Randomized clinical trial of switching to nevirapine-based therapy for infected children exposed to nevirapine prophylaxis
Background: Many pediatric treatment guidelines recommend first-line treatment with Lopinavir/ritonavir (LPV/r)-based regimens for infants due to concern about drug resistance in children exposed to nevirapine used to prevent mother-to-child HIV transmission. The goal of our study was to test if nevirapine prophylaxis-exposed children could switch to nevirapine-based therapy after initial suppression on a LPV/r-based regimen.
Methods: HIV-infected children under the age of two years exposed to nevirapine prophylaxis and who met immunologic and clinical criteria for antiretroviral therapy (n=322) were started on LPV/r, stavudine and lamivudine at one site in Johannesburg, South Africa. Children who achieved and maintained HIV RNA < 400 copies/ml for > 3 months were eligible for randomization (n=195) to either remain on the same regimen (control n=99) or to substitute nevirapine for LPV/r (switch n=96). Children were followed to 24 weeks post-randomization with regular ultrasensitive viral load tests to determine if viral suppression was sustained.
Results: The median age of the randomized children was 11 months (IQR 7-16 months) when initiating treatment and 20 months (IQR 16-25 months) at randomization. In intent-to-treat analysis, 65.6% of children in the switch group consistently tested < 50 copies/ml through 24 weeks post-randomization compared to 49.5% of children in the control group (p=0.02). One child in the switch group and two in the control group died, and two children in each group did not continue in the study. In contrast, fewer children in the switch group (84.9%) than in the control group (96.8%) consistently maintained < 1000 copies/ml through 24 weeks post-randomization (p=0.007).
Conclusion: Our study provides proof of concept that re-use of nevirapine following successful suppression on LPV/r-based therapy is possible under some circumstances for HIV-infected children exposed to nevirapine prophylaxis. Further research is necessary to determine the circumstances and interventions required to safely re-use this agent.
5th IAS Conference on HIV Pathogenesis and Treatment
"A.Coovadia, et al.
Randomized clinical trial of switching to nevirapine-based therapy for infected children exposed to nevirapine prophylaxis .
5th IAS Conference on HIV Pathogenesis and Treatment: