Abstract
INTRODUCTION: There is limited data in children on whether persistence of HIV-1 infected cells is affected by age at initiating antiretroviral therapy (ART), its duration or any subsequent ART interruption. We therefore investigated the effects of both age of ART initiation and duration of ART interruption on HIV-1 DNA decay in children. METHODS: We investigated HIV-1 DNA decay in three groups of children on ART: Group-1 (n = 7) started uninterrupted ART within eight days of life; Group-2 (n = 8) started uninterrupted ART at a median of five months of age; and Group-3 (n = 23) started ART at a median age of 1.8 months for either 40 or 96 weeks, then interrupted ART (median of seven months), and restarted ART based on CD4 count and clinical criteria. Total HIV-1 DNA was assayed using a sensitive HIV-1 subtype C-adapted quantitative PCR for integrase. The duration of ART was square root transformed to fit the observed slowing of HIV-1 DNA decay rate. For each group, point estimates for decay rates were determined after six months of continuous suppressive ART in groups 1 and 2 or six months after restarting ART in Group-3. Groups-2 and 3 were combined using a mixed effect regression model to investigate covariates of HIV-1 DNA decay rate. RESULTS AND DISCUSSION: At six months of continuous suppressive ART, the HIV-1 DNA t½ (95% CI) was shorter in Group-1 (n = 7): 2.7 months (2.1 to 3.8), than 9.2 months (7.4 to 12.1) in Group-2 (n = 8); and 9.6 months (7.6 to 12.6) in Group-3 (n = 23) (p < 0.01). In multivariable analyses, HIV-1 DNA before treatment (p < 0.001) and the change in HIV-1 DNA during interruption (p < 0.01) were independent predictors of slower HIV-1 DNA decay. CONCLUSIONS: These data suggest that ART initiation within the first week of life can reduce the persistence of long-lived infected cells. Delaying ART is associated with slower decay of infected cells.