Pharmacokinetics of Nevirapine, Stavudine and Lamivudine in Indian HIV-infected Children Receiving Generic Fixed Dose Combinations.

ABSTRACT

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 63050mg. 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. Conclusion: The currently available generic pediatric fixed dose antiretroviral combinations in India provide adequate drug exposure in majority of children.