ABSTRACT
BACKGROUND: HIV-specific Antibody Dependent Cell Cytotoxicity (ADCC) has shown to be important in HIV control and resistance. The ADCC is mediated primarily by natural killer cell activated through the binding of FcγRIIIa receptor to the Fc portion of antibody bound to the antigen expressed on the infected cells. However, no data is available on the influence of the polymorphism in FcγRIIIa receptor on HIV-specific ADCC response. METHODS: The Sanger's method of sequencing was used to sequence the exon of FcγRIIIa receptor while the ADCC activity was determined using NK cell activation assay. The polymorphism in FcγRIIIa receptor was assessed in HIV-infected Indian individuals with or without HIV-specific ADCC antibodies and its influence on the magnitude of HIV-specific ADCC responses was analyzed. RESULTS: Two polymorphisms: V176F (rs396991) and Y158H (rs396716) were observed. The Y158H polymorphism is reported for the first time in Indian population. Both, V176F (V/V genotype) (p = 0.004) and Y158H (Y/H genotype) (p = 0.032) were found to be significantly associated with higher magnitude of HIV-specific ADCC response. CONCLUSION: The study underscores the role of polymorphism in the FcγRIIIa receptor on HIV-specific ADCC response and suggests that the screening of the individuals for FcγRIIIa-V176F and Y158H polymorphisms could be useful for prediction of efficient treatment in monoclonal antibody-based therapies aimed at ADCC in HIV infection.
Subject(s)
Antibody-Dependent Cell Cytotoxicity/genetics , HIV Infections/genetics , HIV Infections/immunology , HIV-1/immunology , Killer Cells, Natural/immunology , Polymorphism, Single Nucleotide/genetics , Receptors, IgG/genetics , Adolescent , Adult , Antibodies, Monoclonal/therapeutic use , Female , Gene Frequency/genetics , Genotype , HIV Antibodies/therapeutic use , HIV Infections/therapy , Humans , Immunotherapy , India , Male , Middle Aged , Prognosis , Treatment Outcome , Viral Envelope Proteins/pharmacology , Young AdultABSTRACT
CONTEXT: The clinical and prevention benefits of early initiation of antiretroviral therapy (ART) have led to the adoption of test and treat policy for HIV. Early diagnosis of HIV is crucial for maximal benefits from ART. AIMS: This study aims to assess trends in CD4 cell counts at diagnosis and determinants of late presentation. SETTINGS AND DESIGN: We analyzed 5-year data from a free HIV/sexually transmitted infection referral clinic immune. SUBJECTS AND METHODS: Persons presenting for HIV testing from January 2011 to December 2015, for whom CD4 cell count results were available within 3 months of HIV diagnosis, were included in the analysis. Persons on ART were excluded from the study. STATISTICAL ANALYSIS: The predictors of CD4 cell count at presentation were assessed using univariate and multivariate linear regression. RESULTS: Of 1001 persons diagnosed HIV-1 positive, 659 had received CD4 test within 3 months of diagnosis. The median CD4 count at presentation ranged from 212 to 352 cells/cmm in these 5 years and did not show any significant change with time. Nearly 40% had CD4 cell counts below 200 cells/cmm (AIDS); additionally, 23% presented below 350 cells/cmm. Older age (beta: -5.78; P = 0.001), education above matriculation (beta: -123.72; P = 0.014), having current opportunistic infections (beta: -173.58; P = 0.037), and being symptomatic (beta: -101.8; P = 0.002) were predictors of presenting at lower CD4 counts. CONCLUSION: Between 2011 and 2015, persons with HIV continued to present late in spite of changes in ART access program. Education focused on the benefits of early diagnosis and availability of free immediate treatment in the public sector, are crucial to the achievement of the India's 90-90-90 goals.