KIR2DL1gene is a surrogate marker of protection against infection-related hospitalisation among HIV-1 unexposed versus exposed uninfected infants in Cameroon

Abstract

Background: HIV-exposed uninfected infants (HEU) experience appear more vulnerable to infections compared to their HIV-unexposed uninfected (HUU) peers, generally attributed to poor passive immunity acquired from the mother. This may be due to some genetic factors that could alter the immune system. We thus sought to determine the distribution of Killer Cells Immunoglobulin-Like Receptor (KIR) genes in HEU versus HUU, and study the association between KIR profiling and occurrence of infection-related hospitalization. Methods: A cohortstudy was conducted from May 2019 to April 2020 among HEU and HUU, followed-up at birth, week 6, 12, 24 and 48, in reference pediatric centers in Yaounde, Cameroon. Infant HIV status was determined, types of infections were analyzed, and 15 KIR genes were investigated using the sequence specific primer polymerase chain reaction (PCR-SSP) method. Rate of KIR genes and infection-related hospitalizations were compared in HEU versus HUU, with p<0.05 considered statistically significant. Results: In this cohort, a total of 19 infection-related hospitalizations occurred in 66 infants (14.81%, 04/27 HUU and 38.46%, 15/39 HEU, p=0.037), the majority occurring during the first 24 weeks of life: 10 (25.64%) HEU and 03 (11.11%) HUU, p=0.14. At week 48 (39 HEU and 27 HUU), the relative risk (RR) for infectionrelated hospitalizations was 2.42 (95% CI: 1.028 to 5.823) for HEU versus HUU, with aOR 3.59(95% CI: 1.037 to 12.448). Incidence of hospitalization was 3.2 (95% CI: 1.63 to 7.14) per 1002 infant-months among HEU versus 1.2 (95% CI: 0.57 to 3.60) in HUU, and RR was 2.22 (95% CI: 0.50 to 9.39). KIR2DL1 gene was significantly higher in HUU versus HEU (OR= 0.183, 95%CI: 0.053 to 0.629; p=0.003), and the absence of KIR2DL1 was significantly associated with infection-related hospitalization (p<0.001; OR=0.063; 95%CI: 0.017 to 0.229). Conclusion: Compared to HUU, the vulnerability of HEU is driving by KIR2DL1, indicating the protective role of this KIR against infection and hospitalizations.