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Association of isoniazid preventive therapy with lower early mortality in individuals on antiretroviral therapy in a workplace programme.

ABSTRACT: To describe the association between isoniazid preventive therapy (IPT) and mortality among individuals starting antiretroviral therapy (ART) in a workplace programme in South Africa where tuberculosis (TB) incidence is very high.ART-naive individuals starting ART from January 2004 to December 2007 were followed for up to 12 months. Deaths were ascertained from clinic and human resource data. The association between IPT and mortality was assessed using Cox regression.A total of 3270 individuals were included (median age 45; 93% men; median baseline CD4 cell count 155 cells/?l (interquartile range 87-221); and 45% with WHO stage 3/4]. Nine hundred twenty-two (28%) individuals started IPT either prior to or within 3 months of starting ART. Individuals who started IPT tended to have less advanced HIV disease at ART initiation. Two hundred fifty-nine (7.9%) deaths were observed with overall mortality rate 8.9 per 100 person-years [95% confidence interval (CI) 7.9-10.6]. The unadjusted mortality rate was lower among those who received IPT compared with those who did not [3.7/100 vs. 11.1/100 person-years, respectively, hazard ratio 0.34 (95% CI 0.24-0.49)]; this association remained after adjustment for age, baseline CD4 cell count, baseline WHO stage, year of ART start, and individual company (hazard ratio 0.51, 95% CI 0.32-0.80). In sensitivity analyses restricted to those with no previous history of TB (n = 3036) or with no TB symptoms at ART initiation (n = 2251), IPT remained associated with reduced mortality [adjusted hazard ratios 0.51 (95% CI 0.32-0.81) and 0.48 (95% CI 0.24-0.96), respectively].Mortality was lower among individuals receiving IPT with or prior to ART start. These results support routine use of IPT in conjunction with ART.

SUBMITTER: Charalambous S

PROVIDER: S-EPMC3724406 | biostudies-other | 2010 Nov

REPOSITORIES: biostudies-other

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Association of isoniazid preventive therapy with lower early mortality in individuals on antiretroviral therapy in a workplace programme.

Charalambous Salome S Grant Alison D AD Innes Craig C Hoffmann Christopher J CJ Dowdeswell Rob R Pienaar Jan J Fielding Katherine L KL Churchyard Gavin J GJ

AIDS (London, England) 20101101

<h4>Objective</h4>To describe the association between isoniazid preventive therapy (IPT) and mortality among individuals starting antiretroviral therapy (ART) in a workplace programme in South Africa where tuberculosis (TB) incidence is very high.<h4>Methods</h4>ART-naive individuals starting ART from January 2004 to December 2007 were followed for up to 12 months. Deaths were ascertained from clinic and human resource data. The association between IPT and mortality was assessed using Cox regres ...[more]

PMID: 21079429

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Project description:BackgroundIPT with or without concomitant administration of ART is a proven intervention to prevent tuberculosis among PLHIV. However, there are few data on the routine implementation of this intervention and its effectiveness in settings with limited resources.ObjectivesTo measure the level of uptake and effectiveness of IPT in reducing tuberculosis incidence in a cohort of PLHIV enrolled into HIV care between 2007 and 2010 in five hospitals in southern Ethiopia.MethodsA retrospective cohort analysis of electronic patient database was done. The independent effects of no intervention, "IPT-only," "IPT-before-ART," "IPT-and-ART started simultaneously," "ART-only," and "IPT-after-ART" on TB incidence were measured. Cox-proportional hazards regression was used to assess association of treatment categories with TB incidence.ResultsOf 7,097 patients, 867 were excluded because they were transferred-in; a further 823 (12%) were excluded from the study because they were either identified to have TB through screening (292 patients) or were on TB treatment (531). Among the remaining 5,407 patients observed, IPT had been initiated for 39% of eligible patients. Children, male sex, advanced disease, and those in Pre-ART were less likely to be initiated on IPT. The overall TB incidence was 2.6 per 100 person-years. As compared to those with no intervention, use of "IPT-only" (aHR = 0.36, 95% CI = 0.19-0.66) and "ART-only" (aHR = 0.32, 95% CI = 0.24-0.43) were associated with significant reduction in TB incidence rate. Combining ART and IPT had a more profound effect. Starting IPT-before-ART (aHR = 0.18, 95% CI = 0.08-0.42) or simultaneously with ART (aHR = 0.20, 95% CI = 0.10-0.42) provided further reduction of TB at ? 80%.ConclusionsIPT was found to be effective in reducing TB incidence, independently and with concomitant ART, under programme conditions in resource-limited settings. The level of IPT provision and effectiveness in reducing TB was encouraging in the study setting. Scaling up and strengthening IPT service in addition to ART can have beneficial effect in reducing TB burden among PLHIV in settings with high TB/HIV burden.

