Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Collaborator:
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
Connie Celum, University of Washington
ClinicalTrials.gov Identifier:
NCT00557245
First received: November 8, 2007
Last updated: November 20, 2014
Last verified: November 2014

November 8, 2007
November 20, 2014
May 2008
October 2013   (final data collection date for primary outcome measure)
  • Incidence of HIV-1 Seroconversion Among HIV-1 Uninfected Participants [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
    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.
  • Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Up to 36 months ] [ Designated as safety issue: Yes ]
    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.
  • Efficacy of once daily PrEP in preventing HIV-1 acquisition among uninfected heterosexual HIV-1 discordant couples. [ Time Frame: Up to 24 months-36 months ]
  • Safety of daily TDF or FTC/TDF among HIV-1 uninfected individuals randomized to TDF or FTC/TDF to those randomized to placebo. [ Time Frame: Up to 24-36 months. ]
Complete list of historical versions of study NCT00557245 on ClinicalTrials.gov Archive Site
  • Study Drug Adherence: Total Number of Study Drug Doses Taken of the Total Dispensed Doses. [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
    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.
  • Study Drug Adherence: Self-reported Missed Doses of Study Drug [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
    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.
  • Number of Seroconverters With an HIV-1 Mutation Conferring Resistance to TDF or FTC [ Time Frame: Up to 36 months ] [ Designated as safety issue: Yes ]

    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).

  • Number of Participants With a Sexually Transmitted Infection (STI) During Follow-up [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]

    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).

  • Prevalence of Unprotected Sex During Follow-up [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
    Sexual risk behavior of participants, measured as the percentage of visits when participants reported having unprotected sex during follow-up.
  • Congenital Abnormalities Among Infants Born to Female Participants Taking Study Drug. [ Time Frame: Up to 36 months ] [ Designated as safety issue: Yes ]
    Infant outcomes measured as the number of live-born infants born to female participants taking study drug that had any congenital anomalies.
  • Length Among Infants Born to Female Participants Taking Study Drug [ Time Frame: up to 12 months ] [ Designated as safety issue: Yes ]
    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.
  • Weight Among Infants Born to Female Participants Taking Study Drug [ Time Frame: up to 12 months ] [ Designated as safety issue: Yes ]
    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.
  • Head Circumference Among Infants Born to Female Participants Taking Study Drug [ Time Frame: up to 12 months ] [ Designated as safety issue: Yes ]
    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.
  • Reported risk behaviours, STI prevalence, pill counts and reported adherence. [ Time Frame: Up to 24-36 months ]
  • HIV-1 drug resistance, plasma HIV-1 RNA levels and CD4 T cell counts among HIV-1 seroconverters, [ Time Frame: Up to 24-36 months ]
  • Congenital abnormalities, growth and development among infants born to female participants taking study drug. [ Time Frame: Up to 24-36 months ]
Not Provided
Not Provided
 
Pre-Exposure Prophylaxis to Prevent HIV-1 Acquisition Within HIV-1 Discordant Couples
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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • HIV-1 Infections
  • HIV Infections
  • Drug: Tenofovir Disoproxil Fumarate (TDF)
    TDF 300 mg tablet, once daily + Placebo FTC/TDF orally, once daily.
    Other Name: Viread + Placebo Truvada
  • Drug: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)
    FTC/TDF - 200 mg tablet, once daily + Placebo TDF orally, once daily
    Other Name: Truvada + Placebo Viread
  • Drug: Placebo
    Placebo TDF & Placebo FTC/TDF, 1 tablet each daily.
    Other Name: Placebo + Placebo
  • Active Comparator: Tenofovir Disoproxil Fumarate (TDF)
    TDF 300 mg tablet, once daily + Placebo FTC/TDF orally, once daily.
    Intervention: Drug: Tenofovir Disoproxil Fumarate (TDF)
  • Active Comparator: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)
    FTC/TDF - 200 mg tablet, once daily + Placebo TDF orally, once daily
    Intervention: Drug: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)
  • Placebo Comparator: Placebo
    Placebo TDF + Placebo FTC/TDF orally, once daily.
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
4758
October 2013
October 2013   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Kenya,   Uganda
 
NCT00557245
32528-A, IND 75,365;, 07-7454-A-01
Yes
Connie Celum, University of Washington
University of Washington
Bill and Melinda Gates Foundation
Study Chair: Connie Celum,, MD, MPH University of Washington
Study Director: Jared Baeten, MD, PhD University of Washington
University of Washington
November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP