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

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ClinicalTrials.gov Identifier: NCT00557245
Recruitment Status : Completed
First Posted : November 12, 2007
Results First Posted : November 27, 2014
Last Update Posted : April 19, 2019
Sponsor:
Collaborator:
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
Connie Celum, University of Washington

Tracking Information
First Submitted Date  ICMJE November 8, 2007
First Posted Date  ICMJE November 12, 2007
Results First Submitted Date  ICMJE October 30, 2014
Results First Posted Date  ICMJE November 27, 2014
Last Update Posted Date April 19, 2019
Study Start Date  ICMJE May 2008
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 20, 2014)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 9, 2007)
  • 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. ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2014)
  • 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.
  • 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.
  • 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).
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 9, 2007)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pre-Exposure Prophylaxis to Prevent HIV-1 Acquisition Within HIV-1 Discordant Couples
Official Title  ICMJE Parallel Comparison of Tenofovir and Emtricitabine/Tenofovir Pre-Exposure Prophylaxis to Prevent HIV-1 Acquisition Within HIV-1 Discordant Couples
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • HIV-1 Infections
  • HIV Infections
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 15, 2013)
4758
Original Estimated Enrollment  ICMJE
 (submitted: November 9, 2007)
3900
Actual Study Completion Date  ICMJE October 2013
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Kenya,   Uganda
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00557245
Other Study ID Numbers  ICMJE STUDY00000172
IND 75,365;
07-7454-A-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Connie Celum, University of Washington
Study Sponsor  ICMJE University of Washington
Collaborators  ICMJE Bill and Melinda Gates Foundation
Investigators  ICMJE
Study Chair: Connie Celum,, MD, MPH University of Washington
Study Director: Jared Baeten, MD, PhD University of Washington
PRS Account University of Washington
Verification Date April 2019

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