Long-term decay of the HIV-1 reservoir in HIV-1-infected children treated with highly active antiretroviral therapy

To investigate the decay of the human immunodeficiency virus type 1 (HIV-1) reservoir in children receiving highly active antiretroviral therapy (HAART), we measured HIV-1 DNA in peripheral blood mononuclear cells from 14 children who achieved and maintained suppression of plasma viremia up to 48 months after the initiation of HAART. Levels of intracellular unspliced and multiply spliced HIV-1 RNA were used as markers of residual viral replication. During the first month of HAART, there were significant decays in levels of both plasma HIV-1 RNA and multiply spliced HIV-1 RNA, yet unspliced HIV-1 RNA persisted in most of the children. Greater HIV-1 DNA decay during the first month of HAART correlated with a higher concomitant increase in CD4(+) cell counts (P=.028) and a smaller subsequent HIV-1 DNA decay (P=.0012). Furthermore, HIV-1 DNA decayed faster from 1 to 9 months of HAART (median half-life, 5 months) than during the subsequent follow-up period (median half-life, 30 months). Moreover, after 9 months of HAART, HIV-1 DNA tended to decay more slowly in children with detectable levels of unspliced HIV-1 RNA. These findings suggest that clearance of the viral reservoir in HAART-treated children may be influenced by immune repopulation and residual viral replication and may help in refining long-term treatment strategies.