The initial interim find more pharmacokinetic analysis

occurred after the first 12 patients had received ATV/r 300/100 mg during the third trimester with pre-specified criteria for a dose increase to 400/100 mg for all subsequent mothers entering the third trimester. The pre-specified criteria included requirements for Cmin or AUCτ values. If more than two of 12 patients had an ATV Cmin<150 ng/mL but 10 of 12 patients had an ATV Cmin≥50 ng/mL, then ATV/r would be increased to 400/100 mg qd. The AUCτ criterion stated that, if the geometric mean of ATV AUCτ for these 12 patients was <30 000 ng h/mL but ≥15 000 ngh/mL, then ATV/r would be increased to 400/100 mg qd. The dose increase occurred if either criterion was met, and, if a dose escalation was required, all patients at ≥week 28 were given the higher dose. Prophylaxis for prevention of mother-to-child transmission of HIV infection with ARVs (zidovudine and lamivudine) and Pneumocystis jiroveci pneumonia prophylaxis were recommended for all infants. Blood samples were collected after ≥2 weeks of adherent dosing. Adherence was assessed by pill count and was defined as taking all doses and the number of pills prescribed for each medication prescribed. ATV was sampled over

one dosing interval (24 h post-dose) from the mother in the second trimester, the third Lapatinib trimester and postpartum (median 43 days; range 24–71 days). A single blood collection from the mother and the umbilical from cord was performed at delivery. Samples were assayed by liquid chromatography

and tandem mass spectrometry. For ATV and RTV, the standard curves were fitted by a 1/X2-weighted quadratic equation over the concentration ranges of 10.0–10 000 and 5.0–5000 ng/mL, respectively. Values for precision for the analytical quality control (QC) samples were a coefficient of variation (CV) no greater than 7.9% and 9.4% for ATV and RTV, respectively, with deviations from the nominal concentrations of no more than ± 9.4% for ATV and ± 7.6% for RTV. The historical reference data for the current study were pooled from nonpregnant HIV-infected women and men receiving ATV/r 300/100 mg with a nucleoside reverse transcriptase inhibitor (NRTI) backbone (that did not include tenofovir) in two previous clinical studies that had concluded nearest the start of this study [19,20]. These pooled pharmacokinetic data are also similar to the data in the product label for ATV/r 300/100 mg qd and thus were considered representative data for infected patients. Pharmacokinetic parameters (Cmax, Cmin and AUCτ) were derived by noncompartmental methods.