Botswana TDF/FTC Oral HIV Prophylaxis Trial (TDF2)

January 24, 2020 updated by: Centers for Disease Control and Prevention

Study of the Safety and Efficacy of Daily Oral Antiretroviral Use for the Prevention of HIV Infection in Heterosexually Active Young Adults in Botswana

This study tested whether taking a pill of tenofovir and emtricitabine (two antiretroviral medicines) was safe for sexually-active young adults in Botswana without HIV infection and whether it reduced their risk of getting an HIV infection.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Twelve hundred and nineteen healthy, sexually active women and men, 18-39 years old, without HIV infection were enrolled in Francistown and Gaborone, Botswana. They were provided with free male and female condoms, repeated individualized risk-reduction counseling, diagnosis and treatment of sexually transmitted diseases, and women will be provided with a choice of effective family planning methods. In addition, volunteers were randomized to receive either Tenofovir and emtricitabine (in a single pill) or a placebo pill to take once a day. Volunteers were seen monthly for at least 12 months to monitor for side effects and toxicities and to test their HIV status. Persons who become HIV infected during the trial received ongoing supportive counseling, CD4 and viral load monitoring, education about HIV infection/disease, and access to HIV care including free antiretrovirals when clinically indicated. Volunteer safety was monitored by a local ethics committee, Centers for Disease Control Institutional Review Board (CDC IRB) and an independent data safety and monitoring board

Study Type

Interventional

Enrollment (Actual)

1219

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

  • Botswana
      • Gaborone, Botswana
        • BOTUSA HIV Prevention Research Unit
  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30333
        • Centers for Disease Control and Prevention

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

18 years to 39 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • citizen of Botswana 18-39 years old
  • sexually active
  • HIV uninfected
  • Hepatitis B and C uninfected
  • Calculated creatinine clearance >= 60 mL/min
  • hemoglobin >= 8 gm/dL
  • ALT and AST <= 2x ULN
  • total bilirubin <= 1.5 mg/dL
  • total serum amylase <= 1.5x ULN
  • Serum phosphorus >= 2.2 mg/dL
  • willing to use hormonal contraception (females)
  • living within 1 hours travel of study clinic
  • pass comprehension test
  • willing and able to give informed consent

Exclusion Criteria:

  • 18-20 without parent/guardian consent
  • history of significant renal or bone disease
  • any chronic illness requiring ongoing prescription medication
  • pregnant or breastfeeding
  • planning to move away from site in the next year
  • participating in another HIV prevention or vaccine safety trial
  • any other clinical condition or prior therapy that, in the opinion of the study physician, would make the volunteer unsuitable for the study or unable to comply with the dosing requirements

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: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: TDF-FTC,condoms,adh/risk counseling
Eligible participants were randomized to oral Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg (TDF-FTC) once daily in the form of a single tablet. The ratio of randomization was 1:1. Participants randomized to the active arm received male and female condoms, risk reduction counseling, adherence counseling, and routine monitoring for HIV infection, laboratory abnormalities, and adverse events.
Drug: Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg
Other Names:
  • Truvada
Placebo Comparator: Placebo,condoms,adh/risk counseling
Eligible participants were randomized to the placebo arm and received placebo oral tablets that were visually identical to the TDF-FTC tablet and taken once daily. The placebo tablets contained no active ingredients. The ratio of randomization was 1:1. Participants randomized to the placebo arm received male and female condoms, personalized risk reduction counseling, adherence counseling, and routine monitoring for HIV infection, laboratory abnormalities, and adverse events.
Drug: Placebo Oral Tablet
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Adverse Drug Reactions in the Tenofovir/Emtricitabine and Placebo Arms
Time Frame: Monthly, for up to 3 years
Study visits were scheduled every 30 days until completion of the study, and participants were instructed to return to the clinic for evaluation in the event of an illness. Participants reported any adverse effects at monthly visits and interim visits.
Monthly, for up to 3 years
HIV Incidence in the Tenofovir/Emtricitabine and Placebo Arms
Time Frame: Monthly, for up to 3 years
Study visits were scheduled every 30 days until completion of the study and during monthly study visits, we performed testing for HIV infection. At completion of the study, we tested all participants for HIV infection, using an enzyme-linked immunosorbent assay (ELISA).The primary efficacy end point was the difference in the rates of HIV infection between participants assigned to receive TDF-FTC and those assigned to receive placebo. The initial efficacy analysis included all study participants who were randomly assigned to receive a study medication (intention-to-treat cohort).
Monthly, for up to 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Condom Use During Study: Number of Participants With >=1 Condomless Sex Acts
Time Frame: 12 months
We assessed condom use of the enrolled participants by face-to-face interviews (at baseline and monthly thereafter) and provided a comprehensive package of HIV prevention services, including individualized counseling on risk reduction, free male and female condoms, and screening for sexually transmitted infections followed, if applicable, by partner notification and treatment.
12 months
Rates of Adherence to Study Medication
Time Frame: 36 months
The rates of adherence to study medication by treatment arm was assessed over the entire course of the study. This comparison was done by assessing the percentage of pills taken by participants within each study arm. The difference between the 2 arms was compared with a Fisher' exact test.
36 months
Antiretroviral (ARV) Resistance Patterns in Seroconverters
Time Frame: At time HIV infection diagnosed,1 month post-time of HIV infection diagnosis, and 6 months post-time of HIV infection diagnosis
Participants who seroconverted had blood samples taken at the time of infection and at one month and six months post seroconversion to detect any HIV resistance mutations.
At time HIV infection diagnosed,1 month post-time of HIV infection diagnosis, and 6 months post-time of HIV infection diagnosis
CD4 Evaluation After HIV Seroconversion
Time Frame: 1-year post seroconversion
Study medication was stopped when HIV infected was diagnosed. Seroconvertors were referred for clinical care and followed an additional year with scheduled quarterly CD4+ cell count assessments. A model-estimated geometric mean of the CD4+ cell counts by each treatment group was evaluated.
1-year post 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

Gilead Sciences
Botswana Ministry of Health

Investigators

  • Principal Investigator: Michael Thigpen, MD MPH, National Institutes of Health (NIH)
  • Principal Investigator: Lynn Paxton, MD MPH, 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

March 1, 2007

Primary Completion (Actual)

March 1, 2011

Study Completion (Actual)

March 1, 2011

Study Registration Dates

First Submitted

March 16, 2007

First Submitted That Met QC Criteria

March 16, 2007

First Posted (Estimate)

March 19, 2007

Study Record Updates

Last Update Posted (Actual)

February 5, 2020

Last Update Submitted That Met QC Criteria

January 24, 2020

Last Verified

February 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDC-NCHHSTP-4940
  • BOTUSA MB06 (Other Identifier: CDC-BOTUSA)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Data sharing will be governed by prevailing CDC data sharing policies.

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.

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