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

NCT00557245 | Completed Phase 3 Results DMC

• 3 other identifiers: STUDY00000172IND 75,365;07-7454-A-01
• Study Type: interventional
• Target: 4,758
• Locations: 2 countries
• Sites: 9

Brief Summary

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.

Conditions

HIV-1 Infections; HIV Infections

Keywords

HIV infection; HIV uninfected partners; Double Blind; Placebo; Seroconversion; TDF; FTC TDF; Safety; HIV Seronegativity

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Up to 36 months

Secondary Outcomes (9)

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

  Up to 36 months

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

  Up to 36 months

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

  Up to 36 months

• Number of Participants With a Sexually Transmitted Infection (STI) During Follow-up

  Up to 36 months

• Prevalence of Unprotected Sex During Follow-up

  Up to 36 months

Study Arms (3)

Tenofovir Disoproxil Fumarate (TDF)

ACTIVE COMPARATOR

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

Drug: Tenofovir Disoproxil Fumarate (TDF)

Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)

ACTIVE COMPARATOR

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

Drug: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Tenofovir Disoproxil Fumarate (TDF) DRUG

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

Also known as: Viread + Placebo Truvada

Tenofovir Disoproxil Fumarate (TDF)

Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) DRUG

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

Also known as: Truvada + Placebo Viread

Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)

Placebo DRUG

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

Also known as: Placebo + Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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
• Current use of antiretroviral therapy
• Concurrent enrollment in another HIV-1 treatment trial

Sponsors & Collaborators

• University of Washington: lead
• Bill and Melinda Gates Foundation: collaborator

Study Sites (9)

Moi University - Indiana University

Eldoret, Kenya

Location

CMR, Kemri-UCSF

Kisumu, Kenya

Location

Kenyatta National Hospital/University of Nairobi

Nairobi, Kenya

Location

Partners in Prevention - Thika

Thika, Kenya

Location

Kabwohe Clinical Research Center

Bushenyi, Uganda

Location

Infectious Diseases Institute

Jinja, Uganda

Location

Partners House-Infectious Disease Institute Ltd

Kampala, Uganda

Location

The AIDS Support Organization (TASO)

Mbale, Uganda

Location

The AIDS Support Organization - Tororo Field Station

Tororo, Uganda

Location

Related Publications (10)

• 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.

  PMID: 21998703 BACKGROUND

• 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.

  PMID: 22784037 RESULT

• 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.

  PMID: 34929030 DERIVED

• 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.

  PMID: 30297124 DERIVED

• 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.

  PMID: 29108000 DERIVED

• 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.

  PMID: 27029778 DERIVED

• 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.

  PMID: 25531343 DERIVED

• 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.

  PMID: 25300863 DERIVED

• 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.

  PMID: 25038355 DERIVED

• 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.

  PMID: 24979446 DERIVED

MeSH Terms

Conditions

HIV Infections; HIV Seropositivity

Interventions

Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Connie Celum
• Organization: University of Washington

ccelum@uw.edu

206-520-3824

Study Officials

• Connie Celum,, MD, MPH

  University of Washington

  STUDY CHAIR

• Jared Baeten, MD, PhD

  University of Washington

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, School of Medicine, Global Health

Study Record Dates

• First Submitted: November 8, 2007
• First Posted: November 12, 2007
• Study Start: May 1, 2008
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: April 19, 2019
• Results First Posted: November 27, 2014

Record last verified: 2019-04

Locations

UG (5); KE (4)