Partners Demonstration Project of PrEP and ART

HIV Infection Clinical Trial

Official title:

An Open Label, Pilot Demonstration and Evaluation Project of Antiretroviral-based HIV-1 Prevention Among High-risk Serodiscordant African Couples

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02775929
• Other study ID #: STUDY00001674
• Secondary ID: R01MH095507
• Status: Completed
• Phase: Phase 4
• First received: May 10, 2016
• Last updated: December 7, 2017
• Start date: November 2012
• Est. completion date: June 2016

Study information

• Verified date: December 2017
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this protocol is to determine user preferences for antiretroviral therapy (ART) for HIV-1 infected partners and pre-exposure prophylaxis (PrEP) HIV-1 un-infected partners and to optimize targeted delivery and sustained use of these interventions.

Description:

An open-label, prospective cohort study of higher-risk HIV-1 serodiscordant couples in order to determine barriers and facilitators to uptake and sustained adherence to ART for HIV-1 infected partners and daily oral PrEP for HIV-1 uninfected partners. The investigators developed a risk score tool to identify couples at highest risk for HIV-1 transmission. PrEP was offered as a 'bridge' to ART in the partnership - i.e., until ART initiation by the HIV-infected partner and for the first 6 months after ART is started; ART was recommended following national ART guidelines. A subset (up to 80 couples per site) was invited to participate in qualitative in-depth interview and focus group discussions.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1013
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

For couples

• Risk score defining higher HIV-1 risk (=6)

• Sexually active (defined as having had vaginal intercourse at least 6 times in the previous three months)

• Willing to enter the study as a couple and intending to remain as a couple for the next 12 months

• Did not participate in the Partners PrEP Study

For HIV-1 uninfected members of the couple (partner participants)

• Age =18

• Able and willing to provide written informed consent

• HIV-1 uninfected based on negative HIV-1 rapid tests, both at study screening and at the enrollment visit

• Adequate renal function, defined by normal creatinine levels and estimated creatinine clearance >60 mL/min

• Not infected with hepatitis B virus, as determined by a negative hepatitis B surface antigen test

• Not currently pregnant or breastfeeding

• Not currently enrolled in an HIV-1 prevention clinical trial

• Not currently using PrEP

• Enrollment of individuals with active and serious infections or active clinically significant medical problems will be at the discretion of the site investigator

For HIV-1 infected members of the couple (index participants)

• Age =18

• Able and willing to provide written informed consent

• HIV-1 infected based on positive rapid HIV-1 tests, according to national algorithm

• No history of WHO stage III or IV conditions

• Not currently using ART

• Not currently enrolled in an HIV-1 treatment study

• Note: current pregnancy and breastfeeding are permitted for HIV-1 infected partners

Exclusion Criteria:

• Otherwise not eligible based on the above inclusion criteria

Related Conditions & MeSH terms

• HIV Infection
• HIV Infections

Intervention

Drug:
• FTC-TDF PrEP
FTC-TDF PrEP for HIV-1 uninfected partners
• ART
ART for HIV-1 infected partners

Locations

Country	Name	City	State
Kenya	Kemri-Ucsf	Kisumu
Kenya	Partners in Prevention-Thika	Thika
Uganda	Kabwohe Clinical Research Center	Bushenyi
Uganda	Partners in Prevention-Infectious Diseases Institute LTD	Kampala

Sponsors (4)

Lead Sponsor	Collaborator
University of Washington	Bill and Melinda Gates Foundation, National Institute of Mental Health (NIMH), United States Agency for International Development (USAID)

