy of it. 
Leaving the study 
22. Tell us if you decide to leave the study.  
You are free to leave the study at any time and for any reason. Your care at this 
clinic and your legal rights will not be affected, but it is important for you to let us 
know.  

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We may ask you to come back to the clinic one last time for a physical exam, and 
we may ask to take some blood and urine samples. We will also ask about any 
personal problems or benefits you have experienced from being in the study. We 
will counsel you about the importance of taking your HIV medications and 
following up with your primary HIV care provider. We believe these steps are 
important to protecting your health, but it is up to you whether to complete them.  
Injuries 
Sites: Approval from HVTN Regulatory Affairs (at vtn.core.reg@hvtn.org) is needed 
for any change (other than those that the instructions specifically request or those 
previously approved by HVTN Regulatory Affairs) to the boxed text 
23. If you get sick or injured during the study, contact us immediately. 
Your health is important to us. (Sites: adjust the following 2 sentences if 
applicable to the care available at your site) We will tell you about the care that 
we can give here. For the care that we cannot provide, we will explain how we 
will help you get care elsewhere. 
If you become sick or injured in this study, the HVTN has a process to decide if it 
is related to the procedures. If it is, we call it a study-related injury. There are 
funds to pay for treatment of study-related injuries if certain conditions are met. 
This paragraph for non-US sites only. Sites: adjust the language in this 
paragraph so it is applicable to your site. In this study, our clinic has insurance to 
cover your medical treatment in the case of a study-related injury. In rare cases, 
the insurance funds may not be enough.  
Some injuries are not physical. For example, you might be harmed emotionally by 
being in a study where you stop taking your HIV medication. Or you might lose 
wages because you cannot go to work. However, there are no funds to pay for 
these kinds of injuries, even if they are study related. 
You may disagree with the decision about whether your injury is study related. If 
you wish, the HVTN will ask independent experts to review the decision. You 
always have the right to use the court system if you are not satisfied. 
Questions  
24. If you have questions or problems at any time during your participation in 
this study, use the following important contacts. 
If you have questions about this study, contact 
[name or title and telephone number of the investigator or other study staff]. 

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If you have any symptoms that you think may be related to this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
This study has been reviewed and approved by a committee called the 
[name of local IRB/EC]. If you have questions about your rights as a research 
participant, or problems or concerns about how you are being treated in this study, 
contact [name or title and telephone number of person on IRB/EC] , at the 
committee. 
If you want to leave this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
Your permissions and signature  
25. In Section 15 of this form, we told you about possible other uses of your extra 
samples and information, outside this study. Please choose only one of the 
options below and write your initials or make your mark in the box next to it. 
Whatever you choose, the HVTN keeps track of your decision about how 
your samples and information can be used. You can change your mind after 
signing this form. 
 
 
I allow my extra samples and information to be used for other studies related to HIV, 
vaccines, monoclonal antibodies, the immune system, and other diseases. This may 
include genetic testing and keeping my cells growing over time.  
OR 
 
 
I agree to the option above and also to allow my extra samples and information to be 
used in genome wide studies. 
OR 
 
 
I do not allow my extra samples to be used in any other studies. This includes not 
allowing genetic testing, growing more of my cells, or genome wide studies.  
 
26. If you agree to join this study, you will need to sign or make your mark 
below. Before you sign or make your mark on this consent form, make sure 
of the following: 
• You have read this consent form, or someone has read it to you. 
• You feel that you understand what the study is about and what will happen to 
you if you join. You understand what the possible risks and benefits are. 
• You have had your questions answered and know that you can ask more. 

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• You agree to join this study. 
You will not be giving up any of your rights by signing this consent form. 
 
 
 
 
 
 
 
Participant’s name (print) 
 
Participant’s signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff conducting consent 
discussion (print) 
 
Clinic staff signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the 
signature block below: 
 
 
 
 
 
 
 
Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the entire discussion of this consent form. 

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Appendix B 
Approved contraceptive methods for 
transgender men (for sample informed consent 
form) 
If you were assigned female at birth and are sexually active in a way that could 
lead to pregnancy, you must agree to use effective birth control from 21 days 
before stopping your HIV medication until your viral load drops to undetectable 
after you start taking HIV medication again. 
While you are not taking HIV medication, there is a risk that you could transmit 
HIV to your developing baby. So, you must be careful not to become pregnant. 
Although taking testosterone can lower the chances of becoming pregnant, it is 
not considered an effective method of contraception.  
In addition to using condoms every time you have sex, you must also use one of 
the following contraceptive methods every time you have sex: 
• Drugs that are prescribed specifically for contraception and intended to 
prevent pregnancy—these include pills, shots, patches, vaginal rings, or 
inserts under the skin; 
• Diaphragm or cervical cap with a cream or gel that kills sperm; 
• Intrauterine device (IUD); or 
• Any other contraceptive method approved by the researchers. 
You do not have to use birth control if: 
• You have had a hysterectomy (your uterus removed); 
• You have had an oophorectomy (your ovaries removed); or 
• You are only having sex with a partner or partners who have had a vasectomy. 
(We will ask you some questions to confirm that the vasectomy was 
successful.); 
• You have a tubal ligation (your “tubes tied”) or confirmed successful 
placement of a product that blocks the fallopian tubes; or 
• You are sexually abstinent (no sex at all). 
If you join the study, we will test you for pregnancy at some visits. 

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Appendix C 
Sample consent form for use of samples and 
information in other studies 
Title: Antiretroviral analytical treatment interruption (ATI) to assess immunologic 
and virologic responses in participants who received VRC01 or placebo and 
became HIV-infected during HVTN 704/HPTN 085 
Protocol number: HVTN 804/HPTN 095 
Site: [Insert site name] 
When samples are no longer needed for this study, the study sponsors want to 
keep them for use in other studies by HVTN, HPTN, or other researchers. We will 
call these “extra samples.” 
This form gives you information so you can decide if you want your extra 
samples and information used in other studies. You will mark your decision at the 
end of the form. If you have any questions, please ask. 
Key information 
These are some of the things you should know about the use of your samples and 
information for other studies: 
• The extra samples will be labeled with a code number and some personal 
information. They will not be labeled with your name. The extra samples are 
stored in a secure place. At your request, the HVTN and HPTN will destroy 
all your extra samples. You can still join the main study even if you do not 
agree to the use of your extra samples in other studies. 
• Researchers may do genetic testing on your samples, which could include 
genome wide studies. It is unlikely, but these tests could show you may be at 
risk for certain diseases. In the very unlikely event that others found out, this 
could lead to discrimination or other problems.  
• You will not be paid or otherwise benefit from allowing your extra samples to 
be used in other studies.  
The rest of this form gives more information about use of your extra samples for 
other studies. Please read it carefully. 
1. Do I have to agree? 
No. You are free to say yes or no, or to change your mind after you sign this form. 
At your request, the HVTN and HPTN will destroy all extra samples that they 
have. Your decision will not affect your being in this study or have any negative 
consequences here. 

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2. Where are the samples stored? 
Extra samples are stored in a secure central place called a repository. Your 
samples will be stored in the HVTN repository in the United States. 
3. How long will the samples be stored? 
There is no limit on how long your extra samples will be stored. [Site: Revise the 
previous sentence to insert limits if your regulatory authority imposes them.] 
4. Will I benefit from allowing my samples to be used in other studies? 
We do not expect this to benefit you directly. Results from these other studies are 
not given to you, this clinic, or your doctor. They are not part of your medical 
record. The studies are only being done for research purposes. 
5. Will I be paid for the use of my samples? 
No. Also, a researcher may make a new scientific discovery or product based on 
the use of your samples. If this happens, there is no plan to share any money with 
you. The researcher is not likely to ever know who you are. 
6. Will the HVTN or HPTN sell my samples and information? 
No, but the HVTN and HPTN may share your samples with other researchers. 
Once we share your samples and information, we may not be able to get them 
back. 
7. How do other researchers get my samples and information? 
When a researcher wants to use your samples and information, their research plan 
must be approved by the HVTN and HPTN. Also, the researcher’s institutional 
review board (IRB) or ethics committee (EC) will review their plan. [Site: If 
review by your institution’s IRB/EC/RE is also required, insert a sentence stating 
this.] IRBs/ECs protect the rights and well-being of people in research. If the 
research plan is approved, the HVTN and HPTN will send your samples to the 
researcher’s location. 
8. What information is shared with HVTN, HPTN, or other researchers?  
The samples and information will be labeled with a code number. The key to the 
code will stay at this clinic. It will not be shared with the HVTN, HPTN, other 
researchers or with anyone else who does not need to know your name. Your 
name will not be part of the information. However, some information that the 
HVTN and HPTN share may be personal, such as your race, ethnicity, gender, 
health information from the study, and HIV status. The HVTN and HPTN may 

