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

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

Detailed Description
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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.

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

Conditions
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HIV Infection

Intervention / Treatment
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* Drug: tenofovir disoproxil fumarate
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: active immediate<br>participants in this arm start study product immediately upon enrollment | Drug: tenofovir disoproxil fumarate<br>* study product taken daily<br>* Other names: Viread;|
| Placebo Comparator: placebo immediate<br>participants in this arm start study product immediately upon enrollment | Drug: placebo<br>* study product taken daily<br>|
| Active Comparator: active delayed<br>persons in this arm start study product 9 months after enrollment | Drug: tenofovir disoproxil fumarate<br>* study product taken daily<br>* Other names: Viread;|
| Placebo Comparator: placebo delayed<br>participants in this arm start study product nine months after enrollment | Drug: placebo<br>* study product taken daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Safety--Creatinine Elevations | Grade 3 or 4 Creatinine elevations (per National Institutes of Health Division of AIDS toxicity scale) | 24 months (immediate arm) and 15 months (delayed arm) | 
| Clinical Safety--Hypophosphatemia | Grade 3 or 4 hypophosphatemia (per National Institutes of Health Division of AIDS toxicity scale) | 24 months (immediate arm), 15 months (delayed arm) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Breakthrough HIV Infections | Number of participants with HIV seroconversions occuring while on study drug | 24 months (immediate arm) and 15 months (delayed arm) | 
| Adherence to Study Drug | Estimated exposure to study drug (active and placebo) as assessed by Medication Event Monitoring System (MEMS) caps. | 24 months (immediate arm) and 15 months (delayed arm) | 
| Behavioral Safety--Unprotected Anal Sex (UAS) | Change in percent of participants reporting unprotected anal intercourse--baseline vs. months 3 through 9 on study. | Nine months |