Despite Access to Antiretrovirals for Prevention and Treatment, High Rates of Mortality Persist Among HIV-infected Infants and Young Children

Abstract

Background Outcomes of HIV-infected children before widespread use of antiretroviral therapy (ART) for treatment and prevention of mother-to-child transmission (PMTCT) have been well characterized but less is known about children who acquire HIV infection in the context of good ART access. Methods We enrolled newly-diagnosed HIV-infected children ≤24 months (mos) of age at 3 hospitals and 2 clinics in Johannesburg, South Africa. We report ART initiation and mortality rates during 6 months from enrollment and factors associated with mortality. Results Of 272 children enrolled, median age 6.1mos, 69.5% were diagnosed during hospitalization. By 6mos post-enrollment, 53(19.5%) died and 73(26.8%) were lost-to-follow-up. Using Kaplan-Meier analysis, the probability of death by 6mos after enrollment was 23.5%. The median age of death was 9.1mos (95% confidence interval[CI]: 8.6; 12.0). Overall, 226(83%) children initiated ART which was associated with a 71% reduction in risk of death (Hazard Ratio[HR] =0.29 [95%CI: 0.15; 0.58]). In multivariable analysis of infant factors, weight-for-age z-score <-2SD (HR=2.43[95%CI: 1.03-5.73]), CD4<20% (HR=3.29[95%CI: 1.60-6.76]) and identification during hospitalization (HR=2.89[95%CI: 1.16-7.25]) were independently associated with mortality. In multivariable analysis of maternal factors, CD4≤350/no maternal ART was associated with increased mortality risk (HR=2.57[95%CI: 1.19-5.59]) vs. CD4>350/no maternal ART; exposure to maternal/infant antiretrovirals for PMTCT was associated with reduced mortality risk (HR=0.53[95%CI: 0.28-0.99]) vs. no PMTCT. Conclusions ART initiation is highly protective against death in young children. However, despite improved access to ART, young children remain at risk for early death; innovative approaches to rapidly diagnose and initiate treatment as early in life as possible are needed.

Earlier Antiretroviral Therapy Initiation and Decreasing Mortality Among HIV-infected Infants Initiating Antiretroviral Therapy Within 3 Months of Age in South Africa, 2006–2017

“…19 For example, infants initiating ART between 61-90 days old were more likely to be underweight than those initiating before 30 days old (57% vs 38%) and underweight infants were more likely to die. 10,20 This suggests that older infants are those who missed earlier testing, or were infected during the early postpartum period and only present to care with advanced disease and hence higher risk of mortality. This partially explains the ongoing burden of Previous ART implementation studies in infants before expansion of early diagnosis and ART for prevention and treatment suggests a trend towards decreasing long-term mortality over time.…”

HIV viral suppression and longevity among a cohort of children initiating antiretroviral therapy in Eastern Cape, South Africa

“…Children with advanced disease at ART initiation take longer and are less likely to achieve VS; they are also at risk for having inadequate immune response to treatment . For the infants, the combination of advanced disease at ART initiation with immature immune system often leads to delayed VS particularly when adherence is inadequate and adequate drug levels are not well maintained . Among infants starting ART at a median age of 5.9 months in pooled data from Southern Africa, only 28% and 56% achieved VS <400 copies/mL at six and twelve months .…”

The Effect of Human Immunodeficiency Virus and Cytomegalovirus Infection on Infant Responses to Vaccines: A Review

“…In 2015, there were 1.4 million pregnant women living with HIV ( 3 ), and an estimated 24% of those did not receive antiretroviral therapy (ART) for prevention of mother-to-child transmission (PMTCT) ( 4 ). In infants born with HIV infection, early commencement of combination ART significantly reduces mortality ( 5 , 6 ) and is associated with increased magnitude and quality of infant antibody responses to vaccines ( 7 – 10 ), but there is some evidence of reduced humoral responses to vaccines even in those children starting ART at 6–8 weeks of age, compared with HIV-unexposed infants ( 9 ).…”