Prevention and Treatment of Pediatric HIV Infection

Abstract

The goal of this paper is to review the prevention of mother-to-child HIV transmission (PMTCT) research that informed World Health Organization (WHO) guidelines for PMTCT and describe the impact of worldwide scale-up of PMTCT programs and antiretroviral therapy (ART) coverage. The impact of these interventions on new pediatric infections and infected children’s morbidity and mortality in sub-Saharan Africa are reviewed. The IMPAACT PROMISE study demonstrated that triple therapy consisting of tenofovir (TDF), lamivudine (3TC), and lopinavir/ritonavir (LPVr) or zidovudine (AZT), 3TC, and LPVr initiated in the first trimester reduced vertical transmission at 2 weeks of age to 0.6% and 0.5%, respectively, supporting the current WHO Option B+ recommendation for PMTCT. However, increased adverse pregnancy outcomes in the AZT- and TDF-based triple therapy arms were reported when compared with the AZT prophylaxis arm (low birth weight [20.4% and 16.9% vs. 8.9%; p = 0.004] and premature deliveries [19.7% and 18.5% vs. 13.5%; p = 0.09], respectively). Implementation of Option B+ for PMTCT has led to significant reductions in vertical transmission rates, including elimination of new pediatric infections in some countries. The WHO declared elimination of mother-to-child HIV transmission (MTCT) in Cuba in 2015 and in Armenia, Belarus, and Thailand in 2016. Globally, new pediatric HIV infections have declined significantly since the introduction of effective antiretroviral regimens for PMTCT. Perinatal HIV prevention clinical trials conducted in sub-Saharan Africa informed WHO PMTCT guidelines which led to implementation of PMTCT programs worldwide, leading to a 47% reduction in new pediatric infections since 2009. Support from The United States President's Emergency Plan for AIDS Relief (PEPFAR), the Global Fund for AIDS, Tuberculosis and Malaria, and UN agencies has enabled scale-up of national PMTCT programs, and increased antiretroviral coverage (47% globally) for infected children has led to a decline in HIV/AIDS-related mortality in children. Implementation strategies that improve retention in care and adherence to ART in pregnant and breastfeeding HIV-infected women is critical to ensure that more countries achieve the elimination of MTCT (eMTCT) targets. Assessing the effectiveness of new antiretroviral drugs, including fixed-dose combinations and long-acting formulations, is key to improving ART adherence and reducing the emergence of viral resistance mutations. In addition, interventions to prevent HIV transmission in adolescents and young adults is critical for reducing new HIV infections worldwide. Innovative interventions to improve adherence to ART are required to further improve the survival of HIV-infected children and adolescents.