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share information about the study product you received and how your body 
responded to the AMP study product. 
9. What kind of studies might be done with my extra samples and information? 
The studies will be related to HIV, vaccines, monoclonal antibodies, the immune 
system, and other diseases. 
Researchers may also do genetic testing on your samples. 
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that they can continue to contribute to this study.  
If you agree, your samples could also be used for genome wide studies. In these 
studies, researchers will look at all of your genes (your genome). The researchers 
compare the genomes of many people, looking for common patterns of genes that 
could help them understand diseases. The researchers may put the information 
from the genome-wide studies into a protected database so that other researchers 
can access it, but your name and other personal information will not be included. 
Usually, no one would be able to look at your genome and link it to you as a 
person. However, if another database exists that also has information on your 
genome and your name, someone might be able to compare the databases and 
identify you. If others found out, it could lead to discrimination or other problems. 
The risk of this is very small.  
10. What are the risks of genetic testing? 
It is unlikely, but the genetic tests done on your samples could show you may be 
at risk for certain diseases. If others found out, it could lead to discrimination or 
other problems. However, it is almost impossible for you or others to know your 
test results from the genetic testing. The results are not part of your study records 
and are not given to you. 
US Sites, include the following paragraph  
In the very unlikely event that your genetic information becomes linked to your 
name, a federal law called the Genetic Information Nondiscrimination Act 
(GINA) helps protect you. GINA keeps health insurance companies and 
employers from seeing results of genetic testing when deciding about giving you 
health insurance or offering you work. GINA does not help or protect you against 
discrimination by companies that sell life, disability or long-term care insurance. 
11. Who will have access to my information in studies using my extra samples? 
People who may see your information are: 
• Researchers who use your extra samples and information for other research 

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• Government agencies that fund or monitor the research using your extra 
samples and information 
• Any regulatory agency that reviews clinical trials 
• The researcher’s Institutional Review Board or Ethics Committee 
• The people who work with the researcher 
All of these people will do their best to protect your information. The results of 
any new studies that use your extra samples and information may be published. 
No publication will use your name or identify you personally. 
Questions  
12. If you have questions or problems about allowing your samples and 
information to be used in other studies, use the following important contacts. 
If you have questions about the use of your samples or information or if you want 
to change your mind about their use, contact 
[name or title and telephone number of the investigator or other study staff]. 
If you think you may have been harmed because of studies using your samples or 
information, contact 
[name or title and telephone number of the investigator or other study staff]. 
If you have questions about your rights as a research participant, contact 
[name or title and telephone number of person on IRB/EC . 
13. Please choose only one of the options below and write your initials or make 
your mark in the box next to it. Whatever you choose, the HVTN and HPTN 
keep track of your decision about how your samples and information can be 
used. You can change your mind after signing this form. 
 

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I allow my extra samples and information to be used for other studies related to HIV, 
vaccines, monoclonal antibodies, the immune system, and other diseases. This may 
include genetic testing and keeping my cells growing over time. 
OR 
 
 
I agree to the option above and also to allow my extra samples and information to be 
used in genome wide studies. 
 
OR 
 
 
I do not allow my extra samples to be used in any other studies. This includes not 
allowing genetic testing, growing more of my cells, or genome wide studies.  
 
 
 
 
 
 
 
 
 
 
Participant’s name (print) 
 
Participant’s signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff conducting consent 
discussion (print) 
 
Clinic staff signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the 
signature block below: 
 
 
 
 
 
 
 
Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the entire discussion of this consent form. 
 
 

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Appendix D 
Tables of procedures for sample informed consent form 
Table of procedures for Part 1: Screening and stopping your HIV medications 
 
 
HIV 
medication  
switcha 
Pre-stop 
visit about 
4 weeks 
later 
Time after stopping HIV medications 
 
Screening 
Day 0 
Week 1 
Week 2 
Week 3 
~1 month 
Week 5 
Week 6 
Week 7 
~2 months 
Week 10 
~3 months 
Week 14 
~4 months 
Week 18 
~5 months 
Week 22 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV medication switch (if required) 
 
✓ 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical exam 
✓ 
 
 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Brief physical exam  
 
✓ 
✓ 
 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Pregnancy test and contraception reviewb 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Blood drawn 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
STI testing (blood, urine, and oral & rectal swabs)c 
✓ 
 
 
✓ 
 
 
 
✓ 
 
 
 
✓ 
 
✓ 
 
✓ 
 
✓ 
 
Transmission risk reduction counseling 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Interview/questionnaire 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
TB test 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood drawn 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
SARS-CoV-2 risk reduction counseling 
 
at screening or any study visit as needed 
SARS-CoV-2 testing  
 
at screening or any study visit as needed 
Procedures in gray only for participants switching HIV medications. 
a We will contact you about 2 weeks after you start the new HIV medication to check to see if you have had any side effects or have other concerns. 
b Persons assigned female sex at birth who have reached menopause or who had a hysterectomy, oophorectomy, or tubal ligation verified by medical records are not required to have a 
pregnancy test or contraception review. 
c In addition to STI testing at the checked visits, we will test at other visits if you show symptoms of an STI. 
 
 
 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 132 of 157 
Table of procedures for Part 1: Screening and stopping your HIV medications (continued) 
 
Time after stopping HIV medications 
 
~6 months 
Week 28 
Week 32 
Week 36 
~ 9 months 
Week 44 
Week 48 
1 year 
Extra visitsd 
Study procedures 
 
 
 
 
 
 
 
 
 
Complete physical exam 
 
 
 
 
 
 
 
 
 
Brief physical exam 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Pregnancy test and contraception reviewb 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Transmission risk reduction counseling 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Interview/questionnaire 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
STI testing (blood, urine, and oral & rectal swabs)c 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Blood Drawn 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
SARS-CoV-2 risk reduction counseling 
At screening or any study visit as needed 
SARS-CoV-2 testing  
at screening or any study visit as needed 
a We will contact you about 2 weeks after you start the new HIV medication to check to see if you have had any side effects or have other concerns. 
b Persons assigned female sex at birth who have reached menopause or who had a hysterectomy, oophorectomy, or tubal ligation verified by medical records are not required to have a 
pregnancy test or contraception review. 
c In addition to STI testing at the checked visits, we will test at other visits if you show symptoms of an STI. 
d Extra visits every 3 months for people do not meet criteria for moving to Part 2 or Part 3.  
 
 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 133 of 157 
Table of procedures for Part 2: Monitoring your health and your HIV 
 
Time after starting Part 2 
 
Day 0 
Week 1 
Week 2 
Week 3 
~1 month 
Week 5 
Week 6 
Week 7 
~2 months 
Week 10 
~3 months 
Week 14 
~4 months 
Week 18 
~5 months 
Week 22 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical exam 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Brief physical exam  
 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Pregnancy test and contraception reviewa 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Blood drawn 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
STI testing (blood, urine, and oral & rectal swabs)b 
✓ 
 
 
 
✓ 
 
 
 
✓ 
 
✓ 
 
✓ 
 
✓ 
 
Transmission risk reduction counseling 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Interview/questionnaire 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Blood drawn 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
SARS-CoV-2 risk reduction counseling 
at screening or any study visit as needed 
SARS-CoV-2 testing  
at screening or any study visit as needed 
a Persons assigned female sex at birth who have reached menopause or who had a hysterectomy, oophorectomy, or tubal ligation verified by medical records are not required to have a 
pregnancy test or contraception review. 
b In addition to STI testing at the checked visits, we will test at other visits if you show symptoms of an STI. 
  
 
 
 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 134 of 157 
Table of procedures for Part 2: Monitoring your health and your HIV (continued) 
 
Time after starting Part 2 
 
Week 24 
6 months 
Week 28 
Week 30 
Week 32 
Week 34 
Week 36 
~9 months 
Week 44 
Week 48 
1 year 
Extra visitsc 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical exam 
 
 
 
 
 
 
 
 
 
 
 
 
Brief physical exam  
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Pregnancy test and contraception reviewa 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Blood drawn 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
STI testing (blood, urine, and oral & rectal swabs)b 
✓ 
 
✓ 
 
✓ 
 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Transmission risk reduction counseling 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Interview/questionnaire 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Blood drawn 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
SARS-CoV-2 risk reduction counseling 
at screening or any study visit as needed 
SARS-CoV-2 testing  
at screening or any study visit as needed 
a Persons assigned female sex at birth who have reached menopause or who had a hysterectomy, oophorectomy, or tubal ligation verified by medical records are not required to have a 
pregnancy test or contraception review. 
b In addition to STI testing at the checked visits, we will test if you show symptoms of an STI. 
c Extra visits every 3 months for people do not meet criteria for moving to Part 3.  
 
