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

NCT ID: NCT00557245

Last Updated: 2019-04-19

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

4758 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-05-31

Study Completion Date

2013-10-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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HIV-1 Infections HIV Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Tenofovir Disoproxil Fumarate (TDF)

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

Group Type ACTIVE_COMPARATOR

Tenofovir Disoproxil Fumarate (TDF)

Intervention Type DRUG

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

Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)

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

Group Type ACTIVE_COMPARATOR

Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)

Intervention Type DRUG

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

Placebo

Placebo TDF + Placebo FTC/TDF orally, once daily.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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Tenofovir Disoproxil Fumarate (TDF)

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

Intervention Type DRUG

Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Other Intervention Names

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Viread + Placebo Truvada Truvada + Placebo Viread Placebo + Placebo

Eligibility Criteria

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Inclusion Criteria

* 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


* 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

* 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


* Current use of antiretroviral therapy
* Concurrent enrollment in another HIV-1 treatment trial
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Bill and Melinda Gates Foundation

OTHER

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role lead

Responsible Party

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Connie Celum

Professor, School of Medicine, Global Health

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Connie Celum,, MD, MPH

Role: STUDY_CHAIR

University of Washington

Jared Baeten, MD, PhD

Role: STUDY_DIRECTOR

University of Washington

Locations

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Moi University - Indiana University

Eldoret, , Kenya

Site Status

CMR, Kemri-UCSF

Kisumu, , Kenya

Site Status

Kenyatta National Hospital/University of Nairobi

Nairobi, , Kenya

Site Status

Partners in Prevention - Thika

Thika, , Kenya

Site Status

Kabwohe Clinical Research Center

Bushenyi, , Uganda

Site Status

Infectious Diseases Institute

Jinja, , Uganda

Site Status

Partners House-Infectious Disease Institute Ltd

Kampala, , Uganda

Site Status

The AIDS Support Organization (TASO)

Mbale, , Uganda

Site Status

The AIDS Support Organization - Tororo Field Station

Tororo, , Uganda

Site Status

Countries

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Kenya Uganda

References

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Mujugira A, Baeten JM, Donnell D, Ndase P, Mugo NR, Barnes L, Campbell JD, Wangisi J, Tappero JW, Bukusi E, Cohen CR, Katabira E, Ronald A, Tumwesigye E, Were E, Fife KH, Kiarie J, Farquhar C, John-Stewart G, Kidoguchi L, Panteleeff D, Krows M, Shah H, Revall J, Morrison S, Ondrejcek L, Ingram C, Coombs RW, Lingappa JR, Celum C; Partners PrEP Study Team. Characteristics of HIV-1 serodiscordant couples enrolled in a clinical trial of antiretroviral pre-exposure prophylaxis for HIV-1 prevention. PLoS One. 2011;6(10):e25828. doi: 10.1371/journal.pone.0025828. Epub 2011 Oct 5.

Reference Type BACKGROUND
PMID: 21998703 (View on PubMed)

Baeten JM, Donnell D, Ndase P, Mugo NR, Campbell JD, Wangisi J, Tappero JW, Bukusi EA, Cohen CR, Katabira E, Ronald A, Tumwesigye E, Were E, Fife KH, Kiarie J, Farquhar C, John-Stewart G, Kakia A, Odoyo J, Mucunguzi A, Nakku-Joloba E, Twesigye R, Ngure K, Apaka C, Tamooh H, Gabona F, Mujugira A, Panteleeff D, Thomas KK, Kidoguchi L, Krows M, Revall J, Morrison S, Haugen H, Emmanuel-Ogier M, Ondrejcek L, Coombs RW, Frenkel L, Hendrix C, Bumpus NN, Bangsberg D, Haberer JE, Stevens WS, Lingappa JR, Celum C; Partners PrEP Study Team. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012 Aug 2;367(5):399-410. doi: 10.1056/NEJMoa1108524. Epub 2012 Jul 11.

Reference Type RESULT
PMID: 22784037 (View on PubMed)

Saha A, Escuduero J, Layouni T, Richardson B, Hou S, Mugo N, Mujugira A, Celum C, Baeten JM, Lingappa J, John-Stewart GC, LaCourse SM, Shah JA. Mycobacterium tuberculosis-Specific T-Cell Responses Are Impaired During Late Pregnancy With Elevated Biomarkers of Tuberculosis Risk Postpartum. J Infect Dis. 2022 May 4;225(9):1663-1674. doi: 10.1093/infdis/jiab614.

