Nevirapine levels greatly reduced in Zambian children on rifampicin
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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