Antiretroviral drug concentrations in the male and female genital tract: implications for the sexual transmission of HIV
ABSTRACT To summarize the recent literature (2008-2010) on antiretroviral (ARV) drug disposition into the male and female genital tract.
Recent studies have confirmed that penetration of antiretroviral agents into the male and female genital tracts are both drug and sex specific. Concentrations achieved vary considerably depending on the class of drug studied, the sampling techniques used and the times samples are obtained.
There appear to be several patterns of drug penetration into the male and female genital tract. In addition there appear to be different patterns of genital shedding under the influence of antiretroviral therapy. What effect these factors will have on the sexual transmission of HIV or the evolution and transmission of resistant HIV remains to be seen.
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ABSTRACT: HIV resides within anatomical 'sanctuary sites' where local drug exposure and viral dynamics may differ significantly from the systemic compartment. Widespread implementation of antiretroviral therapy has seen a significant decline in the incidence of mother-to-child transmission (MTCT) of HIV. In addition to suppression of maternal plasma/genital viral loads, antiretroviral agents that cross the placenta and achieve adequate concentrations in the fetal compartment may exert a greater prophylactic effect. Penetration of antiretrovirals in the fetal compartment is expressed by accumulation ratios derived from the measurement of drug concentrations in paired maternal plasma and umbilical cord samples. The nucleoside analogues and nevirapine accumulate extensively in cord blood and in the surrounding amniotic fluid, whereas the protease inhibitors (PIs) exhibit low-to-moderate placental accumulation. Early data suggest that high placental/neonatal concentrations are achieved with raltegravir, but to a lesser extent with etravirine and maraviroc (rank order of accumulation: raltegravir/nucleoside reverse transcriptase inhibitor [tenofovir > zidovudine/lamivudine/emtricitabine/stavudine/abacavir] > non-nucleoside reverse transcriptase inhibitor [nevirapine > etravirine] > PI > maraviroc/enfuvirtide). More comprehensive in vivo pharmacokinetic data are required to justify the potential use of these agents as safe and effective options during pregnancy.Antiviral therapy 01/2011; 16(8):1139-47. DOI:10.3851/IMP1918 · 3.14 Impact Factor