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

    Phase 2
  • Study Type

  • Intervention/Treatment

    tenofovir ...
  • Study Participants

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.
Study Started
Feb 28
Primary Completion
Aug 31
Study Completion
Aug 31
Results Posted
Mar 10
Last Update
Mar 10

Drug tenofovir disoproxil fumarate

study product taken daily

  • Other names: Viread

Drug placebo

study product taken daily

active immediate Active Comparator

participants in this arm start study product immediately upon enrollment

placebo immediate Placebo Comparator

participants in this arm start study product immediately upon enrollment

active delayed Active Comparator

persons in this arm start study product 9 months after enrollment

placebo delayed Placebo Comparator

participants in this arm start study product nine months after enrollment


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.


Tenofovir Disoproxil Fumarate


All Events

Event Type Organ System Event Term Tenofovir Disoproxil Fumarate Placebo

Clinical Safety--Creatinine Elevations

Grade 3 or 4 Creatinine elevations (per National Institutes of Health Division of AIDS toxicity scale)

Tenofovir Disoproxil Fumarate


Clinical Safety--Hypophosphatemia

Grade 3 or 4 hypophosphatemia (per National Institutes of Health Division of AIDS toxicity scale)

Tenofovir Disoproxil Fumarate




Number of Breakthrough HIV Infections

Number of participants with HIV seroconversions occuring while on study drug

Tenofovir Disoproxil Fumarate



Adherence to Study Drug

Estimated exposure to study drug (active and placebo) as assessed by Medication Event Monitoring System (MEMS) caps.

Treatment Emergent Cohort

percentage of doses

Behavioral Safety--Unprotected Anal Sex (UAS)

Change in percent of participants reporting unprotected anal intercourse--baseline vs. months 3 through 9 on study.

All Enrolled Participants

percentage of ppts reporting UAS

>5% Bone Mineral Density Decline at Femoral Neck

Percent of San Francisco participants in the TDF vs. placebo groups who were found to have >5% decline in Bone Mineral Density at the femoral neck.

Tenofovir Disoproxil Fumarate

percentage of participants


percentage of participants



Age, Continuous

years (Mean)
Standard Deviation: 10.2

Age, Categorical

Region of Enrollment

Sex: Female, Male

Overall Study

Tenofovir Disoproxil Fumarate