Extended Safety Study of Tenofovir Disoproxil Fumarate (TDF) Among HIV-1 Negative Men

• Number of HIV infections [ Time Frame: two years post enrollment ] [ Designated as safety issue: Yes ]
• Genetic characteristics of HIV-1 breakthrough viruses [ Time Frame: Two years post-enrollment ] [ Designated as safety issue: Yes ]
• Participants' adherence with daily TDF [ Time Frame: Two years post-enrollment ] [ Designated as safety issue: Yes ]

• Number of HIV infections
• Genetic characteristics of HIV-1 breakthrough viruses
• Participants’ adherence with daily TDF

The purpose of this study is to examine safety and tolerability of daily tenofovir use in HIV-uninfected men.

This study will assess the clinical and behavioral safety and tolerability of oral daily TDF use as pre-exposure prophylaxis (PrEP) to prevent HIV infection in uninfected men.

• Drug: tenofovir disoproxil fumarate
  study product taken daily
  Other Name: Viread
• Drug: placebo
  study product taken daily

• Active Comparator: active immediate
  participants in this arm start study product immediately upon enrollment
  Intervention: Drug: tenofovir disoproxil fumarate
• Placebo Comparator: placebo immediate
  participants in this arm start study product immediately upon enrollment
  Intervention: Drug: placebo
• Active Comparator: active delayed
  persons in this arm start study product 9 months after enrollment
  Intervention: Drug: tenofovir disoproxil fumarate
• Placebo Comparator: placebo delayed
  participants in this arm start study product nine months after enrollment
  Intervention: Drug: placebo

Inclusion Criteria:

• Healthy biologic male (male at birth)
• 18-60 years of age
• HIV-1 negative by licensed, commercially available, FDA-approved whole blood rapid enzyme immunoassay (EIA) at screening and enrollment
• Reports any anal sex with a man in the last 12 months
• Able to understand and pass comprehension assessment questionnaire
• Able to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
• Able to understand English
• Adequate renal function: calculated creatinine clearance of at least 70 mL/min
• Hepatic transaminases (AST and ALT) less than or equal to 2x upper limit of normal (ULN)
• Total bilirubin less than or equal to 1.5 mg/dL
• Absolute neutrophil count at least 1,500/mm3;
• Platelets at least 100,000/mm3;
• Hemoglobin at least 9.5 g/dL
• Serum amylase less than or equal to 1.5 x ULN
• Biochemical profile: within normal limits for serum phosphorus, potassium, sodium, and calcium.
• Hepatitis B surface antigen negative
• Normal urine dipstick or urinalysis (UA)

Exclusion Criteria:

• Active untreated syphilis
• Current uncontrolled hypertension (blood pressure > 160/100 mmHg)
• Mutually monogamous for > one year with a known HIV antibody negative partner
• History of chronic renal disease, known osteoporosis, osteomalacia, or osteopenia
• Current or expected participation in other longitudinal HIV behavioral or biomedical research study
• Current HIV antiretroviral use
• Receiving or planning to receive on-going therapy with any nephrotoxic agents or experimental/investigational agents
• Previous or expected requirements for the administration of immunosuppressive/ immunomodulatory therapy (e.g. chronic systemic steroids, interferon, interleukins, chemotherapy, radiation).
• Evidence of a gastrointestinal malabsorption syndrome or chronic nausea or vomiting which may confer an inability to receive an orally administered medication.
• Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance.
• Imminently life-threatening medical conditions (malignancy, immunosuppressive disease [e.g. lymphoma]), or other serious disease or conditions (e.g. cardiovascular, renal, diabetes) within the last 5 years or that are unstable and/or require chronic medication that would impede compliance with study requirements and complicate the interpretation of adverse events
• Expected to be non-compliant with study visits or planning to move within 24 months to an area where the study will not be conducted
• Any other clinical or social condition, prior therapy, occupation, or other responsibility, that, in the opinion of the investigator, would interfere with, or serve as a contraindication to study participation or compliance with the dosing requirements.

• San Francisco Department of Public Health
• AIDS Research Consortium of Atlanta