Burden of tuberculosis in an antiretroviral treatment programme in sub-Saharan Africa: impact on treatment outcomes and implications for tuberculosis control

Lawn, Stephen D.; Myer, Landon; Bekker, Linda‐Gail; Wood, Robin

doi:10.1097/01.aids.0000238406.93249.cd

Cited by 313 publications

(369 citation statements)

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“…21 Nevertheless, with most patients starting ART at low CD4 cell counts, tuberculosis risk still remained substantial in the presence of HIV treatment. 22,23 The interim policy also failed to provide adequate guidance on how to manage HIV-infected people with suspected but unconfi rmed tuberculosis, thus missing a valuable opportunity to prioritise and steer such people into HIV care and tuberculosis prevention. The 2004 interim policy on collaborative tuberculosis and HIV activities needs to be reviewed and updated to incorporate experience and evidence garnered in the past 6 years.…”

Section: The Interim Policy On Collaborative Tuberculosis and Hiv Actmentioning

confidence: 99%

“…33 A large proportion of people with HIV infection fi rst presents with active tuberculosis and a CD4 cell count of less than 200 cells per μL. 22,23,[29][30][31][32]34 HIV diagnosis and start of ART are therefore too late with regard to tuberculosis prevention. Furthermore, in patients who start ART and have not yet developed tuberculosis, the risk of tuberculosis is high for CD4 cell counts of less than 500 cells per μL.…”

Section: Hiv Testing and Early Start Of Art For Tuberculosis Preventionmentioning

confidence: 99%

“…Mortality risk is reduced by 64-95%, and excellent immunological and virological responses can be achieved, tuberculosis recurrence is reduced, and frequency of bacteriological clearance can be increased. 22,32,[105][106][107][108][109][110] Yet by the end of 2007, only 100 000 (7·3%) of an estimated 1·37 million HIV-infected tuberculosis patients worldwide were reported to have started ART. 26 Increase of uptake is a high priority and is likely to be 36 By contrast with previous guidelines, 35 WHO now recommends that all patients with tuberculosis, irrespective of CD4 cell count, should receive ART as soon as possible after start of tuberculosis treatment.…”

Section: Artmentioning

confidence: 99%

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The HIV-associated tuberculosis epidemic—when will we act?

et al. 2010

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Journal LancetRights Reproduced on this site with permission of Elsevier Ltd. Please see [url] Tuberculosis 3The HIV-associated tuberculosis epidemic-when will we act? Anthony D Harries, Rony Zachariah, Elizabeth L Corbett, Stephen D Lawn, Ezio T Santos-Filho, Rhehab Chimzizi, Mark Harrington, Dermot Maher, Brian G Williams, Kevin M De Cock Despite policies, strategies, and guidelines, the epidemic of HIV-associated tuberculosis continues to rage, particularly in southern Africa. We focus our attention on the regions with the greatest burden of disease, especially sub-Saharan Africa, and concentrate on prevention of tuberculosis in people with HIV infection, a challenge that has been greatly neglected. We argue for a much more aggressive approach to early diagnosis and treatment of HIV infection in aff ected communities, and propose urgent assessment of frequent testing for HIV and early start of antiretroviral treatment (ART). This approach should result in short-term and long-term declines in tuberculosis incidence through individual immune reconstitution and reduced HIV transmission. Implementation of the 3Is policy (intensifi ed tuberculosis case fi nding, infection control, and isoniazid preventive therapy) for prevention of HIV-associated tuberculosis, combined with earlier start of ART, will reduce the burden of tuberculosis in people with HIV infection and provide a safe clinical environment for delivery of ART. Some progress is being made in provision of HIV care to HIV-infected patients with tuberculosis, but too few receive co-trimoxazole prophylaxis and ART. We make practical recommendations about how to improve this situation. Early HIV diagnosis and treatment, the 3Is, and a comprehensive package of HIV care, in association with directly observed therapy, short-course (DOTS) for tuberculosis, form the basis of prevention and control of HIV-associated tuberculosis. This call to action recommends that both HIV and tuberculosis programmes exhort implementation of strategies that are known to be eff ective, and test innovative strategies that could work. The continuing HIV-associated tuberculosis epidemic needs bold but responsible action, without which the future will simply mirror the past.

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Section: The Interim Policy On Collaborative Tuberculosis and Hiv Actmentioning

confidence: 99%

Section: Hiv Testing and Early Start Of Art For Tuberculosis Preventionmentioning

confidence: 99%

Section: Artmentioning

confidence: 99%

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The HIV-associated tuberculosis epidemic—when will we act?

