Latent HIV-1 reservoirs in children: considerations for therapy

Understanding the genetic properties and clinical relevance of latent HIV-1 reservoirs in children is critical for guiding pediatric treatment strategies, especially as antiretroviral drugs gain widespread use in resource-constrained settings in which the inherent risk of early infection with drug-resistant HIV-1 is most challenging.

Latent reservoirs of HIV-1 prevent virus clearance in children on highly active antiretroviral therapy. Effective highly active antiretroviral therapy, however, fixes the genetic composition of the resting CD4 T-cell reservoir, which contains only founder virus in children treated during primary infection. This reservoir otherwise stores both archival variants and drug-resistant variants arising during treatment failure. The persistence of HIV-1 in quiescent CD4 T cells can facilitate immune escape, because genetic evidence suggests that activation of these cells feeds plasma viremia. Ultrasensitive molecular assays can detect low levels of virus in plasma even in children on effective highly active antiretroviral therapy. Importantly, however, this continuous low-level production of plasma virus does not appear to promote antiretroviral drug resistance in the majority of children on effective antiretroviral therapy.

The development and persistence of latent HIV-1 reservoirs occur in children despite effective treatment during primary infection. Making a wide variety of antiretroviral drugs in formulations suitable for dosing in children is necessary to minimize infection and to overcome multi-drug-resistant HIV-1 reservoirs in children. The long-term suppression of HIV-1 in children is an achievable goal.