KIR2DL1 gene is a surrogate marker of protection against infection-related hospitalisation among HIV-1 unexposed versus exposed uninfected infants in Cameroon

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 cohort-study 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 infection-related hospitalizations was 2.42 (95% CI: 1.028-5.823) for HEU versus HUU, with aOR 3.59 (95% CI: 1.037-12.448). Incidence of hospitalization was 3.2 (95% CI: 1.63–7.14) per 100 infant-months among HEU versus 1.2 (95% CI: 0.57–3.60) in HUU, and RR was 2.22 (95% CI: 0.50–9.39). KIR2DL1 gene was significantly higher in HUU versus HEU (OR= 0.183, 95%CI: 0.053-0.629; p=0.003), and the absence of KIR2DL1 was significantly associated with infection-related hospitalization (p<0.001; OR=0.063; 95%CI: 0.017-0.229). Conclusion Compared to HUU, the vulnerability of HEU is driving by KIR2DL1 , indicating the protective role of this KIR against infection and hospitalizations. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Institutional Ethics Committee for Research on Human Health, of the University of Douala (Ethical clearance No. 1639IEC-UD/06/2018/T). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript