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  Table of Contents  
Year : 2019  |  Volume : 37  |  Issue : 1  |  Page : 102-104

Distribution of human leucocyte antigen-C in HIV-1-infected patients in Mumbai, India

1 Department of Infectious Diseases Biology, ICMR-National Institute for Research in Reproductive Health, Mumbai, Maharashtra, India
2 Department of Obstetrics and Gynaecology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
3 Department of Microbiology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India

Date of Web Publication16-Aug-2019

Correspondence Address:
Dr. Jayanti Mania-Pramanik
Department of Infectious Diseases Biology, ICMR-National Institute for Research in Reproductive Health, Jehangir Merwanji Street, Parel, Mumbai - 400 012, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijmm.IJMM_19_84

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 ~ Abstract 

HIV pathogenesis is known to be highly influenced by host genetic factors, such as human leucocyte antigens (HLAs) HLA-A and HLA-B. However, the role of HLA-C remains largely unexplored. We evaluated HLA-C distribution in 186 HIV-1-infected individuals and compared them to ethnically matched data derived from the Allele Frequency Net Database using Chi-square test with Fisher's exact two-tailed test. The frequency of HLA-C*05 and HLA-C*15 was higher in infected group, whereas the frequency of HLA-C*04 and HLA-C*14 was higher in control group. HLA-C*17, a rare allele, was significantly higher in infected group. These data could be useful in designing and testing vaccines in Indian population.

Keywords: HIV-1, human leucocyte antigen-C, India

How to cite this article:
Bardeskar NS, Chavan VR, Ahir-Bist S, Samant-Mavani P, Mehta PR, Mania-Pramanik J. Distribution of human leucocyte antigen-C in HIV-1-infected patients in Mumbai, India. Indian J Med Microbiol 2019;37:102-4

How to cite this URL:
Bardeskar NS, Chavan VR, Ahir-Bist S, Samant-Mavani P, Mehta PR, Mania-Pramanik J. Distribution of human leucocyte antigen-C in HIV-1-infected patients in Mumbai, India. Indian J Med Microbiol [serial online] 2019 [cited 2020 Aug 11];37:102-4. Available from:

 ~ Introduction Top

HIV-1 is a leading cause of morbidity worldwide, with 36.9 million people living with HIV globally.[1] In India, as of 2016, 2.1 million people are living with HIV with a prevalence of 0.27%.[2]

Although there has been extensive research into HIV's pathogenesis and its relation with the host, a curative therapy or a protective vaccine remains elusive. Factors involved in HIV-1 pathogenesis have always been a major focus for clues towards a functional vaccine strategy. Host factors such as human leucocyte antigen (HLA) have the strongest effects on HIV-1 infection outcome. HLA-B*57, B*40 and B*27 have been associated with protection, whereas HLA-B*35 has been shown to be associated with accelerated progression to AIDS.[3] However, there is a paucity of data on HLA-C and its association with HIV. Recently, HLA-C has been shown to be important in the context of HIV infection.[4]

In this study, we have documented the diversity of HLA-C in a group of HIV-1-infected individuals and compared it with the general population.

 ~ Methods Top

This study was conducted on HIV-1-infected individuals attending Shakti Clinic at KEM Hospital, Mumbai, Maharashtra, India, during 2010–2017, with approval from institutional and the collaborating hospital's ethics committees.

Three millilitres of blood was collected by venepuncture in an ethylenediaminetetraacetic acid and a plain tube. Serum was used for HIV-1 diagnostic tests, whereas the cell portion was used for DNA extraction and HLA typing. All patients were tested using the three rapid tests as recommended by the National AIDS Control Organisation, India.[2] If two of the three tests were positive, the patient was considered HIV-1 seropositive. HLA-C typing was performed using HLA-Ready Gene kits following manufacturer's instructions (Inno-train Diagnostik GmbH, Kronberg, Hesse, Germany) and was analysed on Score™ (v4.020T/97). Quality control was also done at the Department of Transplant Immunology and Immunogenetics, All India Institute for Medical Sciences, New Delhi, with 100% reproducible results.

