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

Phase 2

Completed

• Conditions: HIV Infection
• Interventions: Drug: tenofovir disoproxil fumarate; Drug: placebo

• Registration Number: NCT00131677
• Lead Sponsor: Centers for Disease Control and Prevention

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study Start: 2005-02
• Study First Submitted: 2005-08-17
• Study First Submitted QC: 2005-08-17
• Study First Posted: 2005-08-19
• Primary Completion: 2009-08
• Study Completion: 2009-08
• Status Verified: 2013-08
• Results First Submitted: 2013-08-08
• Results First Submitted QC: 2014-01-22
• Last Update Submitted: 2014-01-22
• Results First Posted: 2014-03-10
• Last Update Posted: 2014-03-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 400

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
active immediate	tenofovir disoproxil fumarate	participants in this arm start study product immediately upon enrollment
placebo immediate	placebo	participants in this arm start study product immediately upon enrollment
placebo delayed	placebo	participants in this arm start study product nine months after enrollment
active delayed	tenofovir disoproxil fumarate	persons in this arm start study product 9 months after enrollment

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (3)

San Francisco Department of Public Health; 🇺🇸 San Francisco, California, United States

AIDS Research Consortium of Atlanta; 🇺🇸 Atlanta, Georgia, United States

Fenway Community Health; 🇺🇸 Boston,, Massachusetts, United States