Seroconversions, Resistance, Adverse Events and Drug Adherence Among Adults Taking Truvada® for PrEP: A Nested Case Control Study

This is an observational nested case control study among pre-exposure prophylaxis (PrEP)
observational or clinical studies. The study will assess level of adherence as measured by
drug level and its relationship to renal and bone adverse events, risk of seroconversion, and
resistance development in subjects taking emtricitabine (FTC)/tenofovir disoproxil fumarate
(TDF) (Truvada®) for PrEP.

In the protocols of the parent PrEP observational or clinical studies, participants will have
follow-up visits on average every 3 months for evaluation of adherence, HIV-1 status, renal
and bone adverse events, and seroconversion. Adherence will be determined by the specific
FTC/TDF drug level measurement(s) outlined in the parent protocol.

There are two case definitions: a) One-hundred-fifty subjects who seroconvert (become HIV-1
positive) and b) any subjects who either develop a protocol-defined renal adverse event
(stratified by Division of AIDS [DAIDS] grading) or have a skeletal adverse event (any
fracture) while taking FTC/TDF for PrEP.

Among the estimated 7,000 subjects from Truvada for PrEP observational and clinical studies
all cases, defined as subjects who seroconvert and/or develop either renal or skeletal
adverse events, will be identified. Randomly chosen controls on Truvada will be selected in a
3:1 ratio, from the same site, with a similar treatment duration.