Healthy control groups for comparison of HLA-C were retrieved from the Allele Frequency Net Database (AFND).[5] The populations were retrieved using the method described in [Figure 1].
Figure 1: Retrieving human leucocyte antigen data from the Allele Frequency Net Database

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Allele frequencies were estimated by direct counts, and expressed as percentages. Differences were calculated using 2 × 2 contingency and were considered statistically significant when P < 0.05 using two-tailed Fisher's exact test and on correction with false discovery rate (Epi Info v. 7 (Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA); SPSS v. 19 (IBM, Armonk, NY, USA)).

 ~ Results Top

One hundred and eighty-six HIV-1-infected patients were evaluated for their HLA-C diversity. Out of the 186 individuals, 72 were male (age: 26–60 years) and 114 were female (age: 20–55 years). All males were antiretroviral therapy (ART) naïve and 79 of 114 females were ART naïve; the remaining 35 were on ART. None of the patients had any AIDS-defining illnesses or any opportunistic infections (OIs).

Because HLA-C distribution is not documented elsewhere, we derived HLA-C data of 11 populations (n = 3243) from the AFND. Four populations belonging to the South Indian-Dravidian ethnicity were excluded from the comparison. The remaining seven populations (n = 402) were from North and West India which corresponded to the Indo-Aryan ethnicity of our study group.[6]

Distribution of HLA-C in HIV-1-infected individuals in our study was compared to healthy controls' data retrieved from the AFND [Table 1]. The comparison showed statistically significant difference in six alleles after correction for multiple factors. HLA-C*02 (P = 0.003; odds ratio [OR] = 2.7), HLA-C*05 (P = 0.0003; OR = 3.345), HLA-C*15 (P = 0.0031; OR = 1.787) and HLA-C*17 (P = 0.002; OR = 6.67) were found to be statistically significantly higher in HIV-1-infected individuals, whereas HLA-C*04 (P = 0.0023; OR = 0.4786) and HLA-C*14 (P = 0.0008; OR = 0.1153) were higher in healthy controls.
Table 1: Distribution of human leucocyte antigen-C in HIV-1-infected patients and healthy controls from North and West India combined

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 ~ Discussion Top

We have compared HLA-C of HIV-1-infected individuals to healthy controls retrieved from the AFND. As many as six alleles showed significant difference between the groups in which HLA-C*02, C*05, C*15 and C*17 were higher in infected group, whereas HLA-C*04 and HLA-C*14 were found to be higher in healthy controls.

In a study by Mann et al., C*04 was found to be higher in Kaposi's sarcoma and OI patients as compared to disease-free HIV-infected individuals. HLA-C*07 was also higher in patients with OI and AIDS as compared to disease-free HIV-infected individuals.[7] However, in another study, C*04 association with the risk of development of AIDS was not found.[8] In our study, we found C*04 to be higher in healthy control group, pointing to the fact that this allele may be useful in preventing infection establishment because it presents HIV-1 epitopes efficiently.[9] In another study, C*07 was found to be higher in Hispanic HIV+ versus HIV−, whereas no significant difference was found in Caucasian group and African-American group. HLA-C*08 was higher in HIV+ as compared to HIV− in the Caucasian group.[10] In our study, both HLA-C*07 and C*08 showed no significant difference. Studies from Shankarkumar et al.'s group have shown that HLA-C*15 is present in high frequency in HIV-infected group as compared to healthy controls.[11],[12] In our study also, we have showed that HLA-C*15 is present in significantly higher frequency in infected group as compared to the healthy controls.

Most of these studies were based on disease progression to AIDS and risk to OIs. Our study aimed to document HLA-C diversity in infected individuals and healthy controls so as to evaluate its possible role in HIV-1 transmission. Most studies have attributed HLA-B to have the strongest association with HIV-1 infection outcome. However, both HLA-A and HLA-B are selectively downregulated from the surface of the cells by HIV Nef protein.[13] HLA-C would, hence, be the only classical Class I molecule that may be activating cytotoxic T-lymphocytes. This makes the role of HLA-C much more important in HIV-1 pathogenesis.

