Conditions: HIV-1-infection Methamphetamine-dependence
Keywords: HIV methamphetamine viral transcription inflammation
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 14
Healthy volunteers: no

Brief summary:
The most commonly used illicit stimulant in HIV-infected individuals is methamphetamine (MA). Prior studies demonstrate strong evidence that MA promotes increased HIV transcription as well as immune dysregulation. A challenge in achieving worldwide HIV eradication is targeting specific marginalized populations who are most likely to benefit from an HIV cure but possess poorer immune responses. For this study, HIV+ infected ART-suppressed individuals with no prior history of MA use disorder will be administered oral methamphetamine (the maximum FDA approved daily dose for the treatment of childhood obesity) to determine the effects of short-term MA exposure on residual virus production, gene expression, and inflammation. Measures of MA exposure in urine and serum will then be associated with residual virus production, gene expression, cell surface immune marker protein expression, and systemic markers of inflammation. The clinical trial data will generate advanced gene expression and immunologic data to identify potential novel targets for reversing HIV latency, reducing inflammation, and personalizing future therapies in HIV+ individuals who use MA.

Detailed description:
The most commonly used illicit stimulant in HIV-infected individuals is methamphetamine (MA), and prior studies demonstrate strong evidence that MA promotes increased HIV transcription as well as immune dysregulation. HIV cure has emerged as an important clinical and research priority given evidence of ongoing immune dysfunction in HIV-infected individuals despite effective antiretroviral therapy (ART). A challenge in achieving worldwide HIV eradication is targeting specific vulnerable populations who are most likely to benefit from an HIV cure but possess poorer immune responses as a result of residual viral replication due to suboptimal ART adherence and/or direct immune dysfunction from illicit substance use. Prior non-human studies demonstrate that MA directly induces HIV production and promotes immune activation and inflammation. These preclinical findings suggest that HIV+ individuals who use MA may experience greater immune dysfunction and face additional challenges for future HIV eradication. This study will investigate the effects of short-term MA exposure in HIV+ ART-suppressed individuals without a prior history of MA use. Participants will be enrolled in an interventional study where they will be administered oral methamphetamine (the maximum FDA approved daily dose for the treatment of childhood obesity) to determine the effects of short-term MA exposure on residual virus production, gene expression, inflammation, and trace amine-associated 1 (TAAR1, a promising drug target for psychostimulant addiction) signaling. MA exposure will be quantified with multiple serum samples collected over a 24-hour monitoring period and associated with residual viral transcription, host gene and cell surface protein expression, and inflammation (plasma inflammatory cytokine levels) quantification. The proposed study will be the first human genetic study to directly evaluate the effect of MA exposure on residual viral transcription during effective ART. The overall goals of the study are to integrate a rigorous clinical study designs with high throughput 'omics data to identify novel targets for reversing HIV latency, reducing inflammation, and personalizing future therapeutic strategies specific to HIV+ ART-suppressed individuals who use MA.

Arms:
arm 1: Participants will be randomized to oral methamphetamine first then placebo oral capsule using a random number generator. When oral methamphetamine is administered, an initial 10 mg of oral methamphetamine study drug will be administered to assess tolerability, followed by a subsequent 15 mg oral dose two hours later. Then the participant will receive the placebo oral capsule for their second treatment phase starting at approximately Day 77. For the placebo treatment, one placebo capsule will be administered orally on treatment day, followed by a second oral placebo capsule two hours later. arm 2: Participants will be randomized to a placebo oral capsule first, then oral methamphetamine using a random number generator. For the placebo treatment, one placebo capsule will be administered orally on treatment day, followed by a second oral placebo capsule two hours later. Then the participant will receive the oral methamphetamine capsule for their second treatment phase starting at approximately Day 77. When oral methamphetamine is administered, an initial 10 mg of oral methamphetamine study drug will be administered to assess tolerability, followed by a subsequent 15 mg oral dose two hours later.

Interventions: intervention 1: Oral Methamphetamine intervention 2: Placebo oral capsule
Intervention descriptions: intervention 1: An initial 10 mg of oral methamphetamine (over-encapsulated to look similar to placebo capsule) study drug will be administered to assess tolerability, followed by a subsequent 15 mg oral dose (over-encapsulated to look similar to placebo capsule) two hours later. intervention 2: One placebo capsule will be administered orally on treatment day, followed by a second oral placebo capsule two hours later.

Protocol document:
Prot_SAP_000.pdf: 
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Clinical Research Protocol
EFFECT OF METHAMPHETAMINE ON RESIDUAL LATENT HIV DISEASE 
(EMRLHD) STUDY
Protocol Number:
EMRLHD
Version Date:
June 20, 2021
Development Phase:
Phase IV
Sponsor:
Sulggi Lee, MD PhD
Assistant Professor, Department of Medicine, Division of 
HIV, Infectious Diseases, and Global Medicine 
University of California, San Francisco
995 Potrero Avenue, Building 80, Box 0874
San Francisco, CA 94110
Funding Organization:
NIH/NIDA
Principal Investigator:
Name: Sulggi Lee, MD PhD 
Telephone: (415) 735-5127
Fax: (415) 476-6953
E-mail: sulggi.lee@ucsf.edu
Medical Monitor:
Name: Sulggi Lee, MD PhD 
Telephone: (415) 735-5127
Fax: (415) 476-6953
E-mail: sulggi.lee@ucsf.edu
Coordinating Center:
Single Center - UCSF
Approval:
Sulggi Lee, M.D., Ph.D.
Associate Professor of Medicine, UCSF
Date


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This confidential information about an investigational product is provided for the exclusive use of 
investigators of this product and is subject to recall at any time. The information in this document 
may not be disclosed unless federal or state law or regulations require such disclosure. Subject to the 
foregoing, this information may be disclosed only to those persons involved in the study who have a 
need to know, with the obligation not to further disseminate this information.
Short-term effects of methamphetamine exposure on residual viral 
transcription during treated HIV disease
Principal Investigator
Sulggi Lee, MD PhD
Assistant Professor of Medicine, Division of HIV/AIDS 
University of California
San Francisco, CA
Co-Investigators
Paula Lum, MD
Professor of Medicine, Division of HIV/AIDS 
University of California
San Francisco, CA
Kara Lynch, PhD
Associate Professor of Laboratory Medicine, University of 
California
San Francisco, CA
Additional Support
Elnaz Eilkhani – Study Coordinator
Fiona Beltran – Study Coordinator 
Vivan Pae – Study Coordinator
Sannidhi Sarvadhavabhatla – Study Coordinator


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PROTOCOL AGREEMENT
I have read the protocol specified below. In my formal capacity as Investigator, my duties 
include ensuring the safety of the study participants enrolled under my supervision and 
providing complete and timely information, as outlined in the protocol. It is understood 
that all information pertaining to the study will be held strictly confidential and that this 
confidentiality requirement applies to all study staff at this site. Furthermore, on behalf of 
the study staff and myself, I agree to maintain the procedures required to carry out the 
study in accordance with accepted GCP principles and to abide by the terms of this 
protocol.
Protocol Number: EMRLHD.03
Protocol Title: Short-term effects of methamphetamine exposure on residual viral 
transcription during treated HIV disease
Protocol Date: 06/20/2021
Investigator Signature
Date
Sulggi Lee, M.D., Ph.D. 
Associate Professor of Medicine
Division of HIV, Infectious Diseases, and Global Medicine 
University of California, San Francisco
995 Potrero Avenue, Building 80, Box 0874 
San Francisco, CA 94110
Print Name and Title


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TABLE OF CONTENTS
1
BACKGROUND
13
1.1
Overview of Non-Clinical Studies......................................................................................14
1.2
Overview of Clinical Studies ..............................................................................................14
2
STUDY RATIONALE
15
2.1
Risk / Benefit Assessment...................................................................................................16
3
STUDY OBJECTIVES
17
3.1
Primary Objective ...............................................................................................................17
3.2
Secondary Objectives..........................................................................................................17
4
STUDY DESIGN
18
4.1
Study Overview...................................................................................................................18
5
CRITERIA FOR EVALUATION
18
5.1
Primary Efficacy Endpoint..................................................................................................18
5.2
Safety Evaluations...............................................................................................................18
5.3
Other Evaluations (include only if applicable) ...................................................................18
6
PARTICIPANT SELECTION
19
6.1
Study Population.................................................................................................................19
6.2
Inclusion Criteria.................................................................................................................19
6.3
Exclusion Criteria ...............................................................................................................19
7
CONCURRENT MEDICATIONS
20
7.1
Allowed Medications and Treatments ................................................................................20
8
STUDY TREATMENTS
21
8.1
Method of Assigning Participants to Treatment Groups.....................................................21
8.2
Blinding...............................................................................................................................21
8.3
Formulation of Test and Control Products..........................................................................21
8.4
Supply of Study Drug at the Site.........................................................................................22
8.5
Supply of Study Drug at the Site.........................................................................................23
8.6
Study Drug Accountability .................................................................................................23
8.7
Measures of Treatment Compliance ...................................................................................23
9
STUDY PROCEDURES AND GUIDELINES
24
9.1
Clinical Assessments...........................................................................................................25
9.2
Clinical Laboratory Measurements.....................................................................................25
9.3
Pharmacokinetic Measurements .........................................................................................26
9.4
Research Laboratory Measurements...................................................................................26
10 ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION
27
10.1 Adverse Events...................................................................................................................27
10.2 Serious Adverse Experiences (SAE) ..................................................................................27
10.3 Monitoring..........................................................................................................................28
10.4 Criteria for Discontinuation................................................................................................29


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11 DISCONTINUATION AND REPLACEMENT OF PARTICIPANTS
31
11.1 Early Discontinuation of Study Drug .................................................................................31
12.3 Withdrawal of Participants from the Study ........................................................................31
12.4 Replacement of Participants ...............................................................................................31
12 PROTOCOL VIOLATIONS
32
13 DATA SAFETY MONITORING
32
14 STATISTICAL METHODS AND CONSIDERATIONS
33
14.1 Data Sets Analyzed.............................................................................................................33
14.2 Demographic and Baseline Characteristics ........................................................................33
14.3 Analysis of Primary Endpoint ............................................................................................34
14.4 Analysis of Secondary Endpoints.......................................................................................34
14.5 Sample Size ........................................................................................................................34
15 DATA COLLECTION, RETENTION AND MONITORING
34
15.1 Data Collection Instruments ...............................................................................................34
15.2 Data Management Procedures............................................................................................35
15.3 Data Quality Control and Reporting...................................................................................35
15.4 Archival of Data .................................................................................................................35
15.5 Availability and Retention of Investigational Records.......................................................37
15.6 Participant Confidentiality..................................................................................................37
16 ADMINISTRATIVE, ETHICAL, REGULATORY CONSIDERATIONS
37
16.1 Protocol Amendments ........................................................................................................37
16.2 Institutional Review Boards and Independent Ethics Committees ....................................37
16.3 Informed Consent Form......................................................................................................38
16.4 Publications ........................................................................................................................39
16.5 Investigator Responsibilities...............................................................................................39
17 REFERENCES
40


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LIST OF ABBREVIATIONS
AE
Adverse event
AIDS
Acquired Immunodeficiency Syndrome
ART
Antiretroviral therapy
CA-US RNA
Cell-associated HIV-1 RNA
CBC
Complete blood count
CFR
Code of Federal Regulations
CMP
comprehensive metabolic panel
CRF
Case report form
DMC
Data Monitoring Committee
ECG
Electrocardiogram
FDA
Food and Drug Administration
GCRC
General Clinical Research Center
GMP
Good Manufacturing Practice
HIPAA
Health Insurance Portability and Accountability Act of 1996
HIV
Human Immunodeficiency Virus
ICF
Informed consent form
IEC
Independent Ethics Committee
IRB
Institutional Review Board
LFT
Liver function test
MA
Methamphetamine
NOS
Not otherwise specified
PBMC
Peripheral blood mononuclear cells
PI
Principal Investigator
PID
Participant identification
SAE
Serious adverse experience
SMC
Safety Monitoring Committee
SOP
Standard Operating Procedures
TSH
Thyroid stimulating hormone
UCSF
University of California, San Francisco
ZSFG
Zuckerberg San Francisco General Hospital


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PROTOCOL SYNOPSIS
TITLE
Short-term effects of methamphetamine exposure on residual viral 
transcription during treated HIV disease
SPONSOR
Investigator Initiated Study (Dr. Sulggi Lee)
FUNDING 
ORGANIZATION
NIH/NIDA
NUMBER OF SITES
1
RATIONALE
Methamphetamine (MA) use is highly prevalent among HIV+ 
individuals and is likely to pose challenges for achieving an HIV cure 
in these individuals, even with effective antiretroviral therapy (ART) 
suppression. HIV+ ART-suppressed individuals with a history of MA 
use will be studied to determine whether MA increases virus 
production and systemic inflammation, and to identify the genes and 
immunologic pathways that drive MA-induced effects. Data obtained 
during the course of this study should contribute important and novel 
genetic and immunologic data to the HIV cure and psychostimulant 
addiction research agenda.
STUDY DESIGN
This is a phase IV open label double-blind randomized crossover 
study
PRIMARY 
OBJECTIVE
1. Determine whether short-term MA exposure increases residual 
viral production, markers of inflammation (plasma cytokine 
levels), and cell surface immune marker expression (flow 
cytometry) in blood.
SECONDARY 
OBJECTIVES
1. Identify differentially expressed genes and proteins in blood, 
before and after short-term MA administration.
2. Determine whether trace amine receptor 1 (TAAR1) signaling 
mediates observed effects of MA administration.
NUMBER OF 
PARTICIPANTS
N=10
PARTICIPANT 
SELECTION
CRITERIA
Inclusion Criteria:
1. Willing and able to provide written informed consent
2. Male or female, age ≥ 18 years and ≤ 65 years
3. Laboratory confirmed documentation of HIV-1 infection.
4. Continuous therapy with a DHHS recommended/alternative 
combination ART for least 12 months (at least 3 agents) at 
study entry with no regimen changes in the preceding 12 
weeks
5. Maintenance of undetectable plasma HIV-1 RNA below the 
limit of quantification for at least 12 months. Episodes of


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single HIV plasma RNA 50-500 copies/ml will not exclude 
participation if subsequent HIV plasma RNA is below the 
limit of assay detection.
6. No plans to modify ART during the study period (146 days, or 
approximately 5 months)
7. Participant and your partner(s) are willing to use two forms of 
contraception throughout the study period as well as up to 60 
days after the last day of study completion
8. Ability and availability to participate in the full 146 days of 
the study (approximately 5 month) and maintain the 
inclusion/exclusion criteria
9. No current or prior history of methamphetamine (MA) use 
disorder by DSM-5 diagnostic criteria. Participants may have a 
prior history of taking prescription medications containing 
amphetamines-type stimulants such as Adderall® or 
Dexedrine® or Ritalin for the treatment of conditions such as 
attention deficit hyperactivity disorder as long as the 
participant has not taken these medications in the last 12 
months or plans to take these medications during the entire 
study period.
Exclusion Criteria:
1. History of methamphetamine (“meth”) use disorder by DSM-5 
diagnostic criteria using the 11-symptom checklist.
2. Evidence of MA use other than due to the administered oral 
methamphetamine study drug, based on urine, hair, or serum 
MA measurements collected at baseline and follow-up study 
visits.
3. Current use of prescription medications containing 
amphetamine-type stimulants (e.g., Adderall®, Dexedrine®, 
Ritalin, etc.) within the past 1 year.
4. Sensitivity or allergy to amphetamine-type stimulants
5. Current use of any other “psychoactive” drug within the past 
1 month. These include cocaine, ecstasy, LSD, mushrooms, or 
other recreational drugs – but cannabis, nicotine or caffeine 
use is ok.
6. Use of illicit opioids (heroin, fentanyl) – but ok if use of 
prescription opioid agonists such as methadone, hydrocodone 
(Norco®), buprenorphine/naloxone (Suboxone®), oxycodone 
(Oxycontin®), hydromorphone (Dilaudid®) within the last 3 
months by self-report and/or urine qualitative screening.


