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Although single-dose nevirapine during labor significantly reduces HIV transmission, it is not infallible — and the children who become infected often develop resistance. Previous research has shown that children who receive nevirapine-based regimens after exposure to single-dose nevirapine have high rates of virologic failure (N Engl J Med 2007; 356:135). Now, investigators have evaluated whether children with exposure to single-dose nevirapine might fare better on protease inhibitor (PI)-based regimens.
A total of 164 HIV-infected children in Africa (age range, 6 to 36 months) who had prior exposure to single-dose nevirapine were randomized to initiate antiretroviral therapy with AZT/3TC plus either nevirapine or lopinavir/ritonavir. Investigators compared failure rates between the two treatment arms both overall and by age group. The latter analysis aimed to determine whether the efficacy of nevirapine-based regimens in children depends on time since exposure to single-dose nevirapine, as it seems to in women (JW AIDS Clin Care Oct 18 2010 and N Engl J Med 2010; 363:1499).
At 24 weeks, the nevirapine arm had a significantly higher rate of virologic failure or treatment discontinuation than the lopinavir/r arm (40% vs. 22%). This difference between treatments appeared to be greater among children aged <12 months (45% vs. 23%) than among those aged ≥12 months (29% vs. 18%), but the finding was not statistically significant. Thus, the investigators could not identify a particular age threshold beyond which nevirapine-based regimens would be considered acceptable.
Baseline nevirapine resistance was present in 12% of the 148 children tested. Among these children, failure rates were 83% in the nevirapine arm and 18% in the lopinavir/r arm. Interestingly, among those without documented resistance, failure rates were still relatively high (36% and 20%, respectively), prompting the investigators to plan further ultrasensitive resistance testing.
Palumbo P et al. Antiretroviral treatment for children with peripartum nevirapine exposure. N Engl J Med 2010 Oct 14; 363:1510.
Comment
For young children with perinatal exposure to single-dose nevirapine, PI-based therapy is associated with significantly lower rates of failure than nevirapine-based therapy. Based on these findings, the WHO now recommends lopinavir/r-based therapy for children aged <24 months who have a history of nevirapine exposure. This study also underscores the vital importance of shifting away from single-dose nevirapine to prevention strategies that incorporate nucleoside “tails” or triple-antiretroviral prophylaxis for women presenting during labor. By adopting prophylactic strategies that have been shown to reduce nevirapine resistance, the subsequent efficacy of nevirapine-containing regimens may be improved. Finally, observational studies suggest that lopinavir/r may simply be better than nevirapine for infants and young children, regardless of previous exposure. Thus, results are eagerly anticipated from a parallel trial comparing lopinavir/r- and nevirapine-based therapy in young children without prior nevirapine exposure.