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Darunavir and Ritonavir Levels in Black and Hispanic Women
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9th International Workshop on Clinical Pharmacology of HIV Therapy
April 7-9, 2008
New Orleans
Mark Mascolini
Four-week drug level results from the GRACE study, which aimed to enroll high proportions of women, blacks, and Hispanics in the US, showed darunavir levels 20% higher in women than in men and ritonavir levels 70% higher in women.[1] Darunavir and ritonavir concentrations did not differ between black and Hispanic study participants.
GRACE enrolled 429 adults, 287 of them (67%) women, 265 (62%) black, 96 (22%) Hispanic, and 65 (15%) white. Everyone had a viral load above 1000 copies and had taken at least one protease inhibitor or nonnucleoside regimen for at least 12 weeks. No one had tried darunavir, tipranavir, etravirine, or enfuvirtide. The pharmacokinetic substudy involved 18 women and 12 men, including 12 black women and 7 black men, and 5 Hispanic women and 4 Hispanic men. Viral loads averaged 4.7 log, and the median CD4 count stood at 179 (range 6 to 780).
When the study began, weight and body mass index were similar for women and men. Women had 12% higher alpha-1-acid-glycoprotein, which binds to protease inhibitors and so yields lower unbound plasma concentrations of these drugs. Nevertheless, median darunavir area under the concentration-time curve (AUC) was about 20% higher in women than in men after 4 weeks of therapy (66,990 versus 55,000 ng/h/mL). Median darunavir AUC was similar in blacks and Hispanics (60,235 versus 62,190 ng/h/mL).
At week 48 of the TITAN trial, median darunavir AUC measured 62,280 ng/h/mL in blacks, 54,150 ng/h/mL in Hispanics, and 56,369 ng/h/mL in whites.
Median ritonavir AUC in GRACE stood about 70% higher in women than in men (6641 versus 3782 ng/h/mL) but did not differ much between blacks and Hispanics (4239 versus 4500 ng/h/mL).
Whether these protease inhibitor level differences between women and men affect virologic response or side effect rates will be determined after 48 weeks of treatment.
(Many complete slide sets and posters from this workshop will be available at www.hivpresentation.com shortly after the meeting ends. The poster for this study is online at www.tibotec.com.)
Reference
1. Sekar V, Ryan R, Schaible D, et al. Pharmacokinetic profile of darunavir co-administered with low-dose ritonavir in treatment-experienced women and men with HIV infection: 4-week analysis in a substudy of the GRACE (Gender, Race, And Clinical Experience) study. 9th International Workshop on Clinical Pharmacology of HIV Therapy. April 7-9, 2008. New Orleans. Abstract O16.
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