Nevirapine concentrations were substantially lower in Zambian children under 3 years old who were also taking rifampicin-based therapy for tuberculosis. Adjusted nevirapine doses will have to be studied.
HIV and TB epidemics simultaneously affect many populations. Data on antiretroviral pharmacokinetics remain scarce in children taking rifampicin, which can affect concentrations of several key antiretrovirals.
This study compared nevirapine concentrations in two groups of Zambian children under 3 years old: 22 HIV-positive children taking fixed-dose nevirapine-stavudine-lamivudine using World Health Organization weight bands for dosing plus rifampicin-based anti-TB therapy, and 16 nevirapine-treated children without TB. Researchers measured nevirapine concentrations just before dosing and 1, 2, and 6 hours after dosing.
Ten of the 22 coinfected children (45%) were girls, and 1 boy was dropped from the analysis because of poor adherence. Median age of the HIV group was 1.6 years (range 0.7 to 3.2), and median weight was 8.0 kg (range 5.1 to 10.5). Median pretreatment CD4 percent stood at 13.1% (range 3.9 to 43.6).
Median predose nevirapine concentration stood at 2.93 mg/L (range 1.06 to 11.4) and peak concentration at 6.33 mg/L (range 2.61 to 14.5). Predose nevirapine concentration lay below 3.0 mg/L in 11 of 21 children taking rifampicin and in none of 16 children not taking rifampicin, a highly significant difference (P = 0.001).
Estimated nevirapine area under the concentration-time curve (AUC) up to 12 hours was 52.0 mg * h/L (range 22.6 to 159.7) in children taking rifampicin and 90.9 mg * h/L (range 40.4 to 232.1) in children not taking rifampicin, also a highly significant difference (P < 0.001).
After statistical adjustment for dose per square meter, nevirapine AUC was 41% lower (95% confidence interval 23% to 54%) in children with TB than in the comparison group (P < 0.001).
The researchers call for further study “to define the pharmacokinetics, safety and efficacy of adjusted doses of nevirapine-based ART in young children with tuberculosis.”
Source: J. Mirjama Oudijk, Helen McIlleron, Veronica Mulenga, Chifumbe Chintu, Concepta Merry, A. Sarah Walker, Adrian Cook, Diana M. Gibb, David M. Burger. Pharmacokinetics of nevirapine in HIV-infected children under 3 years on rifampicin-based antituberculosis treatment. AIDS. 2012; 26: 1523-1528.
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