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“…For example, a 65% reduction in the incidence of TB in HIV-infected adults on ART irrespective of the CD4 1 T-cell count has been reported previously (10). However, despite the benefits of ART, TB incidence rates in HIV-infected individuals who received ART for more than 3 years remain 5-to 10-fold higher than HIV-uninfected persons (11).…”

mentioning

confidence: 94%

Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4⁺T-Cell Responses to Mycobacteria

Jambo

Banda

Afran

et al. 2014

Am J Respir Crit Care Med

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Rationale: HIV-infected persons on antiretroviral therapy (ART) remain at higher risk of pulmonary tuberculosis (TB) than HIV-uninfected individuals. This increased susceptibility may be caused by impairment of alveolar macrophage (AM) function and/or mycobacteria-specific alveolar CD4 1 T-cell responses observed in HIV-infected ART-naive adults.Objectives: To determine whether ART was associated with improvement in both AM function, assessed by phagosomal proteolysis, and alveolar CD4 1 T-cell responses to Mycobacterium in HIV-infected individuals.Methods: Peripheral blood was drawn and bronchoalveolar lavage (BAL) performed on healthy, 35 HIV-uninfected, 25 HIV-infected ART-naive, and 50 HIV-infected ART-treated asymptomatic adults. Phagosomal proteolysis of AM was assessed with fluorogenic beads. Mycobacteria-specific CD4 1 T-cell responses were measured by intracellular cytokine staining.Measurements and Main Results: HIV-infected adults on ART exhibited lower plasma HIV viral load and higher blood CD4 1 T-cell count than ART-naive adults. AM proteolysis and total mycobacteria-specific Th1 CD4 1 T-cell responses in individuals on ART for greater than or equal to 4 years were similar to HIVuninfected control subjects but those on ART for less than 4 years had impaired responses. Total influenza-specific alveolar Th1 CD4 1 Tcell responses were intact in all individuals receiving ART. In contrast, BAL and blood mycobacteria-specific polyfunctional CD4 1 T-cell responses were impaired in adults on ART irrespective of duration.Conclusions: AM and mycobacteria-specific alveolar CD4 1 T-cell responses in HIV-infected adults on ART for less than 4 years are impaired and may partly explain the high risk of TB in HIV-infected individuals on ART. Strategies to augment ART to improve lung immune cell function and reduce the high incidence of TB in HIVinfected adults who initiate ART should be investigated.

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“…19 In populations with a high prevalence of HIV, there is a high burden of undiagnosed TB. 12,20 ART is the most effective way to prevent TB in adults with HIV. 21 However, TB unmasking often occurs in patients starting ART, suggesting that early reactivation or subclinical disease exists at the time of ART initiation.…”

Section: Introductionmentioning

confidence: 99%

Prevention of Early Mortality by Presumptive Tuberculosis Therapy Study: An Open Label, Randomized Controlled Trial

Manabe

Worodria

Leth

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. Early mortality after initiation of antiretroviral therapy (ART) occurs in 9-39% of patients in sub-Saharan Africa. A significant proportion of deaths are attributable to tuberculosis (TB). Low baseline CD4 T-cell count and low body mass index (BMI) are strongly associated with early mortality. We hypothesized that initiation of ART concurrent with presumptive anti-TB chemotherapy in high-risk patients would reduce mortality within the first 6 months by treating unrecognized TB. From October 2011 to December 2012, ART-naive, smear-negative participants with a CD4 T-cell count < 50 cells/μL and BMI < 18 kg/m 2 were randomly assigned to undergo either empiric four-drug anti-TB treatment followed 2 weeks later by efavirenz-based ART (N = 23) (ART + TB) or ART only (N = 20). This open-label, 1:1 randomized, controlled trial took place in Uganda, Mozambique, and Gabon and was stopped prematurely by the sponsor for slow recruitment. Overall, the 43 participants had a median CD4 of 22 (interquartile range [IQR]: 9-35) cells/μL and a median BMI of 17.5 (IQR: 16.6-18.0) kg/m 2 . The mortality was 14% (95% confidence interval [CI]: 5.3-27.9); two (10.0%) participants (ART-only group), and four (17.4%; ART + TB group). The associated hazard ratio (HR) for all-cause mortality was 1.6 (95% CI: 0.30-8.90). Despite limited enrollment, the study did not suggest that empiric TB treatment in severely immunosuppressed patients with low BMI decreased mortality and, had an HR in the opposite direction than expected. Notably, two participants in the ART + TB group died with autopsy-confirmed drug-induced hepatotoxicity. Improved TB diagnostics sensitive in immunosuppressed patients presenting late to care are urgently needed for more targeted interventions.

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Burden of tuberculosis in an antiretroviral treatment programme in sub-Saharan Africa: impact on treatment outcomes and implications for tuberculosis control

Cited by 313 publications

References 22 publications

The HIV-associated tuberculosis epidemic—when will we act?

The HIV-associated tuberculosis epidemic—when will we act?

Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4⁺T-Cell Responses to Mycobacteria

Prevention of Early Mortality by Presumptive Tuberculosis Therapy Study: An Open Label, Randomized Controlled Trial

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Burden of tuberculosis in an antiretroviral treatment programme in sub-Saharan Africa: impact on treatment outcomes and implications for tuberculosis control

Cited by 313 publications

References 22 publications

The HIV-associated tuberculosis epidemic—when will we act?

The HIV-associated tuberculosis epidemic—when will we act?

Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4+T-Cell Responses to Mycobacteria

Prevention of Early Mortality by Presumptive Tuberculosis Therapy Study: An Open Label, Randomized Controlled Trial

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Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4⁺T-Cell Responses to Mycobacteria