Botswana TDF/FTC Oral HIV Prophylaxis Trial

Phase 2

Completed

• Conditions: HIV Infections
• Interventions: Drug: Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg; Drug: Placebo Oral Tablet

• Registration Number: NCT00448669
• Lead Sponsor: Centers for Disease Control and Prevention

Brief Summary

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.

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 Timeline

• Study Start: 2007-03
• Study First Submitted: 2007-03-16
• Study First Submitted QC: 2007-03-16
• Study First Posted: 2007-03-19
• Primary Completion: 2011-03
• Study Completion: 2011-03
• Results First Submitted: 2015-05-22
• Status Verified: 2016-02
• Results First Submitted QC: 2020-01-24
• Last Update Submitted: 2020-01-24
• Results First Posted: 2020-02-05
• Last Update Posted: 2020-02-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1219

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TDF-FTC,condoms,adh/risk counseling	Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg	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.
Placebo,condoms,adh/risk counseling	Placebo Oral Tablet	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Adverse Drug Reactions in the Tenofovir/Emtricitabine and Placebo Arms	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.
HIV Incidence in the Tenofovir/Emtricitabine and Placebo Arms	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).

Secondary Outcome Measures

Name	Time	Method
Antiretroviral (ARV) Resistance Patterns in Seroconverters	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.
CD4 Evaluation After HIV Seroconversion	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.
Changes in Condom Use During Study: Number of Participants With >=1 Condomless Sex Acts	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.
Rates of Adherence to Study Medication	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.

Trial Locations

Locations (2)

BOTUSA HIV Prevention Research Unit; 🇧🇼 Gaborone, Botswana

Centers for Disease Control and Prevention; 🇺🇸 Atlanta, Georgia, United States