Partners Demonstration Project of PrEP and ART

University of Washington1,013 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

PREVENTION

Masking

NONE

Enrollment

1,013

Conditions

HIV Infection

Interventions

FTC-TDF PrEPDRUG

FTC-TDF PrEP for HIV-1 uninfected partners

ARTDRUG

ART for HIV-1 infected partners

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (4)

Kemri-Ucsf

Kisumu, Kenya

Partners in Prevention-Thika

Thika, Kenya

Kabwohe Clinical Research Center

Bushenyi, Uganda

Partners in Prevention-Infectious Diseases Institute LTD

Kampala, Uganda

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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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

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 24 months

PrEP adherence: PrEP hold.

Measure the total number of HIV-1 uninfected partners with PrEP hold designated as a safety issue.

Time frame: 24 months

ART initiation.

Measure the number of HIV-1 infected partners initiating ART.

Time frame: 24 months

ART Adherence.

Measure the number of HIV-1 infected partners with suppressed plasma HIV-1 RNA levels.

Time frame: 24 months

Correlates of preferences, uptake and adherence to ART and PrEP: Sexual frequency.

Proportion of visits when participants report having sex.

Time frame: 24 months

Correlates of preferences, uptake and adherence to ART and PrEP: Condom use frequency.

Proportion of visits when participants report having condomless sex.

Time frame: 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.

Time frame: 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.

Time frame: 24 months

Correlates of preferences, uptake and adherence to ART and PrEP: Fertility intentions.

Proportion of couples with desire to conceive a child.

Time frame: 24 months

Correlates of preferences, uptake and adherence to ART and PrEP: Relationship dissolution.

Number of couples continuing their relationship during follow up.

Time frame: 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.

Time frame: 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.

Time frame: 24 months

Correlates of preferences, uptake and adherence to ART and PrEP: Number of children.

Proportion of partnership reporting to have children at baseline.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 24 months

PrEP use and pregnancy: HIV-1 infection.

Number of HIV-1 infections among women who continue PrEP in pregnancy.

Time frame: 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.

Time frame: 24 months

PrEP use and pregnancy: Any serious adverse event.

Number of women who continue PrEP in pregnancy with any serious adverse event.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 24 months