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Women With Tight HIV Control Have Higher Antiretroviral Troughs Than General Population
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11th International Workshop on Clinical Pharmacology and HIV Therapy, April 7-9, 2010, Sorrento
Mark Mascolini
Among Canadian women with an undetectable viral load, minimum concentrations (Cmins) of four antiretrovirals were 22% higher than in a mostly male general-population comparison group [1]. Unboosted or boosted atazanavir maximum concentrations (Cmax) were substantially lower in women than in the general population, and nevirapine Cmins were much higher. Overall, Cmins were highly variable within and between antiretrovirals.
Previous research has found higher antiretroviral concentrations in women than in men, but research on this issue is limited. To get a better fix on concentrations of four major antiretrovirals in women with an undetectable viral load, Charles la Porte and colleagues at 14 Canadian sites conducted a cross-sectional study of 83 women taking their first regimen. The researchers collected timed blood samples weekly for 3 weeks. They compared median Cmax and Cmin in individual women with published average Cmax and Cmin from a general population group consisting mostly of men.
The investigators excluded women with poor antiretroviral adherence, pregnant or breastfeeding women, those not taking standard doses, and those with end-stage organ disease, other significant non-HIV disease, or malignancy requiring chemotherapy.
The 83 women had a median age of 42 years (interquartile range [IQR] 36 to 48) and a median current CD4 count of 490 (IQR 380 to 640). Median weight stood at 67.3 kg (IQR 60.3 to 81.7) and median body mass index at 25.5 kg/m(2) (IQR 22.3 to 31.0). Women had taken their first antiretroviral regimen for a median of 3.8 years (IQR 1.8 to 7.8).
Ten women were taking unboosted atazanavir, 18 boosted atazanavir, 20 lopinavir, 16 efavirenz, and 19 nevirapine.
Overall median antiretroviral Cmin was 22% higher in these women than in the general population group (ratio 1.22, IQR 0.72 to 1.93). That difference was driven by lopinavir (ratio 1.22, IQR 0.79 to 1.81) and nevirapine (ratio 1.62, IQR 0.91 to 2.32). But the study disclosed no significant predictors of high Cmin.
Median Cmax was 14% lower in the women than in the general population (ratio 0.86, IQR 0.59 to 1.25), and that difference could be traced primarily to unboosted atazanavir (ratio 0.53, IQR 0.28 to 0.94), boosted atazanavir (ratio 0.67, IQR 0.54 to 0.85), and efavirenz (ratio 0.79, IQR 0.57 to 1.27).
Percentages of women with a Cmin more than 1.5 times above the population average were 20.0% for unboosted atazanavir, 27.8% for boosted atazanavir, 30.0% for lopinavir, 37.5% for efavirenz, and 52.6% for nevirapine. Percentages of women with a Cmax more than 1.5 times above the population average were 0% for boosted or unboosted atazanavir, 25.0% for lopinavir, 25.0% for efavirenz, and 15.8% for nevirapine.
Within-patient variability for Cmin and Cmax were greatest for unboosted atazanavir (52.3 and 63.9) and lowest for efavirenz (17.7 and 15.5) and nevirapine (17.5 and 15.7)
Black women tended to have a lower Cmin/population Cmin (-0.16, P = 0.08), as did injecting drug users (-0.22, P = 0.08). Higher current CD4 count significantly favored a higher Cmin/population Cmin (0.04 per 100 cells, P = 0.05), as did self-reported antiretroviral side effects (0.25, P < 0.01).
Reference
1. la Porte C, Loutfy M, Walmsley S, et al. Antiretroviral pharmacokinetics in HIV-positive women with full virologic suppression on current regimens. 11th International Workshop on Clinical Pharmacology and HIV Therapy. April 7-9, 2010. Sorrento. Abstract 8.
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