HIV-infected infants should be treated early after diagnosis. Mortality and morbidity peak in the first 6 months after ART initiation and in infants < 1-year-old. Mortality is linked to advanced disease at diagnosis. There are few data about determinants of poor outcome in early-treated infants. The aim is to assess risk factors for poor outcome despite early ART in a cohort of infants in South Africa and Mozambique.
EARTH is a multi-centre cohort enrolling HIV-infected infants diagnosed and treated in the first 3 months of life. Enrolment started in May 2018. ART regimens followed national guidelines. Poor outcome was defined as mortality or severe disease (progression to WHO clinical stage 3 or 4 or CD4 below 25%). Risk factors for poor outcome and viral load (VL) suppression adjusting for socio-demographics, clinical, immunological and virological measures were assessed by multivariable time-dependent Cox-proportional hazards model, including time-dependent coefficient for follow-up VL and CD4.
To date, 135 infants were enrolled. Currently, the median follow-up time is 5.5 months (IQR 2.7-6.9). Median age at enrolment was 38 days (31-75), and median age at ART was 33 days (19-66). Fifty-four percent were male, 37% were premature and 30% had baseline weight-for-age Z-Score (WAZ) <-2SD. Prophylaxis after birth was prescribed to 80%. Median baseline VL was 5.1 logs (3.6-6.1). Median baseline CD4 was 35% (26.3-44.4). During the follow-up, 46% of mothers had health issues or serious life events but no mortality. 12 (9%) of infants died, 7 (5%) progressed to stage 3 or 4, and 16 (12%) had CD4 <25%. In total, 32 (24%) had poor outcomes. Only 34 (25%) infants suppressed VL during follow-up at a median time of 5.2 months. According to the model, determinants of poor outcome were VL and age at ART, after adjustment by site, baseline WAZ and ART regimen. The hazard of poor outcome was almost 3X higher (HR: 2.7 [1.3-5.8], p=0.010) per each VL log persistently elevated during the follow-up, and 50% higher for every month that ART was delayed (HR: 1.5 [1.01-2.2], p=0.049). At this point, time to suppression was influenced only by baseline VL (HR: 0.01 [0.002-0.1], p<0.001) and maternal severe life events/ health issues (HR: 0.4 [0.8-0.9], p=0.042).
Despite early ART, a high proportion of infants have a poor outcome during the first months of life. The poor outcome is mainly influenced by VL during follow-up and age at ART initiation