 
 
 
 
 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 135 of 157 
Table of procedures for Part 3: Restart HIV medications  
 
Time after restarting HIV medications 
 
Week 0 
Week 2 
~1 month 
Week 6 
~2 months 
Week 10 
Week 12 
~4 months 
Week 20 
~6 months 
Week 28 
~9 months 
1 year 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical exam 
 
 
 
 
 
 
 
 
 
 
 
 
✓ 
Brief physical exam 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
Pregnancy test & contraception reviewa 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Transmission risk reduction counseling 
✓ 
✓ 
✓ 
 
✓ 
 
✓ 
 
✓ 
 
✓ 
 
✓ 
Interview/Questionnaire 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
STI testing (blood, urine, and oral & rectal swabs)b 
✓ 
 
✓ 
 
✓ 
 
✓ 
✓c 
✓c 
✓ 
✓c 
✓ 
 
Blood Drawn 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
SARS-CoV-2 risk reduction counseling 
at screening or any study visit as needed 
SARS-CoV-2 testing  
at screening or any study visit as needed 
a Persons assigned female sex at birth who have reached menopause or who had a hysterectomy, oophorectomy, or tubal ligation verified by medical records are not required to 
have a pregnancy test or contraception review. Pregnancy test and contraceptive review are not required once viral load drops to undetectable after restarting HIV medication. 
b In addition to STI testing at the checked visits, we will test if you show symptoms of an STI. 
c STI testing is not required at this visit if viral load has returned to undetectable. 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 136 of 157 
Appendix E 
Laboratory procedures—Schedule 1: Monitoring ATI  
1 
CSR = central specimen repository. 
2 HVTN Laboratories include: Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke University Medical Center (Durham, North Carolina, USA). 
Non-HVTN laboratories: TBD. 
3 Local labs may assign appropriate alternative tube types for locally performed tests.  
4 HCV RNA PCR testing will be performed as a reflex test if indicated by anti-HCV antibody results. 
5 Tuberculin skin test (TST) will be performed if QuantiFERON TB testing is not available. See Procedures at CRS (Appendix H). 
6 FcR-mediated effector function assays may include ADCC, virion capture, and phagocytosis assays. 
7 Chlamydia/gonorrhea testing will be done on urine, and rectal and oropharyngeal swabs. 
8 The "ART switch" phase will only be performed for participants on NNRTIs. These participants will be considered enrolled on the first day of the new ART medication. 
9 The ATI Qualification visit specimens must be obtained at least 28 days after ART switch. If needed, VL retesting may continue until viral suppression has been achieved (up to 84 days after ART 
switch). The last ATI qualification procedures must take place no more than 28 days prior to visit 4 (see HVTN 804/HPTN 095 SSP for more information). 
10 In addition to STI testing at the marked visits, STI testing may occur at any visit if clinically indicated. 
11 Extended follow-up visit type A will occur every 6 months starting with 3 months after visit 27 continuing up to 3 years of this schedule. This follow-up visit may be performed for participants who 
have not met criteria to transition to Schedule 2 or Schedule 3 (see Protocol Section 3.3 and HVTN 804/HPTN 095 SSP for details).  
12 Extended follow-up visit type B will occur every 6 months starting with 6 months after visit 27 continuing up to 3 years of this schedule, and then every 3 months thereafter. This follow-up visit 
may be performed for participants who have not met criteria to transition to Schedule 2 or Schedule 3 (see Protocol Section 3.3 and HVTN 804/HPTN 095 SSP for details). 
13 A confirmatory sample should be drawn at the next visit (within approximately 1-2 weeks) following the first VL result ≥ 200 copies/mL (see Protocol Section 3.3.1 for details. 
Visit:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Days on ATI:
D0
D7
D14
D21
D28
D35
D42
D49
D56
D70
D84
D98
D112
D126
D140
D154
Weeks on ATI:
W0
W1
W2
W3
W4
W5
W6
W7
W8
W10
W12
W14
W16
W18
W20
W22
Procedure
Ship to1 
Assay location1,2
Tube Type3
Tube size
(vol. capacity)3
ATI
BLOOD COLLECTION
Screening or diagnostic assays
HIV PCR viral load13
Local labs
Local labs
EDTA
6mL
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
CD4+/CD8+ T-cell count14
Local labs
Local labs
EDTA
4mL
4
4
4
4
—
4
—
4
—
4
—
4
—
4
—
4
—
4
—
HBsAg/anti-HCV4
Local labs
Local labs
SST
5mL
10
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
QuantiFERON TB testing5
Local labs
Local labs
QFT Gold/Gold-Plus
1mL
4
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Safety labs
Hgb / ANC / PLT
Local labs
Local labs
EDTA
4mL
4
4
4
4
—
—
—
4
—
—
—
4
—
4
—
4
—
4
—
ALT / direct bilirubin / eGFR
Local labs
Local labs
SST
5mL
5
5
5
5
—
—
—
5
—
—
—
5
—
5
—
5
—
5
—
Syphilis10
Local labs
Local labs
SST
5mL
5
—
—
5
—
—
—
5
—
—
—
5
—
5
—
5
—
5
—
Drug levels
ARV detection
CSR
TBD
EDTA
4mL
—
—
—
—
—
—
—
4
—
—
—
4
—
4
—
4
—
4
—
Immunogenicity & Virologic Assays
Cellular assays
ICS
CSR
HVTN labs
ACD
8.5mL
—
—
—
42.5
—
—
—
42.5
—
—
—
42.5
—
42.5
—
42.5
—
42.5
—
Phenotyping
CSR
HVTN labs
ACD
8.5mL
—
—
—
z
—
—
—
z
—
—
—
z
—
z
—
z
—
z
—
Humoral assays
Neutralizing antibody
CSR
HVTN labs
SST
8.5mL
—
—
—
8.5
—
—
—
8.5
—
—
—
8.5
—
8.5
—
8.5
—
8.5
—
FcR-mediated effector functions6
CSR
HVTN labs
SST
8.5mL
—
—
—
y
—
—
—
y
—
—
—
y
—
y
—
y
—
y
—
HIV reservoir assays
CSR
TBD
ACD
8.5mL
—
—
—
51
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Storage
Serum
CSR
SST
8.5mL
—
—
—
8.5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Plasma
CSR
EDTA
10mL
—
—
—
—
—
—
—
—
—
—
—
10
—
10
—
10
—
10
—
PBMC
CSR
ACD
8.5mL
—
—
—
—
—
—
—
—
—
—
—
17
—
17
—
17
—
17
—
Visit total
38
19
19
134.5
6
10
6
79
6
10
6
106
6
106
6
106
6
106
6
56-Day total
38
57
76
210.5
216.5
226.5
232.5
311.5
317.5
327.5
333.5
401.5
229
319
240
330
230
330
230
URINE COLLECTION
Pregnancy Test16
Local labs
Local labs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chlamydia/gonorrhea7,10
Local labs
Local labs
X
—
—
X
—
—
—
X
—
—
—
X
—
X
—
X
—
X
—
RECTAL SWAB COLLECTION
Chlamydia/gonorrhea7,10
Local labs
Local labs
X
—
—
X
—
—
—
X
—
—
—
X
—
X
—
X
—
X
—
OROPHARYNGEAL SWAB COLLECTION
Chlamydia/gonorrhea7,10
Local labs
Local labs
X
—
—
X
—
—
—
X
—
—
—
X
—
X
—
X
—
X
—
OTHER SPECIMEN COLLECTION
SARS-CoV-2 testing
Local labs
Local labs
ART 
Switch8
Screening 
visit15
ATI 
qualification 9
X18

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 137 of 157 
14 A confirmatory sample should be drawn at the next visit (within approximately 1-2 weeks) following the first CD4+ T-cell count < 350 cells/mm3 (see Protocol Section 3.3.2 for details. 
15 Screening visit specimens for participants not undergoing an NNRTI switch should be obtained no later than 2 weeks before Visit 4; see HVTN 804/HPTN 095 for more information. 
16 For persons capable of becoming pregnant, pregnancy test may be performed on urine or blood specimens. 
17 At an early termination visit for a withdrawn or terminated participant (see Protocol Section 6.5), blood should be drawn as shown for Extended follow-up visit type A (see HVTN 804/HPTN 095 
SSP for more information).  
18 SARS-CoV-2 testing may be performed at the screening visit and at any other visit, if clinically indicated. Testing must be by direct detection of SARS-CoV-2 (e.g, nucleic acid or antigen 
detection). See HVTN 804/HPTN 095 SSP for more information. 
y = SST blood collected for neutralizing antibody will also cover specimen needs for FcR-mediated effector functions; no separate blood draw is needed. 
z = PBMC blood collected for ICS will also cover specimen needs for phenotyping; no separate blood draw is needed.  
 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 138 of 157 
Laboratory procedures—Schedule 1: Monitoring ATI (continued) 
 
