An observational study in Pharmacokinetic Study in Healthy Volunteers, sponsored by University of North Carolina, Chapel Hill. Completed at 1 site in United States. Open to participants aged 18 Years to 49 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2012-10-10.
Sponsored by University of North Carolina, Chapel Hill · Observational
This open-label, non-blinded, pharmacokinetic (PK) study will assess both tenofovir and emtricitabine (components of Truvada) concentrations within genital tract of male and females after a single dose of Truvada®. Concentrations of the active drug will be measured in blood (women and men), cervicovaginal aspirates and vaginal tissue (women only), seminal fluid and rectal tissue (men only). Samples will be obtained at 24 hours (1 day), 48 hours (2 days), 5 days, 7 days, 10 days, and 14 days post-dose. Each subject will undergo 2 biopsy days, at least 72 hours apart. Additionally, tissue samples will be evaluated ex-vivo for HIV infectivity.
An estimated 80% of HIV infections worldwide are acquired through sexual transmission.1 Viable methods of preventing the sexual transmission of HIV are urgently needed, especially in resource-poor countries. As these countries now have increased access to generic antiretroviral medications, oral administration of antiretroviral drugs as pre-exposure prophylaxis may serve as a feasible, minimally invasive mechanism of preventing the sexual transmission of HIV globally.
Antiretroviral prophylaxis with the combination of tenofovir and emtricitabine has recently been investigated by the U.S. Centers for Disease Control and Prevention in a series of studies with rhesus macaques. Researchers developed a rectal inoculation model using concentrations of Simian HIV (SIV) that were representative of HIV exposure in humans. With this model, researchers demonstrated that standard doses of tenofovir disoproxil fumarate delayed, or partially protected, animals from the acquisition of Simian HIV during a 14-week time period. In this same model, high dose tenofovir was fully protective from infection.2 However, it is unknown how concentrations in the macaque mucosal surfaces compare to that in humans. Notwithstanding, a number of clinical studies are currently investigating daily dosing of tenofovir or tenofovir with emtricitabine for pre-exposure prophylaxis.3
Since daily dosing of antiretrovirals for pre-exposure prophylaxis is not sustainable long-term, other coitally-dependent (episodic) dosing strategies are needed. However, the extent to which these drugs concentrate in tissues, and the duration of intracellular phosphate exposure after single doses, is currently unknown. This information is required to inform the potential of success with these dosing strategies.
At steady-state concentrations, the mean blood plasma half-life (t½) of tenofovir and emtricitabine are 15.9 hours and 10.7 hours, respectively. 4 However, the intracellular t½ of tenofovir diphosphate and emtricitabine triphosphate are >60 hours and 39 hours, respectively.5 The long intracellular t½ of the active forms of these drugs might hold advantages for episodic dosing. However, the long t½ might also hold disadvantages in terms of the development of viral resistance mutations. This phenomenon (the development of resistance after a single dose of a long t½ drug), has been previously seen with nevirapine given during delivery to HIV-infected women to prevent mother to child transmission of HIV.6 However, these women were chronically infected, rather than newly infected, as would be the case with populations exposed to prevention strategies.
The proposed study aims to augment the information gathered in previous studies by examining intracellular and extracellular tenofovir and emtricitabine drug concentrations in various human compartments after a single dose, and to describe the potential for HIV infectivity in selected tissue samples obtained from these compartments.
University of North Carolina, Chapel Hill is the lead sponsor of 1,340 studies on the registry; 133 are open to participants now.
Of its 155 completed or terminated interventional studies of FDA-regulated products, 136 (88%) have results posted.
Counted across the registry records on this site, refreshed daily.
Twelve adult (18 years or older) healthy volunteers will be recruited to participate in the study. A total of 6 men and 6 women will be enrolled. Subjects of all races and ethnicities may participate, provided they meet study inclusion/exclusion criteria.
(Males Only)
(Females Only)
Exclusion Criteria:
(Males Only)
(Females Only)
Single dose of Truvada
Drug: tenofovir + emtricitabine
tenofovir 300mg + emtricitabine 200mg x one dose
Also known as: Truvada
TFV, TFV-DP, FTC, FTC-TP in blood, CVF, cervical and vaginal and rectal tissue over 14 days
The study aims to examine intra- and extracellular tenofovir and emtricitabine concentrations in various human compartments after a single dose, and to look at the potential for HIV infectivity in tissue samples from these compartments.
Time frame: 14 days
This study is completed, as verified in Oct 2012. You cannot join it, but the record below documents what was studied.
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University of North Carolina, Chapel Hill