Tuberculosis after Initiation of Antiretroviral Therapy in Low-Income and High-Income Countries

Brinkhof, Martin W. G.; Egger, Matthias; Boulle, Andrew; May, Margaret; Hosseinipour, Mina C.; Sprinz, Eduardo; Braitstein, Paula; Dabis, François; Reiss, Peter; Bangsberg,; Rickenbach, Martin; Jm, Miró; Myer, Landon; Mocroft, Amanda; Nash, Denis; Keiser, Olivia; Pascoe, Margaret; Borght, S van der; Schechter, Mauro

doi:10.1086/522986

Cited by 91 publications

(32 citation statements)

References 10 publications

(6 reference statements)

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“…However, TB incidence may rise during the initial months on ART, which is largely due to ART-induced unmasking of subclinical active TB and delayed diagnosed of unspecific symptomatic patients in resource-limited settings[13–15]. The TB incidence pattern following ART initiation in the current study is consistent with findings from previous studies[16–20]. Data from South Africa[18, 20] and Nigeria[19] both demonstrated that TB incidence was higher in the first year of ART, then decreased over time thereafter.…”

Section: Discussionsupporting

confidence: 88%

Tuberculosis incidence rate and risk factors among HIV-infected adults with access to antiretroviral therapy

Liu¹,

Makubi

Drain

et al. 2015

Aids

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Objective To determine the incidence rate and risk factors of tuberculosis (TB) among HIV-infected adults accessing antiretroviral therapy (ART) in Tanzania. Design A prospective observational study among HIV-infected adults attending 47 HIV clinics in Dar es Salaam. Methods We estimated TB incidence rates among HIV-infected patients prior to and after ART initiation. We used Cox proportional hazard regressions to determine the predictors of incident TB among HIV-infected adults enrolled in the HIV care and treatment program. Results We assessed 67,686 patients for a median follow-up period of 24 (interquartile range: 8–49) months; 7,602 patients were diagnosed with active TB. The TB incidence rate was 7.9 (95% Confidence Interval (CI), 7.6–8.2)/100 person-years prior to ART initiation, and 4.4(95%CI, 4.2–4.4)/100 person-years for patients receiving ART. In multivariate analyses, patients on ART in the first 3 months had a 57% higher risk of TB (Hazard Ratio:1.57, 95%CI:1.47–1.68) compared to those not on ART, but the risk significantly decreased with increasing duration of ART. Risk factors for incident TB included being male, having low body mass index or middle upper arm circumference, lower CD4 cell count, and advanced WHO disease stage. There was seasonal variation for incident TB, with higher risk observed following the rainy seasons (May, June, and November). Conclusion In TB endemic regions, HIV-infected patients initiating ART, particularly males and those with poor nutritional status, should be closely monitored for active TB in the months following ART initiation. In addition to increasing the access to ART, interventions should be considered to improve nutritional status among HIV-infected patients.

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Section: Discussionsupporting

confidence: 88%

Tuberculosis incidence rate and risk factors among HIV-infected adults with access to antiretroviral therapy

Liu¹,

Makubi

Drain

et al. 2015

Aids

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“…Up to 70% of patients with TB in sub-Saharan Africa are HIV-infected, and TB incidence rates following ART initiation are high, particularly among those with advanced HIV disease 4, 5 . Autopsy studies from sub-Saharan Africa, South East Asia and the Americas confirm TB as the primary or contributing cause of mortality in the majority of cases with nearly half of the TB undiagnosed pre-mortem 6 .…”

Section: Introductionmentioning

confidence: 99%

Empirical tuberculosis therapy versus isoniazid in adult outpatients with advanced HIV initiating antiretroviral therapy (REMEMBER): a multicountry open-label randomised controlled trial

