A Demonstration Project to Add Pre- or Post-exposure Prophylaxis to Combination HIV Prevention Services

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, acceptability and feasibility of delivery of Pre-Exposure Prophylaxis (PrEP) or Post-Exposure Prophylaxis) PEP as part of combination HIV prevention services for high-risk MSM and transgender women.

Detailed Description
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Two community-based sites (LALGBT Center and The OASIS Clinic) will serve as facilities at which participants may present for screening for prevention services. At the sites, eligibility criteria will be assessed, HIV, Sexually Transmitted Disease (STD) and laboratory testing will be performed, and HIV prevention service referrals will be initiated. Follow-up will be on a monthly basis for the first three months, and then de-escalated to an every-3-month interval. The program stratifies participants into two cohorts on the basis of sexual risk behavior: a low-moderate risk cohort (LM) and a high-risk cohort (H). Participants in the LM cohort will be provided a customized prevention package (CPP) including access to PEP for emergency HIV prevention in the event of unanticipated HIV exposure. Participants in the H cohort will be provided a CPP including daily Truvada-based PrEP. All participants will be followed for 48 weeks. Participants in the LM cohort who, on longitudinal sexual risk behavior surveillance, report increased levels of sexual risk-taking such that they meet enrollment criteria for the H-cohort will be transitioned to the H-cohort. At each follow-up visit, a careful safety assessment will be made, including signs/symptoms and laboratory assessments. STD testing will be performed at 3 month intervals. An escalating-intensity adherence intervention will be implemented based on real-time plasma tenofovir levels. A computer-assisted self-interview (CASI) will be used to capture detailed sexual risk, adherence, and substance use behavior.

Official Title
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A Pilot Demonstration Project to Operationalize Pre-exposure Prophylaxis as Part of Combination HIV Prevention Among Men Who Have Sex With Men (MSM) and Transgender Women in Los Angeles County

Conditions
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HIV Prevention

Intervention / Treatment
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* Drug: emtricitabine 200mg/tenofovir 300mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years of age Able to understand and provide consent in English or Spanish Self identified MSM, MSM/W, or Transfemale At least one male sex partner for anal intercourse in the prior 12 months HIV negative by enzyme immunoassay (EIA) and viral load (VL) CrCl ≥ 60 ml/min (via Cockcroft-Gault formula) No signs or symptoms suggestive of primary HIV infection (PHI). Exclusion Criteria: Participants <18 years of age Unable to understand and provide consent in English or Spanish Known or found on testing to be HIV positive Any condition, which in the opinion of the intake provider, will seriously compromise the participant's ability to comply with the protocol, including adherence to PEP or PrEP medication dosing Use of Antiretroviral therapy (ART) taken for any indication (i.e. PEP or PrEP) within 60 days of study entry Previous participation in an HIV vaccine trial. Participants that were documented to have received only placebo are not excluded. Signs or symptoms suspicious for PHI.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cohort H (PrEP)<br>Participants in the H cohort will be provided with a CPP, including daily oral emtricitabine/tenofovir-based PrEP. High Risk Cohort Criteria (one or more of the following has to be met): No condom use during anal intercourse with ≥3 male sex partners who are HIV-positive or of unknown HIV status during the last three months. STD diagnosis during the last 12 months. Previous PEP use during the last 12 months (* see exclusion criteria) Has at least one HIV infected sexual partner for ≥4 weeks. | Drug: emtricitabine 200mg/tenofovir 300mg<br>* The intervention medication will be tenofovir + emtricitabine, provided as a fixed-dose combination tablet as Truvada®. Dosing is 1 tablet by mouth once daily. For participants with a a confirmed (i.e. two consecutive) reduction in creatinine clearance (CrCl) to <50 mL/min, Truvada will be dose-reduced to 1 tablet by mouth every other day. For patients with CrCl <30 mL/min, Truvada will be discontinued.<br>* Other names: Truvada;|
| Active Comparator: Cohort LM (PEP)<br>Participants who do not meet criteria for High Risk (Cohort H) will be assigned to the LM (low moderate) cohort and will receive a customized prevention package based on baseline assessments (in the same manner as the Cohort H Participants). In addition, they will receive education on the availability and use of post-exposure prophylaxis. | Drug: emtricitabine 200mg/tenofovir 300mg<br>* The intervention medication will be tenofovir + emtricitabine, provided as a fixed-dose combination tablet as Truvada®. Dosing is 1 tablet by mouth once daily. For participants with a a confirmed (i.e. two consecutive) reduction in creatinine clearance (CrCl) to <50 mL/min, Truvada will be dose-reduced to 1 tablet by mouth every other day. For patients with CrCl <30 mL/min, Truvada will be discontinued.<br>* Other names: Truvada;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Grade 2 or Higher Adverse Event by Cohort | Number and frequency rate of clinical and laboratory AEs (Gr 2 and above), including SAEs by Cohort. | Baseline to 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort H PrEP Engagement by Study Visit | Optimal adherence to daily oral emtricitabine/tenofovir disoproxil fumarate by study visit as measured by tenofovir diphosphate (TFV-DP) in dried blood spots (DBS). Optimal adherence is defined as TFV-DP levels great than or equal to 700 femtomoles per punch in DBS samples (approximately 4 or more doses a week over the past 60 days). | Baseline to 48 weeks |