Expression of Killer Immunoglobulin Receptor Genes among HIV-Infected Individuals with Non-AIDS Comorbidities

Farouk F Abou Hassan,Mirna Bou Hamdan,Nada M Melhem,Khalil El Asmar,Jixin Zhong

doi:10.1155/2022/1119611

Farouk F Abou Hassan, Mirna Bou Hamdan + Show 3 more

Open Access

https://doi.org/10.1155/2022/1119611

Copy DOI

Abstract

Combined antiretroviral therapy (cART) increased the life expectancy of people living with HIV (PLHIV) and remarkably reduced the morbidity and mortality associated with HIV infection. However, non-AIDS associated comorbidities including diabetes, hypertension, hyperlipidemia, and cardiovascular diseases (CVD) are increasingly reported among PLHIV receiving cART. Killer cell immunoglobulin receptors (KIRs) expressed on the surface of natural killer (NK) cells have been previously implicated in controlling HIV disease progression. The aim of this study is to investigate the role of KIRs in developing non-AIDS associated comorbidities among PLHIV. Demographic and behavioral data were collected from voluntary participants using a standardized questionnaire. Whole blood samples were collected for KIR genotyping. Hypertension (29.5%) and hyperlipidemia (29.5%) followed by diabetes (23.7%) and CVD (9.7%) were mainly reported among our study participants with higher rate of comorbid conditions observed among participants > 40 years old. The observed KIR frequency (OF) was ≥90% for inhibitory KIR2DL1 and KIR3DL1, activating KIR2DS4 and the pseudogene KIR2DP1 among study participants. We detected significant differences in the expression of KIR3DS4 and KIR3DL1 (p = 0.038) between diabetic and nondiabetic and in the expression of KIR2DL3 between hypertensive and normotensive HIV-infected individuals (p = 0.047). Moreover, KIR2DL1 and KIR2DP1 were associated with significantly reduced odds of having CVD (OR 0.08; 95% CI: 0.01-0.69; p = 0.022). Our study suggests the potential role of KIR in predisposition to non-AIDS comorbidities among PLHIV and underscores the need for more studies to further elucidate the role of KIRs in this population.

Highlights

The use of combined antiretroviral therapy significantly reduced the morbidity and mortality associated with human immunodeficinecy virus (HIV) infection [1]
Killer cell immunoglobulin receptors (KIRs): killer cell immunoglobulin receptor; observed KIR frequency (OF): observed frequency calculated by direct counting; KLF: estimated KIR gene frequency calculated using the formula 1 − √ð1 − OFÞ
Our results showed that the frequency of comorbid conditions increases with age among people living with HIV (PLHIV); 19% of our participants above 40 years old reported one or two comorbid conditions each followed by 10% and 3% suffering from 3 and 4 conditions, respectively (Abou Hassan et al submitted manuscript)

Summary

Introduction

The use of combined antiretroviral therapy (cART) significantly reduced the morbidity and mortality associated with human immunodeficinecy virus (HIV) infection [1] The former contributed to an increase in the life expectancy of people living with HIV (PLHIV) approaching that of HIVnegative individuals [2–4]. With the increasing proportion of people living and aging with HIV, non-AIDS (acquired immunodeficiency syndrome) comorbidities have been increasingly reported among treated PLHIV leading to an increased number of deaths exceeding those of AIDSrelated deaths [6–9]. These comorbidities include cardiovascular disease (CVD) [10–15], liver disease [16, 17], renal disease [11, 14, 18], diabetes [10–13, 15, 19], and neurocognitive abnormalities [20, 21], as well as non-AIDS defining malignancies including liver, brain, anal, and lung cancers [22, 23]. While biological aging was suggested to start earlier among HIV infected individuals (55 vs. 65 years) [24], the subsequent pathway leading to disease manifestation among treated and aging PLHIV is not fully understood

Objectives

Methods

Results

Discussion

Conclusion