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

NCT00119106 | Completed Phase 2 Results DMC

• 1 other identifier: CDC-NCHSTP-4370
• Study Type: interventional
• Target: 2,413
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV Infections

Keywords

HIV; Prevention; Tenofovir; HIV Seronegativity

Outcome Measures

Primary Outcomes (3)

• Rates of HIV Seroconversion

  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

  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

  Number of Participants with adverse clinical events in tenofovir and placebo arms

  Up to 6.9 years

Secondary Outcomes (5)

• Number of Participants Reporting Injecting and Sharing Needles

  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

  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

  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

  At enrolment

• Number of Participants With Tenofovir-associated Resistance Mutations.

  Specimens collected at the time of HIV seroconversion

Study Arms (2)

tenofovir disoproxil fumarate

EXPERIMENTAL

Participants in the Tenofovir arm will receive daily oral tenofovir

Drug: Tenofovir disoproxil

Placebo

PLACEBO COMPARATOR

Participants in the Placebo are will receive daily oral placebo

Drug: Placebo

Interventions

Tenofovir disoproxil DRUG

Antiretroviral

Also known as: Tenofovir

tenofovir disoproxil fumarate

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centers for Disease Control and Prevention: lead
• Ministry of Health, Thailand: collaborator
• Bangkok Metropolitan Administration Medical College and Vajira Hospital: collaborator

Study Sites (1)

Thailand Ministry of Public Health - U.S. CDC Collaboration

Nonthaburi, 11000, Thailand

Location

Related Publications (9)

• Choopanya K, Martin M, Suntharasamai P, Sangkum U, Mock PA, Leethochawalit M, Chiamwongpaet S, Kitisin P, Natrujirote P, Kittimunkong S, Chuachoowong R, Gvetadze RJ, McNicholl JM, Paxton LA, Curlin ME, Hendrix CW, Vanichseni S; Bangkok Tenofovir Study Group. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2013 Jun 15;381(9883):2083-90. doi: 10.1016/S0140-6736(13)61127-7. Epub 2013 Jun 13.

  PMID: 23769234 BACKGROUND

• Martin M, Vanichseni S, Suntharasamai P, Sangkum U, Mock PA, Chaipung B, Worrajittanon D, Leethochawalit M, Chiamwongpaet S, Kittimunkong S, Gvetadze RJ, McNicholl JM, Paxton LA, Curlin ME, Holtz TH, Samandari T, Choopanya K; Bangkok Tenofovir Study Group. Factors associated with the uptake of and adherence to HIV pre-exposure prophylaxis in people who have injected drugs: an observational, open-label extension of the Bangkok Tenofovir Study. Lancet HIV. 2017 Feb;4(2):e59-e66. doi: 10.1016/S2352-3018(16)30207-7. Epub 2016 Nov 18.

  PMID: 27866873 BACKGROUND

• Martin M, Vanichseni S, Suntharasamai P, Sangkum U, Mock PA, Leethochawalit M, Chiamwongpaet S, Curlin ME, Na-Pompet S, Warapronmongkholkul A, Kittimunkong S, Gvetadze RJ, McNicholl JM, Paxton LA, Choopanya K; Bangkok Tenofovir Study Group. The impact of adherence to preexposure prophylaxis on the risk of HIV infection among people who inject drugs. AIDS. 2015 Apr 24;29(7):819-24. doi: 10.1097/QAD.0000000000000613.

  PMID: 25985403 BACKGROUND

• Martin M, Vanichseni S, Suntharasamai P, Sangkum U, Mock PA, Leethochawalit M, Chiamwongpaet S, Gvetadze RJ, Kittimunkong S, Curlin ME, Worrajittanon D, McNicholl JM, Paxton LA, Choopanya K; Bangkok Tenofovir Study Group. Risk behaviors and risk factors for HIV infection among participants in the Bangkok tenofovir study, an HIV pre-exposure prophylaxis trial among people who inject drugs. PLoS One. 2014 Mar 25;9(3):e92809. doi: 10.1371/journal.pone.0092809. eCollection 2014.

