Background:  Sex-related differences in ART pharmacokinetics among HIV-infected adults and the implications for clinical practice have not been well studied. Our primary objective was to compare the area under the concentration time curve (AUC) of lopinavir (LPV) and ritonavir (RTV) between females and males.

Methods:  This was a multi-center, prospective intensive pharmacokinetic study in HIV-infected adults treated with LPV/RTV (400/100 mg twice daily) in soft gel capsule. Enrollment was balanced by race and sex. Eligible subjects were age (18 and on LPV/RTV in combination with ≥ART for (2 weeks prior to screening. Major exclusion criteria were pregnancy, receipt of concomitant second active protease inhibitor (PI), or other concomitant medications interacting with LPV/RTV. Subjects underwent serial pharmacokinetic sampling over 12 hours following an observed dose and a standard breakfast. LPV and RTV concentrations were quantitated by validated high-performance liquid chromatography (HPLC); non-compartmental methods were used to determine pharmacokinetic parameters. A sample size of 78 subjects had 80% power to detect a 30% difference in LPV AUC between females and males. The sex differences in pharmacokinetic parameters were compared using the Wilcoxon rank-sum test.

Results:  We enrolled 78 subjects (40 men and 38 women) and determined pharmacokinetic parameters in 40 men and 37 women. The median age was 43 years (men 41; women 47). Subjects were well balanced with respect to race (white non-Hispanic, 31%; black non-Hispanic, 31%; Hispanic, 31%; Asian/Pacific Islander, 4%; more than 1 race, 4%). The median baseline CD4 cell count was higher in women than in men (576/mm³ vs 432/mm³) while >80% of both male and female subjects had HIV RNA <400 copies/mL. Pharmacokinetic parameters are shown in Tables 1 and 2; pharmacokinetics did not significantly differ by race.

Conclusions:  LPV pharmacokinetics did not differ between women and men. Women had higher RTV AUC and lower CL/F. The clinical significance of the 20% higher RTV AUC in females should be evaluated with other protease inhibitors and other concomitant drugs. Mechanisms of the sex difference in RTV CL/F in HIV-infected women merit further investigation.