Clinical trial NCT01450189: A Key Link for Transmission Prevention
Official title: Acute HIV Infection - A Key Link for Transmission Prevention: A Randomized Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV
Keywords: Acute HIV
Transmission Prevention
Randomized Pilot study
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
First posted: 2011-10-12
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This pilot study will assess the feasibility for the potential public health benefit of behavioral and antiretroviral interventions during acute HIV infection.

Central Hypothesis The investigators hypothesize that delivering behavioral and antiretroviral interventions to acutely infected persons will reduce onward transmission.

Detailed description: The HIV epidemic in sub-Saharan Africa is severe and continues to grow. In urban areas of Malawi, 19% of pregnant women seeking antenatal care and 15.6% of Malawians aged 15-49 years were infected with HIV in 2007. Prevention interventions that prevent onward transmission of HIV are urgently needed.

Persons with acute HIV infection (AHI) may be responsible for a substantial proportion of onward transmission of HIV infection. AHI is characterized by unfettered replication of HIV in a "ramp up viremia". The high concentration of HIV in blood and genital secretions remains elevated for up to 10-12 weeks before it declines to the levels observed in established infection. These high levels of HIV shedding in the genital tract are likely to produce very efficient sexual transmission and the proportion of virions that are infectious may be substantially higher during acute compared to chronic infection. Consequently, the probability of transmission during unprotected intercourse for those with AHI is very high. Identifying persons with AHI and intervening to reduce onward transmission represents a tantalizing, but unproven, opportunity for HIV prevention.

To have maximal impact, a prevention program targeting AHI must identify a substantial number of acutely infected persons and intervene quickly to minimize onward transmission. An effective immediate intervention would require behavioral modification to limit sexual partners and unprotected sex acts, and a biological intervention to reduce infectious viral burden in genital secretions. This is the first study to pilot a combined behavioral and biomedical intervention in individuals with AHI to reduce onward transmission of HIV.

Eligibility criteria: Inclusion Criteria:

Primary participants:

* Acute HIV-1 infection
* Men and women age greater than/= 18 years.
* Intention to remain in the Lilongwe area for the duration of the study.
* Ability and willingness of participant to provide informed consent.
* Willingness to provide contact/locator information, be contacted, and asked to return for AHI results.

Partner Participants:

* Referred by a primary participant and present with a referral card.
* Had vaginal or anal sex with a primary participant within 12 weeks prior to that primary participant's enrolling
* Men and women age greater than/=18 years.
* remain in the Lilongwe area for the duration of the study.
* Ability and willingness of participant to provide informed consent.

Exclusion Criteria:

Primary Participants:

* HIV infection based on two positive HIV antibody rapid tests at the time of screening.
* HIV-negative based on one or more antibody rapid test and an HIV RNA PCR test.
* Serious illness, including tuberculosis or opportunistic infection, requiring systemic treatment and/or hospitalization.
* Active drug or alcohol use or dependence.
* Current imprisonment or involuntary incarceration.
* Any other condition that in the opinion of the study investigator would compromise the safety of the study participant or study staff, or would prevent proper conduct of the study.

Partner Participants:

* Active drug or alcohol use or dependence.
* Current imprisonment or involuntary incarceration in a medical facility for psychiatric or physical illness.

Exclusion for Receipt of Antiretroviral Drugs in the BIA Arm

Note:A key component of this pilot study is to estimate the potential effect of ARVs during acute infection when applied on a large population scale.In effect, this pilot study should be viewed as a pilot for an effectiveness trial. Consequently, we will randomize all eligible participants to one of the three arms. If, however, persons should not receive ARVs for a variety of medically-related reasons, these persons will remain in the BIA arm, but will not receive ARVs. Women who are of reproductive potential but who refuse to use at least one form of contraception (see below), will remain in the BIA arm but will not receive ARVs. Similarly, persons randomized to the BI arm who do not attend all sessions will remain in the BI arm.

Persons randomized to BIA with any of the following conditions will be excluded from receiving ARVs, but will remain in the BIA group for purposes of analysis.

* Laboratory values obtained at Day 0 prior to initiating ARVs at a subsequent visit
* Absolute neutrophil count \<300/mm3
* Hemoglobin \<8.0 g/dL
* Platelet count \<40,000/mm3
* Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase \> 5 x upper limit of normal (ULN)
* Total bilirubin \>2.5 x ULN
* Creatinine Clearance (CrCl) \<60 mL/min
* Hepatitis B surface antigen positivity
* Positive serum or urine pregnancy test at Day 0.
* Breastfeeding
* Refusal to use at least one method of contraception, if a woman is of reproductive potential.

Acceptable forms of contraception include: condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, intrauterine device (IUD), or a hormonal-based contraceptive.

Women not meeting the reproductive potential criteria above may receive the study drugs without using contraception.

* Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation.
* Requirement for any current medications that are prohibited with any study drugs.