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7. Current moderate to severe use of alcohol use disorder (DSM- 
5 criteria) as this might put patient at risk of withdrawal during 
the study.
8. Recent use within the last month of the following medications 
given potential interactions with oral methamphetamine: 
acebrophyline, iobenguane, isocarboxazid, methylene blue, 
moclobemide, phenylzine, procarbazine, rasagiline, 
safinamide, selegiline, tranylcypromine, asunaprevir, 
buproprion, topical cocaine, fluoxetine, iohexol, linezolid, 
paroxetine, potassium citrate, quinidine, sodium bicarbonate, 
sodium citrate, sodium lacate, tipranavir, and tromethamine.
9. Recent hospitalization in the last 90 days.
10. Recent infection in the last 90 days requiring prolonged (e.g.,
>3 weeks) systemic intravenous antibiotics.
11. Known anemia (HIV+ males Hct< 34; females Hct< 32) or 
contraindication to donating blood.
12. Screening hemoglobin below 12.5 g/dL
13. Poorly controlled hypertension or systolic blood pressure > 
140 on repeat measurement in the last 3 months, on more than 
one occasion.
14. Significant myocardial disease (e.g., current myocarditis or 
reduced left ventricular ejection fraction below the lower limit 
of normal) or diagnosed coronary artery disease.
15. History of psychotic symptoms (e.g., hallucinations, 
delusional thinking) in the prior 3 months.
16. History of seizures, abnormal electroencephalogram or brain 
damage with significant persisting neurological deficit in the 
past 3 months or currently on anti-seizure medication.
17. Significant respiratory disease requiring oxygen.
18. Participants of reproductive potential or breastfeeding. Women 
of childbearing potential must have a negative serum 
pregnancy test at screening. All participants of childbearing 
potential must agree to use a double-barrier method of 
contraception throughout the study period and up to 90 days 
after the last dose of MA.
19. Exposure to any immunomodulatory drug (including 
maraviroc) in the 12 weeks prior to study.
20. Prior or current use of experimental agents used with the intent 
to perturb the HIV-1 viral reservoir in the 12 weeks prior to 
study.
21. Pregnancy. A serum pregnant test will be performed. If this 
test is positive, the participant will not be allowed to enter the


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study singe body changes occurring during pregnancy will 
alter the study results.
22. Recent vaccination within the last 2 weeks prior to study 
baseline visit. Routine or standard of care vaccinations (such 
as SARS-CoV-2, influenza, pneumococcal, and 
meningococcal vaccinations) are allowed but must be 
administered greater than 14 days prior to baseline study visit. 
For SARS-CoV-2 vaccination, the last dose must be 
administered at least 14 days prior to baseline study visit.
TEST PRODUCT, 
DOSE, AND ROUTE 
OF 
ADMINISTRATION
Oral methamphetamine hydrochloride (10 mg, then 15 mg) will be 
administered in a double-blind fashion and prepared by over- 
encapsulating commercially available drug with cornstarch.
CONTROL 
PRODUCT, DOSE 
AND ROUTE OF 
ADMINISTRATION
Placebo capsules will be administered in a double-blind fashion and 
prepared by over-encapsulating cornstarch.
DURATION OF 
PARTICIPANT 
PARTICIPATION 
AND DURATION OF 
STUDY
Participants will be randomized to either of two treatment arms, oral 
methamphetamine or placebo, using a crossover design with a 31-day 
washout period in between treatment arms. Participants will be on 
study for up to 146 days.
Screening (for each arm): up to 14 days prior to treatment 
arm.
Treatment (for each arm): 1 day (participants to be admitted 
to outpatient research unit for a total of 5 hours on the 
treatment day)
Follow-up (for each arm): 31 days after the initial dose for 
that treatment arm.
The total duration of the study is expected to be 146 days 
(approximately 5 months).


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CONCOMMITANT 
MEDICATIONS
Prohibited:
Strict criteria for potential medications that could interact with the 
study drug will be used, and the following medications are not 
allowed during the study because of potential interactions with the 
study medication: acebrophyline, iobenguane, isocarboxazid, 
methylene blue, moclobemide, phenylzine, procarbazine, rasagiline, 
safinamide, selegiline, tranylcypromine, asunaprevir, buproprion, 
topical cocaine, fluoxetine, iohexol, linezolid, paroxetine, potassium 
citrate, quinidine, sodium bicarbonate, sodium citrate, sodium lacate, 
tipranavir, and tromethamine. This is because the study medication 
may alter metabolism of the drugs.
Allowed:
Otherwise, participants may use their usual medications, as long as 
they are medically necessary and can be monitored safely during the 
study period.
EFFICACY 
EVALUATIONS
•
HIV virus replication
•
Immune activation (cell surface immune marker expression by 
flow cytometry)
•
Inflammation (plasma cytokine levels)
•
Gene expression changes (RNA-seq)
•
Trace amine receptor 1 (TAAR1) signaling
PRIMARY ENDPOINT
•
HIV virus replication
SECONDARY 
ENDPOINTS
•
Immunologic effect on inflammation (immune marker expression, 
plasma cytokine expression).
•
Gene expression changes
•
Trace amine receptor 1 (TAAR1) metabolite production
OTHER 
EVALUATIONS
SAFETY 
EVALUATIONS
Incidence of adverse events
PLANNED INTERIM 
ANALYSES
During the study, safety will be monitored by a Safety Monitoring 
Committee (SMC), which will be led by an HIV specialist. The SMC 
will review all study procedures before the initiation of the study.
They will have the full and final authority to stop the study for any 
safety concern at any point. The decision to proceed with further drug 
administration will be taken by the Principal Investigator, taking into 
consideration clinical and laboratory adverse events. The decision to 
proceed with the next dosing level will be taken by the SMC. 
Specifically, dosing will be stopped and the SMC will be notified if 
one Grade 4 or two Grade 3 drug related adverse events or laboratory 
abnormalities are reported, becomes pregnant or initiates


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breastfeeding, or is required to initiate one of the prohibited 
concomitant medications listed in section 7.1. If stopping/pausing 
criteria are not met, the remainder of the dosing cohort will be 
enrolled/dosed the subsequent week. The study will proceed to the 
next dosing level provided the stopping/pausing criteria are not met. A 
UCSF Department of Medicine faculty member who is not otherwise 
involved in the study and who will not communicate with the study 
investigators regarding any aspect of the SMC reports will prepare the 
monitoring reports. The SMC will review accrual, adverse events 
summaries, CD4+ T-cell counts and HIV RNA levels/suppression 
over time, off-study rates and completeness of follow-up, by dose 
cohort.
STATISTICS
Primary Analysis Plan
Dr. Lee has expertise in epidemiology and biostatistics. Differences in 
residual viral transcription by MA exposure will be evaluated using 
multivariate negative biniomial regression, as previously described.
Potential covariates will include age, gender, nadir CD4+ T cell count, 
pre-ART HIV RNA, recent CD4+ T cell count, timing of ART 
(estimated date of HIV infection to date of ART initiation), duration 
of ART suppression, and other illicit use (stimulant or opioid 
exposure detected on qualitative urine measurement). Linear 
regressions will be used to associate MA concentrations with urinary
-PEA levels. For the RNA sequencing data, within-individual 
differential gene expression analyses will be performed for each tissue 
type (blood and lymph node) and for each cell type (Tcm CD4+ T 
cells or CD14+ monocytes). Deconvolution of cell-specific gene 
signatures69 will be performed to allow analysis of further cell 
subsets (e.g., “classical” vs. “non-classical” monocytes). For DNA 
variant analyses, SNP-based association tests between variants and 
TAAR1 signaling biomarkers will be performed using PLINK/SEQ, 
while gene-based association tests will be performed using SKAT-O, 
which aggregates variants across a region and assesses whether the 
number of variants with non-zero effect sizes within that region 
exceeds that of chance expectation. Genes and pathways will be 
filtered for those associated with changes in viral transcription using 
several pathway sources - e.g., Ingenuity Pathway Analysis (IPA), 
KEGG, MsigDB (Broad), and Damian Chaussabel’s immune 
modules. Functional Annotate Network (FAN) will be built using 
Genes2FANs and Cytoscape to show the key functional network 
elements that are downstream of candidate genes. String (string- 
db.org) will be used to build protein-protein interaction networks from 
the differentially expressed gene lists. Finally, graph theory analysis 
will be used to identify the functional motifs of the network.


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Rationale for Number 
of Participants
Assuming a log normal distribution of HIV-1 cell-associated (CA)-US 
RNA and a standard deviation of 0.6 log10 copies/106 CD4+ T cells 
(as above for Aim 1125), with 10 participants in the treatment arm, 
and a null hypothesis of no change in CA-US RNA, we estimate that 
the study will have approximately 80% power to detect a 0.5-0.6 
log10 difference in CA-US RNA before and after treatment peak, at 
the 0.05 significance level. For the gene expression analyses, 
assuming a coefficient of variation of 0.32 and approximately 80-90% 
sequencing depth between 5 to 8 copies per base, respectively, we 
estimate having greater than 80% power to detect a two-fold change at 
the 0.05 significance level.


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1
BACKGROUND
The majority of HIV-infected cells during effective antiretroviral therapy (ART) 
persist in lymphoid tissues.1 An effective HIV cure strategy will likely require a 
combination of potent latency reversal agents to purge this “HIV reservoir” and 
immunomodulatory agents to boost the host immune response.2 An additional 
challenge will be targeting specific marginalized populations who are most likely to 
benefit from an HIV cure but possess poorer immune responses as a result of residual 
viral replication due to suboptimal ART adherence3 and/or illicit substance use.4 
Worldwide, methamphetamine (MA) is the second most commonly used illicit 
substance,5 and in San Francisco, up to 39% of HIV+ individuals report recent MA 
use.6 These statistics highlight the need to identify an HIV cure in this population but 
also the importance of determining whether MA use itself may alter the nature of the 
reservoir or the host immune response.
Prior data shows that MA induces HIV transcription via activation of protein kinase C 
(PKC) and NF-B7-9 and increases systemic immune activation10-12 and 
inflammation.13,14 Our study will directly test in humans the hypothesis that MA use 
induces residual HIV transcription at the cellular level during effective ART. Our 
primary objectives are to characterize the reservoir in this population and use this 
experimental model to determine in vivo the molecular pathways that control 
transcription of the HIV genome.
In support of prior ex vivo and animal data demonstrating a link between MA 
exposure and viral transcription and immune activation, we recently studied 55 HIV+ 
ART-suppressed participants15 who use MA and observed that recent MA use was 
associated with significant changes in the expression of genes associated with HIV 
latency (FCGR2A, encoding CD32a16 and PDL1, encoding the immune exhaustion 
marker, programmed cell death-1 ligand17), as well as genes involved in cell cycle 
regulation (FOXO418, RBM3819, MAPK220). MA use was also associated with changes in 
innate immune activation/antigen presentation and inflammation (JAK-STAT 
signaling) pathways, consistent with prior experimental data demonstrating that MA 
exposure influences immune activation10,12,21 and pro-inflammatory cytokine 
release.22,23 Although findings from this cross-sectional study support the scientific 
premise of the proposed study, experimental models are needed to better 
characterize the mechanisms whereby acute MA exposure alters multiple biological 
pathways relevant to HIV persistence at the cellular level. As such, the goals of this 
study are to identify potential interventional targets for future HIV eradication 
strategies. For example, we will also specifically investigate a clinically promising 
target for the treatment of psychostimulant addiction,24-26 trace amine-associated 
receptor 1 (TAAR1) signaling, and a mechanism by which MA may induce PKC 
activation and viral transcription.27,28
1.1
Overview of Non-Clinical Studies
Prior experimental studies suggest that MA may directly increase HIV 
transcription and indirectly promote immune activation and inflammation. MA 
exposure results in increased translocation of NF-κB (a key transcriptional regulator of


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the HIV long terminal repeat [LTR] promoter29) in primary human microglial cells7 and 
leads to dose-dependent increases in HIV reverse transcriptase activity in primary 
monocyte-derived macrophages.8 In humanized mice, MA exposure produces a six-fold 
increase in plasma HIV RNA levels and increased HIV-1 p24 antigen detection in 
splenocytes.9 Rhesus macaques administered MA have increased CSF SIV RNA levels, 
with concomitant increases in the frequency of activated CD14+CD16+ macrophages in 
the brain.30 Though no differences in plasma SIV RNA levels were detected in that 
study, the effect of MA on viral transcription in plasma may have been difficult to detect 
given that the monkeys were not suppressed on ART (had high plasma viremia overall). 
MA leads to dysregulated immune activation and inflammation. MA promotes abnormal 
antigen presentation on phagocytes12,21 and decreased frequencies of dendritic cells and 
natural killer (NK) cells in in vitro studies.11,12 MA modifies thymic and splenic 
cellularity,31 alters T cell populations,31 induces apoptotic death,12,32 and perturbs thymic 
CD4/CD8 ratios31,33 in animals. MA leads to the dysregulation of serum cytokine 
production (e.g., TNF-α, IL-1β, IL-6, IL-2, IL-10, and IL-4) in a mouse model of chronic 
viral infection.13 Short-term administration of the methamphetamine-like compound, 3,4- 
methylenedioxymethamphetamine (MDMA) to healthy human participants reduced 
immunosuppressive cytokines (transforming growth factor [TGF]-β and IL-10) with a 
switch to Th2 cytokines (IL-2 and IL-1).14 Finally, in HIV+ viremic participants, MA use is 
associated with higher toll-like receptor (TLR)-9 and interferon (IFN)-α protein 
expression in peripheral blood mononuclear cells (PBMCs), suggesting that MA may 
also directly activate innate immunity.10 The proposed Aims 1 and 2 will be the first 
human in vivo studies to longitudinally evaluate the long-term and short-term effects of 
MA on gene and protein expression changes relevant to inflammatory and innate 
immune activation pathways.
1.2
Overview of Clinical Studies
A systems biology approach augments the ability to identify host genetic predictors 
of MA addiction that may be relevant to HIV cure. Prior genetic studies of MA addiction 
have focused on candidate genes based upon a priori-selected genes or pathways, such 
as genes related to the dopaminergic system like dopamine receptors 2 and 3 (DRD2, 
DRD3)34,35 and dopamine transporter (DAT).36 Two genome-wide association studies 
(GWAS), which included data from a prior GWAS,37 found no genome-wide significant 
single nucleotide polymorphisms (SNPs) associated with MA addiction disorder,38 though 
CDH13 was nominally associated – a gene previously implicated in subjective responses 
to d-amphetamine exposure.39 Though GWAS genotyping attempts to capture the majority 
of common SNPs throughout the genome, disease-associated SNPs often localize to 
“expression quantitative trait loci” (eQTL),40 regions that are not adequately captured by 
GWAS genotyping alone. RNA sequencing studies of MA use have been limited and 
include reported correlates of MA-induced psychosis (upregulation of circadian clock 
genes: ELK3 and SINA3, and ubiquitin-associated proteolysis: PIGF and UHMK1)41 and 
participant response to topiramate (glutamate and GABA receptor signaling: GRINA, 
PRKACA, PRKCI, SNPA23, TRAK2).42 Most genetic investigations into the etiology of 
complex traits have primarily focused on only a single genetic datasets at a time. In 
addition, GWAS data do not provide direct information about the function of these genes.43 
Meta-dimensional analyses integrating DNA, RNA, and protein-level data have the ability 
to elucidate the molecular mechanisms underlying intricate biological pathways.44 For the 
proposed study, we will use a systems-based approach to prioritize biological 
pathways that may yield potential novel targets for therapeutic intervention in 
psychostimulant addiction and HIV persistence. Despite some understanding now that