 
1 CSR = central specimen repository. 
2 HVTN Laboratories include: Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke University Medical Center (Durham, North Carolina, USA). 
Non-HVTN laboratories: TBD. 
3 Local labs may assign appropriate alternative tube types for locally performed tests. 
4 HCV RNA PCR testing will be performed as a reflex test if indicated by anti-HCV antibody results. 
5 Tuberculin skin test (TST) will be performed if QuantiFERON TB testing is not available. See Procedures at CRS Appendix H). 
Visit:
20
21
22
23
24
25
26
27
Days on ATI:
D168
D196
D224
D252
D280
D308
D336
D364
Weeks on ATI:
W24
W28
W32
W36
W40
W44
W48
W52
Procedure
Ship to1 
Assay location1,2
Tube Type3
Tube size
(vol. capacity)3
Total
BLOOD COLLECTION
Screening or diagnostic assays
HIV PCR viral load13
Local labs
Local labs
EDTA
6mL
6
6
6
6
6
6
6
6
6
6
174
CD4+/CD8+ T-cell count14
Local labs
Local labs
EDTA
4mL
4
4
4
4
—
4
—
4
4
4
76
HBsAg/anti-HCV
Local labs
Local labs
SST
5mL
—
—
—
—
—
—
—
—
—
—
10
QuantiFERON TB testing5
Local labs
Local labs
QFT Gold/Gold-Plus
1mL
—
—
—
—
—
—
—
—
—
—
4
Safety labs
Hgb / ANC / PLT
Local labs
Local labs
EDTA
4mL
4
4
4
4
—
4
—
4
4
4
68
ALT / direct bilirubin / eGFR
Local labs
Local labs
SST
5mL
5
5
5
5
—
5
—
5
5
5
85
Syphilis10
Local labs
Local labs
SST
5mL
5
5
5
5
5
5
5
5
5
5
85
Drug levels
ARV detection
CSR
TBD
EDTA
4mL
4
4
4
4
4
4
4
4
4
4
60
Immunogenicity & Virologic Assays
Cellular assays
ICS
CSR
HVTN labs
ACD
8.5mL
42.5
42.5
42.5
42.5
42.5
42.5
42.5
42.5
—
—
595
Phenotyping
CSR
HVTN labs
ACD
8.5mL
z
z
z
z
z
z
z
z
—
—
0
Humoral assays
Neutralizing antibody
CSR
HVTN labs
SST
8.5mL
8.5
8.5
8.5
8.5
8.5
8.5
8.5
8.5
—
—
119
FcR-mediated effector functions6
CSR
HVTN labs
SST
8.5mL
y
y
y
y
y
y
y
y
—
—
0
HIV reservoir assays
CSR
TBD
ACD
8.5mL
—
—
—
—
—
—
—
—
—
—
51
Storage
Serum
CSR
SST
8.5mL
—
—
—
—
—
—
—
—
8.5
—
17
Plasma
CSR
EDTA
10mL
10
10
10
10
10
10
10
10
10
—
130
PBMC
CSR
ACD
8.5mL
17
17
17
17
17
17
17
17
59.5
—
263.5
Visit total
106
106
106
106
93
106
93
106
106
28
56-Day total
330
324
318
318
305
305
292
305
106
28
URINE COLLECTION
Pregnancy Test16
Local labs
Local labs
X
X
X
X
X
X
X
X
X
X
Chlamydia/gonorrhea7,10
Local labs
Local labs
X
X
X
X
X
X
X
X
X
X
RECTAL SWAB COLLECTION
Chlamydia/gonorrhea7,10
Local labs
Local labs
X
X
X
X
X
X
X
X
X
X
OROPHARYNGEAL SWAB COLLECTION
Chlamydia/gonorrhea7,10
Local labs
Local labs
X
X
X
X
X
X
X
X
X
X
OTHER SPECIMEN COLLECTION
SARS-CoV-2 testing
Local labs
Local labs
Visit Type 
A11,17
Visit Type 
B12
X18

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 139 of 157 
6 FcR-mediated effector function assays may include ADCC, virion capture, and phagocytosis assays. 
7 Chlamydia/gonorrhea testing will be done on urine, and rectal and oropharyngeal swabs. 
8 The "ART switch" phase will only be performed for participants on NNRTIs. These participants will be considered enrolled on the first day of the new ART medication. 
9 The ATI Qualification visit specimens must be obtained at least 28 days after ART switch. If needed, VL retesting may continue until viral suppression has been achieved (up to 84 days after ART 
switch). The last ATI qualification procedures must take place no more than 14 days prior to visit 4 (see HVTN 804/HPTN 095 SSP for more information). 
10 In addition to STI testing at the marked visits, STI testing may occur at any visit if clinically indicated. 
11 Extended follow-up visit type A will occur every 6 months starting with 3 months after visit 27 continuing up to 3 years of this schedule. This follow-up visit may be performed for participants who 
have not met criteria to transition to Schedule 2 or Schedule 3 (see Protocol Section 3.3 and HVTN 804/HPTN 095 SSP for details).  
12 Extended follow-up visit type B will occur every 6 months starting with 6 months after visit 27 continuing up to 3 years of this schedule, and then every 3 months thereafter. This follow-up visit 
may be performed for participants who have not met criteria to transition to Schedule 2 or Schedule 3 (see Protocol Section 3.3 and HVTN 804/HPTN 095 SSP for details). 
13 A confirmatory sample should be drawn at the next visit (within approximately 1-2 weeks) following the first VL result ≥ 200 copies/mL (see Protocol Section 3.3.1 for details. 
14 A confirmatory sample should be drawn at the next visit (within approximately 1-2 weeks) following the first CD4+ T-cell count < 350 cells/mm3. See Protocol Section 3.3.2 for details. 
15 Screening visit specimens for participants not undergoing an NNRTI switch should be obtained no later than 2 weeks before Visit 4; see HVTN 804/HPTN 095 SSP for more information. 
16 For persons capable of becoming pregnant, pregnancy test may be performed on urine or blood specimens. 
17 At an early termination visit for a withdrawn or terminated participant (see Section 6.5), blood should be drawn as shown for Extended follow-up visit type A (see HVTN 804/HPTN 095 SSP for 
more information).  
18 SARS-CoV-2 testing may be performed at the screening visit and at any other visit, if clinically indicated. Testing must be by direct detection of SARS-CoV-2 (e.g, nucleic acid or antigen 
detection). See HVTN 804/HPTN 095 SSP for more information. 
y = SST blood collected for neutralizing antibody will also cover specimen needs for FcR-mediated effector functions; no separate blood draw is needed. 
z = PBMC blood collected for ICS will also cover specimen needs for phenotyping; no separate blood draw is needed. 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 140 of 157 
Appendix F 
Laboratory procedures—Schedule 2: Monitoring ATI with viremia 
 
1 CSR = central specimen repository. 
2 HVTN Laboratories include: Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke University Medical Center (Durham, North Carolina, USA). 
Non-HVTN laboratories: TBD. 
3 Local labs may assign appropriate alternative tube types for locally performed tests. 
4 FcR-mediated effector function assays may include ADCC, virion capture, and phagocytosis assays. 
5 Chlamydia/gonorrhea testing will be done on urine, and rectal and oropharyngeal swabs. 
6 The 56-day blood draw limit also does not include visits from Schedule 1; please see HVTN 804/HPTN 095 SSP for details on prioritizing collections to avoid exceeding the 56-day limit. 
7 In addition to STI testing at the marked visits, STI testing may occur at any visit if clinically indicated. 
8 Extended follow-up visit type A will occur every 6 months starting with 3 months after visit 66 continuing up to 3 years of this schedule. This follow-up visit may be performed for participants who 
have not met criteria to transition to Schedule 2 or Schedule 3 (see Protocol Section 3.3 and HVTN 804/HPTN 095 SSP for details).  
9 Extended follow-up visit type B will occur every 6 months starting with 6 months after visit 66 continuing up to 3 years of this schedule, and then every 3 months thereafter. This follow-up visit may 
be performed for participants who have not met criteria to transition to Schedule 2 or Schedule 3 (see Protocol Section 3.3 and HVTN 804/HPTN 095 SSP for details). 
Visit:
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
D0
D7
D14
D21
D28
D35
D42
D49
D56
D70
D84
D98
D112
D126
D140
D154
W0
W1
W2
W3
W4
W5
W6
W7
W8
W10
W12
W14
W16
W18
W20
W22
Procedure
Ship to1 
Assay location1,2
Tube Type3
Tube size
(vol. capacity)3
BLOOD COLLECTION
Screening or diagnostic assays
HIV PCR viral load10
Local labs
Local labs
EDTA
6mL
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
CD4+/CD8+ T-cell count11
Local labs
Local labs
EDTA
4mL
4
—
4
—
4
—
4
—
4
—
4
—
4
—
4
—
Safety labs
Hgb / ANC / PLT
Local labs
Local labs
EDTA
4mL
4
—
—
—
4
—
—
—
4
—
4
—
4
—
4
—
ALT / direct bilirubin / eGFR
Local labs
Local labs
SST
5mL
5
—
—
—
5
—
—
—
5
—
5
—
5
—
5
—
Syphilis7
Local labs
Local labs
SST
5mL
5
—
—
—
5
—
—
—
5
—
5
—
5
—
5
—
Drug levels
ARV detection
CSR
TBD
EDTA
4mL
—
—
—
—
4
—
—
—
4
—
4
—
4
—
4
—
Immunogenicity & Virologic Assays
Cellular assays
ICS
CSR
HVTN labs
ACD
8.5mL
42.5
—
42.5
—
42.5
—
—
—
42.5
—
42.5
—
42.5
—
42.5
—
Phenotyping
CSR
HVTN labs
ACD
8.5mL
z
—
z
—
z
—
—
—
z
—
z
—
z
—
z
—
Humoral assays
Neutralizing antibody
CSR
HVTN labs
SST
8.5mL
8.5
—
8.5
—
8.5
—
—
—
8.5
—
8.5
—
8.5
—
8.5
—
FcR-mediated effector functions4
CSR
HVTN labs
SST
8.5mL
y
—
y
—
y
—
—
—
y
—
y
—
y
—
y
—
Storage
Serum
CSR
SST
8.5mL
8.5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Plasma
CSR
EDTA
10mL
10
—
—
—
—
—
—
—
10
—
10
—
10
—
10
—
PBMC
CSR
ACD
8.5mL
—
—
—
—
—
—
—
—
17
—
17
—
17
—
17
—
Visit total
93.5
6
61
6
79
6
10
6
106
6
106
6
106
6
106
6
56-Day total6,10,11
93.5
99.5
160.5
166.5
245.5
251.5
261.5
267.5
373.5
280
319
240
330
230
330
230
URINE COLLECTION
Pregnancy Test12
Local labs
Local labs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chlamydia/gonorrhea5,7
Local labs
Local labs
X
—
—
—
X
—
—
—
X
—
X
—
X
—
X
—
RECTAL SWAB COLLECTION
Chlamydia/gonorrhea5,7
Local labs
Local labs
X
—
—
—
X
—
—
—
X
—
X
—
X
—
X
—
OROPHARYNGEAL SWAB COLLECTION
Chlamydia/gonorrhea5,7
Local labs
Local labs
X
—
—
—
X
—
—
—
X
—
X
—
X
—
X
—
OTHER SPECIMEN COLLECTION
SARS-CoV-2 testing
Local labs
Local labs
Days on  ATI with viremia
Weeks on  ATI with viremia
X14