Primary outcomes:
measure: Proportion of Persons Agreeing to be Screened for Acute HIV Infection Among Those Offered Screening
timeFrame: 1 year
measure: Prevalence of AHI Among Persons Screened
timeFrame: 1 year
measure: Proportion of Persons With AHI Successfully Recruited Into the Study
timeFrame: 1 year
measure: Proportion of Participants Completing Full Course of ARVs in Arm BIA
timeFrame: 1 year
measure: Proportion of Participants in Arm BI and BIA (Combined) Who Complete the 4 Behavioral Sessions Within 3 Weeks of Enrollment.
timeFrame: 1 year
measure: Proportion of Persons Completing All Scheduled Visits in Each Study Arm
timeFrame: 1 year
measure: Number of Adverse Events
timeFrame: one year
Secondary outcomes:
measure: Unprotected Sex Acts in Previous One Week - 12 Weeks
timeFrame: 12 weeks
measure: Unprotected Sex Acts in Previous One Week - 26 Weeks
timeFrame: 26 weeks
measure: Unprotected Sex Acts in Previous One Week - 52 Weeks
timeFrame: 52 weeks
measure: Unprotected Sex Acts in Previous One Month - 12 Weeks
timeFrame: 12 weeks
measure: Unprotected Sex Acts in Previous One Month - 26 Weeks
timeFrame: 26 weeks
measure: Unprotected Sex Acts in Previous One Month - 52 Weeks
timeFrame: 52 weeks
measure: Cumulative Incidence of Gonorrhea, Chlamydial Infection and Trichomoniasis (Composite)
timeFrame: 26 weeks
measure: Cumulative Incidence of Gonorrhea, Chlamydial Infection and Trichomoniasis (Composite)
timeFrame: 52 weeks
measure: Cumulative Incidence Herpes Simplex Virus Type 2
timeFrame: 26 weeks
measure: Cumulative Incidence Herpes Simplex Virus Type 2
timeFrame: 52 weeks
measure: Number of Partners Reporting for HIV Testing
timeFrame: 52 weeks
measure: Proportion of Partners Reporting for HIV Testing
timeFrame: 52 weeks
measure: Suppression of HIV RNA to <1000c/ml at 12 Weeks
timeFrame: 12 weeks
measure: Time to HIV RNA Suppression <1000 c/ml
timeFrame: From date of randomization until viral load suppression, up to 52 weeks
measure: Blood HIV RNA Concentration at Week 12
timeFrame: 12 weeks
measure: Blood HIV RNA Concentration at Week 26
timeFrame: 26 weeks
measure: Blood HIV RNA Concentration at Week 52
timeFrame: 52 weeks
measure: Genital HIV RNA Concentration - Week 12, Women
timeFrame: 12 weeks
measure: Genital HIV RNA Concentration - Week 26, Women
timeFrame: 26 weeks
measure: Genital HIV RNA Concentration - Week 52, Women
timeFrame: 52 weeks
measure: Genital HIV RNA Concentration - Week 12, Men
timeFrame: 12 weeks
measure: Genital HIV RNA Concentration - Week 26, Men
timeFrame: 26 weeks
measure: Genital HIV RNA Concentration - Week 52, Men
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Lilongwe
country: Malawi
facility: Lighthouse Trust, Kamuzu Central Hospital
city: Lilongwe
country: Malawi
facility: UNC Project
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: William C Miller, MD, PhD, MPH
role: STUDY_CHAIR
affiliation: University of North Carolina, Chapel Hill
name: Audrey Pettifor, PhD, MPH
role: STUDY_CHAIR
affiliation: Kamuzu Central Hospital
name: Sam Phiri, PhD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chen JS, Pettifor AE, Nelson JAE, Phiri S, Pasquale DK, Kumwenda W, Kamanga G, Cottrell ML, Sykes C, Kashuba ADM, Tegha G, Krysiak R, Thengolose I, Cohen MS, Hoffman IF, Miller WC, Rutstein SE. Brief Report: Blood and Genital Fluid Viral Load Trajectories Among Treated and Untreated Persons With Acute HIV Infection in Malawi. J Acquir Immune Defic Syndr. 2022 May 1;90(1):56-61. doi: 10.1097/QAI.0000000000002917.
citation: Dennis AM, Cohen MS, Rucinski KB, Rutstein SE, Powers KA, Pasquale DK, Phiri S, Hosseinipour MC, Kamanga G, Nsona D, Massa C, Hoffman IF, Pettifor AE, Miller WC. Human Immunodeficiency Virus (HIV)-1 Transmission Among Persons With Acute HIV-1 Infection in Malawi: Demographic, Behavioral, and Phylogenetic Relationships. Clin Infect Dis. 2019 Aug 16;69(5):853-860. doi: 10.1093/cid/ciy1006.
citation: Hino S, Grodensky C, Rutstein SE, Golin C, Smith MK, Christmas L, Miller W, Phiri S, Massa C, Kamanga G, Pettifor A. HIV status disclosure during acute HIV infection in Malawi. PLoS One. 2018 Jul 26;13(7):e0201265. doi: 10.1371/journal.pone.0201265. eCollection 2018.