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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
  Purpose

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.


Condition Intervention Phase
HIV-1 Infections
HIV Infections
Drug: Tenofovir Disoproxil Fumarate (TDF)
Drug: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Parallel Comparison of Tenofovir and Emtricitabine/Tenofovir Pre-Exposure Prophylaxis to Prevent HIV-1 Acquisition Within HIV-1 Discordant Couples

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 4758
Study Start Date: May 2008
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Tenofovir Disoproxil Fumarate (TDF)
TDF 300 mg tablet, once daily + Placebo FTC/TDF orally, once daily.
Drug: Tenofovir Disoproxil Fumarate (TDF)
TDF 300 mg tablet, once daily + Placebo FTC/TDF orally, once daily.
Other Name: Viread + Placebo Truvada
Active Comparator: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)
FTC/TDF - 200 mg tablet, once daily + Placebo TDF orally, once daily
Drug: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)
FTC/TDF - 200 mg tablet, once daily + Placebo TDF orally, once daily
Other Name: Truvada + Placebo Viread
Placebo Comparator: Placebo
Placebo TDF + Placebo FTC/TDF orally, once daily.
Drug: Placebo
Placebo TDF & Placebo FTC/TDF, 1 tablet each daily.
Other Name: Placebo + Placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00557245

Locations
Kenya
Moi University - Indiana University
Eldoret, Kenya
CMR, Kemri-UCSF
Kisumu, Kenya
Kenyatta National Hospital/University of Nairobi
Nairobi, Kenya
Partners in Prevention - Thika
Thika, Kenya
Uganda
Kabwohe Clinical Research Center
Bushenyi, Uganda
Infectious Diseases Institute
Jinja, Uganda
Partners House-Infectious Disease Institute Ltd
Kampala, Uganda
The AIDS Support Organization (TASO)
Mbale, Uganda
The AIDS Support Organization - Tororo Field Station
Tororo, Uganda
Sponsors and Collaborators
University of Washington
Bill and Melinda Gates Foundation
Investigators
Study Chair: Connie Celum,, MD, MPH University of Washington
Study Director: Jared Baeten, MD, PhD University of Washington
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Connie Celum, Protocol Chair, University of Washington
ClinicalTrials.gov Identifier: NCT00557245     History of Changes
Other Study ID Numbers: 32528-A, IND 75,365;, 07-7454-A-01
Study First Received: November 8, 2007
Results First Received: October 30, 2014
Last Updated: November 20, 2014
Health Authority: United States: Food and Drug Administration
Kenya: Ethical Review Committee
Kenya: Institutional Review Board
Kenya: Pharmacy and Poisons Board
Kenya: Ministry of Health
Uganda: Ministry of Health
Uganda: National Council for Science and Technology
Uganda: National Drug Authority
Uganda: Research Ethics Committee

Keywords provided by University of Washington:
HIV infection
HIV uninfected partners
Double Blind
Placebo
Seroconversion
TDF
FTC TDF
Safety
HIV Seronegativity

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Communicable Diseases
Infection
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Emtricitabine
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014