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 141 of 157 
10 Additional weekly viral load monitoring may be required between weeks 8 and 24; after week 24, a confirmatory sample should be drawn at the next visit (within approximately 1-2 weeks) 
following the first VL result ≥ 200 copies/mL (see Protocol Section 3.3.3 and HVTN 804/HPTN 095 SSP for details). The 56-day blood draw limit does not include up to 10mL blood collected per 
visit for this additional monitoring; however, the 56-day limit is not exceeded at any visit by these collections. 
11 A confirmatory sample should be drawn at the next visit (within approximately 1-2 weeks) following the first CD4+ T-cell count < 350 cells/mm3 (see Protocol Section 3.3.3 and HVTN 804/HPTN 
095 SSP for details). 
12 For persons capable of becoming pregnant, pregnancy test may be performed on urine or blood specimens. 
13 At an early termination visit for a withdrawn or terminated participant (see Section 6.5), blood should be drawn as shown for Extended follow-up visit type A (see HVTN 804/HPTN 095 SSP for 
more information).  
14 SARS-CoV-2 testing may be performed at the screening visit and at any other visit, if clinically indicated. Testing must be by direct detection of SARS-CoV-2 (e.g, nucleic acid or antigen 
detection). See HVTN 804/HPTN 095 SSP for more information. 
y = SST blood collected for neutralizing antibody will also cover specimen needs for FcR-mediated effector functions; no separate blood draw is needed. 
z = PBMC blood collected for ICS will also cover specimen needs for phenotyping; no separate blood draw is needed. 
 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 142 of 157 
Laboratory procedures—Schedule 2: Monitoring ATI with viremia (continued) 
 
1 CSR = central specimen repository. 
2 HVTN Laboratories include: Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke University Medical Center (Durham, North Carolina, USA). 
Non-HVTN laboratories: TBD. 
3 Local labs may assign appropriate alternative tube types for locally performed tests. 
4 FcR-mediated effector function assays may include ADCC, virion capture, and phagocytosis assays. 
5 Chlamydia/gonorrhea testing will be done on urine, and rectal and oropharyngeal swabs. 
6 The 56-day blood draw limit also does not include visits from Schedule 1; please see HVTN 804/HPTN 095 SSP for details on prioritizing collections to avoid exceeding the 56-day limit. 
7 In addition to STI testing at the marked visits, STI testing may occur at any visit if clinically indicated. 
8 Extended follow-up visit type A will occur every 6 months starting with 3 months after visit 66 continuing up to 3 years of this schedule. This follow-up visit may be performed for participants who 
have not met criteria to transition to Schedule 2 or Schedule 3 (see Protocol Section 3.3 and HVTN 804/HPTN 095 SSP for details).  
9 Extended follow-up visit type B will occur every 6 months starting with 6 months after visit 66 continuing up to 3 years of this schedule, and then every 3 months thereafter. This follow-up visit may 
be performed for participants who have not met criteria to transition to Schedule 2 or Schedule 3 (see Protocol Section 3.3 and HVTN 804/HPTN 095 SSP for details). 
Visit:
56
57
58
59
60
61
62
63
64
65
66
D168
D182
D196
D210
D224
D238
D252
D280
D308
D336
D364
W24
W26
W28
W30
W32
W34
W36
W40
W44
W48
W52
Procedure
Ship to1 
Assay location1,2
Tube Type3
Tube size
(vol. capacity)3
Total
BLOOD COLLECTION
Screening or diagnostic assays
HIV PCR viral load10
Local labs
Local labs
EDTA
6mL
6
6
6
6
6
6
6
6
6
6
6
6
6
174
CD4+/CD8+ T-cell count11
Local labs
Local labs
EDTA
4mL
4
—
4
—
4
—
4
—
4
—
4
4
4
64
Safety labs
Hgb / ANC / PLT
Local labs
Local labs
EDTA
4mL
4
—
4
—
4
—
4
—
4
—
4
4
4
56
ALT / direct bilirubin / eGFR
Local labs
Local labs
SST
5mL
5
—
5
—
5
—
5
—
5
—
5
5
5
70
Syphilis7
Local labs
Local labs
SST
5mL
5
—
5
—
5
—
5
5
5
5
5
5
5
80
Drug levels
ARV detection
CSR
TBD
EDTA
4mL
4
—
4
—
4
—
4
4
4
4
4
4
4
60
Immunogenicity & Virologic Assays
Cellular assays
ICS
CSR
HVTN labs
ACD
8.5mL
42.5
—
42.5
—
42.5
—
42.5
42.5
42.5
42.5
42.5
—
—
637.5
Phenotyping
CSR
HVTN labs
ACD
8.5mL
z
—
z
—
z
—
z
z
z
z
z
—
—
0
Humoral assays
Neutralizing antibody
CSR
HVTN labs
SST
8.5mL
8.5
—
8.5
—
8.5
—
8.5
8.5
8.5
8.5
8.5
—
—
127.5
FcR-mediated effector functions4
CSR
HVTN labs
SST
8.5mL
y
—
y
—
y
—
y
y
y
y
y
—
—
0
Storage
Serum
CSR
SST
8.5mL
—
—
—
—
—
—
—
—
—
—
—
8.5
—
17
Plasma
CSR
EDTA
10mL
10
—
10
—
10
—
10
10
10
10
10
10
—
140
PBMC
CSR
ACD
8.5mL
17
—
17
—
17
—
17
17
17
17
17
59.5
—
263.5
Visit total
106
6
106
6
106
6
106
93
106
93
106
106
28
56-Day total6,10,11
330
230
330
230
330
230
330
311
305
292
305
106
28
URINE COLLECTION
Pregnancy Test12
Local labs
Local labs
X
X
X
X
X
X
X
X
X
X
X
X
X
Chlamydia/gonorrhea5,7
Local labs
Local labs
X
—
X
—
X
—
X
X
X
X
X
X
X
RECTAL SWAB COLLECTION
Chlamydia/gonorrhea5,7
Local labs
Local labs
X
—
X
—
X
—
X
X
X
X
X
X
X
OROPHARYNGEAL SWAB COLLECTION
Chlamydia/gonorrhea5,7
Local labs
Local labs
X
—
X
—
X
—
X
X
X
X
X
X
X
OTHER SPECIMEN COLLECTION
SARS-CoV-2 testing
Local labs
Local labs
Days on  ATI with viremia
Weeks on  ATI with viremia
Visit Type 
A8,13
Visit type 
B9
X14

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 143 of 157 
10 Additional weekly viral load monitoring may be required between weeks 8 and 24; after week 24, a confirmatory sample should be drawn at the next visit (within approximately 1-2 weeks) 
following the first VL result ≥ 200 copies/mL (see Protocol Section 3.3.3 and HVTN 804/HPTN 095 for details). The 56-day blood draw limit does not include up to 10mL blood collected per visit 
for this additional monitoring; however, the 56-day limit is not exceeded at any visit by these collections. 
11 A confirmatory sample should be drawn at the next visit (within approximately 1-2 weeks) following the first CD4+ T-cell count < 350 cells/mm3 (see Protocol Section 3.3.3 and HVTN 804/HPTN 
095 SSP for details). 
12 For persons capable of becoming pregnant, pregnancy test may be performed on urine or blood specimens. 
13 At an early termination visit for a withdrawn or terminated participant (see Section 6.5), blood should be drawn as shown for Extended follow-up visit type A (see HVTN 804/HPTN 095 SSP for 
more information).  
14 SARS-CoV-2 testing may be performed at the screening visit and at any other visit, if clinically indicated. Testing must be by direct detection of SARS-CoV-2 (e.g, nucleic acid or antigen 
detection). See HVTN 804/HPTN 095 SSP for more information. 
y = SST blood collected for neutralizing antibody will also cover specimen needs for FcR-mediated effector functions; no separate blood draw is needed. 
z = PBMC blood collected for ICS will also cover specimen needs for phenotyping; no separate blood draw is needed. 
 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 144 of 157 
Appendix G 
Laboratory procedures—Schedule 3: Follow-up on ART 
 
