Analysis of human immunodeficiency virus type 1 drug resistance in children receiving nucleoside analogue reverse-transcriptase inhibitors plus nevirapine, nelfinavir, or ritonavir (Pediatric AIDS Clinical Trials Group 377)

In Pediatric AIDS Clinical Trials Group 377, antiretroviral therapy-experie nced children were randomized to 4 treatment arms that included different c ombinations of stavudine, lamivudine (3TC), nevirapine (Nvp), nelfinavir (N fv), and ritonavir (Rtv). Previous treatment with zidovudine (Zdv), didanos ine (ddI), or zalcitabine (ddC) was acceptable. Drug resistance ((R)) mutat ions were assessed before study treatment (baseline) and at virologic failu re. Zdv(R), ddI(R), and ddC(R) mutations were detected frequently at baseli ne but were not associated with virologic failure. Children with drug resis tance mutations at baseline had greater reductions in virus load over time than did children who did not. Nvp(R) and 3TC(R) mutations were detected fr equently at virologic failure, and Nvp(R) mutations were more common among children receiving 3-drug versus 4-drug Nvp-containing regimens. Children w ho were maintained on their study regimen after virologic failure accumulat ed additional Nvp(R) and 3TC(R) mutations plus Rtv(R) and Nfv(R) mutations. However, Rtv(R) and Nfv(R) mutations were detected at unexpectedly low rat es.