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host genetics plays an important role in determining MA addiction, the underlying 
mechanism by which MA induces immune effects and promotes viral production is still 
incompletely understood. Our data will contribute important DNA, RNA, and protein level 
data to current public databases that aim to annotate putative regulatory function and 
tissue-specific regulatory genetic effects.45-47 The proposed study will use these combined 
methods to investigate potential direct and indirect effects of MA on viral transcription 
(possibly mediated by TAAR1) and inflammation in HIV+ ART suppressed individuals.
2
STUDY RATIONALE
Methamphetamine use is associated with poorer clinical outcomes in HIV+ 
individuals, including decreased adherence to HIV treatment48 and increased risk of 
ART resistance.49,50 In San Francisco, as many as 39% of HIV+ individuals report having 
used MA in the prior year. The prevalence of MA use in men who have sex with men 
(MSM) is higher than in the general population, and MA use has been linked to an 
increased risk of HIV acquisition.51 Proposed mechanisms by which MA contributes to 
poorer clinical outcomes include data supporting that MA exposure leads to increased HIV 
transcription,7-9 increased T cell activation and exhaustion, and decreased responsiveness 
to antigenic stimulation.52 Yet, little is known about the effects of MA use on viral 
control during treated HIV disease. The proposed study will utilize the well- 
characterized UCSF SCOPE and Options HIV cohorts to perform in vivo studies to 
elucidate how MA exposure influences viral transcription, using cohort and interventional 
study designs and blood and lymphoid tissue HIV transcription measures. Results from 
this study may help identify novel targets for HIV eradication and control that are broadly 
generalizable to HIV+ ART-suppressed individuals, but also specific to those who use MA.
A remaining challenge is targeting vulnerable populations who will most benefit from an 
HIV cure and yet struggle to receive and remain on treatment. In collaboration with our 
HIV/AIDS Ward 86 Clinic at the Zuckerberg San Francisco General Hospital (ZSFG) and 
the San Francisco Department of Public Health, we have now leveraged the city-wide 
aggressive public health efforts aimed at identifying and immediately treating individuals 
with newly diagnosed HIV infection, to enroll these individuals into our SCOPE/Options 
cohorts. However, significant socioeconomic obstacles, such as substance use 
addiction, make it difficult for these individuals to remain in care and maintain ART 
suppression. Recently, HIV+ participants with suboptimal ART adherence (i.e., residual 
viremia below the limit of detection) demonstrate significantly higher levels of plasma 
biomarkers (e.g., interleukin- 2, -6, and -10; tumor necrosis factor [TNF]-α, and interferon 
[IFN]-γ).3 This finding adds new insight into prior data demonstrating that markers of 
inflammation are significantly higher in HIV+ than in HIV- individuals53-57 and are 
associated with higher rates of aging-associated diseases and mortality compared to 
age-matched HIV- controls.58,59 Overall, this suggests that inflammation may play a 
critical role – perhaps mediated by persistent virus itself – even in treated HIV+ 
individuals, and that in HIV+ individuals who use MA and struggle to maintain optimal 
ART adherence, aggressively targeting residual viral transcription and inflammation will 
be critical to achieving a functional cure in these individuals.
2.1
Risk / Benefit Assessment
Side effects associated with taking the study medication
Likely to occur:


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•
Oral methamphetamine is a stimulant and may cause increased blood 
pressure, heart rate, and palpitations (noticeably rapid, strong, or irregular 
heartbeats).
Less likely to occur:
•
In some cases, oral methamphetamine can cause some dizziness, headache, 
insomnia, elevated mood, depressed mood, restlessness, diarrhea, 
constipation, unpleasant taste, dry mouth, and tremor (hands shaking).
Very unlikely to occur:
•
At very high doses (much higher than the doses being given in this study) 
and if taken for prolonged periods of time (e.g., weeks to months to years), 
oral methamphetamine can lead to a substance use disorder, exacerbation of 
preexisting abnormal movements (called “tics”), psychotic symptoms 
(hearing and seeing things that are not actually there), frequent erections, 
impotence, and changes in libido.
Side effects associated with taking placebo
Very unlikely to occur:
•
In order to make the placebo appear similar to the study medication, the pills 
will be crushed and placed in a capsule. For the placebo phase, cornstarch 
will be placed inside the capsule. Therefore, individuals who have an allergy 
to cornstarch may be at risk of an allergic reaction when taking placebo and 
should notify the study investigator if they have a known allergy to 
cornstarch.
HIV viral load and resistance to antiretroviral therapy risks
Very unlikely to occur:
•
We will be measuring the amount of viral RNA that increases after the study 
drug. This does not necessarily mean that there is an increase in the amount 
of circulating HIV. Nonetheless, since there is a very small chance that there 
could be an in circulating virus, there would be a theoretical risk of 
developing resistance to antiretroviral therapy. The likelihood of this is 
extremely low, given that participants will only be given one day of a single 
day’s maximum pediatric dose of the study medication, and if the study 
medication induces viral rebound, the predicted increases in HIV in the blood 
blood is extremely small.  For these reasons, individuals can only participate 
in this study if there are alternate ART regimens available in the rare event 
that their current ART regimen is compromised as a result of this study. 
During the study, participants will have their HIV viral load followed closely 
(at screening, baseline, and on days 2, and 31 of each treatment arm).
Drug-drug interactions
Very unlikely to occur:
•
We believe that the likelihood of this is extremely low, given that participants 
will only be given one day of a low dose of the study medication. Strict


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criteria for potential medications that could interact with the study drug will 
be used, and the following medications are not allowed during the study 
because of potential interactions with the study medication: acebrophyline, 
iobenguane, isocarboxazid, methylene blue, moclobemide, phenylzine, 
procarbazine, rasagiline, safinamide, selegiline, tranylcypromine, 
asunaprevir, buproprion, topical cocaine, fluoxetine, iohexol, linezolid, 
paroxetine, potassium citrate, quinidine, sodium bicarbonate, sodium citrate, 
sodium lacate, tipranavir, and tromethamine. This is because the study 
medication may alter metabolism of the drugs.
Side effects of taking your blood sample (phlebotomy)
Likely to occur:
•
Drawing blood from a vein may cause some discomfort, bleeding or bruising 
where the needle enters the skin, and rarely, fainting or infection may occur. 
Up to a total of 795 milliliters (about 53 tablespoons) will be collected during 
the course of this study, which has been carefully calculated over the 146 
days of the study to ensure that blood levels are not below American Red 
Cross Guidelines.
•
Less likely to occur:
•
Less common symptoms include lightheadedness, dizziness, fainting and 
nausea. Symptoms of anemia include tiredness, weakness and dizziness. A 
CBC with differential will be collected at all visits from screening through day 
31 of each treatment arm. If the investigator feels that there is a significant 
risk for anemia, the amount of blood collected will be reduced. If the 
participant’s hemoglobin falls below 10 g/dl or the hematocrit falls below 
27%, there will be a 5 ml (1 teaspoon) blood draw check the hemoglobin and 
hematocrit. No more blood will drawn until the participant’s hemoglobin 
rises above 10 g/dl or hematocrit rises above 27%
Confidentiality
Participation in research may involve a loss of privacy; however, your records will be 
handled as confidentially as possible. All study questionnaires and research samples will 
be coded with a study ID. No personal identifiers such as your name will be used for 
stored specimens. Dr. Lee and the research staff as well as the UCSF Committee on 
Human Research will have access to your study records and test results. No individual 
identities will be used in any reports or publications that may result from this study.
California regulations require laboratories to report new cases of tuberculosis, hepatitis B, 
and hepatitis C infection to the county public health department. The reports include the 
patient’s name, social security number, and other identifying information. Information 
about these new infections is used to track these diseases statewide and nationwide. Other 
than this required reporting, your results will be treated confidentially by the study staff. 
Personally identifying information will not be reported to other departments or agencies.
Risk of genetic testing
Genetic information that results from this study does not have medical or treatment 
importance at this time. However, there is a risk that information about taking part in a


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genetic study may influence insurance companies and/or employers regarding a 
participant's health. To further safeguard participant privacy, genetic information 
obtained in this study will not be placed in his/her medical record.
Effect on participating in other studies
Every research study has different requirements for participation, which are known as 
eligibility criteria. If a participant agrees to take part in this study, the procedures required 
for this study may make him/her not eligible to participate in other studies for a period of 
time. How long that period of time is determined by the other study.
Reproductive risks
Methamphetamine is classified as FDA pregnancy risk category C. There are no adequate 
and well-controlled studies of methamphetamine use in pregnant women. Since there are 
limited data on pregnancy risk related to methamphetamine given for a single day at the 
FDA-approved pediatric daily dose, we will take precautions around potential pregnancy 
during the trial. According to the manufacturer, amphetamines are excreted into breast 
milk, and women who are taking amphetamines should refrain from nursing. The effect 
of stimulant medication exposure via breast milk on the neurological development of the 
infant has not been well studied. Breast milk concentrations in one woman taking 20 mg 
daily of racemic amphetamine ranged from 55 to 138 ng/mL with milk to plasma ratios 
of 2.8 to 7.5. For this reason, if a participant is breast-feeding, pregnant or plan to become 
pregnant, she cannot participate in this clinical trial. Female participants will be asked to 
take a pregnancy test at the beginning of the clinical trial and before each dose of 
investigational products in order to determine pregnancy. If a participant is able to 
become pregnant, two of the following forms of birth control are required, one of which 
must be condoms or a diaphragm or cervical cap:
•
Condoms (male of female) with or without a spermicidal agent
•
Diaphragm or cervical cap with spermicide
•
Intrauterine device (IUD) with published data showing that expected failure rate 
is < 1% per year
•
Tubal ligation
•
Hormone-based contraceptive such as oral birth control pills
Participants are advised that even if they use acceptable forms of birth control during the 
clinical trial, there is a chance she could become pregnant. If she does become pregnant 
during the clinical trial she is advised:
•
To call/notify the study doctor immediately
•
To consult an obstetrician or maternal-fetal specialist
•
That she will not be given any additional investigational products
•
That she will be followed to determine the pregnancy outcome
If the participant is a male who is sexually active with a woman capable of becoming 


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course of this research study. He is advised to inform his partner of the potential harm to 
an unborn child. The partner needs to know that if she does become pregnant during the 
study:
•
The participant will need to call/notify the study doctor immediately
•
She will need to consult an obstetrician or maternal-fetal specialist
•
Study staff will ask for her permission to collect information about the pregnancy 
and the health of the baby. This includes information related to the pregnancy/delivery 
and obstetrical history.
3
STUDY OBJECTIVES
3.1
Primary Objective
Determine whether short-term MA exposure increases residual viral production, markers 
of inflammation (plasma cytokine levels), and cell surface immune marker expression 
(flow cytometry) in blood.
3.2
Secondary Objectives
The second objective is to identify differentially expressed genes and proteins in blood, 
before and after short-term MA administration.
The third objective is to determine whether trace amine receptor 1 (TAAR1) signaling 
mediates observed effects of MA administration.
4
STUDY DESIGN
4.1
Study Overview
This is a phase IV open label randomized, double-blinded, placebo-controlled crossover 
study. A placebo treatment arm will be assigned to participants in a randomized crossover 
design. HIV+ ART-suppressed individuals with no prior history of MA use disorder will 
be administered 10mg oral methamphetamine hydrochloride (Desoxyn®), followed by 15 
mg methamphetamine hydrochloride two hours later, for a total of 25mg in one 24-hour 
period (the maximum FDA approved daily dose for the treatment of childhood obesity). 
Participants will complete the study twice (once on a placebo treatment arm and once 
with the Desoxyn® treatment arm). Which treatment arm occurs first will be randomly 
assigned and will include a 31-day washout period between the two phases. The placebo 
is similar in appearance, consistency, and taste to methamphetamine hydrochloride 
tablets, USP (Desoxyn®), without any known drug-drug interactions (e.g., changes in pH 
balance that might affect drug absorption) with HIV antiretroviral therapy.


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5
CRITERIA FOR EVALUATION
5.1
Primary Efficacy Endpoint
There is not a primary efficacy endpoint aim for this phase IV study, though we will be 
reporting changes in measures of HIV transcription, immune activation, and 
inflammation.
5.2
Safety Evaluations
Incidence and nature of adverse events
5.3
Other Evaluations (include only if applicable)
PBMCs will be collected for gene expression analyses. Plasma samples will be stored for 
future PK analyses
6
PARTICIPANT SELECTION
6.1
Study Population
1.
HIV-positive adults age ≥ 18 years and ≤ 65 years suppressed on long-term stable antiretroviral therapy,
with adequate organ function (per criteria listed below).
6.2
Inclusion Criteria
2.
Willing and able to provide written informed consent
3.
Male or female, age ≥ 18 years and ≤ 65 years
4.
Laboratory confirmed documentation of HIV-1 infection.
5.
Continuous therapy with a DHHS recommended/alternative combination ART for 
least 12 months (at least 3 agents) at study entry with no regimen changes in the 
preceding 12 weeks
6.
Maintenance of undetectable plasma HIV-1 RNA below the limit of quantification 
for at least 12 months. Episodes of single HIV plasma RNA 50-500 copies/ml will 
not exclude participation if subsequent HIV plasma RNA is below the limit of assay 
detection.
7.
No plans to modify ART during the study period (146 days, or approximately 5 
months)
8.
Participant and partner(s) are willing to use two forms of contraception throughout 
the study period as well as up to 60 days after the last day of study completion.
9.
Ability and availability to participate in the full 146 days of the study (approximately 
5 month) and maintain the inclusion/exclusion criteria
10. No current or prior history of methamphetamine (MA) use disorder by DSM-5 
diagnostic criteria. Participants may have a prior history of taking prescription


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medications containing amphetamines-type stimulants such as Adderall® or 
Dexedrine® or Ritalin for the treatment of conditions such as attention deficit 
hyperactivity disorder as long as the participant has not taken these medications in 
the last 12 months or plans to take these medications during the entire study period.
6.3
Exclusion Criteria
11. History of methamphetamine (“meth”) use disorder by DSM-5 diagnostic criteria 
using the 11-symptom checklist.
12. Evidence of MA use other than due to the administered oral methamphetamine study 
drug, based on urine, hair, or serum MA measurements collected at baseline and 
follow-up study visits.
13. Current use of prescription medications containing amphetamine-type stimulants 
(e.g., Adderall®, Dexedrine®, Ritalin, etc.) within the past 1 year.
14. Sensitivity or allergy to amphetamine-type stimulants
15. Current use of any other “psychoactive” drug within the last 1 month. These include 
cocaine, ecstasy, LSD, mushrooms, or other recreational drugs – but cannabis, 
nicotine or caffeine use is ok.
16. Use of illicit opioids (heroin, fentanyl) – but ok if use of prescription opioid agonists 
with known prescribed doses, such as methadone, hydrocodone (Norco®), 
buprenorphine/naloxone (Suboxone®), oxycodone (Oxycontin®), hydromorphone 
(Dilaudid®) within the past 3 months by self-report and/or urine qualitative 
screening.
17. Current moderate to severe use of alcohol use disorder (DSM-5 criteria) as this might 
put patient at risk of withdrawal during the study.
18. Recent use within the last month of the following medications given potential 
interactions with oral methamphetamine: acebrophyline, iobenguane, isocarboxazid, 
methylene blue, moclobemide, phenylzine, procarbazine, rasagiline, safinamide, 
selegiline, tranylcypromine, asunaprevir, buproprion, topical cocaine, fluoxetine, 
iohexol, linezolid, paroxetine, potassium citrate, quinidine, sodium bicarbonate, 
sodium citrate, sodium lacate, tipranavir, and tromethamine.
19. Recent hospitalization in the last 90 days.
20. Recent infection in the last 90 days requiring prolonged (e.g., >3 weeks) of systemic 
intravenous antibiotics.
21. Known anemia (HIV+ males Hct< 34; females Hct< 32) or contraindication to 
donating blood.
22. Poorly controlled hypertension or systolic blood pressure > 140 on repeat 
measurement in the last 3 months, on more than one occasion.
23. Significant myocardial disease (e.g., current myocarditis or reduced left ventricular 
ejection fraction below the lower limit of normal) or diagnosed coronary artery 
disease.
24. History of cardiac arrythmia that needs to be medically treated.


