FEM-PrEP (Truvada®): Study to Assess the Role of Truvada® in Preventing HIV Acquisition in Women
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Truvada; Placebo
Intervention description: Daily single oral tablet of Truvada - a fixed-dose combination of emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg).; Daily single oral tablet of Placebo. Tablets are identical to Truvada tablets in taste and appearance; however, they contain no active ingredients.
Intervention MeSH terms: Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 2120.0
Sex: Female
Minimum age: 18 Years
Maximum age: 35 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Aspartate Aminotransferase (AST); Alanine Aminotransferase (ALT); HIV; HIV Prevention; Oral PrEP; Truvada; women; Tenofovir; TDF; FTC; emtricitabine; hepatitis; Pre-exposure Prophylaxis (PrEP); HIV Seronegativity

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Willing and able (see criterion 2) to provide written informed consent to be screened
             for and to participate in the trial

          2. Able to answer a percentage of informed consent screening (75%) and enrollment (100%)
             comprehension quiz questions correctly

          3. Between 18-35 years old, inclusive

          4. At higher risk of becoming HIV infected

          5. 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

          6. Willing to participate in all aspects of the study and to comply with study
             procedures, for up to 60 weeks, including:

               -  Be randomized

               -  Use study product as directed

               -  Adhere to follow-up schedule and willing to be contacted by site staff between
                  study visits (by phone and/or in person)

               -  Use a study-approved effective non-barrier method of contraception for the
                  duration of the study

               -  Take study product, as evidenced by swallowing a vitamin tablet that is similar
                  in size to the study product at enrollment

               -  Provide contact information and agrees to some form of contact method throughout
                  the study

          7. 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)

          8. 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

          9. Not pregnant or breastfeeding, and does not anticipate a desire for pregnancy during
             the 52 weeks of on-product participation

         10. Medically eligible at screening including:

               -  Adequate renal function (serum creatinine ≤ upper limit of normal (ULN) of local
                  range and creatinine clearance ≥ 60ml/min estimated by the Cockcroft-Gault
                  Creatinine Clearance Formula

               -  Adequate hepatic function (hepatic transaminases ALT and AST < 2x ULN [according
                  to local normal ranges])

               -  HBsAg negative

               -  Serum phosphorus levels above the lower limit of the local normal range
                  (according to local normal ranges - grade 3 & 4 hypophosphatemia will be excluded
                  even if within normal local ranges)

         11. 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

         12. No clinical signs of liver disease (e.g., ascites, spider angiomata, hepatomegaly,
             jaundice)

         13. 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.

         14. No history of pathological bone fractures

         15. No history of adverse reaction to latex

         16. 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)