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ONGOING PROJECT
Nature:
Multicentric Study
Principal Investigator:
Dr. Madhuri Thakar, Scientist D, Dept. of Immunology
Brief Description:
CD4+ T cell counts in HIV infected patients are used to monitor the disease progression in HIV infection. It is necessary to know the CD4+ T cell counts in the healthy individuals. The CD4+ T cell counts in healthy Indian adults are not available. The study was undertaken to determine these values; called as reference ranges in healthy Indian adults. The counts are known to be influenced by ethnicity, hence the sample collection is planned to cover near complete Indian population. A total of 1200 healthy Indian adults will be enrolled from four geographical regions of the country (300/ region). Two institutes from each region will conduct this study. The data will be complied and the reference CD4 ranges will be determined. The influence of ethnicity, nutritional status etc will also be determined.
Current status:
The enrollment and samples collection has been completed by most of the centers.
Principal Investigator:
Dr. Madhuri Thakar, Scientist D, Dept. of Immunology
Brief Description:
HIV-specific CTL response has shown to play an important role in controlling viral multiplication. The CTLs recognize epitopes expressed on the target cells in HLA class I mediated manner and kill the target cell. Hence recognition of epitopes inducing strong CTL response is important. The IFN-g secretary ELISPOT assay is being used as a surrogate marker of cytotoxicity because of its ability to screen large number of responses in peripheral blood sample and the responses can be identified to the peptide level. The dept has identified HIV-1 C Gag, Nef and Env epitopes that are frequently recognized by Indian patients. It will be important to study whether recognition of these peptides really induces cytolytic activity of the CTLs.
A study is planned to standardize and use the viral inhibition assay to identify the cytolytic capacity of the CTLs recognizing the identified peptides. The study will generate information on whether the frequently recognized HIV peptides showing correlation with slow disease progression really have the cytolytic ability to kill virally infected cells expressing the peptide. This information will be helpful in designing vaccine strategy
Current status:
The viral load inhibition assay has been standardized. The CTLs showing response to specific epitopes are being studied for the ability to kill HIV infected cells.
Principal Investigator:
Dr. Ashwini Shete, Scientist B,
Brief Description:
Although ART can target actively replicating virus leading to undetectable plasma viral load, it cannot eliminate latent HIV, which persists as a reservoir and acts as a source for persistent HIV infection. Since these latently infected cells do not express HIV antigens, they cannot be eliminated with the help of immune response. Activation of these cells leads to induction of productive HIV infection and expression of viral proteins on cell surfaces, which could be eliminated by host immune surveillance. Activation also accelerates the intrinsic turnover of cells. Latent memory CD4 can get activated in presence of specific antigenic stimulation. Since HIV is found to preferentially infect HIV specific CD4 cells, HIV antigens can be used to activate latently infected memory CD4 cells. The use of specific antigenic stimulation for activation therapy would have added advantage of boosting CTL response against that particular antigen, which would help in elimination of activated cells by CTLs.
Current status:
Thirteen HIV infected patients have been enrolled in the study so far. Productive HIV infection in determined by P24 expression in cells activated using different antigens.
Nature:
Multicentric and longitudinal Study
Principal Investigator:
Dr. N.K.Mehra, AIIMS, New Delhi and Dr. R. S. Paranjape, Director, NARI.
Brief Description:
Host genetic factor play an important role in governing the response to HIV-1, by controlling immune and non-immune function that may affect the rates of progression of AIDS. Inter-individual variability in the rate of disease progression from initial infection with HIV-1 to appearance of AIDS is well known. People infected with this virus have inherent heterogeneity in the innate, humoral and cell mediated immune responses as well as their response to antiretroviral treatment. It has been shown that genetic polymorphisms in chemokine receptors (CCR2, CCR5), their ligands, HLA class I molecules and cytokines play an important role in HIV infection, its transmission and course of progression to AIDS. However, these genetic determinants are highly variable from one race to another and therefore might impart different disease modifying effects in a population specific manner. Moreover, very little information is available in the Indian population with a predominant infection with HIV subtype C.
The main objective of the project is to determine genetic factors that influence HIV transmission, resistance and disease progression in the Indian population. It is proposed to study polymorphism in MHC, chemokine / cytokine and their receptor genes in HIV infected subjects including rapid progressors/ long term non progressors, exposed uninfected high risk groups, discordant couples, The study will be able to identify those genotypes that are associated with increased susceptibility to HIV infection and with rapid disease progression. Information gained through this study will assist develop screening tests for identifying individuals with high risk genotypes and develop therapeutics particularly adapted according to their needs.
Current status:
Identification of study participants and confirmation of their status, generation of DNA bank is ongoing.
Principal Investigator:
Dr. Madhuri Thakar, Scientist D,
Brief Description:
More than 85% HIV transmission occurs through the heterosexual route involving female genital tract as a primary exposed mucosal surface to HIV. The mucosal tissues have been shown to be actively involved in generation of innate and acquired immune responses. The Studies on innate and HIV-specific immune responses at mucosal surfaces will be crucial in understanding pathogenesis of early HIV infection and hence important implications in developing vaccine and microbicides.
A study is proposed to estimate the antimicrobial factors and HIV-specific immune responses in the cervico-vaginal lavages (CVLs) and cytobrush respectively in HIV infected Indian women and to assess the compartmentalization of the immune responses at the genital level by comparing the responses at systemic level. We propose to collect the samples from age matched HIV negative healthy Indian women as a control group for comparison. A total of 30 women in HIV positive and HIV negative group will be enrolled in the study.
Current status:
The enrollment and sample collection is completed for 28 HIV positive and 25 HIV negative women. The characterization of the HIV –specific immune response is ongoing. The HIV-specific neutralizing antibodies and various innate immune factors are being estimated in the CVL samples.
6. Role of Natural killer cells in recent HIV-1 infection.
Principal Investigator:
Dr. Madhuri Thakar, Scientist D,
PhD Student:
Archana Kulkarni-Munje
Brief Description:
The natural killer cells (NK) are important mediators of the innate immunity. In early HIV infection NK cells may play a pivotal role in pathogenesis before the appearance of adaptive immune response. Thus, they may contribute to viral load set point determination and ultimately disease progression. These cells express an array of inhibitory and activatory receptors. The delicate balance between the signals transduced by these receptors decides the executive function of NK cells such as cytokine secretion or cytotoxicity or inhibition of cytotoxic activity against the target cells.
The NK cells form a bridge between the innate and acquired immune response and hence will be important in early HIV infection. The data on NK cells in early HIV infection is limited.
A study has planned to assess the phenotypic characters, functional potency (cytotoxicity and cytokine secreting capacity) of NK cells from 20 individual with recent HIV-1 infection.
Current status:
Up till now the phenotypic characterization, cytotoxicity assessment of NK cells and KIR genotyping of 17 individuals with recent HIV infection is completed. The data is being assessed.
National AIDS Research Institute, Pune All rights reserved.