A Pilot Study of Pre-Exposure Prophylaxis (PrEP) to Evaluate Safety, Acceptability, and Adherence in At-risk Populations in Uganda, Africa

Summary

This study will evaluate the safety and acceptability of intermittent and daily pre-exposure prophylaxis (PrEP) regimens with FTC/TDF (emtricitabine/tenofovir disoproxil fumarate) in HIV discordant couples, and it will directly compare adherence and intracellular drug levels in daily and intermittent PrEP recipients. It will also evaluate the relationship between drug adherence, sexual behavior and intracellular drug levels with an intermittent PrEP regimen. In addition it will evaluate the relationship between adherence to an intermittent PrEP regimen and timing of sexual activity in relation to PrEP dosing. The pilot will use objective medication event monitoring (MEMS) adherence measurement and evaluate the feasibility of newer adherence measurements such as hair sampling and plasma drug levels. This study will also evaluate the feasibility of using text messaging (SMS) to collect sexual activity data in an African setting. It will allow study teams and communities to prepare for potential subsequent larger trials of intermittent PrEP. The study is not sized to evaluate efficacy. If the intermittent PrEP regimen is safe, feasible in terms of adherence, and achieves intracellular drug levels similar to daily PrEP, the data could be used to design a larger phase 2 study with one or more intermittent PrEP regimens. The goal of such a larger trial would be to provide bridging data if daily PrEP regimens are found to be effective or to prepare for efficacy or non-inferiority trials of intermittent versus daily PrEP.

Investigation of immune responses associated with FTC/TDF will also be evaluated in the pilot study. The proportion of volunteers on FTC/TDF with HIV-specific immune responses, due to exposures that did not lead to established HIV infection, will be assessed at 2-3 time points and compared to responses in volunteers assigned to placebo. Immune responses may be correlated with risk behavior and host factors, such as human leukocyte antigen (HLA) type. As noted above, very few HIV infections are expected to occur during the study, so correlation of HIV-specific immune responses and protection from infection or attenuation of disease progression will not be possible until a larger study is conducted.

Conditions

• HIV Infection

Interventions

DRUG

FTC/TDF

emtricitabine/tenofovir disoproxil fumarate

DRUG

Placebo

Placebo

Sponsors & Collaborators

• International AIDS Vaccine Initiative

  lead NETWORK

Principal Investigators

• Heiner Grosskurth, MD · MRC Entebbe

• Anatoli Kamali, MD · MRC Entebbe

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

49 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2009-10-31

Primary Completion

2010-10-31

Completion

2010-10-31

Countries

• Uganda

Study Locations