Genetic Variation in Toll-Like Receptors (TLRs) 2, 4, and 9 Influences HIV Disease Progression Toward Active TB and AIDS

Gaurav Kaushik,1,2 Richa Vashishtha,2 Chaitenya Verma,3 Shipra Sharma,4 Vinay Kumar5 1School of Allied Health Sciences, Sharda University, Greater Noida, Uttar Pradesh, 201310, India; 2Department of Medicine, All India Institute of Medical Sciences, New Delhi, 110029, India; 3Department of Pathology, Wexner Medical Center, Ohio State University, Columbus, OH, USA; 4Shri Guru Ram Rai Institute of Medical & Health Sciences, Dehradun, Uttarakhand, 248001, India; 5Pennsylvania State University Hershey Medical Center, 500 University Dr, Hershey, PA, 17033, USACorrespondence: Gaurav Kaushik; Vinay Kumar, Email gaurav.kaushik@sharda.ac.in; vinayktyagi07@gmail.comBackground: Toll-like receptors (TLRs) are identified as one of the key components of the innate immune system. The objective of this study was to explore the influence of genetic variability in these TLRs on human immunodeficiency virus (HIV) disease progression with and without tuberculosis (TB) co-infection.Materials and Methods: This prospective, cross-sectional, and longitudinal study included 373 HIV-positive patients without TB infection. This study aimed to examine the genetic variation in TLRs (TLR2, TLR4, and TLR9) between patients with HIV-1 infection and those who progressed to active TB during the two years of follow-up.Results: During the two year follow-up of 373 positive patients, 98 patients progressed to active TB/AIDS (acquired immunodeficiency syndrome). When comparing 98 HIV patients who developed active TB/AIDS to 275 HIV patients who did not, it was discovered that the frequency of the A allele in TLR9 was considerably higher (p < 0.001) in HIV patients progressed to active TB/AIDS. Ninety eight HIV individuals who advanced to active TB/AIDS showed a significantly higher frequency of the AA genotype in TLR9 than did in HIV patients who had no TB/AIDS (p < 0.001).Conclusion: The increased association of the AA genotype of TLR9 in HIV patients who progressed to active TB during follow-up suggests that HIV-positive ...