Pharmacokinetics of nevirapine, stavudine and lamivudine in Indian HIV-infected children receiving generic fixed dose combinations.

OBJECTIVE To determine the trough and two hour plasma levels of nevirapine, stavudine, and lamivudine when administered in fixed dose combinations (FDC). DESIGN Cross sectional. SETTING Tertiary care hospital in Northern India. PARTICIPANTS 79 HIV-infected children receiving antiretroviral therapy with FDCs for more than month. INTERVENTION Two-point sampling (0 and 2 hours after the morning dose). OUTCOME MEASURES Plasma concentrations of all three drugs were simultaneously assayed by liquid chromatography/mass spectroscopy. RESULTS Majority (77%) of children were receiving fixed dose combination of stavudine, lamivudine, nevirapine in the ratio of 6:30:50 mg. The median (IQR) trough and 2-hour plasma levels (µg/mL) of nevirapine, stavudine and lamivudine were 5.2 (4.0, 6.3) and 7.9 (6.0, 9.7); 0.1 (0.06, 0.16) and 1.1 (0.59, 1.6); 0.1 (0.02, 0.2) and 2.5 (1.4, 3.1), respectively. Very few children had sub-therapeutic plasma drug levels of stavudine (2.5%), lamivudine (7.6%) and nevirapine (10%). Inadequate viral suppression at 6 months follow up was significantly associated with initial high viral load, low CD4 percentage at the time of enrolment in study, and lower doses of lamivudine and stavudine. CONCLUSIONS The currently available generic pediatric fixed dose antiretroviral combinations in India provide adequate drug exposure in majority of children.