Sequencing paediatric antiretroviral therapy in the context of a public health approach

Abstract

Introduction: As access to prevention of mother-to-child transmission (PMTCT) efforts has increased, the total number of children being born with HIV has significantly decreased. However, those children who do become infected after PMTCT failure are at particular risk of HIV drug resistance, selected by exposure to maternal or paediatric antiretroviral drugs used before, during or after birth. As a consequence, the response to antiretroviral therapy (ART) in these children may be compromised, particularly when non-nucleoside reverse transcriptase inhibitors (NNRTIs) are used as part of the first-line regimen. We review evidence guiding choices of first- and second-line ART.

Discussion: Children generally respond relatively well to ART. Clinical trials show the superiority of protease inhibitor (PI)- over NNRTI-based treatment in young children, but observational reports of NNRTI-containing regimens are usually favourable as well. This is reassuring as national guidelines often still recommend the use of NNRTI-based treatment for PMTCT-unexposed young children, due to the higher costs of PIs. After failure of NNRTI-based, first-line treatment, the rate of acquired drug resistance is high, but HIV may well be suppressed by PIs in second-line ART. By contrast, there are currently no adequate alternatives in resource-limited settings (RLS) for children failing either first- or second-line, PI-containing regimens.

Conclusions: Affordable salvage treatment options for children in RLS are urgently needed.

Keywords: HIV drug resistance; antiretroviral therapy; low- and middle-income countries; non-nucleoside reverse transcriptase inhibitor; paediatric HIV; protease inhibitor.

Figure 1

Summary estimates of virological suppression in children <3 years in LMIC, 6 to 24 months after first-line treatment initiation for NNRTI- and PI-treated children. Random effects meta-analysis was conducted using a Freeman–Tukey arcsine square root transformation to stabilize proportions. No virological suppression rates were available for PI-treated children after 18 and 24 months. NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.