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Clinical, Hematological and Immunological Characteristics of Mycobacterium tuberculosis Patients With and Without HIV-1 Infection: Responses to Six Month Tuberculosis Treatment

Desta M Kassa, Leonie Ran, Wudneh Weldemeskel, Mekashaw Tebeje, Amelewerk Alemu, Yodit Alemayehu, Gebremedhin Gebremichael, Alemayehu Selase, Belete Tegbaru, Dawit Wolday, Tsehaynesh Messele, Debbie van Baarle

Abstract


Comprehensive clinical management of tuberculosis (TB)/human immunodeficiency virus (HIV) patients is a challenge in endemic areas. Clinical, hematological and immunological parameters are important for better patient management and further understanding of TB/HIV interactions. We characterized symptoms of TB, and hematological, immunological, HIV RNA load (VL), and interferon-gamma (IFN-γ) responses to Mycobacterium tuberculosis (Mtb)-specific antigens (ESAT-6/CFP-10), in five clinical groups before and after TB treatment (TT). Adults of both sexes (n=224) included 132 TB cases [HIV-TB+=80; HIV+TB+=52], 67 latent TB infected (LTBI) [HIV-TST+=43; HIV+TST+=24], and 25 controls (HIV-TST-). Cough and weight loss were the common symptoms in HIV-TB+. There was a >70% overlap of cough with CD4+<200 cells/μl in HIV+TB+ patients, indicating late onset of symptoms or late presentation of the patients. There were lower CD4+, total lymphocyte count (TLC), hemoglobin (Hgb), and body mass index (BMI), but higher leukocyte count (WBC) and neutrophil values, in HIV-TB+ (P < 0.05), which all normalized after TT. HIV coinfection (HIV+TB+) further perturbed the immunohematological values, and no significant increase in CD4+ count, decrease in viral load (VL), or normalization of any hematological values after TT was observed. IFN-γ production was elevated in HIV-TST+ but impaired in HIV-TB+ (P = 0.003), and severely impaired in HIV+TB+ (P = 0.07) and HIV+TST+ (P = 0.002). In addition, IFN-γ production was reconstituted after TT in HIV-TB+ (P = 0.02) but not in HIV+TB+ patients, which was correlated with CD4+ counts (r = 0.76, P = 0.006). In conclusion, the distinctive pattern of CD4+, TLC, Hgb, WBC, neutrophils, and BMI in TB and TB/HIV patients shows they may serve as markers for response to TB therapy and for prognosis. Likewise, the distinctive profile of IFN-γ during active TB and LTBI confirms the central role of IFN-γ in controlling Mtb infection, and its potential to serve as a correlate of protective immunity and response to therapy. The higher mortality and the impaired responses of CD4+, VL and IFN-γ to TT in TB/HIV patients indicates severe immunosuppression at diagnosis, and emphasizes the need for early intervention, supporting early initiation of HAART for TB/HIV patients.


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