Beneficial Effect of Isoniazid Preventive Therapy and Antiretroviral Therapy on the Incidence of Tuberculosis in People Living with HIV in Ethiopia

Yirdaw, Kesetebirhan Delele; Jerene, Degu; Gashu, Zewdu; Edginton, M. E.; Kumar, Ajay M. V.; Letamo, Yohannes; Feleke, Beniam; Teklu, Alula M.; Zewdu, Solomon; Weiss, William; Ruff, Andrea

doi:10.1371/journal.pone.0104557

Cited by 71 publications

(84 citation statements)

References 13 publications

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“…22,[28][29][30][31] Evidence for the added value of IPT in patients receiving ART was mostly from patients with CD4+ counts of less than 500 cells per cubic millimeter. [32][33][34][35][36][37][38] Our data are consistent with these previous studies that showed that IPT and ART have additive efficacy with respect to the prevention of tuberculosis and that suggested that the two therapies should be given concomitantly. They also highlight for countries that are reluctant to recommend IPT that isoniazid can be prescribed safely when given early in the course of HIV disease.…”

Section: Discussionsupporting

confidence: 90%

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

2015

N Engl J Med

1,035

447

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BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.)

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Section: Discussionsupporting

confidence: 90%

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

2015

N Engl J Med

1,035

447

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“…Accordingly, the overall TB incidence rate was 2.63 (95% CI 1.9–3.7) per 100 person-years. This finding was comparable to that of a study conducted in south Ethiopia [31]. This might be due to similar socio-economic characteristics, HIV care settings, and HIV care guideline.…”

Section: Discussionsupporting

confidence: 86%

Incidence of tuberculosis in children on antiretroviral therapy: a retrospective cohort study

2018

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ObjectivesBe aware of the burden of tuberculosis among high-risk population is important. Three hundred fifty-two children were participated in this study. Survival analysis was conducted. We assessed the incidence of tuberculosis and its predictors in children on ART.ResultsTuberculosis incidence rate in children on ART was 2.63 per 100 person-years. Those children who were on baseline World Health Organization clinical stages 3 and 4 (AHR (adjusted hazard ratio) = 3.0; 95% CI 1.2–7.7), “fair” and “poor” ART adherence (AHR = 4.0; 95% CI 1.5–10.8), late initiation of ART (AHR = 4.0; 95% CI 1.5–10.6), and less than 6 months duration on ART (AHR = 5.5; 95% CI 1.5–20.6) were more likely to develop tuberculosis infection. The incidence rate of TB in children on ART was high. This study suggests a need to give attention to advanced AIDS stages and improve timely initiation of ART and level of adherence to ART.

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“…19,20 In the present study, one third of PLHIV who did not have active TB were initiated on IPT. This proportion likely underestimates the true uptake of IPT, as we were not able to assess the number of PLHIV determined to be eligible for IPT.…”

Section: Public Health Actionmentioning

confidence: 73%