Causes of Death Among Infants Who Are HIV-exposed and -Unexposed Uninfected Using Minimally Invasive Tissue Sampling...

Infants who are HIV-exposed uninfected (HEU) are at greater risk of death compared with infants who are HIV-unexposed, particularly in the first 6 months of life. We investigated the causes of death (CoD) of HEU and HIV-unexposed infants using postmortem minimally invasive tissue sampling.

This prospective, observational study enrolled decedents less than 6 months of age at a secondary-tertiary level care hospital in Soweto, South Africa. The minimally invasive tissue sampling included needle core-biopsy sampling for histopathology of brain, lung and liver tissue. Microbiologic culture and/or molecular tests were performed on lungs, liver, blood and cerebrospinal fluid. Underlying, immediate and antecedent CoD were determined by a multidisciplinary team of medical experts.

The median age (9 [interquartile range 3, 30] vs. 8 [interquartile range 3, 22] days) and sex distribution (female 58.5% vs. 47.9%) were similar between HEU (n = 65) and HIV-unexposed (n = 119) decedents. A larger proportion of HEU decedents (60%, 39/65) compared with HIV-unexposed decedents (44.5%, 53/119; P = 0.045) had preterm birth as an underlying CoD. Among HEU infants compared with HIV-unexposed infants, sepsis was attributed as an immediate or antecedent cause of death in 46.2% (30/65) versus 36.1% (43/119), respectively. Of the 30 HEU infants with sepsis, 76.7% (23/30) were classified as presumed hospital acquired, most commonly associated with Acinetobacter baumannii (56.5% [13/23]) and Klebsiella pneumoniae (13.0% [3/23]). Similarly, among HIV-unexposed infants with sepsis (n = 43), 72.3% (31/43) were classified as presumed hospital acquired, with A. baumannii (38.9% [12/31]) and K. pneumoniae (38.9% [12/31]) as the predominant pathogens. Pneumonia was attributed as an immediate or antecedent cause of death in 32.3% (21/65) of HEU and 36.1% (43/119) of HIV-unexposed infants. Among those with pneumonia, presumed hospital-acquired pneumonia was identified in 47.6% (10/21) of HEU and 72.1% (31/43) of HIV-unexposed infants (P = 0.035), most frequently due to A. baumannii (50.0% [5/10] HEU; 41.9% [13/31] HIV-unexposed) and K. pneumoniae (30.0% [3/10] HEU; 19.4% [6/31] HIV-unexposed). Presumed community-acquired pneumonia was identified in 52.4% (11/21) of HEU and 27.9% (12/43) of HIV-unexposed infants (P = 0.035). The predominant community-acquired pathogens were respiratory syncytial virus (36.4% [4/11] HEU; 25.0% [3/12] HIV-unexposed) and K. pneumoniae (36.4% [4/11] HEU; 8.3% [1/12] HIV-unexposed).

Our study highlights preterm birth as an important underlying CoD among HEU and HIV-unexposed decedents. There was a larger proportion of presumed community-acquired pneumonia deaths in HEU compared with HIV-unexposed decedents. Further research is warranted to explore these differences and develop effective preventive strategies.