Bangkok Tenofovir Study, an HIV Pre-exposure Prophylaxis Trial, Bangkok, Thailand

January 27, 2021 updated by: Centers for Disease Control and Prevention

Study of the Safety and Efficacy of Daily Tenofovir to Prevent HIV Infection Among Injection Drug Users in Bangkok, Thailand

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

2413

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Thailand
      • Nonthaburi, Thailand, 11000
        • Thailand Ministry of Public Health - U.S. CDC Collaboration

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Report injection drug use in the 6 months before screening
  • Possess a Thai National Identification Card
  • Laboratory values as follows within 2 weeks before enrollment:
  • HIV oral fluid test non-reactive at screening and pre-enrollment visits
  • Hemoglobin 9 gm/dL
  • ALT and AST 2.5 x upper limit of normal (ULN)
  • Total bilirubin 1.5 mg/dL
  • Serum amylase 1.5 x ULN
  • Serum phosphorus 2.2 mg/dL
  • No evidence of current or chronic Hepatitis B infection by serology
  • Calculated creatinine clearance 60 mL/min by the Cockcroft-Gault formula where creatinine clearance in mL/min = Male: (140 - age in years) x (wt in kg)/72 x (serum creatinine in mg/dL) Female:(140 - age in years) x (wt in kg) x 0.85/72 x (serum creatinine in mg/dL)
  • Willing to abstain from sexual intercourse or use effective contraception during the trial (oral, injection, or barrier), for women
  • Willing and able to provide informed consent for study participation
  • Available and committed to DOT or monthly follow-up for at least 12 months

Exclusion Criteria:

  • Clinic physicians will determine if a subject with chronic illness requiring prescription medication can not enroll (medication used for drug treatment is allowed)
  • Positive urine pregnancy test
  • Breastfeeding
  • History of significant renal, liver, or bone disease
  • Any other clinical condition or prior therapy that, in the opinion of the clinic physician, would make the subject unsuitable for the study or unable to comply with the dosing requirements
  • Concurrent participation in any other HIV prevention trial or drug/vaccine safety trial. AIDSVAX B/E HIV vaccine trial (CDC protocol #2076) participants and Extension Study (CDC protocol #3750) participants may be screened for enrollment in the Bangkok Tenofovir Study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: tenofovir disoproxil fumarate
Participants in the Tenofovir arm will receive daily oral tenofovir
Drug: Tenofovir disoproxil
Antiretroviral
Other Names:
  • Tenofovir
Placebo Comparator: Placebo
Participants in the Placebo are will receive daily oral placebo
Drug: Placebo
Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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
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
Blood tested for creatinine level at enrollment and every 3 months, up to 6.9 years
Adverse Events
Time Frame: Up to 6.9 years
Number of Participants with adverse clinical events in tenofovir and placebo arms
Up to 6.9 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Participants were asked about injecting and needle sharing behaviors at enrollment and every 3 month visit, up to 6.9 years
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.
Participants were asked about adherence at 3 month visits, up to 6.9 years.
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.
Among people who seroconverted, viral load was measured at month 1, 2, and every 4 months after HIV seroconversion
Number Participants Who Reported More Than One Sexual Partner at Baseline
Time Frame: At enrolment
Number of participants
At enrolment
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.
Specimens collected at the time of HIV seroconversion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centers for Disease Control and Prevention

Collaborators

Ministry of Health, Thailand
Bangkok Metropolitan Administration Medical College and Vajira Hospital

Investigators

  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2005

Primary Completion (Actual)

July 1, 2013

Study Completion (Actual)

October 1, 2014

Study Registration Dates

First Submitted

July 8, 2005

First Submitted That Met QC Criteria

July 11, 2005

First Posted (Estimate)

July 13, 2005

Study Record Updates

Last Update Posted (Actual)

February 10, 2021

Last Update Submitted That Met QC Criteria

January 27, 2021

Last Verified

February 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDC-NCHSTP-4370

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Concept sheets are reviewed and approved, modified, or declined by research team.

IPD Sharing Time Frame

Data available after 2014

IPD Sharing Access Criteria

Concept sheets are reviewed and approved, modified, or declined by research team.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Informed Consent Form (ICF)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on HIV Infections

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Serbia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe