Partners Demonstration Project of PrEP and ART

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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HIV Infection

Intervention / Treatment
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* Drug: FTC-TDF PrEP
* Drug: ART


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: PrEP as a bridge to ART<br>FTC-TDF PrEP for HIV uninfected partners and ART for HIV infected partners | Drug: FTC-TDF PrEP<br>* FTC-TDF PrEP for HIV-1 uninfected partners<br>Drug: ART<br>* ART for HIV-1 infected partners<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| PrEP adherence: PrEP hold. | Measure the total number of HIV-1 uninfected partners with PrEP hold designated as a safety issue. | 24 months | 
| ART initiation. | Measure the number of HIV-1 infected partners initiating ART. | 24 months | 
| ART Adherence. | Measure the number of HIV-1 infected partners with suppressed plasma HIV-1 RNA levels. | 24 months | 
| Correlates of preferences, uptake and adherence to ART and PrEP: Sexual frequency. | Proportion of visits when participants report having sex. | 24 months | 
| Correlates of preferences, uptake and adherence to ART and PrEP: Condom use frequency. | Proportion of visits when participants report having condomless sex. | 24 months | 
| 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 | 
| 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 | 
| Correlates of preferences, uptake and adherence to ART and PrEP: Fertility intentions. | Proportion of couples with desire to conceive a child. | 24 months | 
| Correlates of preferences, uptake and adherence to ART and PrEP: Relationship dissolution. | Number of couples continuing their relationship during follow up. | 24 months | 
| 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 | 
| 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 | 
| Correlates of preferences, uptake and adherence to ART and PrEP: Number of children. | Proportion of partnership reporting to have children at baseline. | 24 months | 
| 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 | 
| 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 | 
| 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 | 
| PrEP use and pregnancy: HIV-1 infection. | Number of HIV-1 infections among women who continue PrEP in pregnancy. | 24 months | 
| 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 | 
| PrEP use and pregnancy: Any serious adverse event. | Number of women who continue PrEP in pregnancy with any serious adverse event. | 24 months | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tenofovir disoproxil, Emtricitabine, Pre-exposure Prophylaxis, Antiretroviral Therapy, HIV Prevention, FTC TDF, PrEP, HIV Infected Partners, HIV Uninfected Partners