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25. History of psychotic symptoms (e.g., hallucinations, delusional thinking) in the prior 
3 months.
26. History of seizures, abnormal electroencephalogram or brain damage with significant 
persisting neurological deficit in the past 3 months or currently on anti-seizure 
medications
27. Significant respiratory disease requiring oxygen.
28. Exposure to any immunomodulatory drug (including maraviroc) in the 12 weeks 
prior to study.
29. Prior or current use of experimental agents used with the intent to perturb the HIV-1 
viral reservoir in the 12 weeks prior to study.
30. Pregnancy. A serum pregnancy test will be performed. If this test is positive, the 
participant will not be allowed to enter the study since body changes occurring 
during pregnancy will alter the study results.
31. Recent vaccination within the last 2 weeks prior to study baseline visit. Routine or 
standard of care vaccinations (such as SARS-CoV-2, influenza, pneumococcal, and 
meningococcal vaccinations) are allowed but must be administered greater than 14 
days prior to baseline study visit. For SARS-CoV-2 vaccination, the last dose must 
be administered at least 14 days prior to baseline study visit.
7
CONCURRENT MEDICATIONS
Participants may continue to take their usual medications, as long as they are medically 
necessary and can be monitored during the study period.
7.1
Allowed Medications and Treatments
Participants may not have exposure to any immunomodulatory drug (including 
maraviroc) in the 16 weeks prior to study or during study period and may not currently be 
taking experimental latent HIV reversing agents.
Only concomitant medications that are medically necessary will be continued with 
appropriate monitoring. In addition, the following medications are prohibited during the 
study and administration will be considered a protocol violation.
Strict criteria for potential medications that could interact with the study drug will be 
used, and the following medications are not allowed during the study because of potential 
interactions with the study medication: acebrophyline, iobenguane, isocarboxazid, 
methylene blue, moclobemide, phenylzine, procarbazine, rasagiline, safinamide, 
selegiline, tranylcypromine, asunaprevir, buproprion, topical cocaine, fluoxetine, iohexol, 
linezolid, paroxetine, potassium citrate, quinidine, sodium bicarbonate, sodium citrate, 
sodium lacate, tipranavir, and tromethamine. This is because the study medication may 
alter metabolism of the drugs.


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8
STUDY TREATMENTS
8.1
Method of Assigning Participants to Treatment Groups
Participants will be randomized to either oral methamphetamine versus placebo treatment 
first using a random number generator. Whichever treatment the participant receives first, 
they will receive the other treatment (placebo or oral methamphetamine) for their second 
treatment phase staring at Day 77 (See Study Events Table in Other Documents).
8.2
Blinding
The order in which participants complete the two treatment phases (i.e., oral 
methamphetamine and placebo) will be unknown to both the participants and the PI/study 
team. Both the oral methamphetamine and placebo will be prepared in identical capsules 
by the UCSF CTSI investigational pharmacist, out of sight of the study participant, study 
coordinator, and study site PI and administered to the participant to maintain double 
blinding. The investigational pharmacist will randomize each participant according to the 
methods described above. In the event that participant experiences an adverse event that 
requires the identity of the study drug be revealed, the PI will be able to contact the 
investigational pharmacist to break the blind. In the event that a participant blind is 
broken, the study PIs will determine the impact upon the un-blinded participant’s 
continued participation in the study and if a replacement participant is needed on a case- 
by-case basis.
8.3
Formulation of Test and Control Products
8.3.1
Formulation of Test Product
Oral methamphetamine hydrochloride (10 mg, then 15 mg) will be administered in a 
double-blind fashion and prepared by over-encapsulating commercially available 
drug with cornstarch; placebo capsules will contain only cornstarch. Study drug will 
be labeled and stored at <30° Celsius and protected from light. The half-life of oral MA 
is 4-5 hours, with 62% of drug eliminated in the urine within the first 24 hours, (1/3 
as intact drug and the remainder as metabolites).60 Individuals with chronic, tolerant 
MA use are reported to take between 250-500 mg and 1000 mg of MA per episode of 
use.21 Since participants included in this study will have no prior or recent MA use, 
they will be considered to be non-tolerant. Thus, given prior data demonstrating 
physiologic effects61-63 at doses similar to what is proposed here (maximum of 25 mg 
oral per day as recommended for the treatment of attention deficit hyperactivity 
disorder in children60), an initial 10 mg will be administered to assess tolerability, 
followed by a subsequent 15 mg dose two hours later.
8.3.2
Formulation of Control Product
As above; capsules will contain cornstarchonly.


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8.4
Supply of Study Drug at the Site
8.4.1
Dosage/Dosage Regimen
An initial 10 mg of oral methamphetamine study drug will be administered to assess 
tolerability, followed by a subsequent 15 mg oral dose two hours later. For placebo 
treatment phase, one placebo capsule will be administered orally on treatment day, 
followed by a second oral placebo capsule two hours later.
8.4.2
Dispensing
All handling of the study drug and placebo - storage, reconstitution, individual dose 
preparation, and drug accountability will be done by the study investigators and the 
investigational pharmacist.
8.4.3
Administration Instructions
Dr. Lee and study team will instruct study staff on how to administer the study drug or 
placebo with a full 6 oz cup of water. Study staff will then administer the study drug or 
placebo and observe administration and side effects of participants on the treatment days.
8.5
Supply of Study Drug at the Site
The study drug will be purchased through procurement and delivered to the ZSFG 
Investigational Pharmacy located in the main Inpatient Pharmacy, Rooms 4H3 + 4H6.
8.5.1
Storage
Study drug and placebo storage will be in a cool, dry place, away from strong light, heat, 
or moisture. For this study, the study drug and placebo will be stored in a locked cabinet 
in the ZSFG Investigational Pharmacy located in the main Inpatient Pharmacy, Rooms 
4H3 + 4H6. Entrance to the pharmacy is secure by electronic pass key only; limited 
access to pharmacy personnel and housekeeping. Temperature is controlled by air 
conditioning and monitored to be between 59-86 F. Temperature is recorded daily by 
reading an alarmed digital thermometer and recording the reading on a daily log. The 
CRS investigational pharmacist will dispense study drug and maintain the distribution 
records.
8.6
Study Drug Accountability
An accurate and current accounting of the dispensing of study drug for each participant 
will be maintained on an ongoing basis by the study investigators. The number of study 
drug dispensed will be recorded on the Investigational Drug Accountability Record. The 
study investigators will verify these documents throughout the course of the study.
8.7
Measures of Treatment Compliance
Study participants will be monitored in the Clinical Research Services Center (CRS) for 
directly observed therapy on the day(s) when study drug or placebo administered. They 
will be receiving clinical and laboratory assessments on those days for up to 4 hours post- 
treatment.


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9
STUDY PROCEDURES AND GUIDELINES
Prior to conducting any study-related activities, written informed consent and the Health 
Insurance Portability and Accountability Act (HIPAA) authorization must be signed and 
dated by the participant.
A full schedule of events is shown in the Study Events Table.
Clinical Assessments
9.1.1
Concomitant Medications
All concomitant medications taken within 30 days prior to screening and entry and a 
complete history of ART, HIV-1 related vaccines, and immune-based therapies will be 
documented at the Screening and Entry visits. At each subsequent visit, all additions or 
discontinuations of prescription medications should be recorded. Actual or estimated start 
and stop dates should be recorded.
9.1.2
Demographics
Demographic information (date of birth, sex, race and ethnicity) will be recorded at 
Screening.
9.1.3
Medical History
At Screening, the first Baseline visit (B1) and Entry (Day 0), the medical history must 
include all diagnoses within the past 30 days and, regardless of when the diagnosis was 
made, a complete history of chronic conditions, malignancies, and AIDS-defining 
conditions. Self-reported or documented nadir CD4+ T cell count should be recorded. 
Any allergies to any medications or their formulations should also be recorded.
9.1.4
Physical Examination
A complete physical examination which includes vitals will be performed by a study 
physician at Screening. Targeted physical examination which includes vitals will be 
performed on Baseline, Study Treatment Day(s), and at Study Days 2, 31, 78, and 107..
9.1.5
Vital Signs
Body temperature, blood pressure, pulse and respirations will be performed after resting 
for 5 minutes at Baseline/Screening, Study Treatment Day(s), and at Study Days 2 and 
31.
9.1.6
12-Lead Electrocardiogram
A 12-lead electrocardiogram (ECG) will be obtained on treatment days to evaluate for 
symptomatic, cardiac conduction abnormality/atrioventricular heart block that would 
warrant medical treatment, including: AV Block-First degree, AV Block-Second degree 
Mobitz Type I (Wenckebach), AV Block-Second degree Mobitz Type II, AV Block- 
Third degree (Complete AV block), Conduction abnormality NOS, Sick Sinus Syndrome, 
Stokes-Adams Syndrome, Wolff-Parkinson-White Syndrome


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9.1.7
Adverse Events
Information regarding occurrence of adverse events will be captured throughout the 
study. Duration (start and stop dates and times), severity/grade, outcome, treatment and 
relation to study drug will be recorded on the case report form (CRF). Criteria for 
participant management, dose interruptions, modifications, and discontinuation of 
treatment will be mandated only for toxicities attributable to study drug.
9.2
Clinical Laboratory Measurements
9.2.1
Basic Laboratory Measures
Blood will be obtained and sent to the Zuckerberg San Francisco General Hospital 
clinical laboratory for complete blood count (hemoglobin, hematocrit, red blood cell 
count, white blood cell count, white blood cell differential, and platelet count), blood 
chemistry profile (serum sodium, potassium, chloride, bicarbonate, random glucose, 
blood urea nitrogen, creatinine), and liver enzymes (aspartate aminotransferase [AST], 
alanine aminotransferase [ALT], alkaline phosphatase, total bilirubin, direct bilirubin). At 
screening, additional laboratory measures will include Hepatitis B surface antigen and 
Hepatitis C antibody, thyroid panel (thyroid stimulating hormone [TSH]), and plasma β-
hCG (females only).
9.3
Research Laboratory Measurements
9.3.1
HIV Clinical Laboratory Assay Measures
Blood will be obtained and sent to San Francisco General Hospital clinical laboratory for 
real-time determination of CD4+ and CD8+ T cell counts and plasma HIV RNA (viral 
load).
9.3.2
HIV Virologic Research Assay Measures
Cryopreserved PBMCs will be enriched for CD4+ T cells (StemCell, Vancouver, 
Canada), and DNA/RNA extracted (AllPrep Universal Kit, Qiagen, Hilden, Germany). 
CA-US and ms RNA will be quantified by an in-house qPCR TaqMan assay using LTR- 
specific primers,64,65 and 2-LTR DNA will be quantified using primers specific for the 
2-LTR junctions.66 Participant specimens will be assayed with up to 800 ng total 
cellular RNA or DNA in replicate reaction wells and copy number determined by 
extrapolation against a 7-point standard curve (1 – 10,000 cps) performed in 
triplicate.
9.3.3
Immunophenotyping
We will measure the host and viral transcriptome pre- and post-dosing by performing 
RNA sequencing (RNA-seq) on isolated CD4+ T-cells and applying validated 
bioinformatic pipelines for gene expression analysis. Transcriptomic profiling of 
longitudinal samples will enable characterization of the effects of oral methamphetamine 
on host gene expression. In addition, consideration of the gene expression data within the 
context of the aforementioned virologic measurements will allow us to identify specific 
host transcriptomic correlates of viral reactivation. We hypothesize that the expression of


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particular genes (NFkB pathway components, cell-cycle regulators, cell-intrinsic immune 
factors) will be associated with the degree of viral reactivation.
9.3.4
Plasma cytokine measurement
Cryopreserved plasma from participants will be used to perform custom Meso Scale 
Discovery (Meso Scale Diagnostics, Rockland, MD) multiplex human inflammatory 
assays. Analytes will be assayed using an electrochemiluminescence immunoassay 
technique per the manufacturer’s protocol and analyzed on a Meso Scale Discovery 
Sector Imager 2400 (MSD, Rockville, MD). TNF-α, IL 6, and IL-10 will be analyzed 
simultaneously in a 3-plex analysis, while TGF-β1, TGF-β2 and TGF-β3 will be analyzed 
in a separate 3-plex cytokine analysis. The dynamic range for TNF-α, IL 6, IL-10, TGF- 
β1, TGF-β2, and TGF-β3 per manufacturer’s specifications are (in pg/mL): 0.54-3,700; 
0.33-2,000; 0.14-3,700; 9.1-37,000; 2.5-38,900; and 1.4-38,600, respectively.
9.3.5
Serum and breath methamphetamine and amphetamine quantification
Amphetamine and methamphetamine concentrations in serum and breath will be 
determined using a clinically validated liquid-chromatography tandem mass 
spectrometry (LC-MS/MS) method. Sample preparation consists of acetonitrile 
protein precipitation, nitrogen-drying of supernatant, and reconstitution in starting 
LC conditions. For LC, a Shimadzu Prominence UPLC is used with a C18 column and 
a gradient of mobile phase A (0.05% formic acid) and B (acetonitrile/methanol).
Detection is carried out with a SCIEX 4500 QTRAP® tandem mass spectrometer, 
with an estimated LLOD of 5 ng/mL.
9.3.6
Urine qualitative toxicology
Urine qualitative toxicology testing will be performed at baseline, screening, treatment 
day, and post-24 hours and post-day 31 after treatment day using a liquid 
chromatography high mass resolution tandem mass spectrometry (LC-HRMS) method67 
that allows for the identification of drugs and their metabolites in one assay that has 
enhanced sensitivity/specificity compared to traditional drug screening immunoassays 
using LC-MS/MS. Prior to analysis, urine samples will be extracted using matrix dilution 
method, respectively. The data can be retrospectively analyzed for drugs and metabolites 
of interest given the untargeted acquisition method, with data collected for all compounds 
within the mass range of 50-700 daltons. The method has been fully validated for the 
qualitative detection of 250 drugs and metabolites with lower limits of detection (LLOD) 
ranging from 0.1 – 50 ng/mL.
9.3.7
Hair ART and MA measurements
Concentrations of ART will be quantified from human hair samples at baseline only. 
Hair ART and MA assessment will be performed using validated liquid 
chromatography/ tandem mass spectrometry (LC-MS/MS) methods.68-70 
Measurements from this validated assay allow quantification of protease inhibitors 
(PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and integrase 
strand transferase inhibitors (INSTIs) using 20-30 strands of human hair (~1-3 mg) 
and tenofovir (TFV) and emtricitabine (FTC) from 50-100 strands of hair (~5-10


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mg). TFV measurements include tenofovir disoproxil fumarate (TDF) as well as 
tenofovir alafenamide (TAF).71 These methods are now being adapted in the UCSF 
Hair Lab to analyze MA and its metabolites, applying previously published 
methods,71,72 and costs have been included in the budget of this proposal to allow 
adequate ability for the development and validation of these measures
9.3.8
Trace amine receptor 1 metabolite quantification
Beta-phenethylamine (-PEA) concentrations in urine will be determined using a 
clinically validated LC-MS/MS method by Dr. Kara Lynch at the ZSFG Toxicology lab; 
this will include costs to perform assay development to identify additional trace amines, 
such as tryptamine and -tyramine.73 LC will be performed using a Shimadzu 
Prominence UPLC with a C18 column. Detection will be carried out with a SCIEX 4500 
QTRAP® tandem mass spectrometer.
10 ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION
10.1 Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical investigation of a 
patient administered a pharmaceutical product and that does not necessarily have a causal 
relationship with the treatment. An AE is therefore any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom or disease temporally associated 
with the administration of an investigational product, whether or not related to that 
investigational product. An unexpected AE is one of a type not identified in nature, 
severity, or frequency in the current Investigator’s Brochure or of greater severity or 
frequency than expected based on the information in the Investigator’s Brochure.
The Investigator will probe, via discussion with the participant, for the occurrence of AEs 
during each participant visit and record the information in the site’s source documents.
Adverse events will be recorded in the patient CRF. Adverse events will be described by 
duration (start and stop dates and times), severity, outcome, treatment and relation to 
study drug, or if unrelated, the cause.
AE Severity
The National Cancer Institute’s Common Terminology Criteria for Adverse Events 
(CTCAE) Version 3.0 should be used to assess and grade AE severity, including 
laboratory abnormalities judged to be clinically significant. The modified criteria can be 
found in the study manual. If the experience is not covered in the modified criteria, the 
guidelines shown in Table 1 below should be used to grade severity. It should be pointed 
out that the term “severe” is a measure of intensity and that a severe AE is not necessarily 
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Table 1. AE Severity Grading
Severity (Toxicity Grade)
Description
Mild (1)
Transient or mild discomfort; no limitation in activity; no medical 
intervention or therapy required. The participant may be aware of the 
sign or symptom but tolerates it reasonably well.
Moderate (2)
Mild to moderate limitation in activity, no or minimal medical 
intervention/therapy required.
Severe (3)
Marked limitation in activity, medical intervention/therapy required, 
hospitalizations possible.
Life-threatening (4)
The participant is at risk of death due to the adverse experience as it 
occurred. This does not refer to an experience that hypothetically 
might have caused death if it were more severe.
The specific adverse events that will be solicited include cardiovascular outcomes, using 
the Division of AIDS (DAIDS) Adverse Events Grading Criteria 
(https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf).


