Factors affecting antiretroviral pharmacokinetics in HIV-infected women with virologic suppression on combination antiretroviral therapy: a cross-sectional study

摘要

Background Although some studies show higher antiretroviral concentrations in women compared to men, data are limited. We conducted a cross-sectional study of HIV-positive women to determine if protease inhibitor (PI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) C_min and C_max values were significantly different than historical general population (predominantly male) averages and to evaluate correlates of higher concentrations. Methods HIV-positive women with virologic suppression (viral load min and C_max were drawn weekly for 3 weeks. The ratio of each individual’s median C_min and C_max to the published population mean values for their PI or NNRTI was calculated and assessed using Wilcoxon sign-rank. Intra- and inter-patient variability of antiretroviral drug levels was assessed using coefficient of variation and intra-class correlation. Linear regression was used to identify correlates of the square root-transformed C_min and C_max ratios. Results Data from 82 women were analyzed. Their median age was 41 years (IQR=36-48) and duration of antiretrovirals was 20 months (IQR=9-45). Median antiretroviral C_min and C_max ratios were 1.21 (IQR=0.72-1.89, p=0.003) (highest ratios for nevirapine and lopinavir) and 0.82 (IQR=0.59-1.14, p=0.004), respectively. Nevirapine and efavirenz showed the least and unboosted atazanavir showed the most intra- and inter-patient variability. Higher CD4+ count correlated with higher C_min. No significant correlates for C_max were found. Conclusions Compared to historical control data, C_min in the women enrolled was significantly higher whereas C_max was significantly lower. Antiretroviral C_min ratios were highly variable within and between participants. There were no clinically relevant correlates of drug concentrations. Trial registration NCT00433979