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

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.

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