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

HIV Infections Clinical Trial

— Partners PrEP  

Official title:

Parallel Comparison of Tenofovir and Emtricitabine/Tenofovir Pre-Exposure Prophylaxis to Prevent HIV-1 Acquisition Within HIV-1 Discordant Couples

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00557245
• Other study ID #: STUDY00000172
• Secondary ID: IND 75,365;07-74
• Status: Completed
• Phase: Phase 3
• Start date: May 2008
• Est. completion date: October 2013

Study information

• Verified date: April 2019
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4758
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• HIV Infections
• HIV-1 Infections
• Infection

Intervention

Drug:
• Tenofovir Disoproxil Fumarate (TDF)
TDF 300 mg tablet, once daily + Placebo FTC/TDF orally, once daily.
• Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)
FTC/TDF - 200 mg tablet, once daily + Placebo TDF orally, once daily
• Placebo
Placebo TDF & Placebo FTC/TDF, 1 tablet each daily.

Locations

Country	Name	City	State
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
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

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	Bill and Melinda Gates Foundation

Countries where clinical trial is conducted

Kenya,  Uganda, 

References & Publications (2)

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, — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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.	Up to 36 months
Secondary	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.	Up to 36 months
Secondary	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).	Up to 36 months
Secondary	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.; 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).	Up to 36 months
Secondary	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.	Up to 36 months
Secondary	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.	Up to 36 months
Secondary	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.	up to 12 months
Secondary	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.	up to 12 months
Secondary	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.	up to 12 months