Botswana TDF/FTC Oral HIV Prophylaxis Trial

Study Overview
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Brief Summary
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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
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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

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

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: TDF-FTC,condoms,adh/risk counseling<br>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<br> <br> * Other names: Truvada;|
| Placebo Comparator: Placebo,condoms,adh/risk counseling<br>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<br> <br> * Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Drug Reactions in the Tenofovir/Emtricitabine and Placebo Arms | 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 | 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 | 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 | 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 | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV incidence, HIV prevention, Tenofovir, Emtricitabine, Botswana, HIV seronegativity