Pre-Exposure Prophylaxis to Prevent HIV-1 Acquisition Within HIV-1 Discordant Couples (Partners PrEP)

April 16, 2019 updated by: Connie Celum, University of Washington

Parallel Comparison of Tenofovir and Emtricitabine/Tenofovir Pre-Exposure Prophylaxis to Prevent HIV-1 Acquisition Within HIV-1 Discordant Couples

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Actual)

4758

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Kenya
      • Eldoret, Kenya
        • Moi University - Indiana University
      • Kisumu, Kenya
        • CMR, Kemri-UCSF
      • Nairobi, Kenya
        • Kenyatta National Hospital/University of Nairobi
      • Thika, Kenya
        • Partners in Prevention - Thika
  • Uganda
      • Bushenyi, Uganda
        • Kabwohe Clinical Research Center
      • Jinja, Uganda
        • Infectious Diseases Institute
      • Kampala, Uganda
        • Partners House-Infectious Disease Institute Ltd
      • Mbale, Uganda
        • The AIDS Support Organization (TASO)
      • Tororo, Uganda
        • The AIDS Support Organization - Tororo Field Station

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Tenofovir Disoproxil Fumarate (TDF)
TDF 300 mg tablet, once daily + Placebo FTC/TDF orally, once daily.
Drug: Tenofovir Disoproxil Fumarate (TDF)
TDF 300 mg tablet, once daily + Placebo FTC/TDF orally, once daily.
Other Names:
  • Viread + Placebo Truvada
Active Comparator: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)
FTC/TDF - 200 mg tablet, once daily + Placebo TDF orally, once daily
Drug: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)
FTC/TDF - 200 mg tablet, once daily + Placebo TDF orally, once daily
Other Names:
  • Truvada + Placebo Viread
Placebo Comparator: Placebo
Placebo TDF + Placebo FTC/TDF orally, once daily.
Drug: Placebo
Placebo TDF & Placebo FTC/TDF, 1 tablet each daily.
Other Names:
  • Placebo + Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of HIV-1 Seroconversion Among HIV-1 Uninfected Participants
Time Frame: Up to 36 months
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.
Up to 36 months
Number of Participants With Serious Adverse Events (SAEs)
Time Frame: Up to 36 months
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.
Up to 36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Study Drug Adherence: Total Number of Study Drug Doses Taken of the Total Dispensed Doses.
Time Frame: Up to 36 months
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.
Up to 36 months
Study Drug Adherence: Self-reported Missed Doses of Study Drug
Time Frame: Up to 36 months
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.
Up to 36 months
Number of Seroconverters With an HIV-1 Mutation Conferring Resistance to TDF or FTC
Time Frame: Up to 36 months

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).
Up to 36 months
Number of Participants With a Sexually Transmitted Infection (STI) During Follow-up
Time Frame: Up to 36 months

Prevalence of STIs measured as the number of participants with a positive test result for N. gonorrhoeae, C. trachomatis, or T. vaginalis during follow-up. Participants were tested for STIs at annual follow-up visits and at intervening visits at which the participant presented with symptoms of an STI. Assessment for symptomatic sexually transmitted infections was conducted quarterly.

N. gonorrhoeae and C. trachomatis testing were by APTIMA Combo 2 (Gen-Probe) or COBAS Amplicor (Roche Diagnostics). T. vaginalis testing was by APTIMA TV TMA (Gen-Probe) or In Pouch TV (Biomed Diagnostics).
Up to 36 months
Prevalence of Unprotected Sex During Follow-up
Time Frame: Up to 36 months
Sexual risk behavior of participants, measured as the percentage of visits when participants reported having unprotected sex during follow-up.
Up to 36 months
Congenital Abnormalities Among Infants Born to Female Participants Taking Study Drug.
Time Frame: Up to 36 months
Infant outcomes measured as the number of live-born infants born to female participants taking study drug that had any congenital anomalies.
Up to 36 months
Length Among Infants Born to Female Participants Taking Study Drug
Time Frame: up to 12 months
The slope of the linear model of the growth of infants (length) during the entirety of follow-up. The length of the infant was measured as a z-score, in terms of standard deviations from the age and gender specific median using the World Health Organization growth curve, accounting for skewness. The slope, representing the change over time of the z-score, was calculated using all available z-scores over 12 months and regressing against study month.
up to 12 months
Weight Among Infants Born to Female Participants Taking Study Drug
Time Frame: up to 12 months
The slope of the linear model of the growth of infants (weight) during the entirety of follow-up. The weight of the infant was measured as a z-score, in terms of standard deviations from the age and gender specific median using the World Health Organization growth curve, accounting for skewness. The slope, representing the change over time of the z-score, was calculated using all available z-scores over 12 months and regressing against study month.
up to 12 months
Head Circumference Among Infants Born to Female Participants Taking Study Drug
Time Frame: up to 12 months
The slope of the linear model of the growth of infants (head circumference) during the entirety of follow-up. The head circumference of the infant was measured as a z-score, in terms of standard deviations from the age and gender specific median using the World Health Organization growth curve, accounting for skewness. The slope, representing the change over time of the z-score, was calculated using all available z-scores over 12 months and regressing against study month.
up to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Collaborators

Bill and Melinda Gates Foundation

Investigators

  • Study Chair: Connie Celum,, MD, MPH, University of Washington
  • Study Director: Jared Baeten, MD, PhD, University of Washington

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2008

Primary Completion (Actual)

October 1, 2013

Study Completion (Actual)

October 1, 2013

Study Registration Dates

First Submitted

November 8, 2007

First Submitted That Met QC Criteria

November 9, 2007

First Posted (Estimate)

November 12, 2007

Study Record Updates

Last Update Posted (Actual)

April 19, 2019

Last Update Submitted That Met QC Criteria

April 16, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00000172
  • IND 75,365;
  • 07-7454-A-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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