  PMID: 24667938 BACKGROUND

• Vanichseni S, Martin M, Suntharasamai P, Sangkum U, Mock PA, Gvetadze RJ, Curlin ME, Leethochawalit M, Chiamwongpaet S, Chaipung B, McNicholl JM, Paxton LA, Kittimunkong S, Choopanya K. High Mortality Among Non-HIV-Infected People Who Inject Drugs in Bangkok, Thailand, 2005-2012. Am J Public Health. 2015 Jun;105(6):1136-41. doi: 10.2105/AJPH.2014.302473. Epub 2015 Apr 16.

  PMID: 25880964 BACKGROUND

• Parker I, Khalil G, Martin A, Martin M, Vanichseni S, Leelawiwat W, McNicholl J, Hickey A, Garcia-Lerma JG, Choopanya K, Curtis KA. Altered Antibody Responses in Persons Infected with HIV-1 While Using Preexposure Prophylaxis. AIDS Res Hum Retroviruses. 2021 Mar;37(3):189-195. doi: 10.1089/AID.2020.0137. Epub 2020 Dec 9.

  PMID: 33126825 DERIVED

• Suntharasamai P, Martin M, Choopanya K, Vanichseni S, Sangkum U, Tararut P, Leelawiwat W, Anekvorapong R, Mock PA, Cherdtrakulkiat T, Leethochawalit M, Chiamwongpaet S, Gvetadze RJ, McNicholl JM, Paxton LA, Kittimunkong S, Curlin ME. Assessment of Oral Fluid HIV Test Performance in an HIV Pre-Exposure Prophylaxis Trial in Bangkok, Thailand. PLoS One. 2015 Dec 30;10(12):e0145859. doi: 10.1371/journal.pone.0145859. eCollection 2015.

  PMID: 26717405 DERIVED

• Martin M, Vanichseni S, Suntharasamai P, Sangkum U, Mock PA, Gvetadze RJ, Curlin ME, Leethochawalit M, Chiamwongpaet S, Cherdtrakulkiat T, Anekvorapong R, Leelawiwat W, Chantharojwong N, McNicholl JM, Paxton LA, Kittimunkong S, Choopanya K; Bangkok Tenofovir Study Group. Renal function of participants in the Bangkok tenofovir study--Thailand, 2005-2012. Clin Infect Dis. 2014 Sep 1;59(5):716-24. doi: 10.1093/cid/ciu355. Epub 2014 May 14.

  PMID: 24829212 DERIVED

• Martin M, Vanichseni S, Suntharasamai P, Sangkum U, Chuachoowong R, Mock PA, Leethochawalit M, Chiamwongpaet S, Kittimunkong S, van Griensven F, McNicholl JM, Paxton L, Choopanya K; Bangkok Tenofovir Study Group. Enrollment characteristics and risk behaviors of injection drug users participating in the Bangkok Tenofovir Study, Thailand. PLoS One. 2011;6(9):e25127. doi: 10.1371/journal.pone.0025127. Epub 2011 Sep 28.

  PMID: 21969870 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Tenofovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Participants could have under-reported stigmatised behaviours such as injecting drugs.30

Results Point of Contact

• Title: Dr. Michael Martin
• Organization: CDC

ZND9@CDC.GOV

662 580 0669

Study Officials

• Kachit Choopanya, MD

  Bangkok Tenofovir Study Group

  PRINCIPAL INVESTIGATOR

• Michael T Martin, MD, MPH

  Centers for Disease Control and Prevention

  STUDY DIRECTOR

• Lynn Paxton, MD

  Centers for Disease Control and Prevention

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2005
• First Posted: July 13, 2005
• Study Start: June 1, 2005
• Primary Completion: July 1, 2013
• Study Completion: October 1, 2014
• Last Updated: February 10, 2021
• Results First Posted: January 27, 2021

Record last verified: 2015-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data available after 2014
• Access Criteria: Concept sheets are reviewed and approved, modified, or declined by research team.

Locations

TH (1)