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

Study Description

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Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
HIV Infection	Drug: tenofovir disoproxil fumarate; Drug: placebo	Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	400 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Prevention
Official Title:	Phase II Extended Safety Study of Tenofovir Disoproxil Fumarate (TDF) Among HIV-1 Negative Men
Study Start Date :	February 2005
Actual Primary Completion Date :	August 2009
Actual Study Completion Date :	August 2009

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: active immediate; participants in this arm start study product immediately upon enrollment	Drug: tenofovir disoproxil fumarate; study product taken daily; Other Name: Viread
Placebo Comparator: placebo immediate; participants in this arm start study product immediately upon enrollment	Drug: placebo; study product taken daily
Active Comparator: active delayed; persons in this arm start study product 9 months after enrollment	Drug: tenofovir disoproxil fumarate; study product taken daily; Other Name: Viread
Placebo Comparator: placebo delayed; participants in this arm start study product nine months after enrollment	Drug: placebo; study product taken daily

Outcome Measures

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Primary Outcome Measures :

1. Clinical Safety--Creatinine Elevations [ Time Frame: 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)
2. Clinical Safety--Hypophosphatemia [ Time Frame: 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 :

1. Number of Breakthrough HIV Infections [ Time Frame: 24 months (immediate arm) and 15 months (delayed arm) ]
   Number of participants with HIV seroconversions occuring while on study drug
2. Adherence to Study Drug [ Time Frame: 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.
3. Behavioral Safety--Unprotected Anal Sex (UAS) [ Time Frame: Nine months ]
   Change in percent of participants reporting unprotected anal intercourse--baseline vs. months 3 through 9 on study.

Other Outcome Measures:

1. >5% Bone Mineral Density Decline at Femoral Neck [ Time Frame: 24 months (immediate arm), 15 months (delayed arm) ]
   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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 60 Years (Adult)
Sexes Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

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.

Contacts and Locations

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Locations

United States, California
San Francisco Department of Public Health
San Francisco, California, United States, 94102
United States, Georgia
AIDS Research Consortium of Atlanta
Atlanta, Georgia, United States, 30308
United States, Massachusetts
Fenway Community Health
Boston,, Massachusetts, United States, 02115

Sponsors and Collaborators

Centers for Disease Control and Prevention

San Francisco Department of Public Health

AIDS Research Consortium of Atlanta

Investigators

Principal Investigator:	Kata L Chillag, PhD	Centers for Disease Control and Prevention
Principal Investigator:	Lisa A Grohskopf, MD, MPH	Centers for Disease Control and Prevention
Principal Investigator:	Susan Buchbinder, MD	San Francisco Dept. of Public Health
Principal Investigator:	Melanie Thompson, MD	AIDS Research Consortium of Atlanta
Principal Investigator:	Kenneth H. Mayer, MD	Fenway Community Health

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Baxi SM, Vittinghoff E, Bacchetti P, Huang Y, Chillag K, Wiegand R, Anderson PL, Grant R, Greenblatt RM, Buchbinder S, Gandhi M, Liu AY. Comparing pharmacologic measures of tenofovir exposure in a U.S. pre-exposure prophylaxis randomized trial. PLoS One. 2018 Jan 9;13(1):e0190118. doi: 10.1371/journal.pone.0190118. eCollection 2018.

Liu AY, Vittinghoff E, Sellmeyer DE, Irvin R, Mulligan K, Mayer K, Thompson M, Grant R, Pathak S, O'Hara B, Gvetadze R, Chillag K, Grohskopf L, Buchbinder SP. Bone mineral density in HIV-negative men participating in a tenofovir pre-exposure prophylaxis randomized clinical trial in San Francisco. PLoS One. 2011;6(8):e23688. doi: 10.1371/journal.pone.0023688. Epub 2011 Aug 29.

Responsible Party:	Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:	NCT00131677 History of Changes
Other Study ID Numbers:	CDC-NCHHSTP-4323
First Posted:	August 19, 2005
Results First Posted:	March 10, 2014
Last Update Posted:	March 10, 2014
Last Verified:	August 2013

Additional relevant MeSH terms:

HIV Infections; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases	Tenofovir; Antiviral Agents; Anti-Infective Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Retroviral Agents; Anti-HIV Agents