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

Mona Rafik Loutfy, Sharon Lynn Walmsley, Marina Barbara Klein, Janet Raboud, Alice Lin-In Tseng, Sandra Lauren Blitz, Neora Pick, Brian Conway, Jonathan Benjamin Angel, Anita Rochelle Rachlis, Kevin Gough, Jeff Cohen, David Haase, David Burdge, Fiona Mary Smaill, Alexandra de Pokomandy, Hugues Loemba, Sylvie Trottier, Charles Jean la Porte, Mona Rafik Loutfy, Sharon Lynn Walmsley, Marina Barbara Klein, Janet Raboud, Alice Lin-In Tseng, Sandra Lauren Blitz, Neora Pick, Brian Conway, Jonathan Benjamin Angel, Anita Rochelle Rachlis, Kevin Gough, Jeff Cohen, David Haase, David Burdge, Fiona Mary Smaill, Alexandra de Pokomandy, Hugues Loemba, Sylvie Trottier, Charles Jean la Porte

Abstract

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 Cmax 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 < 50copies/mL) on their first antiretroviral regimen were enrolled. Timed blood samples for C(min) and Cmax were drawn weekly for 3 weeks. The ratio of each individual's median C(min) and Cmax 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 Cmax 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 Cmax 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 Cmax were found.

Conclusions: Compared to historical control data, C(min) in the women enrolled was significantly higher whereas Cmax 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.

Figures

Figure 1
Figure 1
Paired Cmin and Cmax values for each participant by antiretroviral drug and dose. The Cmin values are identified by circles and the Cmax values by triangles. The reported population mean Cmin and Cmax values for each antiretroviral drug and dose are presented with the hatched lines (−−−).

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