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AE Relationship to Study Drug
The relationship of an AE to the study drug should be assessed using the following the 
guidelines in Table 2.
Table 2. AE Relationship to Study Drug
Relationship 
to Drug
Comment
Definitely
Previously known toxicity of agent; or an event that follows a reasonable temporal 
sequence from administration of the drug; that follows a known or expected response 
pattern to the suspected drug; that is confirmed by stopping or reducing the dosage of 
the drug; and that is not explained by any other reasonable hypothesis.
Probably
An event that follows a reasonable temporal sequence from administration of the 
drug; that follows a known or expected response pattern to the suspected drug; that is 
confirmed by stopping or reducing the dosage of the drug; and that is unlikely to be 
explained by the known characteristics of the participant’s clinical state or by other 
interventions.
Possibly
An event that follows a reasonable temporal sequence from administration of the 
drug; that follows a known or expected response pattern to that suspected drug; but 
that could readily have been produced by a number of other factors.


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Unrelated
An event that can be determined with certainty to have no relationship to the study 
drug.
10.2 Serious Adverse Experiences (SAE)
An SAE is defined as any AE occurring at any dose that results in any of the following 
outcomes:
•
death
•
a life-threatening adverse experience
•
inpatient hospitalization or prolongation of existing hospitalization
•
a persistent or significant disability/incapacity
•
a congenital anomaly/birth defect
Other important medical events may also be considered an SAE when, based on 
appropriate medical judgment, they jeopardize the participant or require intervention to 
prevent one of the outcomes listed.
10.2.1 Serious Adverse Experience Reporting
The study site will document all SAEs that occur (whether or not related to study drug) 
per UCSF CHR Guidelines. The collection period for all SAEs will begin after informed 
consent is obtained and end after procedures for the final study visit have been 
completed.
In accordance with the standard operating procedures and policies of the local 
Institutional Review Board (IRB), the site investigator will report SAEs to the IRB.


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10.3 Monitoring
During the study, safety will be monitored by a Safety Monitoring Committee (SMC), 
which will be led by a qualified UCSF faculty member in the Department of Medicine 
with expertise in HIV clinical research (see Section 13 below). The SMC will review all 
study procedures before the initiation of the study. They will have the full and final 
authority to stop the study for any safety concern at any point. The Principal Investigator 
will be the primary medical monitor responsible for study adverse event monitoring and 
will report adverse events and unanticipated problems to the UCSF IRB and the SMC. 
All participants will be followed for possible adverse events and unanticipated problems 
throughout the study period.
Participants will be monitored in an outpatient clinic during the first 6 hours post-dose on 
dosing days. At each visit, participants will be assessed for any new symptoms, and a 
study coordinator will obtain vital signs. The study will require 48-hour reporting of all 
laboratory values, signs/symptoms, and serious adverse events (SAEs). The study will 
have intensive Phase I safety monitoring, which will include regular and frequent team 
review (every week for the first 2 months of the study; then every two weeks thereafter) 
of all reported events. In addition, for any Grade 3 or 4 events, sites will be instructed to 
contact the study team by email.
•
Grade 1 or 2 Toxicity: Participants who develop a Grade 1 or 2 AE or toxicity 
may continue study treatment. If a participant chooses to discontinue study 
treatment, the site should notify the study protocol core team as noted above, and 
encourage the participant to complete any remaining study visits.
•
Grade 3 or 4 Toxicity: Participants experiencing Grade 3 or 4 AEs requiring 
permanent discontinuation of study treatment should be followed closely for 
resolution of the AE to Grade ≤ 3 and the protocol core team must be notified. 
Participants discontinuing study treatment should be encouraged to complete any 
remaining study visits.
Dr. Sulggi Lee will be contacted directly to report medical concerns or questions 
regarding safety.
Phone: (415) 735-5127
10.4 Criteria for Discontinuation
Safety will be monitored by the dedicated SMC, led by a qualified Drug and Substance 
Abuse specialist in the UCSF Department of Medicine (see Section 13 below). The SMC 
will have full and final authority to stop the study at any point for safety concerns. The 
decision to proceed with further drug administration will be taken by the Principal 
Investigator, taking into consideration clinical and laboratory adverse events. The 
decision to proceed with the next dosing level will be taken by the SMC. Specifically,


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dosing will be paused and the SMC will be consulted if one Grade 4 or two Grade 3 drug 
related adverse events or laboratory abnormalities are reported.
Specifically, safety discontinuation criteria will include:
1. Any serious adverse event assessed as at least possibly related to study treatment:
a.
Any Grade 4 drug-related adverse event or laboratory abnormality
b. Two Grade 3 drug-related adverse event or laboratory abnormality
2. Pregnancy or breastfeeding
3. Requirement for prohibited concomitant medications (see section 7.1)
4. Clinical reasons believed life threatening by the physician, even if not addressed 
in the toxicity section of the protocol
Study drug-specific hold criteria after the first methamphetamine dose will be based on 
established protocols adapted from prior stimulant interventional trials (Walsh et. al.
Drug Alcohol Depend. 2010 Jan 1;106(1):28-37. doi: 10.1016/j.drugalcdep.2009.07.011):
•
SBP ≥ 165 mm Hg or
•
DBP ≥ 100 mm Hg or
•
HR ≥ 130 BPM
Resume methamphetamine administration only if values are below the above 
parameters for at least 3 consecutive minutes.
Stop further methamphetamine administration if the following are reached for 4 
minutes or more:
•
SBP ≥ 180 mm Hg or
•
DBP ≥ 120 mm Hg or
•
HR ≥ submaximal HR (i.e., 220 - [age x 0.85])
Such a participant will be observed until cardiac parameters return to normal and 
will be discontinued from the study.
In addition, any significant ECG abnormality (determined by monitoring medical staff) 
will suspend further dosing.
If stopping/pausing criteria are not met, the remainder of the dosing cohort will be 
enrolled/dosed the subsequent week. The study will proceed to the next dosing level 
provided the stopping/pausing criteria are not met. A UCSF Department of Medicine 
faculty member who is not otherwise involved in the study and who will not 
communicate with the study investigators regarding any aspect of the SMC reports will 
prepare the monitoring reports. The SMC will review accrual, adverse events summaries, 
CD4+ T-cell counts and HIV RNA levels/suppression over time, off-study rates and 
completeness of follow-up, by dose cohort.


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11 DISCONTINUATION AND REPLACEMENT OF PARTICIPANTS
11.1 Early Discontinuation of Study Drug
A participant may be discontinued from study treatment at any time if the participant or 
the investigator feels that it is not in the participant’s best interest to continue. The 
following is a list of possible reasons for study treatment discontinuation:
•
Participant withdrawal of consent
•
Participant is not compliant with study procedures
•
Adverse event that in the opinion of the investigator would be in the best interest 
of the participant to discontinue study treatment
•
Protocol violation requiring discontinuation of study treatment
•
Lost to follow-up
•
Sponsor request for early termination of study
•
Positive pregnancy test or breastfeeding (females)
If a participant is withdrawn from treatment due to an adverse event, the participant will 
be followed and treated by the Investigator until the abnormal parameter or symptom has 
resolved or stabilized.
All participants who discontinue study treatment should come in for an early 
discontinuation visit as soon as possible and then should be encouraged to complete all 
remaining scheduled visits and procedures.
All participants are free to withdraw from participation at any time, for any reason, 
specified or unspecified, and without prejudice.
Reasonable attempts will be made by the investigator to provide a reason for participant 
withdrawals. The reason for the participant’s withdrawal from the study will be specified 
in the participant’s source documents (refer to early termination procedures).
12.3
Withdrawal of Participants from the Study
A participant may be withdrawn from the study at any time if the participant, the 
investigator, or the Sponsor feels that it is not in the participant’s best interest to 
continue.
12.4
Replacement of Participants
Participants who withdraw from the study treatment before last day of study drug dosing 
will be replaced by another enrolled participant to maintain total study numbers.
The CRF will document the reason for the withdrawal and date of withdrawal. Date of 
withdrawal will be documented as the date of last study drug treatment, not the date that 
the decision to withdraw treatment was made.


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Participants will be followed after withdrawal from the study for 3 calendar days after 
cessation of treatment. All adverse events during that period will be reported.
12 PROTOCOL VIOLATIONS
A protocol violation occurs when the participant or the study investigator fails to adhere 
to significant protocol requirements affecting the inclusion, exclusion, participant safety 
and primary endpoint criteria. Protocol violations for this study include, but are not 
limited to, the following:
•
Failure to meet inclusion/exclusion criteria
•
Use of a prohibited concomitant medication
Failure to comply with Good Clinical Practice (GCP) guidelines will also result in a 
protocol violation. The Principal Investigator will determine if a protocol violation will 
result in withdrawal of a participant.
When a protocol violation occurs, it will be discussed with the investigator and a Protocol 
Violation Form detailing the violation will be generated. A copy of the form will be filed 
in the site’s regulatory binder and in the Sponsor’s files.
13 DATA SAFETY MONITORING
Safety monitoring will include team review of adverse events (including all reported 
signs/symptoms, laboratory abnormalities, diagnoses, and SAEs) and team assessment as 
to the possible relationship of adverse events to the study treatment. The review will also 
include assessment any participants with an unconfirmed CD4+ T cell or HIV RNA 
measurement indicating a potential safety endpoint. Regular team monitoring will also 
assess early study discontinuations and visit/sample completeness. In addition, study 
accrual and baseline characteristics of study participants will be reviewed periodically 
during accrual. After a dose cohort has completed accrual and sufficient follow-up time is 
available, the team will evaluate whether to dose-escalate and open the next dose cohort 
to accrual, as described below.
Safety Monitoring Committee (SMC). We have established an independent Safety 
Monitoring Committee (SMC) for this study which include well-recognized experts in 
HIV clinical care and research: Dr. David Tompkins (Associate Professor of Medicine, 
UCSF, and Director of the Division of Substance Abuse and Addiction Medicine) and 
Annie Luetkemeyer (Professor of Medicine, UCSF, and expert on HIV management and 
clinical trials). The committee will be chaired by Dr. Tompkins who has experience in the 
regulatory aspects of clinical trials and will independently deliberate using study data.
The SMC will meet after completion of each dose cohort to review safety data. The 
meeting will occur no earlier that two weeks after the last dose. The decision to move to 
the next dose cohort will be made by the SMC, after consultation with the study 
investigators.
A study data coordinator will produce administrative reports regularly describing study 
progress including the following: (1) accrual, (2) demographics, (3) study subject status,


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(4) laboratory data, and (5) number and type of serious AEs. Reviews will be 
communicated to the UCSF Committee on Human Research (CHR), study sponsor, 
and/or federal agencies, as appropriate. The SMC will have access to treatment 
assignment. The study will be discontinued if the SMC determines that it is in the best 
interest of the subjects.
Grade 1 or 2 AEs will not result in any change to the study plans. If there is evidence for 
a Grade 3 AE that is not caused by the study drug, the study will continue as planned. On 
the other hand, Grade 3 AEs thought to be possibly caused by the intervention and any 
Grade 4 AEs will result in a hold on any future enrollments until a decision to proceed or 
to stop the study is made by the SMC
14 STATISTICAL METHODS AND CONSIDERATIONS
14.1 Data Sets Analyzed
Dr. Lee and her computational data specialist will be performing the data analysis for the 
study.
14.2 Demographic and Baseline Characteristics
The following demographic variables at screening will be summarized by dose level: 
race, gender, age, height and weight.
14.3 Analysis of Primary Endpoint
Paired analyses using Wilcoxon signed rank tests will be performed to evaluate whether 
there is a statistically significant change in markers of immune activation (e.g., CD69, 
CD38, and/or HLA-DR) on CD4+ and CD8+ T cells, as well as log-transformed levels of 
plasma cytokines (e.g., IL-6, IL-1b, IFN-g) after study drug compared to baseline 
(reference will be the average of the three baseline measures). Multivariate analyses will 
then be performed to evaluate the association between study drug and measures of 
immune activation at post-dosing, using linear mixed effects models, which account for 
within-participant correlation of observations and allows for greater stability in the 
estimate of the outcome measures within individuals. Similarly, for measures of the HIV 
transcription, linear mixed effects regression to compare CA-US RNA levels before and 
after study drug will be performed. Negative binomial mixed effects regression (a method 
to analyze over-dispersed count data) to compare plasma HIV RNA levels before and 
after study drug administration (reference will be the average of three baseline measures).
14.4 Analysis of Secondary Endpoints
Differences in residual viral transcription by MA exposure will be evaluated using 
multivariate negative biniomial regression, as previously described.74 Potential 
covariates will include age, gender, nadir CD4+ T cell count, pre-ART HIV RNA, 
recent CD4+ T cell count, timing of ART (estimated date of HIV infection to date of


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ART initiation), duration of ART suppression, and other illicit use (stimulant or 
opioid exposure detected on qualitative urine measurement).  Linear regressions 
will be used to associate MA concentrations with beta-PEA levels. For the RNA 
sequencing data, within-individual differential gene expression analyses will be 
performed for each tissue type (blood and lymph node) and for each cell type (Tcm 
CD4+ T cells or CD14+ monocytes). Genes and pathways will be filtered for those 
associated with changes in viral transcription using several pathway sources - e.g., 
Ingenuity Pathway Analysis (IPA),75 KEGG,76 MsigDB (Broad),77 and Damian 
Chaussabel’s immune modules.78 Functional Annotate Network (FAN) will be built 
using Genes2FANs79 and Cytoscape80 to show the key functional network elements 
that are downstream of candidate genes. String (string-db.org) will be used to build 
protein-protein interaction networks from the differentially expressed gene lists.
Finally, graph theory analysis81 will be used to identify the functional motifs of the 
network.
14.5 Sample Size
Assuming a log normal distribution of HIV-1 cell-associated (CA)-US RNA and a 
standard deviation of 0.6 log10 copies/106 CD4+ T cells (as above for Aim 1125), 
with 10 participants in the treatment arm, and a null hypothesis of no change in CA- 
US RNA, we estimate that the study will have approximately 80% power to detect a 
0.5-0.6 log10 difference in CA-US RNA before and after treatment peak, at the 0.05 
significance level. For the gene expression analyses, assuming a coefficient of 
variation of 0.32 and approximately 80-90% sequencing depth between 5 to 8 
copies per base, respectively, we estimate having greater than 80% power to detect 
a two-fold change at the 0.05 significance level.
15 DATA COLLECTION, RETENTION AND MONITORING
15.1 Data Collection Instruments
The Investigator will prepare and maintain adequate and accurate source documents 
designed to record all observations and other pertinent data for each participant treated with 
the study drug.
Case report forms (CRFs) will be provided for each participant. Study personnel will 
enter data from source documents corresponding to a participant’s visit into the protocol- 
specific paper CRF when the information corresponding to that visit is available.
Participants will not be identified by name in the study database or on any study 
documents to be collected by the study investigators, but will be identified by a four-digit 
patient identification number (PID). If a correction is made on a CRF, the study staff 
member will line through the incorrect data, write in the correct data and initial and date 
the change.
The Principal Investigator is responsible for all information collected on participants 
enrolled in this study. All data collected during the course of this study must be reviewed 
and verified for completeness and accuracy by the Principal Investigator. A copy of the 
CRF will remain at the study site at the completion of the study.


