Pre-Exposure Prophylaxis to Prevent HIV-1 Acquisition Within HIV-1 Discordant Couples

University of Washington4,758 enrolled

Overview

Randomized, blinded, placebo-controlled trial to demonstrate if pre-exposure prophylaxis decreases HIV-1 acquisition among HIV-1 uninfected individuals within HIV-1 discordant couples.

HIV-1 uninfected individuals within HIV-1 discordant partnerships are at high-risk for HIV-acquisition. The majority of HIV-1 transmissions to adults in Africa occur within stable, HIV-1 discordant couples. Pre-exposure chemoprophylaxis, in which an HIV-1 uninfected individual at high risk for contracting HIV-1 takes antiretroviral medications to maintain blood and genital drug levels sufficient to prevent HIV-1 acquisition, has been proposed as a potential HIV-1 prevention strategy. This study was a randomized, blinded, placebo-controlled trial to demonstrate if pre-exposure prophylaxis decreases HIV-1 acquisition among HIV-1 uninfected individuals within HIV-1 discordant couples. The HIV-1 uninfected partner was randomized in a 1:1:1 ratio to one of three arms: once daily Tenofovir Disoproxil Fumarate (TDF), Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) or Placebo. Couples were followed up to 36 months; the HIV uninfected partner attended monthly visits and the HIV infected partner quarterly visits. All participants received a comprehensive package of HIV prevention services including individual and couples counseling, free condoms, and male circumcision referrals. Participants who seroconverted during follow-up stopped the study drug but continued with follow-up.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

4,758

Conditions

HIV-1 Infections HIV Infections

Interventions

Tenofovir Disoproxil Fumarate (TDF)DRUG

TDF 300 mg tablet, once daily + Placebo FTC/TDF orally, once daily.

Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)DRUG

FTC/TDF - 200 mg tablet, once daily + Placebo TDF orally, once daily

PlaceboDRUG

Placebo TDF \& Placebo FTC/TDF, 1 tablet each daily.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria for HIV-1 uninfected partner: * Partner within an HIV-1 discordant heterosexual relationship * One partner meets study eligibility for HIV-1 uninfected study participant and the other partner meets study eligibility criteria for HIV-1 infected participant * Plan to remain in the relationship for the duration of the study period * Adequate renal, hepatic \& hematologic function * Negative Hepatitis B surface antigen test * Willing and able to provide written informed consent \& locator information Exclusion Criteria for HIV-1 uninfected partner: * Current pregnancy, or planning to become pregnant during the study period * Currently breastfeeding * Concurrent enrollment in another HIV-1 vaccine or prevention trial * Receiving ongoing antiretroviral therapy * Repeated positive urine dipstick tests for glycosuria or proteinuria * Active and serious infections * History of pathological bone fractures not related to trauma Inclusion Criteria for HIV-1 infected partner: * Partner within an HIV-1 discordant heterosexual relationship * One partner meets study eligibility for HIV-1 uninfected study participant and the other partner meets study eligibility criteria for HIV-1 infected participant * HIV-1 infected based on positive EIA * No history of any clinical AIDS-defining diagnoses * Plan to remain in the relationship for the duration of the study period * Willing and able to provide written informed consent \& locator information Exclusion Criteria for HIV-1 infected partner: * Current use of antiretroviral therapy * Concurrent enrollment in another HIV-1 treatment trial

Locations (9)

Moi University - Indiana University

Eldoret, Kenya

CMR, Kemri-UCSF

Kisumu, Kenya

Kenyatta National Hospital/University of Nairobi

Nairobi, Kenya

Partners in Prevention - Thika

Thika, Kenya

Outcomes

Primary Outcomes

Incidence of HIV-1 Seroconversion Among HIV-1 Uninfected Participants

The efficacy of once daily PrEP in preventing HIV-1 acquisition among uninfected heterosexuals in HIV-1 discordant partnerships, measured by calculating the HIV incidence per 100 person-years in each of three arms.

Time frame: Up to 36 months

Number of Participants With Serious Adverse Events (SAEs)

Safety of daily TDF or FTC/TDF among HIV-1 uninfected individuals randomized to TDF or FTC/TDF compared to those randomized to placebo measured as the number of participants with Serious Adverse Events (SAEs) during follow-up.

Time frame: Up to 36 months

Secondary Outcomes

Study Drug Adherence: Total Number of Study Drug Doses Taken of the Total Dispensed Doses.

Adherence to study medication as assessed by pill count at follow-up visits. We assessed the total number of doses taken of the total dispensed doses.

Time frame: Up to 36 months

Study Drug Adherence: Self-reported Missed Doses of Study Drug

Adherence to study drug measured as the percentage of visits when participants reported missing 1) any dose of study drug in the prior month and 2) 2 or more consecutive doses of study drug.

Time frame: Up to 36 months

Number of Seroconverters With an HIV-1 Mutation Conferring Resistance to TDF or FTC

HIV-1 resistance as measured by the number of seroconverters who had an HIV-1 reverse transcriptase mutation (K65R, K70E, M184I, or M184V) conferring resistance to TDF or FTC. These mutation types were pre-defined. Plasma samples for resistance testing were collected at the visit seroconversion was first detected and again at a visit within 1 month of seroconversion. Mutations detected at either of those visits are reported. Both seroconverters found to have a resistance mutation had been HIV infected at enrollment (TDF arm: n=1; FTC-TDF arm: n=1).

Data from ClinicalTrials.gov

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