Bangkok Tenofovir Study, an HIV Pre-exposure Prophylaxis Trial, Bangkok, Thailand
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|ClinicalTrials.gov Identifier: NCT00119106|
Recruitment Status : Completed
First Posted : July 13, 2005
Results First Posted : January 27, 2021
Last Update Posted : February 10, 2021
|Condition or disease||Intervention/treatment||Phase|
|HIV Infections||Drug: Tenofovir disoproxil Drug: Placebo||Phase 2 Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||2413 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Study of the Safety and Efficacy of Daily Tenofovir to Prevent HIV Infection Among Injection Drug Users in Bangkok, Thailand|
|Study Start Date :||June 2005|
|Actual Primary Completion Date :||July 2013|
|Actual Study Completion Date :||October 2014|
Experimental: tenofovir disoproxil fumarate
Participants in the Tenofovir arm will receive daily oral tenofovir
Drug: Tenofovir disoproxil
Other Name: Tenofovir
Placebo Comparator: Placebo
Participants in the Placebo are will receive daily oral placebo
- Rates of HIV Seroconversion [ Time Frame: From date of randomization until the date of first documented seroconversion or date of death from any cause, whichever came first, assessed for an average of 4.0 years, with a maximum duration of 6.9 years ]Kaplan Meier survival curve.
- Renal Toxicity [ Time Frame: Blood tested for creatinine level at enrollment and every 3 months, up to 6.9 years ]Number of Participants with Grade 3 or 4 Renal Laboratory Toxicities
- Adverse Events [ Time Frame: Up to 6.9 years ]Number of Participants with adverse clinical events in tenofovir and placebo arms
- Number of Participants Reporting Injecting and Sharing Needles [ Time Frame: Participants were asked about injecting and needle sharing behaviors at enrollment and every 3 month visit, up to 6.9 years ]
Number of Participants reporting injecting and sharing needles:
Assessed injecting and sharing at baseline and every 3 months during follow-up. We used GEE to determine if there was a significant decline in injecting and sharing.
- Adherence to Study Drug/Placebo [ Time Frame: Participants were asked about adherence at 3 month visits, up to 6.9 years. ]Mean number of days that participants took study drug based on study drug diaries by study group.
- HIV Viral Load Copies/mL Measured at First Positive HIV Test Result by Group [ Time Frame: Among people who seroconverted, viral load was measured at month 1, 2, and every 4 months after HIV seroconversion ]Plasma HIV RNA concentrations.
- Number Participants Who Reported More Than One Sexual Partner at Baseline [ Time Frame: At enrolment ]Number of participants
- Number of Participants With Tenofovir-associated Resistance Mutations. [ Time Frame: Specimens collected at the time of HIV seroconversion ]Measure tenofovir associated resistance mutations (ie, K65R and K70E) in amplified viral RNA specimens from HIV-positive participants in the placebo and tenofovir groups.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00119106
|Thailand Ministry of Public Health - U.S. CDC Collaboration|
|Nonthaburi, Thailand, 11000|
|Principal Investigator:||Kachit Choopanya, MD||Bangkok Tenofovir Study Group|
|Study Director:||Michael T Martin, MD, MPH||Centers for Disease Control and Prevention|
|Study Director:||Lynn Paxton, MD||Centers for Disease Control and Prevention|