Botswana TDF/FTC Oral HIV Prophylaxis Trial (TDF2)

• Adverse drug reactions in the tenofovir/emtricitabine and placebo arms; [ Time Frame: monthly ] [ Designated as safety issue: Yes ]
  Participants reported any adverse effects at monthly visits.
• HIV incidence in the tenofovir/emtricitabine and placebo arms [ Time Frame: monthly ] [ Designated as safety issue: Yes ]
  Participants HIV status was checked monthly

• Adverse drug reactions in the tenofovir/emtricitabine and placebo arms;
• HIV incidence in the tenofovir/emtricitabine and placebo arms

• Secondary: Changes in levels of unprotected sex during the trial; [ Time Frame: quarterly ] [ Designated as safety issue: No ]
  Participants provided information about their sexual activity on a quarterly basis
• Adherence to medication; [ Time Frame: monthly ] [ Designated as safety issue: No ]
  Participants provided information about their adherence to medication on a quarterly basis. Pill counts were done monthly.
• Antiretroviral (ARV) resistance patterns in seroconverters; [ Time Frame: at time of seroconversion ] [ Designated as safety issue: Yes ]
  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.
• Viral set point in seroconverters [ Time Frame: At time of seroconversion and six months afterward ] [ Designated as safety issue: Yes ]
  Participants who HIV seroconverted during the study had their CD4 count evaluated at the time of seroconversion and at 6 months post seroconversion.

• Secondary: Changes in levels of unprotected sex during the trial;
• Adherence to medication;
• Antiretroviral (ARV) resistance patterns in seroconverters;
• Viral set point in seroconverters

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.

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

• Drug: Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg
  Daily oral single dose pill containing 300 mg TDF and 200 mg FTC.
  Other Name: Truvada
• Drug: TDF-FTC placebo
  Placebo comparator for TDF-FTC

• Active Comparator: TDF-FTC, condoms, risk counseling
  Participants randomized to the active arm received daily oral TDF-FTC along with male and female condoms, personalized risk reduction counseling, adherence counseling, and routine monitoring for HIV infection, laboratory abnormalities, and adverse events.
  Intervention: Drug: Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg
• Placebo Comparator: Placebo, condoms, risk counseling
  Participants randomized to the placebo arm received a daily oral placebo tablet along with male and female condoms, personalized risk reduction counseling, adherence counseling, and routine monitoring for HIV infection, laboratory abnormalities, and adverse events.
  Intervention: Drug: TDF-FTC placebo

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

• Botswana Ministry of Health
• Gilead Sciences