Antiretroviral Treatment for Children with Peripartum Nevirapine Exposure

Abstract

BACKGROUND Single-dose nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis. The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose nevirapine is unknown. METHODS We conducted a randomized trial of initial therapy with zidovudine and lamivudine plus either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6 to 36 months of age, in six African countries, who qualified for treatment according to World Health Organization (WHO) criteria. Results are reported for the cohort that included children exposed to single-dose nevirapine prophylaxis. The primary end point was virologic failure or discontinuation of treatment by study week 24. Enrollment in this cohort was terminated early on the recommendation of the data and safety monitoring board. RESULTS A total of 164 children were enrolled. The median percentage of CD4+ lymphocytes was 19%; a total of 56% of the children had WHO stage 3 or 4 disease. More children in the nevirapine group than in the ritonavir-boosted lopinavir group reached a primary end point (39.6% vs. 21.7%; weighted difference, 18.6 percentage-points; 95% confidence interval, 3.7 to 33.6; nominal P = 0.02). Baseline resistance to nevirapine was detected in 18 of 148 children (12%) and was predictive of treatment failure. No significant between-group differences were seen in the rate of adverse events. CONCLUSIONS Among children with prior exposure to single-dose nevirapine for perinatal prevention of HIV transmission, antiretroviral treatment consisting of zidovudine and lamivudine plus ritonavir-boosted lopinavir resulted in better outcomes than did treatment with zidovudine and lamivudine plus nevirapine. Since nevirapine is used for both treatment and perinatal prevention of HIV infection in resource-limited settings, alternative strategies for the prevention of HIV transmission from mother to child, as well as for the treatment of HIV infection, are urgently required. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00307151.)

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

“…Infected infants exposed to NVP during failed PMTCT (or in whom perinatal NVP exposure cannot be excluded) should be started on a boosted PI‐containing regimen, as transmitted resistance may lead to failure of NVP‐containing ART 64, 65. LPV/r should not be administered to premature neonates or to term neonates below 2 weeks of postnatal age because of the increased risk of toxicities reported in premature and very young babies 66, 67.…”

Nevirapine- Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy in HIV-Infected Infants and Young Children: Long-term Follow-up of the IMPAACT P1060 Randomized Trial

“…By 12 months, the lopinavir/ritonavir (LPV/r)-based regimen was associated with fewer virologic treatment failures or deaths compared with the NVP-based regimen. However, improvements in CD4 percentage (CD4%) and growth (weight-for-age and height-for-age z score) marginally favored NVP [11,12]. To better understand the comparative long-term effect of these 2 ART regimens in an HIV-infected pediatric population, we present data from extended follow-up in this multicenter clinical trial.…”

Antiretroviral therapy for the management of HIV in children

“…[18] In children started on ART >3 years of age, the PENPACT-1 study showed that, after 4 years on ART, viral suppression and CD4 + count were similar on NNRTI and PI-based ART. [19] Of note, the PI most commonly used was unboosted nelfinavir, an unacceptable choice given current knowledge.…”

“…[29] In the P1060 study, approximately 80% of children on LPV/r achieved a viral load of <400 copies/mL at week 24. [18] In the International epidemiologic Databases to Evaluate AIDS (IeDEA) cohort, children starting ART at around 3.5 years of age had a 20% rate of virological failure after 3 years. [30] The ARROW study confirmed this finding, with 83% of children on two NRTIs and an NNRTI having a viral load of <400 copies/mL after a median of 3.7 years on therapy.…”