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15.2 Data Management Procedures
All data for our proposed study will be managed by the UCSF Data Coordinating Center, 
which is housed in the Department of Epidemiology and Biostatistics. This center 
currently serves 25 multicenter cohort and randomized trials throughout the world
The UCSF Department of Epidemiology and Biostatistics complies with federal, state, 
University, and campus electronic information security requirements through a 
combination of physical, technical, procedural, and management controls. At the 
procedural level, all Coordinating Center (CC) personnel sign a confidentiality agreement 
and undergo security awareness training for HIPAA and the handling of sensitive data.
All employees of the University of California, San Francisco were required to obtain 
Security Awareness Training and implement appropriate security measures. New 
employees who use computers must take this training. Remote users of the data also 
receive training from the Data Management Group prior to gaining access to data 
systems.
15.3 Data Quality Control and Reporting
After data have been entered into the study database, a system of computerized data 
validation checks will be implemented and applied to the database on a regular basis. 
Query reports (Data Clarification Requests) pertaining to data omissions and 
discrepancies will be forwarded to the Investigators and study monitors for resolution. 
The study database will be updated in accordance with the resolved queries. All changes 
to the study database will be documented.
15.4 Archival of Data
The database is safeguarded against unauthorized access by established security 
procedures; appropriate backup copies of the database and related software files will be 
maintained. Databases are backed up by the database administrator in conjunction with 
any updates or changes to the database.
The network at UCSF CC is privately maintained, hardware firewalled and none of the 
workstations or database servers can be directly addressed from outside the Local Area 
Network. Website communications are encrypted using an SSL certificate. Network OS 
is Windows Active Directory. Remote access is via SSL-VPN. A network administrator 
and server administrators support the network and servers and the Data Systems Services 
Group (developers/database administrators) support the database and web applications. 
The support team is paged 24/7 when servers or critical data center equipment 
experiences issues.
All study data is housed at the UCSF CC in a secure server room. The building is locked 
outside of normal business hours. All system servers are located in a limited access suite 
fitted with an Access Control System. Within the locked suite is a locked server room 
fitted with an additional secure door. Only critical Information Systems staff possesses 
the access code required to enter the room. All who enter the system server room must 
sign a server room access log in accordance with UCSF CC IT Security SOPs.
Study database access is controlled via two-factor password security. Development 
workstation access is controlled via Microsoft logon. Once a workstation is accessible,


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access to the study data on the SQL server via any development application requires 
appropriate logon-specific permission assigned in SQL Security Manager.
Communication between study servers and client machines on the UCSF network are 
encrypted using an SSL certificate. All servers are protected from viruses by McAfee 
VirusScan. This software automatically checks for virus signature file updates from a 
McAfee FTP site once an hour, and if necessary directly updates itself. All anti-virus 
software is monitored and network personnel notified in the event that the software stops 
functioning on a given server.
All study data are stored on SQL servers managed by the UCSF Coordinating Center. All 
servers are housed in a secure server room.
Web site access: The study web sites are protected by two hardware-based firewalls to 
shape incoming and outgoing traffic. Access to the study management web site is 
restricted to approved personnel only. Approved personnel gain access to the system 
using a multi-layered authentication scheme. A log of all personnel with level of access 
is kept and updated regularly. Once a clinic site user accesses the system they are only 
permitted to view data received from their site, with the exception of official aggregate 
reports. Users are not permitted to view or alter another clinic's data.
Data transmission from web server to client: The UCSF CC currently utilizes Secure 
Socket Layer (SSL) protocol which protects all data transmission sent over the Internet 
between the CC IIS Web Server and every client machine which accesses our study web 
sites.
System Backup
Back-ups: All department workstations and servers are automatically backed-up every 
night. Back-up systems are monitored daily.
Failover Site: As part of the nightly database maintenance procedures, all SQL databases 
are backed up to a "failover" site at our co-location facility. This site has copies of the 
study databases as well as all associated systems required to carry on a study in the event 
of a disaster at the primary location.
Off-site Storage: Network back-ups are written to tape and sent to an off-site vendor 
every two weeks, with tapes being rotated every two months.
Recovery/File Restores: If important files or data from the network are accidentally 
deleted, the IT staff can locate the items and restore data within an hour in most cases.
15.5 Availability and Retention of Investigational Records
The Investigator must make study data accessible to the monitor, IRB, and Regulatory 
Agency (e.g., FDA) inspectors upon request. A file for each participant must be 
maintained that includes the signed Informed Consent, HIPAA Authorization and copies 
of all source documentation related to that participant. The Investigator must ensure the 
reliability and availability of source documents from which the information on the CRF 
was derived.
All study documents (patient files, signed informed consent forms, copies of CRFs, Study 
File Notebook, etc.) must be kept secured for a period of two years following marketing


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of the investigational product or for two years after centers have been notified that the 
IND has been discontinued.
15.6 Participant Confidentiality
In order to maintain participant confidentiality, only a site number, participant number 
and participant initials will identify all study participants on CRFs and other 
documentation submitted to the Sponsor.
16 ADMINISTRATIVE, ETHICAL, REGULATORY CONSIDERATIONS
The study will be conducted according to the Declaration of Helsinki, Protection of 
Human Volunteers (21 CFR 50), Institutional Review Boards (21 CFR 56), and 
Obligations of Clinical Investigators (21 CFR 312).
To maintain confidentiality, all laboratory specimens, evaluation forms, reports and other 
records will be identified by a coded number and initials only. All study records will be 
kept in a locked file cabinet and code sheets linking a patient’s name to a patient 
identification number will be stored separately in another locked file cabinet. Clinical 
information will not be released without written permission of the participant, except as 
necessary for monitoring by the FDA. The Investigator must also comply with all 
applicable privacy regulations (e.g., Health Insurance Portability and Accountability Act 
of 1996, EU Data Protection Directive 95/46/EC).
16.1 Protocol Amendments
Any amendment to the protocol will be written by the study investigators. Protocol 
amendments cannot be implemented without prior written IRB approval except as 
necessary to eliminate immediate safety hazards to patients. A protocol amendment 
intended to eliminate an apparent immediate hazard to patients may be implemented 
immediately, provided the IRBs are notified within five working days.
16.2 Institutional Review Boards and Independent Ethics Committees
The protocol and consent form will be reviewed and approved by the IRB of the 
participating center prior to study initiation. Serious adverse experiences regardless of 
causality will be reported to the IRB in accordance with the standard operating 
procedures and policies of the IRB, and the Investigator will keep the IRB informed as to 
the progress of the study. The Investigator will obtain assurance of IRB compliance with 
regulations.
Any documents that the IRB may need to fulfill its responsibilities (such as protocol, 
protocol amendments, Investigator’s Brochure, consent forms, information concerning 
patient recruitment, payment or compensation procedures, or other pertinent information) 
will be submitted to the IRB. The IRB written unconditional approval of the study 
protocol and the informed consent form will be in the possession of the Investigator 
before the study is initiated. The IRB unconditional approval statement will be 
transmitted by the Investigator prior to the shipment of study supplies to the site. This


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approval must refer to the study by exact protocol title and number and should identify 
the documents reviewed and the date of review.
Protocol and/or informed consent modifications or changes may not be initiated without 
prior written IRB approval except when necessary to eliminate immediate hazards to the 
patients or when the change(s) involves only logistical or administrative aspects of the 
study. Such modifications will be submitted to the IRB and written verification that the 
modification was submitted and subsequently approved should be obtained.
The IRB must be informed of revisions to other documents originally submitted for 
review; serious and/or unexpected adverse experiences occurring during the study in 
accordance with the standard operating procedures and policies of the IRB; new 
information that may affect adversely the safety of the patients of the conduct of the 
study; an annual update and/or request for re-approval; and when the study has been 
completed.
16.3 Informed Consent Form
Informed consent will be obtained in accordance with the Declaration of Helsinki, ICH 
GCP, US Code of Federal Regulations for Protection of Human Participants (21 CFR 
50.25[a,b], CFR 50.27, and CFR Part 56, Subpart A), the Health Insurance Portability 
and Accountability Act (HIPAA, if applicable), and local regulations.
The Investigator will prepare the informed consent form and HIPAA authorization and 
provide the documents to the Sponsor or designee for approval prior to submission to the 
IRB. The consent form generated by the Investigator must be acceptable to the Sponsor 
and be approved by the IRB. The written consent document will embody the elements of 
informed consent as described in the International Conference on Harmonisation and will 
also comply with local regulations. The Investigator will send an IRB-approved copy of 
the Informed Consent Form to the Sponsor (or designee) for the study file.
A properly executed, written, informed consent will be obtained from each participant 
prior to entering the participant into the trial. Information should be given in both oral 
and written form and participants must be given ample opportunity to inquire about 
details of the study. A copy of the signed consent form will be given to the participant, 
and the original will be maintained with the participant’s records.
16.4 Publications
The publication or presentation of any study results shall comply with all applicable 
privacy laws, including, but not limited to, the Health Insurance Portability and 
Accountability Act of 1996.
16.5
Investigator Responsibilities
By signing the Agreement of Investigator form, the Investigator agrees to:
1.
Conduct the study in accordance with the protocol and only make changes after 
notifying the Sponsor (or designee), except when to protect the safety, rights or 
welfare of participants.
2.
Personally conduct or supervise the study (or investigation).


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3.
Ensure that the requirements relating to obtaining informed consent and IRB review 
and approval meet federal guidelines, as stated in § 21 CFR, parts 50 and 56.
4.
Report to the Sponsor or designee any AEs that occur in the course of the study, in 
accordance with §21 CFR 312.64.
5.
Ensure that all associates, colleagues and employees assisting in the conduct of the 
study are informed about their obligations in meeting the above commitments.
6.
Maintain adequate and accurate records in accordance with §21 CFR 312.62 and to 
make those records available for inspection with the Sponsor (or designee).
7.
Ensure that an IRB that complies with the requirements of §21 CFR part 56 will be 
responsible for initial and continuing review and approval of the clinical study.
8.
Promptly report to the IRB and the Sponsor (or designee) all changes in the research 
activity and all unanticipated problems involving risks to participants or others (to 
include amendments and IND safety reports).
9.
Seek IRB approval before any changes are made in the research study, except when 
necessary to eliminate hazards to the patients/participants.
10. Comply with all other requirements regarding the obligations of clinical investigators 
and all other pertinent requirements listed in § 21 CFR part 312.


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Protocol Template © CFFT TDN Effective: 12 SEP 2007
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ICF_001.pdf: 
HIV methamphetamine study 
Prepared 06/20/2021
PAGE 1 OF 15
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO 
SAN FRANCISCO GENERAL HOSPITAL
CONSENT TO PARTICIPATE IN A RESEARCH STUDY
EMRLHD (Effect of Methamphetamine on Residual Latent HIV Disease) Study
This is a medical research study sponsored by the National Institutes of Health (National 
Institute on Drug Abuse). Your study doctor, Dr. Sulggi Lee, MD, or a member of her 
research team will explain this study to you.
Medical research studies include only people who choose to take part. You should take 
your time to make your decision about participating. You may discuss your decision with 
your family and friends and with your health care team. If you have any questions, you 
may ask your study doctor.
You are being asked to take part in this study because:
•
you have HIV infection
•
you are ≥ 18 years and ≤ 65 years of age
•
you are currently and have been taking antiretroviral therapy (ARVs) that include at least 3 drugs 
for at least the last 12 months (with no ARV changes in the last 12 weeks)
•
you have had an undetectable HIV viral load for at least 12 months
•
you will not be modifying your ARVs during the study period (146 days, approximately 5 months)
•
you and your partner(s) are willing to use two forms of contraception throughout the study period 
as well as up to 60 days after the last day of study completion
•
you do not have a current or past history of methamphetamine use disorder that could put you at 
risk of potential return to use by participating in this study
•
you are available to participate in the full study which includes 2 study treatment phases, spaced 
approximately 1 month apart for a total of about 146 days (approximately 5 months)
•
you are not currently using methamphetamine or any prescription medications containing 
amphetamine-type stimulants (e.g., Adderall®, Dexedrine®, Ritalin®, etc.) within the last 1 year
•
you do not have an allergy or sensitivity to amphetamine-like stimulants
•
you have not used any other “psychoactive” drugs (cocaine, ecstasy, LSD, mushrooms, or other 
recreational drugs) in the last 1 month, but nicotine/tobacco, cannabis/marijuana or caffeine do 
not count
•
you have not used any illicit opioids such as heroin or fentanyl in the past 3 months – but 
prescription opioid treatments with known prescribed doses such as methadone, hydrocodone 
(Norco®), buprenorphine/naloxone (Suboxone®), oxycodone (Oxycontin®), or hydromorphone 
(Dilaudid®) are ok
•
you have not recently used in the last month any medications that could potentially have a drug 
interaction with oral methamphetamine (e.g., an anti-depressant called a monoamine oxidase 
inhibitor)
•
you have not had a recent hospitalization or serious infection requiring intravenous antibiotics in the 
last 90 days
•
you are not anemic (HIV+ males Hct < 34; females Hct < 32) or contraindication to donating blood.
•
you do not a screening hemoglobin below 12.5 g/dL
•
you do not have a history of poorly controlled high blood pressure or a systolic blood pressure >140 
(after repeat measurement) in the last 3 months
•
you do not have significant myocardial disease (e.g., current myocarditis or reduced left ventricular
IRB NUMBER: 18-26765
IRB APPROVAL DATE: 02/03/2022
IRB EXPIRATION DATE: 02/02/2023


HIV methamphetamine study 
Prepared 06/20/2021
PAGE 2 OF 15
ejection fraction below the lower limit of normal) or diagnose coronary artery disease.
•
you do not have a prior history of heart attack or heart disease
•
you do not have an abnormal heart rhythm that needs to be medically treated
•
you do not have a history of psychosis (e.g., hallucinations –seeing or hearing things that are not 
there) in the past 3 months
•
you do not have a history of seizures, brain damage, or abnormal brain electrical activity (on 
electroencephalogram) in the past 3 months or currently taking anti-seizure medications
•
you do not have significant history of respiratory disease requiring oxygen
•
you do not have a recent history of receiving any drugs that modify the immune system in the 12 
weeks prior to study
•
you are not pregnant
•
you have not had a recent vaccination within the last 2 weeks
Why is this study being done?
This is a medical research study where we will be giving oral methamphetamine 
(Desoxyn®) to study participants for a single day, split into two doses. The total dose that 
you will receive in that single day is no more than the FDA allows children to take for the 
treatment of obesity.
This study is being done in HIV-infected individuals who have excellent control of their HIV 
in order to see if oral methamphetamine temporarily increases low levels of HIV RNA and 
levels of “activated” immune cells. Findings from this study may help identify ways to force 
persistent virus out of the body in order to achieve an HIV cure and reduce potential 
negative immune effects in HIV+ patients who use methamphetamine.
What will happen if I am in the study?
If you are in the study you will be given only one day of study medication. You will also be 
given one day of “placebo,” or a pill that looks like the study medication but contains no 
active substance. After each treatment day (study medication or placebo) you will be 
followed for up to 31 days to study your body’s response to the pill. In addition, the two 
treatment phases will be separated by 31 days to ensure that there is enough time for 
your body to “wash out” study medication (or placebo) and compare to the other 
treatment.
The timing of when you will receive the study medication or placebo will be randomly 
determined, like the toss of a coin. You will not know whether you are randomly assigned 
to receive the study medication first or second.
This is an open-label study, so even though you will not know when you will receive the 
study medication, you will know what dose of the study medication you are given. You will 
receive 10 milligrams of the study medication, followed by 15 milligrams of the study 
medication given 2 hours later, for a total dose of 25 milligrams of the study medication on 
the treatment day.
We will be monitoring any side effects to be sure that any side effects experienced during 
the study period is due to the study drug and not to other causes. In addition, based on 
what we know about potential drug-drug interactions between the study medication and 
HIV medications or other medications, you can only continue taking medically necessary 
medications that can be monitored during the study period. If you feel you cannot do this 
then you cannot enroll in this study.
Who is paying for this study?
IRB NUMBER: 18-26765
IRB APPROVAL DATE: 02/03/2022
IRB EXPIRATION DATE: 02/02/2023


