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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/2190

Title: Assessment of Specific Immune Responses to Tuberculosis in HIV infected Patients before and during Highly Active Antiretroviral Treatment (HAART)
Authors: Tesfaye, Berhanu,
Advisors: Dr Daniel Asrat & Dr Yimtubezinash Woldeamanuel
Keywords: Tuberculosis
CD4 cell count
IRIS
HAART
immune response and Ethiopia.
Copyright: Mar-2009
Date Added: 3-May-2012
Abstract: xii ABSTRACT BACKGROUND: HAART greatly reduces the risk of developing tuberculosis in HIVinfected persons. However, individuals who initiate HAART may still be reported as having TB, either because they are developing active TB due to persistent immunodeficiency or because they have sub clinical TB that becomes apparent in the immune reconstitution inflammatory syndrome (IRIS). Despite the severity of the problem, little information is available on the extent to which HAART restores TB specific immune response or CD4 cell and characteristics of patients who develop TB while taking HAART and proportion of immune reconstitution syndrome associated with TB. OBJECTIVES: To assess specific immune response to tuberculosis in HIV-1 infected patients before and during HAART and to assess the characteristics of patients who developed ART associated TB and to determine the incidence rate of TB IRIS. METHODS: In a longitudinal prospective cohort study, 177 study participants naive to HAART were enrolled and followed for six months after starting HAART at ALERT Hospital, Addis Ababa Ethiopia. The study period was from June 2006 to September 2008. Blood samples were collected before initiation of HAART (at baseline), at 3rd and 6th month of HAART and at occurrence of suspected TB IRIS. T lymphocyte sub set enumerated and the immune response to tuberculosis was assessed in vitro, using ELISPOT assay in PBMC stimulated with TB antigens (PPD, ESAT-6, and CFP-10), and in vivo using tuberculin skin test (TST) at the specified time points. RESULTS Recovery of TB specific immune response: The proportion of TST positive responses increased significantly from baseline 17.5% to 26.8% at 3rd month and to 28.9% at the 6th month (p= 0.02). TST response increased significantly among groups with CD4 cell count <50 cells/mm3 when the group is stratified according to baseline CD4 cell count and among group with active TB at baseline investigation when the group is stratified according to baseline TB status. Quantitative IFN-γ ELISPOT response to TB antigens (PPD, ESAT-6 and CFP-10) also increased after HAART in the whole cohort. Median SFC/million to PPD xiii and ESAT-6 significantly increased among group with baseline CD4<50 cells/mm3 when the group is stratified according to baseline CD4 cell count. Although the difference was not statistically significant (except for quantitative ELSPOT response to PPD), the proportion of TST response and median SFC/million ELISPOT response to TB antigens after HAART were also higher in those with baseline CD4 ≥100 cells/mm3 than < 100 cells/mm3. ART associated TB, unmasking and paradoxical TB IRIS: the incidence rate of ART associated TB in our cohort was 12.7 cases /100 PY during the first 6 months of HAART. The majority (62.5%) of TB cases occurred within the first month of HAART. Baseline TST response > 5 mm induration, baseline hemoglobin < 12 gm/dl and being male were the strongest predictors of occurrence of TB during HAART. Only 3/8 (37.5%) episodes of TB were presented as unmasking tuberculosis IRIS. The proportion of paradoxical IRIS was 9.6 % (3/31) and the incidence rate was 22.5 cases per 100 persons per year. CONCLUSIONS AND RECOMMENDATIONS: The majority of the study participants attained CD4 cell counts above the zone of severe immunodeficiency within the first 3 months of treatment. However, the relative risk of attaining CD4 cell > 200 cells/mm3 decreased significantly with decreasing baseline CD4 cell count. Thus, individuals who initiated HAART with CD4 < 50 cells/mm3 are likely to have high risk of morbidity and mortality for longer period. This underscores the need of designing strategy to identify and treat patients before they get into a stage of profound CD4 lymphcytopenia. Our study indicates that TB specific T cell repertoire may not be totally lost in HIV infected individuals with CD4 < 50 cells/ mm3 and their levels can still be improved by HAART. Our findings provide useful baseline information for further research to assess overall potential of HAART in the restoration of immunity to tuberculosis. Finally, in this study, we observed a high rate of tuberculosis in our cohort during the initial months of HAART indicating the need for careful screening for TB before initiation of HAART. More sensitive and specific diagnostic methods for TB may assist in early diagnosis. In addition, our study confirmed that a sub set of patients who developed TB during HAART manifested as IRIS.
URI: http://hdl.handle.net/123456789/2190
Appears in:Thesis - Medical Microbiology

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