Countries where clinical trial is conducted

Kenya,  Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ability to recruit high-risk HIV-1 serodiscordant couples: Screen-to-eligible ratio.	High-risk couples defined by a validated risk scoring tool. Ability to recruit high-risk HIV-1 serodiscordant couples will be measured as screen-to-eligible ratio of HIV-1 serodiscordant couples.	24 months
Primary	Ability to recruit high-risk HIV-1 serodiscordant couples: Eligible couples who decide to enroll in the cohort.	High-risk couples defined by a validated risk scoring tool. We will measure the proportion of eligible couples who decide to enroll in the cohort.	24 months
Primary	Ability to recruit high-risk HIV-1 serodiscordant couples: Costs of screening and targeting high-risk couples decide to enroll in the cohort.	High-risk couples were defined by a validated risk scoring tool. The cost-effectiveness analysis will follow World Health Organization (WHO) guidelines and report summary estimates for the PrEP intervention which allow comparison to other strategies to decrease HIV-1 transmission among serodiscordant couples. Costs of offering and delivering PrEP as a bridging strategy to ART, including recruitment costs for targeting higher-risk couples and PrEP delivery and monitoring costs will be collected. The incremental cost-effectiveness ratio (ICER) per HIV related infection, death and Disability-Adjusted Life Year (DALY) averted will be estimated. Results will be reported as the ICER of PrEP compared to current practice per incident HIV-1 case, HIV related death and DALY averted.	24 months
Primary	User preferences for ART initiation for HIV-1 infected partners and PrEP for HIV-1 uninfected partners: preferred ART-based HIV prevention method.	Measure the number of couples choosing to use PrEP or ART for HIV-1 prevention or both.	24 months
Primary	User preferences for ART initiation for HIV-1 infected partners and PrEP for HIV-1 uninfected partners: reasons for choice and concerns about both methods.	Quantitative questionnaire will be used to elicit reasons for the choice and concerns about both methods. Reasons for or concerns about both methods measured as proportion of participants reporting a particular reason for or concerns about both methods	24 months
Primary	PrEP initiation by HIV uninfected partners.	Measure the number of HIV-1 uninfected partners initiating PrEP.; Proportion of samples with detectable and quantifiable PrEP levels	24 months
Primary	PrEP adherence: Self-reported missed doses of PrEP.	Measure the proportion of visits when HIV-uninfected partner reported missing 1) any dose of PrEP in the prior quarter 2) 2 or more consecutive doses of PrEP.	24 months
Primary	PrEP adherence: Detectable and quantifiable PrEP levels in plasma.	Measure the proportion of plasma samples of HIV-1 uninfected partners with detectable and quantifiable PrEP levels.	24 months
Primary	PrEP adherence: PrEP hold.	Measure the total number of HIV-1 uninfected partners with PrEP hold designated as a safety issue.	24 months
Primary	ART initiation.	Measure the number of HIV-1 infected partners initiating ART.	24 months
Primary	ART Adherence.	Measure the number of HIV-1 infected partners with suppressed plasma HIV-1 RNA levels.	24 months
Primary	Correlates of preferences, uptake and adherence to ART and PrEP: Sexual frequency.	Proportion of visits when participants report having sex.	24 months
Primary	Correlates of preferences, uptake and adherence to ART and PrEP: Condom use frequency.	Proportion of visits when participants report having condomless sex.	24 months
Primary	Correlates of preferences, uptake and adherence to ART and PrEP: Outside partners for HIV-1 uninfected partners.	Proportion of visits when HIV-1 uninfected partners report outside partners.	24 months
Primary	Correlates of preferences, uptake and adherence to ART and PrEP: Gender of the HIV-1 uninfected partner.	Proportion of couples in which the HIV-1 uninfected partner is female.	24 months
Primary	Correlates of preferences, uptake and adherence to ART and PrEP: Fertility intentions.	Proportion of couples with desire to conceive a child.	24 months
Primary	Correlates of preferences, uptake and adherence to ART and PrEP: Relationship dissolution.	Number of couples continuing their relationship during follow up.	24 months
Primary	Correlates of preferences, uptake, and adherence to ART and PrEP: Depression and substance use.	Annual interviewer-administered questionnaire to collect depression and substance use indicators. Measure proportion of participants with depression and substance use.	24 months
Primary	Correlates of preferences, uptake and adherence to ART and PrEP: ART initiation by HIV-1 infected partner.	Proportion of HIV-1 infected partners initiating ART.	24 months
Primary	Correlates of preferences, uptake and adherence to ART and PrEP: Number of children.	Proportion of partnership reporting to have children at baseline.	24 months
Primary	Correlates of preferences, uptake and adherence to ART and PrEP: CD4 count.	Proportion of HIV infected partners with CD4 count >200, >350, >500.	24 months
Primary	Correlates of preferences, uptake and adherence to ART and PrEP: WHO stage of HIV-1 infected partner.	Proportion HIV-1 infected partners with WHO HIV-1 stage 1, 2, 3, or 4.	24 months
Primary	Feasibility to PrEP discontinuation in couples when the HIV-1 infected partner initiates ART.	We will conduct in-depth interviews and focus group discussions. Qualitative analyses will identify and describe key themes and explore variation within themes of participants' attitudes and understanding of PrEP discontinuation.	24 months
Primary	PrEP use and pregnancy: HIV-1 infection.	Number of HIV-1 infections among women who continue PrEP in pregnancy.	24 months
Primary	PrEP use and pregnancy: Congenital abnormalities among infants born to female Participants taking PrEP.	Infant outcomes measured as the number of live-born infants born to female participants taking PrEP that had any congenital anomalie.	24 months
Primary	PrEP use and pregnancy: Any serious adverse event.	Number of women who continue PrEP in pregnancy with any serious adverse event.	24 months
Primary	Infant growth for women who continue PrEP in pregnancy: Length.	Length of infants born to female Participants taking PrEP. The slope of the linear model of the growth of infants (length) during the entirety of follow-up. The length of the infant 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, will be calculated using all available z-scores over study duration and regressing against study month.	24 months
Primary	Infant growth for women who continue PrEP in pregnancy: Weight.	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, will be calculated using all available z-scores over study duration and regressing against study month.	24 months
Primary	Infant growth for women who continue PrEP in pregnancy: Head circumference.	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 will be 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, will be calculated using all available z-scores over study duration and regressing against study month.	24 months