HIV methamphetamine study 
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PAGE 3 OF 15
This study is sponsored by the National Institutes of Health (National Institute on Drug 
Abuse). The company that makes the study medication for this study is not involved in this 
research.
How many people will take part in this study?
The study is being done in San Francisco, California. A total of 10 adults who are living 
with HIV will be enrolled in this study at UCSF.
Where will I be seen for this study?
All study visits will take place at the Positive Health Program HIV/AIDS Clinic, Building 80, 
Wards 84/86, 995 Potrero Avenue, San Francisco or at the CTSI Clinical Research 
Center, Ward 5B, 1001 Potrero Avenue, San Francisco. Both clinics are at San Francisco 
General Hospital.
How long will I be in this study?
The whole study will last up to 146 days. Treatment phase 1 will include one dosing day 
(when you receive study medication or placebo), plus 31 days of follow up. Treatment 
phase 1 will be followed by a 31-day “washout” period to make sure that the effects of 
treatment 1 is no longer in your body by the time you receive Treat 2. The washout period 
is also to ensure that you do not become anemic from too many blood draws during the 
entire 146 days of the study. Then you will receive treatment phase 2, which includes one 
dosing day (when you receive placebo or study medication, the opposite of what you 
received during treatment phase 1), plus 31 days of follow up. Your final visit will be 132 
days after the first dose.
1st Treatment Phase 
Screening Period 
(14 Days)
1st Treatment Phase: 
Study Med OR 
Placebo
Washout Period 
(31-Days)
2nd Treatment Phase 
Screening Period 
(14 Days)
2nd Treatment Phase: 
Placebo OR Study 
Med
End of 
Study
IRB NUMBER: 18-26765
IRB APPROVAL DATE: 02/03/2022
IRB EXPIRATION DATE: 02/02/2023


HIV methamphetamine study 
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PAGE 4 OF 15
What are my responsibilities?
Your participation in the full 146 days (approximately 5 months) of the study is critical to 
understand the effect of the study medication. It is very important during the entire study 
that you remain fully adherent to your HIV medications and do not use illicit substances or 
medications that would exclude you from participating in the remainder of the study. This 
is the reason that we perform a second screening visit at the beginning of Treatment 
phase 2. If you anticipate scheduling conflicts or problems in attending visits, you should 
notify the study doctor.
Detailed Summary of Study Visits:
Screening Visit (Day -14) 
If you agree to participate in this study you will be asked to have a screening examination at the research clinic. 
The screening will take approximately 1.5 hours. During the screening visit:
•
You will have a complete physical examination, which will be conducted by one of the study medical staff 
to determine your health status.
•
Your medical history will be documented.
•
You will be asked to complete applicable HIV-related questionnaires that will ask for questions about your 
current and previous health, illnesses, HIV-treatment, medications, and lifestyle.
•
You will also be asked to provide blood samples to check your health. Included will be tests for CD4 T-cell 
count, HIV viral load, blood count including hemoglobin, hepatitis B and C antibody, tuberculosis 
exposure, and liver, thyroid, and kidney functions.
•
You will also beasked to provide a urine sample to check tobe sure that you are still eligible for this study 
and have not recently used any of the substances that would exclude you from participating in the study.
•
If you are a woman and you are capable of having children, a serum pregnancy testwill be performed. If 
this test is positive, you will not be allowed to enter the study since body changes occurring during 
pregnancy will alter the study results. You also agree to use a double-barrier method of contraception 
throughout the study period.
•
You will be asked a series of extensive questions regarding any current symptoms.
The results of the screening evaluation will be reviewed to determine if you are eligible to participate in the study 
and you and your primary care provider will be notified of all your screening bloods results. Given the potential 
for changes in some of the laboratory measurements based on what time of day that you blood is drawn, it is 
critical that this blood draw will occur between 7:30 to 9:30 am.
Baseline Visit #1 (Day -7)
If you are eligible, you will return for a baseline visit. The same questionnaires that you completed at the Screening 
Visit will be repeated. Blood will be drawn and stored at this visit. Given the potential for changes in some of the 
laboratory measurements based on what time of day that you blood is drawn, it is critical that this blood draw will 
occur between 7:30 to 9:30 am. In addition, if you agree to provide an optional hair sample and have at least 1 
inch of hair, a small thatch of hair (~300 fibers of hair) at the back of your head will be cut close to the scalp to 
measure the amount of HIV medications that you have been taking for approximately the last 90 days. We will 
also use thehair to measure for any potential substances that might exclude you from participating in the study. 
As at the screening visit, urine will also be collected to similarly ensure that you have not had any recent use of 
the substances that might exclude from participating in the study.
IRB NUMBER: 18-26765
IRB APPROVAL DATE: 02/03/2022
IRB EXPIRATION DATE: 02/02/2023


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Treatment Phase #1 Day 1 Visit
Following randomization the first dose (the study medication or placebo) will be given on Day 1. Because the effect 
of the study medication on your virus is expected to be rapid and transient, you will be seen several times during 
the day on the Day 1 Visit. Given the potential for changes in some of the laboratory measurements based on 
what time of day that you blood is drawn, it is critical that this first blood draw on the treatment day occurs 
between 7:30 to 9:30 am. A urine sample will again be collected to ensure that you are still eligible for this study 
and have not recently used any of the substances that would exclude you from participating in the study.
You will have a brief physical examination and will be asked whether there has been any change in your health 
(illness or health problems) and whether you have taken any new medications since your last visit. In addition, 
an electrocardiogram (ECG) will be performed to evaluate for any abnormal electrical activity in your heart. This will occur at 
0, 2, and 4 hours after you take the initial pill. You will be asked to complete a shortened version of the 
questionnaires you completed previously. A blood draw will be completed before the first dose is given. This 
blood will be used to monitor general health screening tests. A urine sample will again be collected to ensure that 
you are still eligible forthis study and have not recently used any of the substances that would exclude you from 
participating in the study. Blood will also be used to determine the amount of HIV in your blood (viral load) and 
the amount of white blood cells that fight infection (CD4 count). Blood will also be collected for study-specific 
tests including teststo measure theamount of HIV that remains in your body (even while taking HIV medications 
every day) and levels of inflammation in your body that might be caused by HIV.
Aftertheseblood tests are obtained, you will be asked totake the study medication with a glass of water. Forthe 
study medication phase of the study, you will first receive 10 mg of the study medication at “hour 0” at the time 
of your first blood draw. You will then receive your second dose of the study medication (15 mg) at “hour 2.” Your 
blood will be drawn at 5 timepoints on this day: 0, 0.5, 2, 2.5, and 4 hours after you take the initial pill. These 
frequent tests are being done as it is expected that the study medication’s effect may be rapid and transient. You 
will be asked to stay at the study clinic for the entire visit and will be done with the treatment day approximately
1 hour after the last blood draw. The study medication will be measured in both blood and urine.
Treatment Phase #1 Day 2 Visit
You will return to the clinic for the Day 2 Visit. Given the potential for changes in some of the laboratory 
measurements by the time of day at which blood is drawn, it is critical that this blood draw will occur between 
7:30 to 9:30 am. At this visit, you will have a single timepoint blood collection complete to monitor routine 
laboratory tests and to determine how much virus is in your body. A urine sample will be collected at this visit to 
measure methamphetamine levels after being administered the study medication (or placebo) dose the day prior. 
You will also have a brief physical exam, collection of vitals, health and medication questions, and completion 
of follow-up questionnaires.
Treatment Phase #1 Day 31 Visit
You will return to the clinic 31 days from the first day of the treatment cycle. No Study medication will be given 
on this day. You will have a brief physical examination, will be asked if there has been any change in your health 
(illness or health problems), if you have missed any of your antiretroviral medications, and whether you have 
taken any new medications since your last visit. You will again complete the shortened version of the 
questionnaires you completed previously. You will have a single timepoint blood collection completed to monitor 
routine laboratory tests and to determine how much virus is in your body. Given the potential for changes in some 
of the laboratory measurements by the time of day at which blood is drawn, it is critical that this blood draw will 
occur between 7:30 to 9:30 am. A urine sample will again be collected to ensure that you are still eligible for this 
study and have not recently used any of the substances that would exclude you from participating in the study.
Washout Period (Day 32-62)
The washout is a 31-day period in which any effects from the first phase can resolve and return you to your pre-
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IRB APPROVAL DATE: 02/03/2022
IRB EXPIRATION DATE: 02/02/2023


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study baseline state. No study procedures are completed during this period, but it is important that you continue 
to follow and maintain the list of inclusion criteria shown on page 1 in order to remain eligible for the remainder 
of the study.
Baseline Visit #2 (Day 63) 
The same procedures completed on the Day -14 Screening Visit prior to the first phase (described earlier) will be 
completed in preparation for the second phase.
Treatment Phase #2 Visits: Day 77 and 24-Hour Follow-up (Day 78)
The same procedures that occurred on the Day 1 Visit from Phase 1 (described earlier) will occur in Phase 2 as the 
Day 77 and 78 Visits, respectively.
Treatment Phase #2 Day 107 Follow-up Visit
The same procedures completed on the Day 31 Follow-up Visit from Phase 1 (described earlier) will be completed 
for the second phase. This is the final study visit.
Early Withdrawal Visit
You may discontinue the study or be withdrawn from the study at any time if you, the study doctor, or the study 
sponsor feels that it is not in your best interest to continue. The following is a list of possible reasons for study 
treatment discontinuation:
•
You choose to withdraw consent and stop study participation. This is discussed in further detail later.
•
The study doctor thinks it necessary for your health or safety
•
You have not followed study instructions.
•
The sponsor decides to stop the study.
•
If you are a female of childbearing potential and have a positive pregnancy test or start breastfeeding.
For any early withdrawal from the study, you will be asked to return to the clinic for an Early Withdrawal Visit as 
soon as possible. At the visit you will receive a complete physical examination, vitals will be collected, medication 
use will be reviewed, the follow-up questionnaires will be administered, and any changes to your health will be 
discussed. A blood sample will be collected for clinical laboratory tests, to check your health, and to measure the 
amount of HIV in your body. Blood will be used to monitor routine laboratory tests and to determine how much 
virus is in your body.
If you are withdrawn from treatment due to a side effect or adverse event, you will be followed and treated by 
the study doctor until the abnormal condition or symptom has resolved or stabilized. Except in the event of 
withdrawal of consent, you will be asked to complete all remaining scheduled visits and procedures.
What will happen with your blood samples?
Blood will also be sent for routine safety monitoring at most visits. HIV “viral load” and CD4+ T cell 
counts, liver and kidney function will be measured at many visits.
By consenting to participate in this study, you consent to the storage of some of your blood 
samples. As part of this study, a portion of the blood obtained at some of the study visits will be 
stored at the UCSF AIDS Specimen Bank and/or the ARI Clinical Laboratory of Virology. Stored 
specimens will be sent directly to a research laboratory and/or stored for future research studies. 
The specimens stored for future use will be coded. This code will be kept confidential and only Dr. 
Lee and her research collaborators will have access to these specimens and key linking them to 
the study participants.
IRB NUMBER: 18-26765
IRB APPROVAL DATE: 02/03/2022
IRB EXPIRATION DATE: 02/02/2023


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Future studies using your specimens may be performed by scientists based at the University of 
California, San Francisco and/or by scientists based at other institutions, such as other 
universities, the NIH and commercial laboratories. All efforts to minimize personally identifying 
information will be carried out. No personal identifiers will be kept with your sample or shared 
with other researchers. The possible typesof studies which may be performed include tests for 
infections that are common in HIV-infected patients such as cytomegalovirus or human 
herpesvirus 8, genetic testing, as well as new tests measure the amount of “latent” HIV reservoir 
(the very low amounts of virus that remain in your body despite you taking antiretroviral therapy 
and having “undetectable” viral loads on your clinical labs).
If you agree, any information obtained from the laboratory studies that may be important for your 
clinical care will be shared with you and/or your primary care provider, but research-related 
results that are currently unimportant to your clinical care will not be shared with you, as they are 
exploratory in nature. Specimens will be kept until they are used up or destroyed For the current 
study, the following research tests may be performed: (1) the activation level of your T cells, (2) 
the amount of HIV in your blood, and (3) the amount of HIV in your cells. Other tests related to 
this study, which are unknown at this time, may be performed. Results from the research 
performed on these samples for this study and/or future studies will not be shared with you, as 
they are experimental in nature. However, you can receive results of standard laboratory tests 
performed by the study, such as CD4+ T cell counts, routine HIV viral load tests, etc.
Donating data may involve a loss of privacy, but information about you will be handled as 
confidentially as possible. Study data will be physically and electronically secured. As with any use 
of electronic means to store data, there is a risk of breach of data security.
There will be no direct benefit to you from allowing your data to be kept and used for future 
research. However, we hope we will learn something that will contribute tothe advancement of 
science and understanding of health and disease. If the data or any new products, tests or 
discoveries that result from this research have potential commercial value, you will not share in 
any financial benefits. If you decide later that you do not want your information to be used for 
future research, you can notify the investigator in writing (sulggi.lee@ucsf.edu or 995 Potrero 
Avenue,Building80,Box0874,SanFrancisco,CA94110),andanyremainingspecimensanddata 
will be destroyed. However, we cannot retract any data has been shared with other researchers.
Can I stop being in the study?
Your participation in this study is voluntary. If you do participate, you may freely withdraw from 
the study at any time. Your decision will not change your future medical care at any of the study 
sites or at the San Francisco General Hospital.
Your participation in this study may be stopped at any time by the study doctor or the sponsor 
without your consent. The reasons might include:
•
the study doctor thinks it necessary for your health or safety; you have not followed study 
instructions;
•
the sponsor has stopped the study; or administrative reasons require your withdrawal.
If you leave the study before thefinal regularly scheduled visit, you may be asked by the study 
doctor to make a final visit for some of the end of study procedures.
IRB NUMBER: 18-26765
IRB APPROVAL DATE: 02/03/2022
IRB EXPIRATION DATE: 02/02/2023


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What if I become pregnant during this study?
You should not become pregnant or father a baby while on this study, because the study medication 
may affectan unbornbaby. If you are a woman and you are capable of havingchildren, apregnancy 
test will be performed. If this test is positive, you will not be allowed to enter the study. Women 
should not breastfeed a baby while on this study. It is important to understand that you need to use 
birth control while on this study. You must agree to use at least two effective methods of 
contraception throughout the study period and up to 90 days after the last dose of study treatment. 
Since there are limited data on pregnancy risk related to methamphetamine given for a 
single day at the FDA-approved pediatric daily dose, we will take precautions around 
potential pregnancy during the trial. 
If a participant is able to become pregnant, two of the following forms of birth control are required, 
one of which must be condoms or a diaphragm or cervical cap:
•
Condoms (male of female) with or without a spermicidal agent
•
Diaphragm or cervical cap with spermicide
•
Intrauterine device (IUD) – this must be a brand that has a reported failure rate is < 1% per 
year
•
Tubal ligation
•
Hormone-based contraceptive such as oral birth control pills
If you are a female and become pregnant during the clinical trial, you are advised:
•
To call/notify the study doctor immediately
•
To consult an obstetrician or maternal-fetal specialist
•
You will not be given any additional investigational products
•
You will be followed to determine the pregnancy outcome
If you are a male who is sexually active with a woman capable of becoming pregnant, you must 
agree to use a medically accepted form of birth control during the course of this research study. You 
must inform your partner of the potential harm to an unborn child. Your partner needs to know 
that if she does become pregnant during the study:
•
You will need to call/notify the study doctor immediately
•
She will need to consult an obstetrician or maternal-fetal specialist
•
Study staff will ask for her permission to collect information about the pregnancy and the 
health of the baby. This includes information related to the pregnancy/delivery and 
obstetrical history.
If you or your partner become pregnant while on study, you must tell the study staff right away 
and stop taking the study medication. You (or your partner) should also see your doctor to 
get the best care possible. You may remain on study during your pregnancy or you may leave 
the study. Either way, the study staff will contact you to find out about any events that happen 
during the pregnancy and about the health of the baby.
What side effects or risks can I expect from being in the study?
If you decide to participate in this study, you will receive the study medication for 1 d a y . 
You will be required to remain on your stable antiretroviral regimen throughout the study. 
Below is a description of most of the side effects that may occur during this study, but not all 
possible side effects.
What are potential risks and discomforts from participating in the study?
Side effects associated with taking the study medication 
Likely to occur:
IRB NUMBER: 18-26765
IRB APPROVAL DATE: 02/03/2022
IRB EXPIRATION DATE: 02/02/2023