1 CSR = central specimen repository. 
2 HVTN Laboratories include: Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke University Medical Center (Durham, North Carolina, USA). 
Non-HVTN laboratories: TBD 
3 Local labs may assign appropriate alternative tube types for locally performed tests. 
4 FcR-mediated effector function assays may include ADCC, virion capture, and phagocytosis assays. 
5 56-day totals do not include visit totals from Schedule 1 or 2. Please see HVTN 804/HPTN 095 SSP for details on prioritizing collections to avoid exceeding the 56-day limit. 
6 Chlamydia/gonorrhea testing will be done on both urine, and rectal and oropharyngeal swabs; in addition, testing may occur at any visit if clinically indicated.  
7 Samples for visit 80 should be collected after ART re-initiation criteria have been met, but prior to ART re-initiation.  
8 HIV antiretroviral resistance testing will be tested only if indicated by viral load results. 
9 In addition to STI testing at the marked visits, STI testing may occur at any visit if clinically indicated. 
10 Pregnancy testing is not required if viral load has returned to undetectable. 
Visit:
807
81
82
83
84
85
86
87
88
89
90
9112
92
D0
D14
D28
D42
D56
D70
D84
D112
D140
D168
D196
D280
D364
W0
W2
W4
W6
W8
W10
W12
W16
W20
W24
W28
W40
W52
Procedure
Ship to1 
Tube Type3
Total
BLOOD COLLECTION
Screening or diagnostic assays
HIV PCR viral load
Local labs
Local labs
EDTA
6mL
6
6
6
6
6
6
6
6
6
6
6
6
6
78
CD4+/CD8+ T-cell count
Local labs
Local labs
EDTA
4mL
4
—
4
—
4
—
4
—
4
—
4
4
4
32
Safety labs
Hgb / ANC / PLT
Local labs
Local labs
EDTA
4mL
—
—
4
—
4
—
4
—
—
4
—
4
—
20
ALT / direct bilirubin / eGFR
Local labs
Local labs
SST
5mL
—
—
5
—
5
—
5
—
—
5
—
5
—
25
Syphilis9
Local labs
Local labs
SST
5mL
5
—
5
—
5
—
5
513
513
5
513
5
—
45
HIV genotypic antiretroviral resistance8
CSR
TBD
EDTA
5mL
—
—
—
—
15
—
—
—
—
—
—
—
—
15
Immunogenicity & Virologic Assays
Viral isolation/sequencing
CSR
HVTN Labs
EDTA
10mL
10
10
—
—
—
—
10
—
—
10
—
10
10
60
   Cellular assays
ICS
CSR
HVTN Labs
ACD
8.5mL
—
—
—
—
—
—
42.5
—
—
42.5
—
42.5
42.5
170
Phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
—
—
—
—
—
z
—
—
z
—
z
z
0
    Humoral assays
Neutralizing antibody
CSR
HVTN Labs
SST
8.5mL
—
—
—
—
—
—
8.5
—
—
8.5
—
8.5
8.5
34
FcR-mediated effector functions4
CSR
HVTN Labs
SST
8.5mL
—
—
—
—
—
—
y
—
—
y
—
y
y
0
HIV reservoir assays
CSR
TBD
ACD
8.5mL
34
—
—
—
—
—
—
—
—
51
—
51
51
187
Storage
Serum
CSR
SST
8.5mL
8.5
—
—
—
—
—
8.5
—
—
8.5
—
8.5
8.5
42.5
Plasma
CSR
EDTA
10mL
—
—
—
—
—
—
10
—
—
10
—
10
10
40
PBMC
CSR
ACD
8.5mL
42.5
—
—
—
—
—
102
—
—
51
—
51
51
297.5
Visit total
110
16
24
6
39
6
205.5
11
15
201.5
15
205.5
191.5
56-Day total5
126
150
156
195
91
280.5
261.5
231.5
227.5
231.5
205.5
191.5
URINE COLLECTION
Pregnancy Test11
Local labs
Local labs
X
X10
X10
X10
X10
X10
X
X10
X10
X
X10
X
X
Chlamydia/gonorrhea6,9
Local labs
Local labs
X
—
X
—
X
—
X
X13
X13
X
X13
X
—
RECTAL SWAB COLLECTION
Chlamydia/gonorrhea6,9
Local labs
Local labs
X
—
X
—
X
—
X
X13
X13
X
X13
X
—
OROPHARYNGEAL SWAB COLLECTION
Chlamydia/gonorrhea6,9
Local labs
Local labs
X
—
X
—
X
—
X
X13
X13
X
X13
X
—
OTHER SPECIMEN COLLECTION
SARS-CoV-2 testing
Local labs
Local labs
Weeks post ART re-initiation:
Days post ART re-initiation
Tube size
(vol. capacity)3
Assay location1,2
ART re-
initiation visit
X14

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 145 of 157 
11 For persons capable of becoming pregnant, pregnancy test may be performed on urine or blood specimens. 
12 At an early termination visit for a withdrawn or terminated participant (see Section 6.5), blood should be drawn as shown for Visit 91 (see HVTN 804/HPTN 095 SSP for more information). 
13 Syphilis, chlamydia, and gonorrhea testing is not required at this visit if viral load has returned to undetectable. 
14 SARS-CoV-2 testing may be performed at the screening visit and at any other visit, if clinically indicated. Testing must be by direct detection of SARS-CoV-2 (e.g, nucleic acid or antigen 
detection). See HVTN 804/HPTN 095 SSP for more information. 
y = SST blood collected for neutralizing antibody will also cover specimen needs for FcR-mediated effector functions; no separate blood draw is needed. 
z = PBMC blood collected for ICS will also cover specimen needs for phenotyping; no separate blood draw is needed. 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 146 of 157 
Appendix H 
Procedures at CRS—Schedule 1: Monitoring ATI 
Visit: 
011 
02 
03 
043 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Days on ATI: 
Screening 
ART  
Switch2 
ATI 
qualification 
D0 
D7 
D14 
D21 
D28 
D35 
D42 
D49 
D56 
D70 
D84 
D98 
D112 
D126 
D140 
D154 
Weeks on ATI: 
W0 
W1 
W2 
W3 
W4 
W5 
W6 
W7 
W8 
W10 
W12 
W14 
W16 
W18 
W20 
W22 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening consent (if used) 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol consent 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assessment of understanding 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical exam 
✓ 
 
 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Targeted physical exam4 
 
✓ 
✓ 
 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Concomitant medications4 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Intercurrent illness/adverse experience4 
 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
ART re-initiation assessment4 
 
 
 
 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Transmission risk reduction counseling4 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
SARS-CoV-2 risk reduction counseling5 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Contraception status assessment6 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Decision aid 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Decision-making assessment 
 
✓ 
 
✓ 
 
 
 
 
 
 
 
 
 
✓ 
 
 
 
 
 
Psychosocial assessment 
 
✓ 
 
✓ 
 
 
 
 
 
 
 
 
 
✓ 
 
 
 
 
 
Social impact assessment4 
 
 
 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Social impact assessment questionnaire 
 
 
 
 
 
 
 
 
 
 
 
 
 
✓ 
 
 
 
 
 
QuantiFERON tuberculosis test7 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirm eligibility 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Specimen collection8 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
1 Screening procedures may occur over the course of several contacts/visits up to and including the day of enrollment, except for blood collection for participants not on NNRTIs, which may occur up 
to 14 days before enrollment, as defined in Section 6.1.2.  
2 For participants undergoing switch from NNRTI-based to protease- or integrase-based ART regimen. Participants undergoing an “ART switch” will be considered enrolled on first day of the new 
ART medication. The "ART switch" phase will not be performed for participants not on NNRTIs. For procedure timing during the “ART switch,” see Section 6.1.3 and HVTN 804/HPTN 095 SSP. 
3 Enrollment visit for participants who do not undergo ART switch. 
4 Procedure to be performed at interim visits held to draw confirmatory viral load samples or confirmatory samples for CD4+ T cell counts (see Sections 3.3.1, 3.3.2, and 3.3.3). 
5 SARS-CoV-2 risk reduction counseling will be provided at any visit, if indicated. See HVTN 804/HPTN 095 SSP for more information. 
6 Contraception status assessment is required only for participants who were assigned female sex at birth and who can become pregnant (does not include those persons not of reproductive potential 
due to having undergone hysterectomy or bilateral oophorectomy [verified by medical records]). 
7 If QuantiFERON TB testing cannot be performed, a tuberculin skin test (TST) should be conducted. Additional risk/clinical/diagnostic assessment may be performed at the discretion of the clinician 
to meet institutional standard of care for evaluation and treatment of latent TB.  
8 For specimen collection requirements, see Appendix E. 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 147 of 157 
Procedures at CRS—Schedule 1: Monitoring ATI (continued) 
Visit: 
20 
21 
22 
23 
24 
25 
26 
27 
Visit 
Type 
A9, 11 
Visit 
Type 
B10 
Days on ATI: 
D168 
D196 
D224 
D252 
D280 
D308 
D336 
D364 
Weeks on ATI: 
W24 
W28 
W32 
W36 
W40 
W44 
W48 
W52 
Study procedures 
 
 
 
 
 
 
 
 
 
 
Screening consent (if used) 
 
 
 
 
 
 
 
 
 
 
Protocol consent 
 
 
 
 
 
 
 
 
 
 
Assessment of understanding 
 
 
 
 
 
 
 
 
 
 
Medical history 
 
 
 
 
 
 
 
 
 
 
Complete physical exam 
 
 
 
 
 
 
 
 
 
 
Targeted physical exam4 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Concomitant medications4 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Intercurrent illness/adverse experience4 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
ART re-initiation assessment4 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Transmission risk reduction counseling4 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
SARS-CoV-2 risk reduction counseling5 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Contraception status assessment6 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Decision aid 
 
 
 
 
 
 
 
 
 
 
Decision-making assessment 
✓ 
 
 
✓ 
 
 
 
✓ 
 
✓ 
Psychosocial assessment 
✓ 
 
 
✓ 
 
 
 
✓ 
 
✓ 
Social impact assessment4 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Social impact assessment questionnaire 
✓ 
 
 
✓ 
 
 
 
✓ 
 
✓ 
QuantiFERON tuberculosis test 7 
 
 
 
 
 
 
 
 
 
 
Confirm eligibility 
 
 
 
 
 
 
 
