Treatment of young children with HIV infection: using evidence to inform policymakers

• Published in: PLoS medicine 2012-07, Vol.9 (7), p.e1001273-e1001273
• Main Authors: Prendergast, Andrew J, Penazzato, Martina, Cotton, Mark, Musoke, Philippa, Mulenga, Veronica, Abrams, Elaine J, Gibb, Diana M
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Administrative Personnel; AIDS; Analysis; Antiretroviral drugs; Antiretroviral Therapy, Highly Active; Child; Demographic aspects; Disease transmission; Drug therapy; Evidence-Based Medicine; Health aspects; Health Plan Implementation; Health Planning Guidelines; Health Policy; HIV; HIV infection; HIV Infections - drug therapy; HIV patients; Human immunodeficiency virus; Humans; Medicine; Mortality; Mother and child; Policy Forum
• ISSN: 1549-1676; 1549-1277; 1549-1676
• DOI: 10.1371/journal.pmed.1001273

Summary Points * Early initiation of antiretroviral therapy (ART) in infants with HIV leads to a 4-fold reduction in mortality compared to deferred ART * Young children starting a first-line ART regimen containing a non-nucleoside reverse transcriptase inhibitor (nevirapine; NVP) have a 2-fold higher risk of treatment failure than those who start a regimen containing a protease inhibitor (lopinavir/ritonavir; LPV/r) * Use of LPV/r in infants is challenging due to its expense, unpalatable formulation, and potential long-term toxicity * Better formulations of ART are urgently required for infants and young children Despite efforts to scale up prevention of mother-to-child transmission (PMTCT) of HIV, over 1,000 infants continue to be infected daily, particularly in sub-Saharan Africa [1]. Challenges in the Treatment of Infants and Young Children with HIV * Virological testing is required to ascertain HIV infection status * Identification of infected infants is frequently delayed * Disease progression is rapid, with mortality peaking in the first few months of life * No reliable markers to predict rapid disease progression * Limited repertoire of antiretroviral drugs and drug formulations * Liquid formulations expensive, unpalatable, and difficult to carry/store * Pharmacokinetics variable, due to developing metabolic pathways * Frequent adjustment in dosing is required due to rapid growth during infancy * Need for strategic drug sequencing in the context of lifelong treatment * Adherence is challenging, with reliance on caregivers to administer medication * Risk of drug resistance due to high viral loads during infancy * Potential long-term toxicity of treatment, as ART is started during a developmentally sensitive period of early life Table 1.\n Alternative Approaches An alternative approach to long-term PI treatment, explored in the South African NEVEREST trial (Table 1), is to start all infants on LPV/r, and later substitute NVP [3],[4].