Approaches Towards Avoiding Lifelong Antiretroviral Therapy in Paediatric HIV Infection

Abstract

Paediatric HIV infection is a substantial global public health problem in its own right. Approximately one in six new HIV infections worldwide arises as a result of mother-to-child transmission (MTCT). In contrast to adult infection, progression to AIDS and death is rapid in most infected children and cannot be satisfactorily predicted in the youngest children based on viral load or CD4 count. For this reason, the current revised WHO guidelines recommending antiretroviral therapy (ART) be initiated in HIV-infected children from birth, or as soon after birth as possible, are fully justified. However, this presents the daunting challenge of a life-time on ART, starting from the perinatal period. Given the major difficulties of maintaining adherence and avoiding toxicity from infancy through to adolescence, it would seem imperative to consider what alternative strategies to a life-time on ART may be considered in paediatric HIV infection, to avoid the prospect in 10 years of an epidemic of HIV-infected adolescents on failing salvage therapy regimens. Furthermore, at the current rate of growth, the number of children living with HIV will double within 5 years, and the cost of maintaining ART, together with monitoring of CD4 counts and viral load, in these numbers would be hard to sustain. This review addresses, first, the particular differences between paediatric and adult HIV infection, and the immune responses most effective in control of HIV, with specific reference to the anti-HIV CD8+ T-cell response; and, second, the ART interruption strategies currently being explored that could provide an alternative to lifelong ART for infected children.