title: Virologic and immunologic outcome of HAART in Human Immunodeficiency Virus (HIV)-1 infected patients with and without tuberculosis (TB) and latent TB infection (LTBI) in Addis Ababa, Ethiopia.
abstract: BACKGROUND
  HIV/TB coinfection remains a major challenge even after the initiation of HAART. Little is known about Mycobacterium tuberculosis (Mtb) specific immune restoration in relation to immunologic and virologic outcomes after long-term HAART during co-infections with latent and active TB.
  
  
  METHODS
  A total of 232 adults, including 59 HIV patients with clinical TB (HIV + TB+), 125 HIV patients without clinical TB (HIV + TB-), 13 HIV negative active TB patients (HIV-TB+), and 10 HIV negative Tuberculin Skin TST positive (HIV-TST+), and 25 HIV-TST- individuals were recruited. HAART was initiated in 113 HIV + patients (28 TB + and 85 TB-), and anti-TB treatment for all TB cases. CD4+ T-cell count, HIV RNA load, and IFN-γ responses to ESAT-6/CFP-10 were measured at baseline, 6 months (M6), 18 months (M18) and 24 months (M24) after HAART initiation.
  
  
  RESULTS
  The majority of HIV + TB- (70%, 81%, 84%) as well as HIV + TB + patients (60%, 77%, 80%) had virologic success (HIV RNA < 50 copies/ml) by M6, M18 and M24, respectively. HAART also significantly increased CD4+ T-cell counts at 2 years in HIV + TB + (from 110.3 to 289.9 cells/μl), HIV + TB- patients (197.8 to 332.3 cells/μl), HIV + TST- (199 to 347 cells/μl) and HIV + TST + individuals (195 to 319 cells/μl). Overall, there was no significant difference in the percentage of patients that achieved virologic success and in total CD4+ counts increased between HIV patients with and without TB or LTBI. The Mtb specific IFN-γ response at baseline was significantly lower in HIV + TB + (3.6 pg/ml) compared to HIV-TB + patients (34.4 pg/ml) and HIV + TST + (46.3 pg/ml) individuals; and in HIV-TB + patients compared to HIV-TST + individuals (491.2 pg/ml). By M18 on HAART, the IFN-γ response remained impaired in HIV + TB + patients (18.1 pg/ml) while it normalized in HIV + TST + individuals (from 46.3 to 414.2 pg/ml).
  
  
  CONCLUSIONS
  Our data show that clinical and latent TB infections do not influence virologic and immunologic outcomes of ART in HIV patients. Despite this, HAART was unable to restore optimal TB responsiveness as measured by Mtb specific IFN-γ response in HIV/TB patients. Improvement of Mtb-specific immune restoration should be the focus of future therapeutic strategies.
authors.affiliation: Infectious and non-infectious diseases research directorate, Ethiopian Health and Nutrition Research Institute (EHNRI), P.O. Box 1242, Addis Ababa, Ethiopia ; Department of Internal Medicine and Infectious Diseases and Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Desta
authors.initials: D
authors.lastname: Kassa
authors.affiliation: Infectious and non-infectious diseases research directorate, Ethiopian Health and Nutrition Research Institute (EHNRI), P.O. Box 1242, Addis Ababa, Ethiopia.
authors.forename: Gebremedhin
authors.initials: G
authors.lastname: Gebremichael
authors.affiliation: Infectious and non-infectious diseases research directorate, Ethiopian Health and Nutrition Research Institute (EHNRI), P.O. Box 1242, Addis Ababa, Ethiopia.
authors.forename: Yodit
authors.initials: Y
authors.lastname: Alemayehu
authors.affiliation: Medical Biotech Laboratory, Addis Ababa, Ethiopia.
authors.forename: Dawit
authors.initials: D
authors.lastname: Wolday
authors.affiliation: Infectious and non-infectious diseases research directorate, Ethiopian Health and Nutrition Research Institute (EHNRI), P.O. Box 1242, Addis Ababa, Ethiopia.
authors.forename: Tsehaynesh
authors.initials: T
authors.lastname: Messele
authors.affiliation: Department of Internal Medicine and Infectious Diseases and Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
keywords: HAART; HIV; Tuberculosis