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

BackgroundHIV/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.MethodsA 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.ResultsThe 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).ConclusionsOur 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.

High Level of Virological Suppression among HIV-Infected Adults Receiving Combination Antiretroviral Therapy in Addis Ababa, Ethiopia

“…This result was even higher than 94% when a viral load threshold of <400 copies/ml was used or when only patients who had received cART for ≥12 months were included. Both estimates were comparable with, or considerably higher than previous study findings from public ART programmes in Ethiopia and other resource-limited or middle-income settings [11,12,15,27]. When LTFU, dead or stopped patients were all assumed to be alive and having had a detectable viral load above 40 copies/ml, the percentage of patients with suppressed viral load would drop to about 71.6%.…”

Virological success after 12 and 24 months of antiretroviral therapy in sub-Saharan Africa: Comparing results of trials, cohorts and cross-sectional studies using a systematic review and meta-analysis

“…Of the 48 independent cohorts, 31 reported results from the overall cohort [24, 62, 64–92], while 17 reported results from two different groups within the cohort [59, 93–108], although for two of these studies, only one group was considered in our meta-analysis due to sample size restriction [100, 107]. This gave 63 distinct populations.…”

HIV/AIDS Treatment Failure and its Determinant Factors among First Line HAART Patients at Felege-Hiwot Referral Hospital, Bahir Dar, Northwest Ethiopia

“…Due to HIV's error-prone replication, high mutation rate and viral recombination, development of some HIV drug resistance (HIVDR) is inevitable, even with appropriate ART prescribing and adherence [5][6][7][8]. HIVDR has significant human and financial implications: it limits treatment options.…”

“…Monitoring of ART program factors known to be associated with the emergence of treatment failure for the purpose of improving programmatic functioning, may minimize the emergence of preventable HIVDR, especially at ART sites where viral load is not routinely available [6,8,18,19]. Inappropriate prescribing, treatment interruptions due to suboptimal patient adherence, poor patient retention on ART, or late initiation or when stock-outs occur.…”

“…Inappropriate prescribing, treatment interruptions due to suboptimal patient adherence, poor patient retention on ART, or late initiation or when stock-outs occur. These factors have been shown to be associated with the development of HIV treatment failure [6,8,20].…”