Neonatal ART < 7 days VS 7-28 days reduced time to suppression

Tags: | July 28th, 2019

Authors: Tagarro A, Dominguez Rodriguez S, Puthanakit T, et al.

Published: Oral presentation at 27th Conference on Retroviruses and Opportunistic Infections, March 4th-7th, 2019 – Seattle, WA

Abstract: Early antiretroviral therapy (ART) in children is associated with better clinical and virological outcome. Few data are available about long-term outcome of children starting ART in the neonatal period. Our hypothesis is that HIV-perinatally infected neonates initiating ART within <7 days of life have a better long-term clinical and virological response than neonates treated ≥7 days and ≤28 days of life.

44 children with perinatal HIV aged ≤28 days at start of ART were included from 4 cohorts (11%UK, 52% Spain, 7% Italy, and 29% Thailand). Primary endpoints were clinical – mortality, and progression to AIDS – and virological: time to suppression, time to virological failure, and proportion of time suppressed. Data were collected up to 15-years of follow-up. Those subjects who received triple postpartum prophylaxis and subsequently transitioned to ART within <15 days were considered as starting ART from date of prophylaxis initiation. A flexible spline interval censored survival model was applied adjusting for CD4 and viral load (VL) at the start of ART.

57% were female and 35% preterm. Median follow-up was 11.5[IQR 8.2-15.6] years. No patient died. 84% received postpartum prophylaxis. At ART initiation, children were aged 15.5 [0.00;24.2] days, with CD4 total 2766[2126;3368], CD4:CD8 2.5[1.6;3.1], and log10VL 4.2[2.9;5.2] copies/ml. 36/44 (83%) ever suppressed (VL≤50). Time to viral suppression was 0.57[0.25;1.04] years. 12/44 (34%) had subsequent virological failure after suppression (median time to failure, 2.40 [1.01;9.61] years). Participants had 2.9 ±1.8 ART regimen switches, 26% progressed to AIDS. 19/44 (43%) patients started ART <7 days of age. Viral load was higher in children treated <7 days (log10VL 4.4 [4.2;5.4] vs 3.3 [2.9;4.4], p=0.018). Time to suppression was shorter in those treated in the first 7 days of life (18.9[7;41.7] y 44.1[24.6;61.0] weeks, p = 0.038). The probability of suppression decreased by 24% for each week the ART initiation was delayed (aHR=0.76 [0.6;0.97], p=0.035, Figure 1). No differences were observed in progression to AIDS, ART switches, time to immunological recovery (CD4:CD8>1), time to virological failure or proportion of time suppressed.

Even among children initiating ART<28 days of age, children starting ART in the first week of life suppress earlier. There was similar long-term clinical, virological and immunological outcomes in children treated <7 days vs. 7 to 28 days.