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•
Oral methamphetamine is a stimulant and may cause increased blood pressure, heart rate, 
and palpitations (noticeably rapid, strong, or irregular heartbeats).
Less likely to occur:
IRB NUMBER: 18-26765
IRB APPROVAL DATE: 02/03/2022
IRB EXPIRATION DATE: 02/02/2023


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•
In some cases, oral methamphetamine can cause some dizziness, headache, insomnia, 
elevated mood, depressed mood, restlessness, diarrhea, constipation, unpleasant taste, dry 
mouth, and tremor (hands shaking).
Very unlikely to occur:
•
At very high doses (much higher than the doses being given in this study) and if taken for 
prolonged periods of time (e.g., weeks to months to years), oral methamphetamine can lead 
to a substance use disorder, exacerbation of preexisting abnormal movements (called “tics”), 
psychotic symptoms (hearing and seeing things that are not actually there), frequent 
erections, impotence, and changes in libido.
•
Long-term effects that cannot be known
Sideeffects associated with taking Placebo 
Very unlikely tooccur:
•
In order to make the placebo appear similar tothe study medication, the pills will be crushed 
and placed in a capsule. For the placebo phase, cornstarch will be placed inside the capsule. 
Therefore, individuals who have an allergy to cornstarch may be at risk of an allergic reaction 
when taking placebo and should notify the study investigator if theyhave a known allergy to 
corn starch.
Wewill be monitoring your response tothe study drug very closely. Intheevent of a serious 
adverse event, we will provide you appropriate medical care immediately.
HIV viral load and resistance to antiretroviral therapy risks
•
We will be measuring the amount of viral RNA that increases in your blood after giving 
you the study drug. This does not necessarily mean that there is an increase in the 
amount of circulating HIV. Nonetheless, since there is a very small chance that the study 
drug might transiently increase you HIV viral load, there would be a theoretical risk of 
developing resistance to antiretroviral therapy and of transmitting HIV to uninfected 
persons if you were not on a stable regimen and adequately suppressed on your ARVs. 
The likelihood of this is extremely low, given that you will only be given one day of a single 
day’s maximum (child) dose of the study medication, and if the study medication causes 
your viral load to increase, the predicted increases in HIV in theblood is extremely small. 
For these reasons, you can only participate in this study if there are alternate ART 
regimens available in the rare event that your current ART regimen is compromised asa 
result of this study. During the study, you will also have your HIV viral load followed 
closely (at screening, baseline, and on days 2, and 31 of each treatment arm).
Drug-drug interactions
•
The following medications are not allowed during the study because of potential 
interactions with the study medication: acebrophyline, iobenguane, isocarboxazid, 
methylene blue, moclobemide, phenylzine, procarbazine, rasagiline, safinamide, 
selegiline, tranylcypromine, asunaprevir, buproprion, topical cocaine, fluoxetine, iohexol, 
linezolid, paroxetine, potassium citrate, quinidine, sodium bicarbonate, sodium citrate, 
sodium lacate, tipranavir, and tromethamine. This is because the study medication may 
alter metabolism of the drugs.
Side effects of taking your blood sample (phlebotomy) 
Likely to occur:
•
Drawing blood from a vein may cause some discomfort, bleeding or bruising where the needle
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enters the skin, and rarely, fainting or infection may occur. Up to a total of 795 milliliters 
(about 53 tablespoons) will be collected during the course of this study, and the maximum 
volume of blood per visit will be 52 milliliters, all of which has been carefully calculated over 
the 146 days of the study to ensure that your blood levels are not below American Red Cross 
Guidelines.
Less likely to occur:
•
Less common symptoms include lightheadedness, dizziness, fainting and nausea. Symptoms of 
anemia include tiredness, weakness and dizziness. You will be checked for anemia at all visits 
from screening through day 31 of each treatment arm. If the investigator feels that you are at 
significant risk for anemia, the amount of blood collected will be reduced. If your hemoglobin 
falls below 10 g/dl or your hematocrit falls below 27%, you will have 5 ml (1 teaspoon) of 
blood drawn to check your hemoglobin and hematocrit. Other than the blood required to 
check your hemoglobin and hematocrit, you will not have more blood drawn until your 
hemoglobin rises above 10 g/dl or your hematocrit rises above 27%
We will measure your baseline hemoglobin to ensure that it is safe for you to participate in 
this study. In order to participate in this study, your baseline hemoglobin must be >12 g/dl. You 
should know that the prediction of side effects in any individual cannot be done with certainty and 
unexpected potentially harmful effects occasionally occur with the administration of any type of drug 
or study procedure. If serious side effects occur, the study will be stopped.
Confidentiality
Participation in research may involve a loss of privacy; however, your records will be handled as 
confidentially as possible. All study questionnaires and research samples will be coded with a 
study ID. No personal identifiers such as your name will be used for stored specimens. Dr. Lee and 
the research staff as well as the UCSF Institutional Review Board will have access to your study 
records and test results. In addition, your records may be inspected by the Research Advisory 
Panel of California. No individual identities will be used in any reports or publications that may 
result from this study. California regulations require laboratories to report new cases of 
tuberculosis, hepatitis B, and hepatitis C infection to the county public health department. The 
reports include the patient’s name, social security number, and other identifying information.
Information about these new infections is used to track these diseases statewide and nationwide. 
Other than this required reporting, your results will be treated confidentially by the study staff. 
Personally identifying information will not be reported to other departments or agencies.
Are there benefits to taking part in the study?
This study will not provide you with any direct benefit. It is hoped that this study will help learn 
how to reduce the total amount of HIV in the body, but this may not happen. This study will not 
result in a cure.
What other choices do I have if I do not take part in this study?
The alternative to this study is to choose not to participate.
Will my medical information be kept private?
Records of this study will be kept confidential and you will not be identified in any written or 
verbal reports with the following possible exceptions. Your records may be inspected by the 
UCSF Institutional Review Board (IRB), which is a committeethat watches over the safety and 
rights of research subjects or the Food and Drug Administration (FDA) if required for an internal 
audit, National Institute of Health (NIH), Office of Human Research Protections (OHRP). Your 
confidentiality will be protected in accordance with applicable research practice. All research 
records will be kept in locked files located within locked rooms to which only study staff have
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access and/or within limited access, computer files available only to investigators and study 
personnel. Your name will be removed from all research study records. Only initials and code 
numbers will be present on study records and documents. Any publication or presentation of 
study results will not identify you by name. A medical record is created when you are admitted 
to the Clinical Research Center at San Francisco General Hospital. This record will have 
personally identifying information in it, but will be kept confidential, as would any hospital 
medical record.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by
U.S. Law. This Web site will not include information that can identify you. At most, the Web site will 
include a summary of the results. You can search this Web site at any time.
Participation in research can cause a loss of privacy. In this study you will be asked about 
drug use and other possibly illegal activities. The researcher will keep information about you 
as confidential as possible, but complete confidentiality cannot be guaranteed. On rare occasions, 
research records have been subpoenaed by a court.
What are the costs of taking part in this study?
There are no charges for the study visits. Any laboratory tests and visits required by the study 
will be provided at no cost to you. You will receive the study drug free of charge. Neither you nor 
your insurance company will be responsible for any study-associated costs.
Will I be paid for taking part in this study?
Yes. You will be paid for each visit. If you are eligible for this study and choose to 
participate, in return for your time, effort, and travel expenses, you will be paid $35 in cash or 
with amazon e-code at the completion of each standard study visit. If you agree to the optional 
hair collection, you will be paid $25 in cash or amazon e-code for a small sample of hair 
collected at the baseline 1 and 2 visits only. Due to the length of time required for the study 
medication (and placebo) dosing days, for these visits you will be paid $150 (as amazon e- 
code or as $50 in cash and $100 by check) at the completion of each (the study medication or 
placebo administration phase) day and also be provided with a meal and refreshments.
This is atotal of up to $630 forcompletionof all study visits. We will need your social security 
number to report the income to the Internal Revenue Services if the total amount of 
research compensation for the study exceeds $600 in one calendar year.
What happens if I am injured because I took part in this study?
It is important that you tell the study doctor, Dr. Sulggi Lee, if you feel that you have been injured 
because of taking part in this study. You can tell the doctor in person or call her at (415) 735- 
5127.
Treatment and Compensation for Injury: If you are injuredas a result of being inthis study, the 
University of California will provide necessary medical treatment. The costs of the treatment may be 
billed to you or your insurer just like any other medical costs, or covered by the University of 
California, depending on anumber of factors. The Universitydoes not normallyprovide any other 
form of compensation for injury. For further information about this, you may call the UCSF 
Institutional Review Board at 415- 476-1814.
What are my rights if I take part in this study?
Taking part in this study is your choice. You may choose either to take part or not to take part in 
the study. If you decide to take part in this study, you may leave the study at any time. No
IRB NUMBER: 18-26765
IRB APPROVAL DATE: 02/03/2022
IRB EXPIRATION DATE: 02/02/2023


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matter what decision you make, there will be no penalty to you and you will not lose any of your 
regular benefits. Leaving the study will not affect your medical care. You can still receive your 
medical care from our institution.
We will tell you about new information or changes in the study that may affect your health or 
your willingness to continue in the study.
In the case of injury resulting from this study, you do not lose any of your legal rights to seek 
payment by signing this form.
Who can answer my questions about the study?
In the future, you may have questions about your study participation. You may also have 
questions about a possible side effect, reaction to study medication, or a possible research- 
related injury. If you have any questions, please contact Dr. Lee (the study investigator) at phone:
(415) 735-5127, email: sulggi.lee@ucsf.edu
For questions about your rights while taking part in this study, you can call the UCSF 
Institutional Review Board (a group of people who review the researchto protect your rights) 
can be reached at (415) 476-1814.
Do not sign this consent form unless you have had a chance to ask questions and have 
received satisfactory answers to all of your questions.
IRB NUMBER: 18-26765
IRB APPROVAL DATE: 02/03/2022
IRB EXPIRATION DATE: 02/02/2023


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CONSENT
You have been given copies of this consent form and the Experimental Subject's Bill of Rights to 
keep. PARTICIPATION IN RESEARCH IS VOLUNTARY. You have the right to decline to participate 
or to withdraw at any point in this study without penalty or loss of benefits to which you are 
otherwise entitled.
You will be asked to sign a separate form authorizing access, use, creation, or disclosure of 
health information about you.
I have read this information, which is printed in English. This is a language that I read and understand.
Participant Name, printed
Participant Signature
Date
SignatureofPersonConductingInformedConsentDiscussion
Date
CONSENT FOR GENETIC TESTING
Genetic information (also known as genotype data) and the medical record data (also known as 
phenotype data) may be shared broadly in a coded form for future genetic research or analysis. 
We may give certain medical information about you (for example, diagnosis, blood pressure, age if 
less than 85) to other scientists or companies not at UCSF, including to a public government 
health research database, but we will not give them your name, address, phone number, or any 
other identifiable information. Research results fromthese studies will not be returned to you, as 
they are exploratory in nature. Results of this testing will not be available to you or your 
providers, just to the researchers in the study.
Genetic information that results from this study does not have medical or treatment importance 
at this time. However, there is a risk that information about taking part in a genetic study may 
influence insurance companies and/or employers regarding your health. Taking part in a genetic 
study may also have a negative impact or unintended consequences on family or other 
relationships. It is possible that future research could one day help people of the same race, 
ethnicity, or sex as you. However, it is also possible throughthese kinds of studies that genetic 
traits might come to be associated with your group. In some cases, this could reinforce harmful 
stereotypes.
Please indicate below if you do not agree to genetic testing on the sample collected for 
this study.
 
(initials) YES, I agree
 
(initials) NO, I do not agree
CONSENT FOR HAIR SAMPLE COLLECTION
Drug levels in hair samples can tell research investigators how much medication gets into a 
person’s body. For this study, you will be asked to have a small sample of hair (about 200 strands)
IRB NUMBER: 18-26765
IRB APPROVAL DATE: 02/03/2022
IRB EXPIRATION DATE: 02/02/2023


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cut from your head so that we can measure levels of HIV drugs inthis small hair sample. Levels in 
hair may give us a better idea of long-term exposure to a drug. Of note, humans lose about 100 
hairs fromtheir head every day naturally so this amount of hair removal should not be noticeable. 
There is a small chance of cutting or nicking the scalp from the cutting of the hair sample. This 
process will not be disruptive to your hairstyle. Results of this testing will not be available to you 
or your providers, just to the researchers in the study.
Please indicate below if you do not agree to have a small amount of your hair collected for this 
study.
 
(initials) YES, I agree
 
(initials) NO, I do not agree
CONSENT FOR URINE SAMPLE COLLECTION
Drug levels in urine samples can tell research investigators how much medication gets into a 
person’s body over the past few days. For this study, you will be asked to provide a urine sample 
at each study visit so that we can measure levels of drugs, including methamphetamine, cocaine, 
marijuana, and opioids. Results of thistestingwill not be available to you or your providers, just to 
the researchers in the study.
Please indicate below if you do not agree to have urine collected for this study.
 
(initials) YES, I agree
 
(initials) NO, I do not agree
IRB NUMBER: 18-26765
IRB APPROVAL DATE: 02/03/2022
IRB EXPIRATION DATE: 02/02/2023


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UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
EXPERIMENTAL SUBJECT'S
BILL OF RIGHTS
The rights below are the rights of every person who is asked to be in a research study. As an 
experimental subject I have the following rights:
1)
To be told what the study is trying to find out,
2)
To be told what will happen to me and whether any of the procedures, drugs, 
or devices is different from what would be used in standard practice,
3)
To be told about the frequent and/or important risks, side effects, or discomforts of 
the things that will happen to me for research purposes,
4)
To be told if I can expect any benefit from participating, and, if so, what the benefit 
might be,
5)
To be told of the other choices I have and how they may be better or worse than 
being in the study,
6)
To be allowed to ask any questions concerning the study both before agreeing to 
be involved and during the course of the study,
7)
To be told what sort of medical treatment is available if any complications arise,
8)
To refuse to participate at all or to change my mind about participation after the 
study is started. This decision will not affect my right to receive the care I would 
receive if I were not in the study,
9)
To receive a copy of the signed and dated consent form,
10)
To be free of pressure when considering whether I wish to agree to be in the study.
If I have other questions I should ask the researcher or the research assistant. In addition, I may contact 
the Institutional Review Board, which is concerned with protection of volunteers in research projects. I 
may reach the committee office by calling: (415) 476-1814 from 8:00 AM to 5:00 PM, Monday to Friday, 
or by writing to the UCSF Human Research Protection Program, Box 0962, 3333 California St., Ste. 315, 
San Francisco, CA 94143.
Call 476-1814 for information on translations.
IRB NUMBER: 18-26765
IRB APPROVAL DATE: 02/03/2022
IRB EXPIRATION DATE: 02/02/2023