Project description:BackgroundIsoniazid preventive therapy prevents active tuberculosis in people with HIV, but previous studies have found no evidence of benefit in people with HIV who had a negative tuberculin skin test, and a non-significant effect on mortality. We aimed to estimate the effect of isoniazid preventive therapy given with antiretroviral therapy (ART) for the prevention of tuberculosis and death among people with HIV across population subgroups.MethodsWe searched PubMed, Embase, the Cochrane database, and conference abstracts from database inception to Jan 15, 2019, to identify potentially eligible randomised trials. Eligible studies were trials that enrolled HIV-positive adults (age ≥15 years) taking ART who were randomly assigned to either daily isoniazid preventive therapy plus ART or ART alone and followed up longitudinally for outcomes of incident tuberculosis and mortality. We approached all authors of included trials and requested individual participant data: coprimary outcomes were relative risk of incident tuberculosis and all-cause mortality. We did a single-stage meta-analysis of individual participant data using stratified Cox-proportional hazards models. We did prespecified subgroup analyses by sex, CD4 cell count, and evidence of immune sensitisation to tuberculosis (indicated by tuberculin skin test or interferon-γ release assays [IGRAs]). We also assessed the relative risk of liver injury in an additional prespecified analysis. This study is registered with PROSPERO, CRD42019121400.FindingsOf 838 records, we included three trials with data for 2611 participants and 8584·8 person-years of follow-up for the outcome of incident tuberculosis, and a subset of 2362 participants with 8631·6 person-years of follow-up for the coprimary outcome of all-cause mortality. Risk for tuberculosis was lower in participants given isoniazid preventive therapy and ART than participants given ART alone (hazard ratio [HR] 0·68, 95% CI 0·49-0·95, p=0·02). Risk of all-cause mortality was lower in participants given isoniazid preventive therapy and ART than participants given ART alone, but this difference was non-significant (HR 0·69, 95% CI 0·43-1·10, p=0·12). Participants with baseline CD4 counts of less than 500 cells per μL had increased risk of tuberculosis, but there was no significant difference in the benefit of isoniazid preventive therapy with ART by sex, baseline CD4 count, or results of tuberculin skin test or IGRAs. 65 (2·5%) of 2611 participants had raised alanine aminotransferase, but data were insufficient to calculate an HR.InterpretationIsoniazid preventive therapy with ART prevents tuberculosis across demographic and HIV-specific and tuberculosis-specific subgroups, which supports efforts to further increase use of isoniazid preventive therapy with ART broadly among people living with HIV.FundingNational Institutes of Health and National Institute of Allergy and Infectious Diseases.

Project description:BACKGROUND:The safety, efficacy, and appropriate timing of isoniazid therapy to prevent tuberculosis in pregnant women with human immunodeficiency virus (HIV) infection who are receiving antiretroviral therapy are unknown. METHODS:In this multicenter, double-blind, placebo-controlled, noninferiority trial, we randomly assigned pregnant women with HIV infection to receive isoniazid preventive therapy for 28 weeks, initiated either during pregnancy (immediate group) or at week 12 after delivery (deferred group). Mothers and infants were followed through week 48 after delivery. The primary outcome was a composite of treatment-related maternal adverse events of grade 3 or higher or permanent discontinuation of the trial regimen because of toxic effects. The noninferiority margin was an upper boundary of the 95% confidence interval for the between-group difference in the rate of the primary outcome of less than 5 events per 100 person-years. RESULTS:A total of 956 women were enrolled. A primary outcome event occurred in 72 of 477 women (15.1%) in the immediate group and in 73 of 479 (15.2%) in the deferred group (incidence rate, 15.03 and 14.93 events per 100 person-years, respectively; rate difference, 0.10; 95% confidence interval [CI], -4.77 to 4.98, which met the criterion for noninferiority). Two women in the immediate group and 4 women in the deferred group died (incidence rate, 0.40 and 0.78 per 100 person-years, respectively; rate difference, -0.39; 95% CI, -1.33 to 0.56); all deaths occurred during the postpartum period, and 4 were from liver failure (2 of the women who died from liver failure had received isoniazid [1 in each group]). Tuberculosis developed in 6 women (3 in each group); the incidence rate was 0.60 per 100 person-years in the immediate group and 0.59 per 100 person-years in the deferred group (rate difference, 0.01; 95% CI, -0.94 to 0.96). There was a higher incidence in the immediate group than in the deferred group of an event included in the composite adverse pregnancy outcome (stillbirth or spontaneous abortion, low birth weight in an infant, preterm delivery, or congenital anomalies in an infant) (23.6% vs. 17.0%; difference, 6.7 percentage points; 95% CI, 0.8 to 11.9). CONCLUSIONS:The risks associated with initiation of isoniazid preventive therapy during pregnancy appeared to be greater than those associated with initiation of therapy during the postpartum period. (Funded by the National Institutes of Health; IMPAACT P1078 TB APPRISE ClinicalTrials.gov number, NCT01494038.).

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Association of isoniazid preventive therapy with lower early mortality in individuals on antiretroviral therapy in a workplace programme.

Publications

Association of isoniazid preventive therapy with lower early mortality in individuals on antiretroviral therapy in a workplace programme.

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