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Projected population-wide impact of antiretroviral therapy-linked isoniazid preventive therapy in a high-burden setting.

ABSTRACT: OBJECTIVE:Both isoniazid preventive therapy (IPT) and antiretroviral therapy (ART) reduce tuberculosis risk in individuals living with HIV. We sought to estimate the broader, population-wide impact of providing a pragmatically implemented 12-month IPT regimen to ART recipients in a high-burden community. DESIGN:Dynamic transmission model of a tuberculosis (TB)-HIV epidemic, calibrated to site-specific, historical epidemiologic and clinical trial data from Khayelitsha, South Africa. METHODS:We projected the 5-year impact of delivering a 12-month IPT regimen community-wide to 85% of new ART initiators and 15%/year of those already on ART, accounting for IPT-attributable reductions in TB infection, progression, and transmission. We also evaluated scenarios of continuously-delivered IPT, ongoing ART scale-up, and lower tuberculosis incidence. RESULTS:Under historical (early 2010) ART coverage, this ART-linked IPT intervention prevented one tuberculosis case per 18 [95% credible interval (CrI) 11-29] people treated. It lowered TB incidence by a projected 23% (95% CrI 14-30%) among people receiving ART, and by 5.2% (95% CrI 2.9-8.7%) in the total population. Continuous IPT reduced the number needed to treat to prevent one case of TB to 10 (95% CrI 7-16), though it required 74% more person-years of therapy (95% CrI 64-94%) to prevent one TB case, relative to 12-month therapy. Under expanding ART coverage, the tuberculosis incidence reduction achieved by 12-month IPT grew to 7.6% (95% CrI 4.3-12.6%). Effect sizes were similar in a simulated setting of lower TB incidence. CONCLUSIONS:IPT in conjunction with ART reduces tuberculosis incidence among those who receive therapy and has additional impact on tuberculosis transmission in the population.

SUBMITTER: Kendall EA

PROVIDER: S-EPMC6355370 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Projected population-wide impact of antiretroviral therapy-linked isoniazid preventive therapy in a high-burden setting.

Kendall Emily A EA Azman Andrew S AS Maartens Gary G Boulle Andrew A Wilkinson Robert J RJ Dowdy David W DW Rangaka Molebogeng X MX

AIDS (London, England) 20190301 3

<h4>Objective</h4>Both isoniazid preventive therapy (IPT) and antiretroviral therapy (ART) reduce tuberculosis risk in individuals living with HIV. We sought to estimate the broader, population-wide impact of providing a pragmatically implemented 12-month IPT regimen to ART recipients in a high-burden community.<h4>Design</h4>Dynamic transmission model of a tuberculosis (TB)-HIV epidemic, calibrated to site-specific, historical epidemiologic and clinical trial data from Khayelitsha, South Africa ...[more]

PMID: 30325773

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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.

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Projected population-wide impact of antiretroviral therapy-linked isoniazid preventive therapy in a high-burden setting.

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Projected population-wide impact of antiretroviral therapy-linked isoniazid preventive therapy in a high-burden setting.

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