Abstract
BackgroundHuman Immunodeficiency Virus (HIV) and Schistosomiasis co-infection is common among residents at the shores of Lake Victoria in Kenya. About 36% of this population initiating antiretroviral therapy (ART) experience Immune Reconstitution Inflammatory Syndrome (IRIS) that complicates recovery. Several IL-23R alleles have been associated with susceptibility to both autoimmune and inflammatory diseases through T-helper type 17 (TH17) cells. However, whether or not variants within the IL-23R increase susceptibility to IRIS in western Kenya is unknown. The objective of the current study was to determine the association between IL-23R gene polymorphisms, CD4+ cell counts and HIV RNA levels and IRIS in HIV and Schistosoma mansoni co-infected patients undergoing highly active anti-retroviral therapy (HAART).MethodsA three-month case–control study was conducted on antiretroviral naïve schistosomiasis/HIV co-infected fishermen starting HAART in Uyoma Rarieda, Siaya County, Kenya. Seventy one patients were sampled at baseline and followed up for three months, to establish if they developed Schistosoma-related IRIS. In addition, the CD4+ cell counts and HIV RNA levels were determined in pre- and post-administration of HAART. Variations at five polymorphic sites of IL-23R (rs1884444, rs11465754, rs6682925, rs7530511 and rs7539625) based on >10% minor allele frequency in Yoruban reference population was determined using Allelic Discrimination Assay. The association between the five variants and susceptibility to IRIS was determined using logistic regression while controlling for potential confounders. In addition, the functional differences between the baseline CD4 + Cell counts and viral loads were determined using medians while across IL-23R genotypes were determined using Kruskal-Wallis tests.ResultsOverall, 26 (36.6%) patients developed schistosomiasis-associated IRIS at a median age of 35.5 years. Carriage of the TT genotype at the non-synonymous rs1884444 T > G relative to GG, was associated with a decreased risk of schistosomiasis-associated IRIS (OR, 0.25, 95% CI, 0.07-0.96, P = 0.043) while both baseline CD4+ cell counts and viral loads had no association with IRIS.ConclusionThese findings indicate that the non-synonymous variant rs1884444 T > G of IL-23R is associated with a decreased risk to schistosomiasis-associated IRIS. However, additional studies in a larger cohort and with an all inclusive polymorphic variants in the synonymous and non-synonymous regions need to be evaluated.
Highlights
Human Immunodeficiency Virus (HIV) and Schistosomiasis co-infection is common among residents at the shores of Lake Victoria in Kenya
Prevalence of IL-23 receptor (IL-23R) genotypes in S. mansoni-infected patients undergoing highly active anti-retroviral therapy (HAART) Samples from the 71 S. mansoni-infected individuals undergoing HAART were genotyped for the IL-23R polymorphisms (Table 2)
This study investigated the association between five IL23R variants and risk to schistosomiasis-associated Immune Reconstitution Inflammatory Syndrome (IRIS) in a Kenyan population naturally exposed to schistosomiasis
Summary
Human Immunodeficiency Virus (HIV) and Schistosomiasis co-infection is common among residents at the shores of Lake Victoria in Kenya. The objective of the current study was to determine the association between IL-23R gene polymorphisms, CD4+ cell counts and HIV RNA levels and IRIS in HIV and Schistosoma mansoni co-infected patients undergoing highly active anti-retroviral therapy (HAART). A significant number of AIDS cases develop into severe clinical manifestations described as Immune Reconstitution Inflammatory Syndrome (IRIS) during the first few months of starting highly active antiretroviral therapy (HAART) [2,3,4,5,6], leading to additional HIV-related morbidity and mortality. Binding of IL-23 to its receptor causes activation of Janus kinases (Jaks) which phosphorylates IL-23R at certain locations, forming docking sites for the STATs, and further enabling them to translocate to the nucleus where transcription of pro-inflammatory genes such as IL-17 and interferon-γ (IFN-γ) are initiated [19]
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