Background: In a perinatally HIV-infected child, ART at 30 hours of life was associated with reduced human immunodeficiency virus (HIV) reservoirs and 27 months of virologic remission. Knowledge of infected cell frequencies and decay as a function of age at ART is important for informing clinical trials aimed to study these effects.
Methods: 18 perinatally HIV infected infants in a multicenter, open-label, phase I/II, trial of lopinavir+ritonavir-based ART (IMPAACT P1030 trial) initiated before (early-treated [ET]) or after (late-treated [LT]) 6 weeks (wks) of age were studied. Infants with available samples (n=18) were included in the study if they either achieved a 2-log viral load (VL) decrease from baseline and sustained VL<400 by 48 weeks or achieved and maintained VL to <400 by 24 weeks.Total PBMC HIV DNA and 2-LTR circles were quantifed by droplet digital PCR (<3 copies/million (c/m) at baseline, 24, 48, and 96 wks of ART and linear decay rates were estimated for each infant. Total HIV DNA was correlated with age at ART, and HIV DNA levels during ART. All data are reported as mean and 95% confidence interval, except for age of ART which is reported as median and range.
Results: The median age of ART initiation was 5.71 (4.30-5.86) and 11.14 (6.86-23.43) wks for ET (n=5) and LT (n=13) infants, respectively. Before ART, HIV DNA in ET and LT was 3.16 [2.53, 3.78] and 3.27 [2.80,3.73] log10 copies/million (c/m) (p=1.00). Overall, HIV DNA decayed faster in ET vs. LT (-0.034 [-0.054,-0.015] vs. (-0.017 [-0.022, -0.013] log10 c per wk; p=0.03). From 0 to 24 wks of ART, HIV DNA decreased by 1.25 [0.96,1.55] and 0.89 [0.75,1.02] log10 c/m in ET and LT, respectively (p=0.008), but did not differ between groups from 24 to 48 wks (p=0.58). After 48 weeks of ART, there was a trend towards lower HIV DNA in ET vs. LT (1.26 [-0.19,2.71] vs. 2.11 [1.51, 2.71] log10 c/m; p=0.08). Overall, HIV DNA load at baseline was highly correlated with HIV DNA load at 24, 48 and 96 wks of ART (p<0.001). 2-LTR circles were detectable at baseline in 80% and 77% (p=1.00) , at 24 weeks in 25% and 83.4% (p=0.12) and at 48 weeks in 0% and 80% (p=0.03) of ET and LT infants, respectively.
Conclusions: Earlier initiation of ART did not substantially affect pre-ART infected cell frequencies but was associated with faster HIV decay. However, HIV-1 DNA burden established before initiation of ART determined the DNA reservoir during suppressive ART.