Bangkok Tenofovir Study, an HIV Pre-exposure Prophylaxis Trial, Bangkok, Thailand
Condition: HIV Infections
MeSH terms: Infections; HIV Infections; Acquired Immunodeficiency Syndrome
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The primary goals of this study are to assess the safety and efficacy of daily tenofovir to
      prevent parenteral HIV infection among injection drug users (IDUs). Assessment of changes in
      HIV associated risk behaviors, adherence to study drug, and, among IDU who become
      HIV-infected during the trial, evaluation of HIV viral load set point, CD4 counts, genetic
      characterization of infecting HIV viruses, and antiretroviral resistance will also be done.
    

Detailed description: 
      This is a phase II/III, randomized, double-blind, placebo-controlled study of the safety and
      efficacy of chemoprophylactic tenofovir, administered orally once daily to IDUs. The study
      will be conducted in Bangkok at 17 BMA Drug Treatment Clinics. Study participants will be
      randomized (1:1) to receive tenofovir 300 mg or placebo. Participants will be evaluated for
      adverse events and HIV seroconversion.

      Primary endpoints: The primary efficacy endpoint will be measured by rates of HIV
      seroconversion measured at monthly intervals. The primary safety endpoints will be measured
      by the frequency of Grade 3 or 4 renal or hepatic function laboratory toxicities or clinical
      toxicities in blinded tenofovir and placebo arms, as defined by the Gilead-modified NIAID
      Adult Common Toxicity Tables, and which cannot be directly attributed to a cause other than
      study medications; and the frequency of adverse clinical events in tenofovir and placebo
      arms.

      Secondary endpoints: Changes in HIV associated risk behaviors will be measured by rates of
      reported injection drug use and injection drug use frequency during the trial; rates of
      reported needle sharing; the number of unprotected sexual acts over the course of the trial;
      number of reported sexual partners over the course of the trial; and proportional use of
      condoms during sexual intercourse.

      Medication adherence will be measured as: rates, by interview and documentation on tenofovir
      adherence card, of participants taking at least six (86%) of seven daily doses of study drug
      each of the four weeks preceding the monthly study visit. Differences in virologic and
      immunologic responses to HIV infection among tenofovir and placebo recipients will be
      measured by: plasma viral load, measured by quantitative RNA PCR, a predictor of clinical
      progression of HIV disease; 14 CD4 cell counts will be measured by flow cytometry. Rates and
      nature of HIV antiretroviral genotypic and phenotypic resistance will be measured. Genetic
      characteristics of infecting HIV viruses including DNA sequence analysis and antibody binding
      studies will be conducted.

      In phase II, participants will be followed months 0, 1, 2, 3, then 3 monthly with hematology
      and chemistry tests and laboratory evaluations of renal and hepatic function until 200
      person-years of observation are accrued. At that point, a DSMB safety assessment will be
      conducted. Follow-up of enrolled participants will continue during the DSMB safety
      assessment. If safety is confirmed, all phase II participants will continue, and additional
      participants will be enrolled into the phase III portion of the trial. Accrual of the target
      enrollment of 2,400 IDUs is anticipated to take 48 months.

      Participants will choose between two follow-up schedules: monthly (every 4 weeks) or monthly
      plus daily with directly observed therapy (DOT). During DOT visits clinic staff will witness
      the participant swallow his/her study medication and clinic staff will initial the
      participant's tenofovir adherence card. Monthly visits will be the same for both groups and
      will include an assessment of tenofovir adherence and adverse events, a pill count and
      collection of unused pills, provision of a new 1 month supply of study medication, pre- and
      post-test HIV counseling, rapid oral HIV testing, urine pregnancy test (for female
      participants), HIV risk reduction counseling, and medication adherence counseling. At 3, 6,
      and every 3 months thereafter monthly procedures will be supplemented with a risk behavior
      questionnaire.
    

Intervention name(s): Tenofovir disoproxil; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Antiretroviral; Placebo
Other intervention name(s): Tenofovir
Intervention MeSH terms: Tenofovir
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: HIV; Prevention; Tenofovir; HIV Seronegativity