Concentrations have been examined at various times in the dosing interval, and the cervicovaginal concentrations vary significantly from drug to drug. One study examined how quickly each drug achieved concentrations in the genital tract compared to plasma at steady state in 27 women.57 They reported the median rank order of drugs with highest Palbociclib to lowest genital tract concentrations. As the authors anticipated, the commonly used nucleoside reverse transcriptase inhibitors tended to be high on the list while efavirenz was the lowest, with protease inhibitors (PIs) falling in the middle. This study confirmed findings from an earlier study of seven women.58 Another study with a larger sample
size (34) examined both drug concentrations as well as virologic response to drug.59 The use of ART in patients is an incredibly important factor in the determination of genital immunity. As these drugs appear in measurable concentrations in the genital fluids, it is also important to note that any in vitro models using live virus will not perform properly if using genital fluids from women taking ART. Although there is a strong correlation between plasma
viral load and genital tract viral load, there selleck is evidence of compartmentalization between the blood and genital tract in both men and women. Evidence of compartmentalization occurs in terms of resistance patterns.60–62 An interesting study examined the theory that virologic failure might occur in one compartment and not another. The authors examined 14 women with detectable HIV-1 in both plasma and genital tract despite antiretroviral therapy.63 Fifty-seven percent
of the patients exhibited Thiamet G mutations conferring high-level HIV-1 drug resistance. Interestingly, in one patient, resistance mutations appeared only in the plasma while all genital variants were susceptible. It has also been shown that resistance mutations detected in the genital tract can persist for years.64 Differences in resistance patterns as well as the possibility of resistance must be considered in studies including HIV-infected women. The HIV pandemic continues to result in millions of deaths annually on a global scale. Despite the advent of antiretroviral therapy, the spread of the infection has not been halted. The millions of dollars of research aimed at determining the pathogenesis of HIV spread have led to marked improvements in the understanding of disease. This has brought a change in life expectancy of those diagnosed with HIV in the United States from terminal to chronic illness. It has also caused a shift in attention from the blood compartment to the genital compartment as the major point-of-entry for HIV and thus for research endeavors. The many clinical characteristics that must be considered when studying the blood compartment must be expanded when considering research work on the genital compartment.