Clinical trial NCT00131677: Extended Safety Study of Tenofovir Disoproxil Fumarate (TDF) Among HIV-1 Negative Men
Official title: Phase II Extended Safety Study of Tenofovir Disoproxil Fumarate (TDF) Among HIV-1 Negative Men
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infection
Lead sponsor: Centers for Disease Control and Prevention
Sponsor class: FED
Collaborators: name: San Francisco Department of Public Health
name: AIDS Research Consortium of Atlanta
First posted: 2005-08-19
Enrollment: 400
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: 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.

Eligibility 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.

Primary outcomes:
measure: Clinical Safety--Creatinine Elevations
timeFrame: 24 months (immediate arm) and 15 months (delayed arm)
measure: Clinical Safety--Hypophosphatemia
timeFrame: 24 months (immediate arm), 15 months (delayed arm)
Secondary outcomes:
measure: Number of Breakthrough HIV Infections
timeFrame: 24 months (immediate arm) and 15 months (delayed arm)
measure: Adherence to Study Drug
timeFrame: 24 months (immediate arm) and 15 months (delayed arm)
measure: Behavioral Safety--Unprotected Anal Sex (UAS)
timeFrame: Nine months
Other outcomes:
measure: >5% Bone Mineral Density Decline at Femoral Neck
timeFrame: 24 months (immediate arm), 15 months (delayed arm)
Locations:
city: San Francisco
country: United States
facility: San Francisco Department of Public Health
state: California
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Boston,
country: United States
facility: Fenway Community Health
state: Massachusetts
Study officials:
affiliation: Centers for Disease Control and Prevention
name: Kata L Chillag, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centers for Disease Control and Prevention
name: Lisa A Grohskopf, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: San Francisco Dept. of Public Health
name: Susan Buchbinder, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: AIDS Research Consortium of Atlanta
name: Melanie Thompson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fenway Community Health
name: Kenneth H. Mayer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.