Reference Type DERIVED
PMID: 34929030 (View on PubMed)

Mugo NR, Eckert L, Magaret AS, Cheng A, Mwaniki L, Ngure K, Celum C, Baeten JM, Galloway DA, Wamalwa D, Wald A. Quadrivalent HPV vaccine in HIV-1-infected early adolescent girls and boys in Kenya: Month 7 and 12 post vaccine immunogenicity and correlation with immune status. Vaccine. 2018 Nov 12;36(46):7025-7032. doi: 10.1016/j.vaccine.2018.09.059. Epub 2018 Oct 5.

Reference Type DERIVED
PMID: 30297124 (View on PubMed)

Mackelprang RD, Bamshad MJ, Chong JX, Hou X, Buckingham KJ, Shively K, deBruyn G, Mugo NR, Mullins JI, McElrath MJ, Baeten JM, Celum C, Emond MJ, Lingappa JR; Partners in Prevention HSV/HIV Transmission Study and the Partners PrEP Study Teams. Whole genome sequencing of extreme phenotypes identifies variants in CD101 and UBE2V1 associated with increased risk of sexually acquired HIV-1. PLoS Pathog. 2017 Nov 6;13(11):e1006703. doi: 10.1371/journal.ppat.1006703. eCollection 2017 Nov.

Reference Type DERIVED
PMID: 29108000 (View on PubMed)

Mugwanya K, Baeten J, Celum C, Donnell D, Nickolas T, Mugo N, Branch A, Tappero J, Kiarie J, Ronald A, Yin M, Wyatt C; Partners PrEP Study Team. Low Risk of Proximal Tubular Dysfunction Associated With Emtricitabine-Tenofovir Disoproxil Fumarate Preexposure Prophylaxis in Men and Women. J Infect Dis. 2016 Oct 1;214(7):1050-7. doi: 10.1093/infdis/jiw125. Epub 2016 Mar 29.

Reference Type DERIVED
PMID: 27029778 (View on PubMed)

Mugwanya KK, Wyatt C, Celum C, Donnell D, Mugo NR, Tappero J, Kiarie J, Ronald A, Baeten JM; Partners PrEP Study Team. Changes in glomerular kidney function among HIV-1-uninfected men and women receiving emtricitabine-tenofovir disoproxil fumarate preexposure prophylaxis: a randomized clinical trial. JAMA Intern Med. 2015 Feb;175(2):246-54. doi: 10.1001/jamainternmed.2014.6786.

Reference Type DERIVED
PMID: 25531343 (View on PubMed)

Baeten JM, Donnell D, Mugo NR, Ndase P, Thomas KK, Campbell JD, Wangisi J, Tappero JW, Bukusi EA, Cohen CR, Katabira E, Ronald A, Tumwesigye E, Were E, Fife KH, Kiarie J, Farquhar C, John-Stewart G, Kidoguchi L, Coombs RW, Hendrix C, Marzinke MA, Frenkel L, Haberer JE, Bangsberg D, Celum C; Partners PrEP Study Team. Single-agent tenofovir versus combination emtricitabine plus tenofovir for pre-exposure prophylaxis for HIV-1 acquisition: an update of data from a randomised, double-blind, phase 3 trial. Lancet Infect Dis. 2014 Nov;14(11):1055-1064. doi: 10.1016/S1473-3099(14)70937-5. Epub 2014 Oct 7.

Reference Type DERIVED
PMID: 25300863 (View on PubMed)

Mugo NR, Hong T, Celum C, Donnell D, Bukusi EA, John-Stewart G, Wangisi J, Were E, Heffron R, Matthews LT, Morrison S, Ngure K, Baeten JM; Partners PrEP Study Team. Pregnancy incidence and outcomes among women receiving preexposure prophylaxis for HIV prevention: a randomized clinical trial. JAMA. 2014 Jul 23-30;312(4):362-71. doi: 10.1001/jama.2014.8735.

Reference Type DERIVED
PMID: 25038355 (View on PubMed)

Celum C, Morrow RA, Donnell D, Hong T, Hendrix CW, Thomas KK, Fife KH, Nakku-Joloba E, Mujugira A, Baeten JM; Partners PrEP Study Team. Daily oral tenofovir and emtricitabine-tenofovir preexposure prophylaxis reduces herpes simplex virus type 2 acquisition among heterosexual HIV-1-uninfected men and women: a subgroup analysis of a randomized trial. Ann Intern Med. 2014 Jul 1;161(1):11-9. doi: 10.7326/M13-2471.

Reference Type DERIVED
PMID: 24979446 (View on PubMed)

Other Identifiers

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IND 75,365;

Identifier Type: -

Identifier Source: secondary_id

07-7454-A-01

Identifier Type: -

Identifier Source: secondary_id

STUDY00000172

Identifier Type: -

Identifier Source: org_study_id

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