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. 2019 Aug;22(8):e25368.
doi: 10.1002/jia2.25368.

HIV-1 DNA decay is faster in children who initiate ART shortly after birth than later

Kirsten A Veldsman  1 , Anita Janse van Rensburg  2 , Shahieda Isaacs  1 , Shalena Naidoo  1 , Barbara Laughton  2 , Carl Lombard  3   4 , Mark F Cotton  2 , John W Mellors  5 , Gert U van Zyl  1   6
Affiliations

HIV-1 DNA decay is faster in children who initiate ART shortly after birth than later

Kirsten A Veldsman et al. J Int AIDS Soc. 2019 Aug.

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.

Keywords: Africa; HIV-1 DNA kinetics; HIV-1 persistence; early infant HIV-1 diagnosis; early treatment; paediatrics.

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Figures

Figure 1
Figure 1. HIV‐1 DNA decay in three groups of children on ART
(a) Group‐1: Continued ART from before eight days (median five days) (n = 7). (b) Group‐2 began continued suppressive ART at a median of five months of age (n = 8). (c) Group‐3: Early ART for 40 or 96 weeks from a median of 1.8 months (n = 23); ART interruption for a median of seven months and continued ART from a median age of 20 months. HIV‐1 DNA levels reached levels <10 copies/million cells in six of seven (85.7%) very early treated individuals (Group‐1) at a median of 6.7 months on ART compared to three of five (60%) of never‐interrupted children starting later, and five of eighteen (28%) of interrupted children, after a median of eight to nine years on treatment.
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