et al. 2016

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Summary Background Mortality within the first 6 months after initiating antiretroviral therapy (ART) is common in resource-limited settings and is often due to tuberculosis (TB) among patients with advanced HIV disease. Isoniazid preventive therapy (IPT) is recommended in HIV-infected adults, but sub-clinical TB can be difficult to diagnose. We hypothesized that empiric TB treatment would reduce early mortality compared to IPT in high-burden settings. Methods We conducted a multi-country randomized clinical trial comparing empiric TB therapy (Empiric) vs. isoniazid preventive therapy (IPT) in HIV-infected outpatients initiating ART with CD4 counts <50 cells/mm3. Individuals were screened for TB using a symptom screen, locally available diagnostics, and the GeneXpert MTB/RIF assay when available. The primary endpoint was survival (death or unknown status) at 24 weeks post randomization. Kaplan Meier estimates of the endpoint rates across arms were compared by the z-test. Registered at ClinicalTrials.gov (NCT01380080). Findings From October 31, 2011 until June 9, 2014, we randomized 850 participants (424 in Empiric arm and 426 in IPT arm); the median CD4 count at baseline was 18 cells/mm3 (IQR: 9, 32). At week 24, each arm had 22 primary endpoints, for rates of 5.2% in each arm (95% CI: 3.5% to 7.8% for Empiric and 3.4% to 7.8% for IPT; absolute risk difference of -0.06% (95% CI: −3.05% to 2.94%). Grade 3 or 4 signs or symptoms occurred in 50 (12%) in the Empiric arm and 46 (11%) in the IPT arm. Grade 3 or 4 laboratory abnormalities occurred in 99 (23%) in the Empiric arm and 97 (23%) in the IPT arm. Incident TB was more common in the Empiric arm (31 vs. 18 events, p=0.01). Interpretation Empiric TB therapy did not reduce mortality at 24 weeks in outpatient adults initiating ART with advanced HIV disease. The low mortality rate of the trial supports implementation of systematic TB screening and IPT in outpatients with advanced HIV disease.

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“…TB incidence rates are very high during the initial months of ART and decrease with increasing duration of treatment [23, 24, 42-44] (Figure 5). Although overall rates are much higher in resource-limited settings, the proportionate reduction in rates during ART is similar in high- and low-income settings [44].…”

Section: Introductionmentioning

confidence: 99%

“…Although overall rates are much higher in resource-limited settings, the proportionate reduction in rates during ART is similar in high- and low-income settings [44]. In a South African study, TB risk was strongly associated with changes in CD4 cell counts measured serially during ART [12**].…”

Section: Introductionmentioning

confidence: 99%

Strategies to reduce early morbidity and mortality in adults receiving antiretroviral therapy in resource-limited settings

Lawn

Harries

Wood

2010

Current Opinion in HIV and AIDS

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Purpose of review We review recently published literature concerning early morbidity and mortality during antiretroviral therapy (ART) among patients in resource-limited settings. We focus on articles providing insights into this burden of disease and strategies to address it. Recent findings In sub-Saharan Africa mortality rates during the first year of ART are very high (8%-26%), with most deaths occurring in the first few months. This compares to 3%-13% in programmes in Latin America and the Caribbean and 11%-13% in South-East Asia. Risk factors generally reflect late presentation with advanced symptomatic disease. Key causes of morbidity and mortality include tuberculosis, acute sepsis, cryptococcal meningitis, malignancy, wasting syndrome/chronic diarrhoea. Current literature shows the fundamental need is for much earlier HIV diagnosis and initiation of ART. In addition, further studies provide data on the role of screening and prophylaxis against opportunistic diseases (particularly TB, bacterial sepsis and cryptococcal disease) and the management of specific opportunistic diseases and complications of ART. Effective and sustainable delivery of these interventions requires strengthening of programmes. Summary Strategies to address this disease burden should include earlier HIV diagnosis and ART initiation, screening and prophylaxis for opportunistic infections, optimised management of specific diseases and treatment complications, and programme strengthening.

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Tuberculosis after Initiation of Antiretroviral Therapy in Low-Income and High-Income Countries

Cited by 91 publications

References 10 publications

Tuberculosis incidence rate and risk factors among HIV-infected adults with access to antiretroviral therapy

Tuberculosis incidence rate and risk factors among HIV-infected adults with access to antiretroviral therapy

Empirical tuberculosis therapy versus isoniazid in adult outpatients with advanced HIV initiating antiretroviral therapy (REMEMBER): a multicountry open-label randomised controlled trial

Strategies to reduce early morbidity and mortality in adults receiving antiretroviral therapy in resource-limited settings

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