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.