Safety and Pharmacokinetics of Tenofovir and Emtricitabine in HIV Negative Thai Women

Investigator: Kimberly Page, PhD, MPH
Sponsor: University of New South Wales

Location(s): Thailand


 The long term objective of this application is to determine whether Tenofovir, and Tenofovir in combination with Emtricitabine, are safe when administered over an extended time period to Women in an Asian population. The rationale for testing the Safety of these drugs in this population is that they are being considered as possible prophylactic agents against the acquisition of HIV infection. Chemoprophylaxis against HIV infection using antiretroviral drugs has appeal as a prevention strategy for Women at risk of sexual exposure who are not always in a position to ensure that male partners use condoms. Among the antiretroviral drugs,Tenofovir has been of particular interest for Chemoprophylaxis, because of its generally favorable toxicity profile, its long biological half-life, and the results of experiments inmacaques that demonstrate its ability to prevent infection with SIV. Emtricitabine has a somewhat shorter half-life but is also associated with very limited side effects, and is available in a co-formulation with Tenofovir. Prevention studies involving Tenofovir are now underway, and it is likely that within the next two years, efficacy results will be available from several studies, but none will provide information on the Safety and tolerability of Tenofovir in HIV Negative Women of Asian background. If Tenofovir proves effective in HIV prevention, it will still need to be tested for Safety in populations that differ from those in which the efficacy studies were conducted. in studies of people withHIV infection, Tenofovir has been associated with some renal and bone toxicities, as well as gastrointestinal symptoms. Neither Tenofovir nor Emtricitabine has been investigated in large numbers of people who do not have HIV infection. If Tenofovir has sub-optimal efficacy for HIV infection (e.g. less than 80%), the addition ofEmtricitabine may produced substantially enhanced protection. The study described in this application proposes the comprehensive investigation of the Safety of Tenofovir, and the combination of Tenofovir and Emtricitabine in HIV-uninfected Thai Women, through a double blind, placebo controlled trial over twelve months. Participants in the study will be recruited through a voluntary counseling and testing center in Bangkok, and will undergo monthly assessments for clinical and laboratory markers of toxicity, with a particular emphasis on outcomes that indicate renal or bone damage. There will be 150 Women in each treatment arm. The primary endpoints of the Safety study will be bone density as measured by DXA scanning, and renal function as measure by creatinine clearance. A key secondary endpoint will be the number of Grade 3 and 4 adverse events. Under this application, the Safety study would be preceded by a short-term pharmacokinetic study, that would determine whether adequate intracellular drug levels can be achieved by a reduced level of dosing, involving second daily administration. If not, the Safety study will be conducted at the standard therapeutic doses.