 
 
 
Specimen collection8 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
1 Screening procedures may occur over the course of several contacts/visits up to and including the day of enrollment, except for blood collection for participants not on NNRTIs, which may occur up 
to 14 days before enrollment, as defined in Section 6.1.2.  
2 For participants undergoing switch from NNRTI-based to protease- or integrase-based ART regimen. Participants undergoing an “ART switch” will be considered enrolled on first day of the new 
ART medication. The "ART switch" phase will not be performed for participants not on NNRTIs. For procedure timing during the “ART switch,” see Section 6.1.3 and HVTN 804/HPTN 095 SSP. 
3 Enrollment visit for participants who do not undergo ART switch. 
4 Procedure to be performed at interim visits held to draw confirmatory viral load samples or confirmatory samples for CD4+ T cell counts (see Sections 3.3.1, 3.3.2, and 3.3.3). 
5 SARS-CoV-2 risk reduction counseling will be provided at any visit, if indicated. See HVTN 804/HPTN 095 SSP for more information. 
6 Contraception status assessment is required only for participants who were assigned female sex at birth and who can become pregnant (does not include those persons not of reproductive potential 
due to having undergone hysterectomy or bilateral oophorectomy [verified by medical records]). 
7 If QuantiFERON TB testing cannot be performed (see Appendix E), TST should be conducted. Additional risk/clinical/diagnostic assessment may be performed at the discretion of the clinician to 
meet institutional standard of care for treatment of latent TB. 
8 For specimen collection requirements, see Appendix E. 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 148 of 157 
9 Extended follow-up visit type A will occur every 6 months starting with 3 months after visit 27, continuing up to 3 years of this schedule. This follow-up visit may be performed for participants who 
have not met ART re-initiation criteria (see Protocol Section 3.3 and HVTN 804/HPTN 095 SSP for details). 
10 Extended follow-up visit type B will occur every 6 months starting with 6 months after visit 27, continuing up 3 years of this schedule and then every 3 months thereafter. This follow-up visit may 
be performed for participants who have not met ART re-initiation criteria (see Protocol Section 3.3 and HVTN 804/HPTN 095 SSP for details). 
11 At an early termination visit for a withdrawn or terminated participant, CRS staff should consider performing procedures specified for Extended follow-up visit Type A (see Section 6.5 and HVTN 
804/HPTN 095 SSP for details). 
 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 149 of 157 
Appendix I 
Procedures at CRS—Schedule 2: Monitoring ATI with viremia 
Visit: 
40 
41 
42 
43 
44 
45 
46 
47 
48 
49 
50 
51 
52 
53 
54 
55 
Days on ATI with viremia: 
D0 
D7 
D14 
D21 
D28 
D35 
D42 
D49 
D56 
D70 
D84 
D98 
D112 
D126 
D140 
D154 
Weeks on ATI with viremia: 
W0 
W1 
W2 
W3 
W4 
W5 
W6 
W7 
W8 
W10 
W12 
W14 
W16 
W18 
W20 
W22 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical exam 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Targeted physical exam1 
 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Concomitant medications1 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Intercurrent illness/adverse experience1 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
ART re-initiation assessment1 
 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Transmission risk reduction counseling1 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
SARS-CoV-2 risk reduction counseling2 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Contraception status assessment3 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Decision-making assessment 
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Psychosocial assessment 
✓ 
 
 
 
 
 
 
 
 
 
✓ 
 
 
 
 
 
Social impact assessment1 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Social impact assessment questionnaire 
 
 
 
 
 
 
 
 
 
 
✓ 
 
 
 
 
 
Specimen collection4 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
1 Procedure to be performed at interim visits held to draw confirmatory viral load samples or confirmatory samples for CD4+ T cell counts (see Sections 3.3.1, 3.3.2, and 3.3.3). 
2 SARS-CoV-2 risk reduction counseling will be provided at any visit, if indicated. See HVTN 804/HPTN 095 SSP for more information. 
3 Contraception status assessment is required only for participants who were assigned female sex at birth and who can become pregnant (does not include those persons not of reproductive potential 
due to having undergone hysterectomy or bilateral oophorectomy [verified by medical records]). 
4 For specimen collection requirements, see Appendix F. 
 
 
 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 150 of 157 
Procedures at CRS—Schedule 2: Monitoring ATI with viremia (continued) 
Visit: 
56 
57 
58 
59 
60 
61 
62 
63 
64 
65 
66 
Visit 
Type 
A5, 7 
Visit 
Type 
B6 
Days on ATI with viremia: 
D168 
D182 
D196 
D210 
D224 
D238 
D252 
D280 
D308 
D336 
D364 
Weeks on ATI with viremia: 
W24 
W26 
W28 
W30 
W32 
W34 
W36 
W40 
W44 
W48 
W52 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
Targeted physical exam1 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Concomitant medications1 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Intercurrent illness/adverse experience1 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
ART re-initiation assessment1 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Transmission risk reduction counseling1 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
SARS-CoV-2 risk reduction counseling2 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Contraception status assessment3 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Decision-making assessment 
✓ 
 
 
 
 
 
✓ 
 
 
 
✓ 
 
✓ 
Psychosocial assessment 
✓ 
 
 
 
 
 
✓ 
 
 
 
✓ 
 
✓ 
Social impact assessment1 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Social impact assessment questionnaire 
✓ 
 
 
 
 
 
✓ 
 
 
 
✓ 
 
✓ 
Specimen collection4 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
1 Procedure to be performed at interim visits held to draw confirmatory viral load samples or confirmatory samples for CD4+ T cell counts (see Sections 3.3.1, 3.3.2, and 3.3.3). 
2 SARS-CoV-2 risk reduction counseling will be provided at any visit, if indicated. See HVTN 804/HPTN 095 SSP for more information. 
3 Contraception status assessment is required only for participants who were assigned female sex at birth and who can become pregnant (does not include those persons not of reproductive potential 
due to having undergone hysterectomy or bilateral oophorectomy [verified by medical records]). 
4 For specimen collection requirements, see Appendix F. 
5 Extended follow-up visit type A will occur every 6 months starting with 3 months after visit 66, continuing up to 3 years of this schedule. This follow-up visit may be performed for participants who 
have not met ART re-initiation criteria (see Protocol Section 3.3 and HVTN 804/HPTN 095 SSP for details). 
6 Extended follow-up visit type B will occur every 6 months starting with 6 months after visit 66, continuing up 3 years of this schedule and then every 3 months thereafter. This follow-up visit may 
be performed for participants who have not met ART re-initiation criteria (see Protocol Section 3.3 and HVTN 804/HPTN 095 SSP for details). 
7 At an early termination visit for a withdrawn or terminated participant, CRS staff should consider performing procedures specified for Extended follow-up visit Type A (see Section 6.5 and HVTN 
804/HPTN 095 SSP for details). 
 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 151 of 157 
Appendix J 
Procedures at CRS—Schedule 3: Follow-up on ART 
Visit: 
801 
81 
82 
83 
84 
85 
86 
87 
88 
89 
90 
91 
925 
Days after ART re-initiation: 
D0 
D14 
D28 
D42 
D56 
D70 
D84 
D112 
D140 
D168 
D196 
D280 
D364 
Weeks after ART re-initiation: 
W0 
W2 
W4 
W6 
W8 
W10 
W12 
W16 
W20 
W24 
W28 
W40 
W52 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical exam 
 
 
 
 
 
 
 
 
 
 
 
 
✓ 
Targeted physical exam 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
 
Concomitant medications 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Intercurrent illness/adverse experience 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Transmission risk reduction counseling 
✓ 
✓ 
✓ 
 
✓ 
 
✓ 
 
✓ 
 
✓ 
 
✓ 
SARS-CoV-2 risk reduction counseling2 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Contraception status assessment3 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Decision-making assessment 
✓ 
 
 
 
 
 
✓ 
 
 
✓ 
 
 
✓ 
Psychosocial assessment 
✓ 
 
 
 
 
 
✓ 
 
 
✓ 
 
 
✓ 
Social impact assessment 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Social impact assessment questionnaire 
 
 
 
 
 
 
✓ 
 
 
✓ 
 
 
✓ 
Specimen collection4 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
1 ART re-initiation visit. 
2 SARS-CoV-2 risk reduction counseling will be provided at any visit, if indicated. See HVTN 804/HPTN 095 SSP for more information. 
3 Contraception status assessment is required only for participants who were assigned female sex at birth and who can become pregnant (does not include those persons not of reproductive potential 
due to having undergone hysterectomy or bilateral oophorectomy [verified by medical records]). Contraception status assessment is not required if participant VL has returned to undetectable. 
4 For specimen collection requirements, see Appendix G. 
5 At an early termination visit for a withdrawn or terminated participant, CRS staff should consider performing procedures specified for Visit 92 (see Section 6.5 and HVTN 804/HPTN 095 SSP for 
more details).  
 
