Assessment of Pre-Exposure Prophylaxis (PrEP) Administered at Sexually Transmitted Disease (STD) Clinics

Study Overview
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Brief Summary
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This study will assess the uptake, acceptability, safety, and feasibility of HIV pre-exposure prophylaxis (PrEP), consisting of a once-daily fixed-dose combination tablet of emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF), administered at sexually transmitted disease (STD) clinics and a community health center in the United States.

Detailed Description
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A previous study (iPrEx) showed that daily PrEP with FTC/TDF provided with a comprehensive package of prevention services is effective in preventing HIV infection among men who have sex with men (MSM). The PrEP administered in that study was given in the context of a research setting/controlled trial, but it is important to evaluate the acceptability, sustainability, and safety of PrEP in a real world setting. This study will evaluate PrEP administered to HIV-uninfected MSM and transgender females at two STD clinics and one community health center in the United States. Each participant will receive PrEP for up to 1 year and will have up to 8 study visits. PrEP will consist of one fixed-dose FTC/TDF combination tablet orally each day. All participants will have study visits at screening, enrollment, and 4 weeks after enrollment; participants will continue to have visits at Weeks 12, 24, 36, 48, and 52 if they do not seroconvert. Participants who seroconvert will discontinue PrEP and will have a post-drug discontinuation visit 4 weeks after discontinuing PrEP. At most visits, participants will undergo blood, urine, and hair sample collection; give a medical history; undergo a physical exam; receive risk-reduction counseling and condoms; undergo testing for HIV and other STDs; receive study drugs; and undergo a pill count and adherence assessment (follow-up visits only). For participants who stop taking the study drug but remain in the study, urine, blood, and hair samples will not be collected at 12-week follow-up visits if all stop procedures have been completed and if there are no lab abnormalities that require additional follow-up. Participants will also answer questionnaires at screening, 12-week visits, and at study exit.

Official Title
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Implementation of HIV Pre-exposure Prophylaxis (PrEP): A Demonstration Project

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: FTC 200 mg/TDF 300 mg fixed-dose combination tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be either a man who has sex with men or a transgender female Male sex (at birth) Willing and able to provide written informed consent HIV-1 uninfected, defined as having a negative rapid HIV antibody test at both screening visit and enrollment and a negative 4th generation antibody/antigen test at screening No laboratory evidence of a detectable HIV viral load (San Francisco site only) Evidence of risk of acquiring HIV-1 infection including any one of the following: (1) Condomless anal sex with two or more male or transgender female sex partners during the last 12 months; or (2) two or more episodes of anal sex with at least one HIV-positive partner during the last 12 months; or (3) sex with a male or transgender female partner and any of the following STDs diagnosed during the last 12 months or at screening: syphilis, rectal gonorrhea, or rectal chlamydia. Able to provide a street address of residence or phone number for themselves or two personal contacts who would know their whereabouts during the period of the demonstration project Adequate renal function: creatinine clearance of 60 ml/min or greater as estimated by the Cockcroft-Gault equation within 45 days of enrollment A urine dipstick with a negative or trace result for protein within 45 days of enrollment Fluent in English or in Spanish Exclusion Criteria: Signs or symptoms of acute HIV infection Previously diagnosed active and serious infections including active tuberculosis infection or osteomyelitis and all infections requiring parenteral antibiotic therapy (other than STDs requiring intramuscular injections of antibiotics); active clinically significant medical problems including poorly controlled cardiac disease (e.g., symptoms of ischemia or congestive heart failure) or previously diagnosed malignancy expected to require further treatment Hepatitis B surface antigen (HBsAg) positive History of pathological bone fractures not related to trauma Receiving ongoing therapy with any of the following: investigational antiretroviral agents (PEP is allowed as described in the protocol), interferon (alpha, beta, or gamma) or interleukin (e.g., IL-2) therapy, agents with significant nephrotoxic potential, other agents that may inhibit or compete for elimination via active renal tubular secretion (e.g., probenecid), and/or other investigational agents Concomitant participation in a clinical trial using investigational agents, including placebo-controlled clinical trials using such agents At enrollment, has any other condition that, based on the opinion of the investigator or designee, would preclude provision of informed consent; make participation in the project unsafe; complicate interpretation of outcome data; or otherwise interfere with achieving the project objectives

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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Accepts Healthy Volunteers

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 |
| --- | --- |
| Experimental: Emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)<br>All study participants will be assigned to this arm and will receive one FTC/TDF tablet orally once a day. | Drug: FTC 200 mg/TDF 300 mg fixed-dose combination tablet<br>* Each participant will be directed to take one FTC/TDF tablet orally once a day, with or without food.<br>* Other names: Truvada;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of Acceptance Rate of PrEP |  | Measured through enrollment (Week 0) | 
| Measurement of Refusal Rate of PrEP |  | Measured through enrollment (Week 0) | 
| Duration of PrEP Use | Number of study drug interruptions | Participants were followed for 48 weeks, or up to the point of early termination | 
| Duration of PrEP Use | Mean duration of interruptions | Participants were followed for 48 weeks, or up to the point of early termination | 
| Measurement of Side Effects/Toxicities |  | Participants were followed for 48 weeks, or up to the point of early termination | 
| Measurement of PrEP Adherence by TFV-DP Levels in DBS |  | Participants were followed for 48 weeks, or up to the point of early termination | 
| Number of Male Sexual Partners |  | Participants were followed for 48 weeks, or up to the point of early termination | 
| Measurement of PrEP Adherence by Medication Possession Ratio | Medication possession ratio is defined as the number of dispensed pills divided by the number of days between visits | Participants were followed for 48 weeks, or up to the point of early termination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Seroconvert |  | Participants were followed for 48 weeks, or up to the point of early termination | 
| Measurement of HIV Drug Resistance Patterns Among Participants Who Become Infected |  | Participants were followed for 48 weeks, or up to the point of early termination |