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HIV-1 InfectionsPhase 3Partners PrEPNCT00557245

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

A Phase 3 study testing Tenofovir Disoproxil Fumarate (TDF) and Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) in people with HIV-1 Infections and HIV Infections, run by University of Washington at 9 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
HIV-1 Infections, HIV Infections
What is being tested?
Tenofovir Disoproxil Fumarate (TDF) and Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
4,758 participants
Where
9 sitesin 2 countries
Study dates
May 2008to Oct 2013
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • History of pathological bone fractures not related to trauma
  • Current use of antiretroviral therapy
  • Concurrent enrollment in another HIV-1 treatment trial

Trial locations and contacts

9 sites in 2 countries.

9 sites in 2 countries

Uganda5 sites

  • Kabwohe Clinical Research Center

    Bushenyi

  • Infectious Diseases Institute

    Jinja

  • Partners House-Infectious Disease Institute Ltd

    Kampala

  • The AIDS Support Organization (TASO)

    Mbale

  • The AIDS Support Organization - Tororo Field Station

    Tororo

Other trials in Uganda

Kenya4 sites

  • Moi University - Indiana University

    Eldoret

  • CMR, Kemri-UCSF

    Kisumu

  • Kenyatta National Hospital/University of Nairobi

    Nairobi

  • Partners in Prevention - Thika

    Thika

Other trials in Kenya

About this study

Official title: 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.

Read the 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.

Being tested
Tenofovir Disoproxil Fumarate (TDF), Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF), Placebo
Keywords
HIV infection, HIV uninfected partners, Double Blind, Placebo, Seroconversion, TDF, FTC TDF, Safety, HIV Seronegativity
Medical subject headings
HIV Infections, HIV Seropositivity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tenofovir Disoproxil Fumarate (TDF)Drug

    Also called Viread + Placebo Truvada

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

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

    Also called Truvada + Placebo Viread

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

  • PlaceboDrug

    Also called Placebo + Placebo

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

Study groups in NCT00557245
Study groupRoleWhat they receive
Tenofovir Disoproxil Fumarate (TDF)Active comparatorTDF 300 mg tablet, once daily + Placebo FTC/TDF orally, once daily.
Receives: Drug: Tenofovir Disoproxil Fumarate (TDF)
Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)Active comparatorFTC/TDF - 200 mg tablet, once daily + Placebo TDF orally, once daily
Receives: Drug: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)
PlaceboPlacebo comparatorPlacebo TDF + Placebo FTC/TDF orally, once daily.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 36 months

  2. 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.

    Measured: Up to 36 months

Secondary outcomes (9)

  1. 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.

    Measured: Up to 36 months

  2. 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.

    Measured: Up to 36 months

  3. 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).

    Measured: Up to 36 months

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

    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.

    1. 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).

    Measured: Up to 36 months

  5. Prevalence of Unprotected Sex During Follow-up

    Sexual risk behavior of participants, measured as the percentage of visits when participants reported having unprotected sex during follow-up.

    Measured: Up to 36 months

  6. Congenital Abnormalities Among Infants Born to Female Participants Taking Study Drug.

    Infant outcomes measured as the number of live-born infants born to female participants taking study drug that had any congenital anomalies.

    Measured: Up to 36 months

  7. Length Among Infants Born to Female Participants Taking Study Drug

    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.

    Measured: up to 12 months

  8. Weight Among Infants Born to Female Participants Taking Study Drug

    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.

    Measured: up to 12 months

  9. Head Circumference Among Infants Born to Female Participants Taking Study Drug

    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.

    Measured: up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Nov 2007 (estimated)
  2. Study startMay 2008
  3. Primary completionOct 2013
  4. Study completionOct 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
4,758 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00557245
Sponsor's protocol ID
STUDY00000172
Other IDs
IND 75,365;, 07-7454-A-01
Acronym
Partners PrEP
Status last verified
Apr 2019
First submitted
8 Nov 2007
Last updated
19 Apr 2019
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 21998703

  • 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.

    PubMed 22784037

  • 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.

    PubMed 34929030

  • 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.

    PubMed 30297124

  • 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.

    PubMed 29108000

  • 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.

    PubMed 27029778

  • 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.

    PubMed 25531343

  • 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.

    PubMed 25300863

  • 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.

    PubMed 25038355

  • 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.

    PubMed 24979446

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tenofovir Disoproxil Fumarate (TDF) and Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) in people with HIV-1 Infections and HIV Infections, run by University of Washington at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Uganda, Kenya. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of HIV-1 Seroconversion Among HIV-1 Uninfected Participants (time frame: Up to 36 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00557245, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2019.

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