Abstract
BackgroundIn HIV-infected individuals, mechanisms underlying unsatisfactory immune recovery during effective combination antiretroviral therapy (cART) have yet to be fully understood. We investigated whether polymorphism of genes encoding immune-regulating molecules, such as killer immunoglobulin-like receptors (KIR) and their ligands class I human leukocyte antigen (HLA), could influence immunological response to cART.MethodsKIR and HLA frequencies were analyzed in 154 HIV-infected and cART-treated patients with undetectable viral load divided into two groups: ‘immunological non responders’ (INR, N = 50, CD4+ T-cell count <200/mm3) and full responders (FR, N = 104, CD4+ T-cell count >350/mm3). Molecular KIR were typed using polymerase chain reaction-based genotyping. Comparisons were adjusted for baseline patient characteristics.ResultsThe frequency of KIR2DL3 allele was significantly higher in FR than in INR (83.7% vs. 62%, P = 0.005). The functional compound genotype HLA-C1+/KIR2DL3+, even at multivariable analysis, when adjusted for nadir CD4+ T-cell count, was associated with reduced risk of INR status: odds ratio (95% Confidence Intervals) 0.34 (0.13−0.88), P = 0.03.ConclusionsReduced presence of the inhibitory KIR2DL3 genotype detected in INR might provoke an imbalance in NK function, possibly leading to increased immune activation, impaired killing of latently infected cells, and higher proviral burden. These factors would hinder full immune recovery during therapy.
Highlights
Combination antiretroviral therapy has dramatically reduced morbidity and mortality in individuals infected with human immunodeficiency virus (HIV) [1]
The two groups were similar in clinical-epidemiological and HIVrelated characteristics, except for nadir CD4+ T-cell count, which was significantly lower in immunological non responders (INR) than full responders (FR)
No statistically significant differences were observed in other variables sometimes associated with reduced immunological response, such as hepatitis C coinfection, age, and years of HIV infection, while the long exposure to combination antiretroviral therapy (cART) was lower for INR
Summary
Combination antiretroviral therapy (cART) has dramatically reduced morbidity and mortality in individuals infected with human immunodeficiency virus (HIV) [1]. Up to 30% of HIV-infected patients, despite virologically effective cART with undetectable plasma viral load, fail to achieve a satisfactory immunological recovery [2], defined as a CD4+ T-cell count $200/mm. As yet undefined host factors might explain the diversity between patients of immunological responses to cART: a role of genetic polymorphisms of cytokines [5] and human leukocyte antigen (HLA) molecules [6] has been suggested. In HIV-infected individuals, mechanisms underlying unsatisfactory immune recovery during effective combination antiretroviral therapy (cART) have yet to be fully understood. We investigated whether polymorphism of genes encoding immune-regulating molecules, such as killer immunoglobulin-like receptors (KIR) and their ligands class I human leukocyte antigen (HLA), could influence immunological response to cART
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
