Phase 3, Multi-center, Double-blind, Randomized, Placebo-controlled Effectiveness and Safety Study to Assess the Role of Truvada® in Preventing HIV Acquisition in Women
Phase 3, Multi-center, Double-blind, Randomized, Placebo-controlled Effectiveness and Safety Study to Assess the Role of Truvada® in Preventing HIV Acquisition in Women
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.
After enrollment, each participant was followed every four weeks. All participants were followed for an additional eight weeks after study drug was stopped. Incidence rates of HIV infection were compared between the two groups (active drug and placebo) using the intent-to-treat principle.
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 were followed for an additional eight weeks after study drug was stopped. Participants at risk for Hepatitis B Virus (HBV) flare were 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 were referred for care and treatment. Participants who became pregnant stopped taking the study drug but continued follow-up visits. Incidence rates of HIV infection were compared between the two groups (active drug and placebo) using the intent-to-treat principle.
Inclusion Criteria:
Willing and able (see criterion 2) to provide written informed consent to be screened for and to participate in the trial
Able to answer a percentage of informed consent screening (75%) and enrollment (100%) comprehension quiz questions correctly
Between 18-35 years old, inclusive
At higher risk of becoming HIV infected
Have a final negative result according to the site-specific screening HIV testing algorithm and a final negative result at enrollment according to the study HIV testing algorithm
Willing to participate in all aspects of the study and to comply with study procedures, for up to 60 weeks, including:
Not intending to relocate out of the area for the duration of the study participation and does not have a job or other obligations that may require long absences from the area ( > 1 month at a time)
In general good health and have no condition (social or medical) which, in the opinion of the Site Investigator, would make study participation unsafe or complicate data interpretation
Not pregnant or breastfeeding, and does not anticipate a desire for pregnancy during the 52 weeks of on-product participation
Medically eligible at screening including:
Not received or receiving an experimental HIV vaccine, participating in another HIV prevention study or participating in any other clinical trial with a biomedical intervention
No clinical signs of liver disease (e.g., ascites, spider angiomata, hepatomegaly, jaundice)
No definite evidence of glycosuria or proteinuria (i.e., no repeated positive [ ≥ + 1 ] urine dipstick). If a urine dipstick is positive for either glucose and/or protein at the first test, a second urine sample will be tested.
No history of pathological bone fractures
No history of adverse reaction to latex
Not taking any of the following medications: nephrotoxic agents; aminoglycoside antibiotics (including gentamicin); intravenous (IV) amphotericin B; cidofovir; cisplatin; foscarnet; IV pentamidine; oral or IV vancomycin; oral or IV gancyclovir; other agents with significant nephrotoxic potential; drugs that slow renal excretion; probenecid; immune system modulators; systemic chemotherapeutic agents (i.e. cancer treatment medications); systemic corticosteroids; interleukin-2 (IL-2); immunomodulators; interferon (alpha, beta, or gamma); other antiretrovirals (including nucleoside analogs, non-nucleoside reverse transcriptase inhibitors, protease inhibitors or investigational antiretroviral agents)