Abstract Body

Antiretroviral treatment (ART) started in the first week of life may limit HIV viral reservoir and improve treatment outcomes, but little information is available about safety, viral efficacy, and pharmacokinetics (PK) of ART in early infancy.

HIV+ infants <7 days of age, >35 weeks gestation, and >2000g were offered enrollment in the Early Infant Treatment Study (EIT) in Botswana and started on treatment doses of NVP (6mg/kg BID), ZDV, and 3TC as initial ART, and changed to LPV/r, ZDV, 3TC after 2-5 weeks (when >2 weeks of life and >40 weeks gestational age equivalent). Study visits and HIV RNA testing occurred at weeks 0, 1, 2, 4, 8, 12. PK testing of NVP trough values occurred at weeks 1 and 2. Comparisons were by Wilcoxon rank sum testing and Spearman correlations.

From April 2015-July 2018, 40 HIV+ infants were enrolled; 37 (93%) had reached 12 wks on ART as of 20 September 2018. Median age at screening was 1 day after birth (range 0, 4), and median age at ART initiation was 2 days after birth (range 1, 5). Median change from NVP-based to LPV/r-based ART was after 2.7 wks (range 2.3, 4.4 wks). No deaths or loss to follow-up occurred in the first 12 wks, and no modification of ART for toxicity occurred. Only 1 grade 3/4 neutropenia and no grade 3/4 anemias were reported through 12 wks. HIV RNA declined from a median of 4.05 log copies/mL at baseline (IQR 2.79, 4.86 log copies/mL) to 2.54 log copies/mL at 2 wks (IQR 1.86, 3.21) and <1.60 log copies/mL at 12 wks (IQR <1.60, 1.89 log copies/mL) (Figure 1), and did not differ by infant HIV RNA at baseline (p=0.10). At 12 wks of ART, 21 (57%) of 37 had HIV RNA < 40 copies/mL, and only 3 (8%) were > 400 copies/mL. However, 9 (22.5%) infants had transient increases in HIV RNA in the 4-wk period following transition to LPV/r-based ART, thought to be adherence-related. Median NVP trough concentration at 1 and 2 wks was 3.01 mcg/mL (at median 15 hrs); 48% of concentrations were below the therapeutic target of 3.0 mcg/mL (including 10% BQL, indicating non-adherence); concentrations did not correlate with the magnitude of decline in HIV RNA log copies/mL at either 2 or 4 wks.

NVP, ZDV, 3TC started in the first week of life was safe and effective, even among infants with NVP levels below the ideal therapeutic PK target. Although poor tolerability often led to transient viral rebound following transition to LPV/r-based ART, almost all children were able to achieve HIV RNA declines to < 400 copies/mL by 12 weeks of life.