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|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|
CD4 cell count
immune response and Ethiopia.
|Copyright: ||Mar-2009 |
|Date Added: ||3-May-2012 |
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.
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
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.|
|Appears in:||Thesis - Medical Microbiology|
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