The study may not consist of 'true' healthy controls i.e., we do not know with absolute certainty whether the healthy controls retrieved from the AFND were not exposed to HIV-1. However, to address or minimise this particular issue, we have selected data from only anthropological and other transplant-related studies. HLA class I haplotyping with a larger sample size to evaluate whether HLA-C acts independently or in linkage disequilibrium (LD) with other HLA alleles would confirm the observations in this study. To our knowledge, this is one of the few studies which has documented HLA-C diversity in an HIV-1-infected cohort. This information could be useful in designing and testing vaccines in Indian population.


We thank Ms Shilpa Kerkar for patient sample collection. We also thank the collaborating hospital staff for help in counselling and enrolment of the patients for the study. NSB is supported by the University Grants Commission – Senior Research Fellowship (UGC-SRF).

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 ~ References Top

UNAIDS. Global HIV & AIDS Statistics – 2018 Fact Sheet. UNAIDS; 2018. Available from: [Last accessed on 2019 Feb 05].  Back to cited text no. 1
National AIDS Control Organisation. National Guidelines for HIV Testing. National AIDS Control Organisation; 2015. Available from: Guidelines for HIV Testing_21Apr2016.pdf. [Last accessed on 2018 Apr 14].  Back to cited text no. 2
Bardeskar NS, Mania-Pramanik J. HIV and host immunogenetics: Unraveling the role of HLA-C. HLA 2016;88:221-31.  Back to cited text no. 3
Fellay J, Shianna KV, Ge D, Colombo S, Ledergerber B, Weale M, et al. A whole-genome association study of major determinants for host control of HIV-1. Science 2007;317:944-7.  Back to cited text no. 4
González-Galarza FF, Takeshita LY, Santos EJ, Kempson F, Maia MH, da Silva AL, et al. Allele frequency net 2015 update: New features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations. Nucleic Acids Res 2015;43:D784-8.  Back to cited text no. 5
Moorjani P, Thangaraj K, Patterson N, Lipson M, Loh PR, Govindaraj P, et al. Genetic evidence for recent population mixture in India. Am J Hum Genet 2013;93:422-38.  Back to cited text no. 6
Mann DL, Murray C, Yarchoan R, Blattner WA, Goedert JJ. HLA antigen frequencies in HIV-1 seropositive disease-free individuals and patients with AIDS. J Acquir Immune Defic Syndr 1988;1:13-7.  Back to cited text no. 7
Jeannet M, Sztajzel R, Carpentier N, Hirschel B, Tiercy JM. HLA antigens are risk factors for development of AIDS. J Acquir Immune Defic Syndr 1989;2:28-32.  Back to cited text no. 8
Carrington M, Nelson GW, Martin MP, Kissner T, Vlahov D, Goedert JJ, et al. HLA and HIV-1: Heterozygote advantage and B*35-cw*04 disadvantage. Science 1999;283:1748-52.  Back to cited text no. 9
Rohowsky-Kochan C, Skurnick J, Molinaro D, Louria D. HLA antigens associated with susceptibility/resistance to HIV-1 infection. Hum Immunol 1998;59:802-15.  Back to cited text no. 10
Shankarkumar U, Thakar M, Mehendale S, Praranjape RS, Mohanty D. Association of HLA B*3520, B*1801, and cw*1507 with HIV-1 infection Maharashtra, India. J Acquir Immune Defic Syndr 2003;34:113-4.  Back to cited text no. 11
Umapathy S, Pawar A, Ghosh K. Specific human leukocyte antigen alleles associated with HIV-1 infection in an Indian population. J Acquir Immune Defic Syndr 2007;44:489-90.  Back to cited text no. 12
Cohen GB, Gandhi RT, Davis DM, Mandelboim O, Chen BK, Strominger JL, et al. The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-infected cells from NK cells. Immunity 1999;10:661-71.  Back to cited text no. 13


  [Figure 1]

  [Table 1]


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