Differences in response to antiretroviral therapy in HIV-positive patients being treated for tuberculosis in Eastern Europe, Western Europe and Latin America

Abstract

BackgroundEfavirenz-based antiretroviral therapy (ART) regimens are preferred for treatment of adult HIV-positive patients co-infected with tuberculosis (HIV/TB). Few studies have compared outcomes among HIV/TB patients treated with efavirenz or non-efavirenz containing regimens.MethodsHIV-positive patients aged ≥16 years with a diagnosis of tuberculosis recruited to the TB:HIV study between Jan 1, 2011, and Dec 31, 2013 in 19 countries in Eastern Europe (EE), Western Europe (WE), and Latin America (LA) who received ART concomitantly with TB treatment were included. Patients either received efavirenz-containing ART starting between 15 days prior to, during, or within 90 days after starting tuberculosis treatment, (efavirenz group), or other ART regimens (non-efavirenz group). Patients who started ART more than 90 days after initiation of TB treatment, or who experienced ART interruption of more than 15 days during TB treatment were excluded. We describe rates and factors associated with death, virological suppression, and loss to follow up at 12 months using univariate, multivariate Cox, and marginal structural models to compare the two groups of patients.ResultsOf 965 patients (647 receiving efavirenz-containing ART, and 318 a non-efavirenz regimen) 50% were from EE, 28% from WE, and 22% from LA. Among those not receiving efavirenz-containing ART, regimens mainly contained a ritonavir-boosted protease inhibitor (57%), or raltegravir (22%). At 12 months 1.4% of patients in WE had died, compared to 20% in EE: rates of virological suppression ranged from 21% in EE to 61% in WE. After adjusting for potential confounders, rates of death (adjusted Hazard Ratio; aHR, 95%CI: 1.13, 0.72–1.78), virological suppression (aHR, 95%CI: 0.97, 0.76–1.22), and loss to follow up (aHR, 95%CI: 1.17, 0.81–1.67), were similar in patients treated with efavirenz and non-efavirenz containing ART regimens.ConclusionIn this large, prospective cohort, the response to ART varied significantly across geographical regions, whereas the ART regimen (efavirenz or non-efavirenz containing) did not impact on the proportion of patients who were virologically-suppressed, lost to follow up or dead at 12 months.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3077-x) contains supplementary material, which is available to authorized users.

Tuberculosis treatment intermittency in the continuation phase and mortality in HIV-positive persons receiving antiretroviral therapy

“…However, this reflects the reality of clinical settings in Latin America and throughout the world. Our results are consistent with recent studies [ 16 , 22 , 31 – 33 ], but additional data are needed to inform the care of persons with HIV-related TB optimally. Prospective, randomized controlled trials of different TB treatment dosing intervals that include different regions in the globe affected by tuberculosis, would help identify the most effective and cost-effective regimens for TB treatment in persons with HIV who concomitantly receive ART.…”

“…More individuals in the daily group achieved clinical cure (73.0% vs. 44.1%, P < 0.001), with no significant differences in relapse/recurrence or all-cause mortality between groups. [ 31 ] The lack of a difference in all-cause mortality was similar to our findings in the multivariable analysis stratified by study site.…”

Improving healthcare for patients with HIV, tuberculosis and hepatitis C in eastern Europe: a review of current challenges and important next steps

“…In most regions of the world TB is the most common cause of death among PLWH [23]. However, appropriate initiation of antiretroviral therapy (ART) and TB therapy can reduce mortality significantly [24].…”

Integrase inhibitors versus efavirenz combination antiretroviral therapies for TB/HIV coinfection: a meta-analysis of randomized controlled trials

“…When combined with RIF, the effect may magnify [ 12 – 14 ]. Some studies recommend increasing the dosage of EFV to counteract the inductive effects of RIF [ 15 , 16 ], but there is no sufficient evidence to support the efficacy of this approach [ 14 , 17 , 18 ]. Besides, there remain several challenges about EFV, such as EFV-related adverse effects and drug resistance [ 19 , 20 ].…”