A trial of three antiretroviral regimens in HIV-1-infected children

BACKGROUND Depletion of CD4 T-cell counts or progression of human immunodeficiency virus (HIV) disease occurs rapidly in children, but few data address the efficacy of aggressive therapy for HIV-infected children. METHODS We evaluated the safety, tolerability, and activity of three regimens of antiretroviral therapy in a multicenter, open-label, phase 1 - 2 trial. Children infected with HIV type 1 (HIV-1) were stratified at entry according to age - three months or younger ( early therapy) or older than three months ( delayed therapy) - and assigned sequentially to one of three regimens. Children continued to receive treatment for up to 200 weeks if the plasma HIV-1 RNA level was less than 1000 copies per milliliter by 16 weeks. RESULTS Plasma HIV-1 RNA levels fell from a median of 5.3 log copies per milliliter ( range, 3.3 to 6.4 log copies per milliliter) at baseline to less than 1000 copies per milliliter at 16 weeks in 32 of 52 infants ( 62 percent). Plasma HIV-1 RNA levels were below 400 copies per milliliter at 48 weeks in 26 infants ( 50 percent) and at 200 weeks in 23 infants ( 44 percent). An intention-to-treat analysis revealed that significantly more children who received stavudine, lamivudine, nevirapine, and nelfinavir had plasma HIV-1 RNA levels of less than 400 copies per milliliter at 48 weeks ( 83 percent) and 200 weeks ( 72 percent) than children who received reverse-transcriptase inhibitors alone ( P=0.001 and P=0.01, respectively). Fewer infants in the delayed-therapy group than in the early-therapy group ( 30 percent vs. 60 percent) had plasma HIV-1 RNA levels of less than 400 copies per milliliter at 200 weeks ( P=0.03). Treatment-associated adverse effects were infrequent. CONCLUSIONS In this phase 1 - 2 trial involving HIV-1 - infected children, an age of three months or younger at the initiation of therapy and treatment with stavudine, lamivudine, nevirapine, and nelfinavir were associated with improved long-term viral suppression. Larger, randomized trials are required to define the optimal time to initiate therapy and the optimal regimen for these infants.