• Combined incidence of HIV-1 and HIV-2 infection [ Time Frame: 10-26 months per site ] [ Designated as safety issue: Yes ]
  as determined by infection (first detected via HIV rapid tests at the site); for participants who seroconvert, HIV RNA-PCR will be done on the previous visit(s) sample(s) to better determine the time of infection and to assess whether the participant was truly HIV-1 uninfected at her previous visit(s).
  
  
• Incidence of confirmed Grade 2 or higher serum creatinine toxicity, and Grade 3 or higher AST, ALT, or phosphorus toxicity during and 4 weeks after study product administration [ Time Frame: 10-26 months per site ] [ Designated as safety issue: Yes ]
  
• Frequency and nature of adverse events (AEs) during and within 4 weeks after study product administration [ Time Frame: 10-26 months per site ] [ Designated as safety issue: Yes ]
  

• Viral load and CD4+ T cell counts at the time of HIV diagnosis and at 4, 8, 12, 16, 24, 36 and 52 weeks later [ Time Frame: 10-38 months per site ] [ Designated as safety issue: Yes ]
  
• FTC and/or tenofovir resistance at the time of HIV diagnosis and 4 weeks later. If resistance is present, testing will be repeated at weeks 12, 24, 36 and 52 as necessary (resistance testing will stop if no resistance is detected) [ Time Frame: 10-38 months per site ] [ Designated as safety issue: Yes ]
  
• Incidence of pregnancy loss, prematurity, low birth weight, and congenital abnormalities [ Time Frame: 10-35 months per site ] [ Designated as safety issue: Yes ]
  
• Pill counts and participant report of adherence to once-daily pill taking [ Time Frame: 10-24 months per site ] [ Designated as safety issue: No ]
  
• Participant report of the number of sexual partners and frequency of unprotected sexual acts over time [ Time Frame: 10-26 months per site ] [ Designated as safety issue: No ]
  
• • Participant report of sexual behaviors and sex partner characteristics by participants who seroconvert and HIV negative participants [ Time Frame: 10-26 months per site ] [ Designated as safety issue: No ]
  

This Phase III, double-blind, randomized, placebo-controlled trial enrolled HIV-negative women from 4 sites in 3 countries (Kenya, Tanzania, South Africa). The study's purpose was to investigate the safety and effectiveness of a once-daily Truvada® pill (compared with placebo) in preventing HIV among HIV-uninfected women at risk of becoming infected through sexual intercourse.

The study population included HIV-antibody-negative women between the ages of 18-35 who were at risk of HIV acquisition through sexual intercourse. Each participant was randomized to take either a daily single oral tablet of Truvada®, which is a fixed-dose combination of emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg), or an identical placebo. All participants received risk reduction counseling and condoms. Women had to be using a study-approved effective non-barrier contraceptive method at the time of enrollment and were asked to do so for the whole period they were on study drug. They received contraceptive counseling throughout the study. Any diagnosed, treatable sexually transmitted infection was treated free of charge.

After enrollment, each participant was followed every four weeks. All participants will be followed for an additional eight weeks after study drug was stopped. Participants at risk for Hepatitis B Virus (HBV) flare will be followed every four weeks for 12 weeks after stopping study product. Participants who acquired HIV infection during the study stopped taking the study drug at the time of HIV diagnosis, and will be followed for 52 weeks post diagnosis and will be referred for care and treatment. Participants who became pregnant stopped taking the study drug but will continue follow-up visits. After the study, incidence rates of HIV infection will be compared between the two groups (active drug and placebo) using the intent-to-treat principle.