Quantifying the dynamics of HIV decline in perinatally-infected neonates on antiretroviral therapy

Abstract

Background: Mathematical modeling has provided important insights into HIV infection dynamics in adults undergoing antiretroviral treatment (ART). However, much less is known about the corresponding dynamics in perinatally-infected neonates initiating early ART.

Setting: From 2014-2017, HIV viral load (VL) was monitored in 122 perinatally-infected infants identified at birth and initiating ART within a median of two days. Pre-treatment infant and maternal covariates, including CD4 T cell counts and percentages, were also measured.

Methods: From the initial cohort, 53 infants demonstrated consistent decline and suppressed VL below the detection threshold (20 copies/ml) within one year. For 43 of these infants with sufficient VL data, we fit a mathematical model describing the loss of short and long-lived infected cells during ART. We then estimated the lifespans of infected cells and the time to viral suppression, and tested for correlations with pre-treatment covariates.

Results: The majority of parameters governing the kinetics of VL decline were consistent with those obtained previously from adults and other infants. However, our estimates of the lifespan of short-lived infected cells were longer than published values. This difference may reflect sparse sampling during the early stages of VL decline, when the loss of short-lived cells is most apparent. In addition, infants with higher pre-treatment CD4 percentage or lower pre-treatment VL trended towards more rapid viral suppression.

Conclusions: HIV dynamics in perinatally-infected neonates initiating early ART are broadly similar to those observed in other age groups. Accelerated viral suppression is also associated with higher CD4 percentage and lower VL.

Publication
JAIDS

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