 
 
 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 152 of 157 
Appendix K 
Visit Windows  
 
Visit Windows – Schedule 1: Monitoring ATI 
 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
Lower 
Target Day 
Target Day4  
Upper 
Target Day 
Upper 
Allowable 
Window  
Relative dates of reference are noted in individual cells below. 
01.0¹ 
 
Participants not on 
NNRTIs 
Screening: 
Blood collection 
only  
56 days 
before Visit 
4 
 
- 
- 
- 
14 days before 
Visit 4 
Screening: 
All other 
screening 
procedures  
56 days 
before Visit 
4 
- 
- 
- 
0 days before 
Visit 4 
Participants on NNRTIs 
[ART Switch Participants] 
Screening  
 
56 days 
before Visit 
2 
- 
- 
- 
0 days before 
Visit 2 
02.0 
ART Switch 
 
For participants on NNRTIs, Visit 2 is considered the enrollment visit.  
03.0 
ATI Qualification²  28 days 
after Visit 2 
- 
- 
- 
84 days after  
Visit 2 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
Lower 
Target Day 
Target Day3 
Relative to 
initiation of ATI 
Upper 
Target Day 
Upper 
Allowable 
Window  
04.0  
Week 0 
Initiation of ATI 
- 
- 
0 
- 
- 
05.0  
Week 1 
-3 
-2 
7 
+2 
+3 
06.0 
Week 2 
-3 
-2 
14 
+2 
+3 
07.0 
Week 3 
-3 
-2 
21 
+2 
+3 
08.0 
Week 4 
-3 
-2 
28 
+2 
+3 
09.0 
Week 5 
-3 
-2 
35 
+2 
+3 
10.0 
Week 6 
-3 
-2 
42 
+2 
+3 
11.0 
Week 7 
-3 
-2 
49 
+2 
+3 
12.0 
Week 8 
-3 
-2 
56 
+2 
+7 
13.0 
Week 10 
-6 
-4 
70 
+4 
+7 
14.0 
Week 12  
-6 
-4 
84 
+4 
+7 
15.0 
Week 14  
-6 
-4 
98 
+4 
+7 
16.0 
Week 16  
-6 
-4 
112 
+4 
+7 
17.0 
Week 18 
-6 
-4 
126 
+4 
+7 
18.0 
Week 20  
-6 
-4 
140 
+4 
+7 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 153 of 157 
19.0 
Week 22 
-6 
-4 
154 
+4 
+7 
20.0 
Week 24 
-6 
-4 
168 
+4 
+14 
21.0 
Week 28 
-13 
-8 
196 
+8 
+14 
22.0 
Week 32 
-13 
-8 
224 
+8 
+14 
23.0 
Week 36 
-13 
-8 
252 
+8 
+14 
24.0 
Week 40 
-13 
-8 
280 
+8 
+14 
25.0 
Week 44 
-13 
-8 
308 
+8 
+14 
26.0 
Week 48 
-13 
-8 
336 
+8 
+14 
27.0 
Week 52 
-13 
-8 
364 
+8 
+14 
Visit Type 
A4 
Follow-up (Schedule 1: 
Visit Type A) 
-42 
-28 
Visit Type A will 
occur every 6 
months starting 
with 3 months 
after visit 27 
continuing up to 
three years of 
this schedule 
+28 
+42 
Visit Type 
B4 
Follow-up (Schedule 1: 
Visit Type B) 
-42 
-28 
Visit Type B will 
occur every 6 
months starting 
with 6 months 
after visit 27 
continuing up to 
three years of 
this schedule, 
and then every 
3 months 
thereafter 
+28 
+42  
¹ Screening procedures may occur over the course of several contacts/visits up to and including the day of enrollment, 
except for blood collection for participants not on NNRTIs, which may occur up to 14 days before enrollment, as defined 
in Section 6.1.2.  
2 If needed, VL retesting may continue up to 84 days after ART switch until viral suppression has been achieved. The final 
ATI qualification procedures must take place no more than 14 days prior to visit 4. 
3 Viral load sample collection should occur as close to the target day as possible and must occur at least 2 days apart (this 
applies to both scheduled visits and interim visits). See Visit Scheduling and Coding SSP for further details. 
4 Type A and Type B visits must be at least 8 weeks apart.  
 
 
 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 154 of 157 
Visit Windows – Schedule 2: Monitoring ATI with viremia 
 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
Lower 
Target Day 
Target Day1  
Upper 
Target Day 
Upper 
Allowable 
Window  
40.0 
First visit after 
confirmed ATI 
VL ≥ 200 copies/mL  
- 
- 
0 
- 
- 
41.0 
Week 1 
-3 
-2 
7 
+2 
+3 
42.0 
Week 2 
-3 
-2 
14 
+2 
+3 
43.0 
Week 3 
-3 
-2 
21 
+2 
+3 
44.0 
Week 4 
-3 
-2 
28 
+2 
+3 
45.0 
Week 5 
-3 
-2 
35 
+2 
+3 
46.0 
Week 6 
-3 
-2 
42 
+2 
+3 
47.0 
Week 7 
-3 
-2 
49 
+2 
+3 
48.0 
Week 8 
-3 
-2 
56 
+2 
+7 
49.0 
Week 10 
-6 
-4 
70 
+4 
+7 
50.0 
Week 12 
-6 
-4 
84 
+4 
+7 
51.0 
Week 14 
-6 
-4 
98 
+4 
+7 
52.0 
Week 16 
-6 
-4 
112 
+4 
+7 
53.0 
Week 18 
-6 
-4 
126 
+4 
+7 
54.0 
Week 20 
-6 
-4 
140 
+4 
+7 
55.0 
Week 22 
-6 
-4 
154 
+4 
+7 
56.0 
Week 24 
-6 
-4 
168 
+4 
+7 
57.0 
Week 26 
-6 
-4 
182 
+4 
+7 
58.0 
Week 28 
-6 
-4 
196 
+4 
+7 
59.0 
Week 30 
-6 
-4 
210 
+4 
+7 
60.0 
Week 32  
-6 
-4 
224 
+4 
+7 
61.0 
Week 34 
-6 
-4 
238 
+4 
+7 
62.0 
Week 36  
-6 
-4 
252 
+8 
+14 
63.0 
Week 40  
-13 
-8 
280 
+8 
+14 
64.0 
Week 44 
-13 
-8 
308 
+8 
+14 
65.0 
Week 48  
-13 
-8 
336 
+8 
+14 
66.0 
Week 52 
 
-13 
-8 
364 
+8 
+14 
Visit Type 
A2 
Follow-up (Schedule 2: 
Visit Type A) 
-42 
-28 
Visit Type A will 
occur every 6 
months starting 
with 3 months 
after visit 66 
continuing up to 
+28 
+42 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 155 of 157 
three years of 
this schedule 
Visit Type 
B2 
Follow-up (Schedule 2: 
Visit Type B) 
-42 
-28 
Visit Type B will 
occur every 6 
months starting 
with 6 months 
after visit 66 
continuing up to 
three years of 
this schedule, 
and then every 
3 months 
thereafter 
+28 
+42 
1Viral load sample collection should occur as close to the target day as possible and must occur at least 2 days apart (this 
applies to both scheduled visits and interim visits). See Visit Scheduling and Coding SSP for further details. 
2Type A and Type B visits must be at least 8 weeks apart. 
 
 
 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 156 of 157 
Visit Windows – Schedule 3: Follow-up on ART 
   
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
Lower 
Target Day 
Target Day1 
relative to ART 
re-initiation 
Upper 
Target Day 
Upper 
Allowable 
Window  
80.0 
ART Re-initiation  
- 
- 
0 
- 
- 
81.0 
Week 2 
-6 
-4 
14 
+4 
+7 
82.0 
Week 4 
-6 
-4 
28 
+4 
+7 
83.0 
Week 6 
-6 
-4 
42 
+4 
+7 
84.0 
Week 8 
-6 
-4 
56 
+4 
+7 
85.0 
Week 10 
-6 
-4 
70 
+4 
+7 
86.0 
Week 12 
-6 
-4 
84 
+4 
+14 
87.0 
Week 16 
-13 
-8 
112 
+8 
+14 
88.0 
Week 20 
-13 
-8 
140 
+8 
+14 
89.0 
Week 24 
-13 
-8 
168 
+8 
+14 
90.0¹ 
Week 28 
-13 
-8 
196 
+8 
+14 
91.0¹ 
Week 40 
-42 
-14 
280 
+14 
+42 
92.0¹ 
Week 52 
-28 
-14 
364 
+14 
+42 
¹There must be at least 8 weeks between visits 90.0 and 91.0, and visits 91.0 and 92.0.   
 

HVTN 804/HPTN 095 Version 3.0 / March 22, 2022 
HVTN804_HPTN095_v3.0_Final / Page 157 of 157 
Appendix L 
Protocol Signature Page 
 
Antiretroviral analytical treatment interruption (ATI) to assess immunologic and 
virologic responses in participants who received VRC01 or placebo and became 
HIV-infected during HVTN 704/HPTN 085 
I will conduct the study in accordance with the provisions of this protocol and all 
applicable protocol-related documents. I agree to conduct this study in 
compliance with United States (U.S.) Health and Human Service regulations (45 
CFR 46); applicable U.S. Food and Drug Administration regulations; standards of 
the International Conference on Harmonization Guideline for Good Clinical 
Practice (E6); Institutional Review Board/Ethics Committee determinations; all 
applicable in-country, state, and local laws and regulations; and other applicable 
requirements (eg, U.S. National Institutes of Health, Division of AIDS) and 
institutional policies 
 
 
 
 
 
 
 
 
 
Investigator of Record Name (print) 
 
Investigator of Record Signature 
 
Date 
 
 
DAIDS Protocol Number: HVTN 804/HPTN 095 
DAIDS Protocol Version: Version 3.0 
Protocol Date: March 22, 2022