Research Article: 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

Date Published: July 10, 2013

Publisher: BioMed Central

Author(s): Desta Kassa, Gebremedhin Gebremichael, Yodit Alemayehu, Dawit Wolday, Tsehaynesh Messele, Debbie van Baarle.

http://doi.org/10.1186/1742-6405-10-18

Abstract

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.

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.

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). 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.

Partial Text

Human immunodeficiency virus/Acquired immunodeficiency syndrome (HIV/AIDS) associated morbidity and mortality has reduced substantially since the introduction of Highly Active Antiretroviral Therapy (HAART) in the mid 90’s
[1,2]. Access to Antiretroviral Therapy (ART) in low and middle income countries has been expanded following the launche of “3 by 5” global initiative
[3], though only 54% of those eligible for ART were on treatment by 2011
[2]. In Ethiopia, where free ART was started in 2005, >250,000 (~79%) of the adults requiring ART were actually treated
[4].

In this study, we determined the long-term outcome of HAART in HIV patients with and without TB and LTBI by comprehensively measuring HIV RNA suppression, CD4+ T-cell recovery, and immune reconstitution specific to Mtb.

In this observational cohort study, we showed sustained outcomes of long-term HAART in HIV patients with and without TB and LTBI as evidenced by clinical, immunologic and virologic data. Advanced pre-ART disease stages were the risk factors for diminished CD4+ and virologic responses to HAART and high mortality, which strongly indicated the need of early identification of eligible patients and early access to care and treatment. Mtb specific immune reconstitution in HIV/TB patients remained impaired after 18 months on HAART, which suggested the need of strong prevention, earlier diagnosis, and treatment of TB, as well as earlier initiation of HAART. Factors contributing to impaired Mtb specific immune restoration in HIV/TB patients after HAART need to be investigated in order to develop intervention methods which could boost the immune response. In addition, we should do further study on the immunological mechanisms associated with HIV/TB coinfection.

The authors declare that they have no competing interests.

DK was a lead author on planning, implementation of the study, data analysis, and writing of the draft, interim and final version of the manuscript; GG and YA participated in different laboratory tests; AA participated in counseling the study participants, filling study questionnaires and sample collection; DW, TE and DB – participated in providing advice and help during data analysis and also offered inputs and recommendations during the draft, interim and final version of the manuscript. All authors have seen and approved the final manuscript.

 

Source:

http://doi.org/10.1186/1742-6405-10-18

 

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