Implementation of isoniazid preventive therapy for people living with HIV worldwide: barriers and solutions

Getahun, Haileyesus; Granich, Reuben; Sculier, Delphine; Gunneberg, Christian; Blanc, L; Nunn, Paul; Raviglione, Mario

doi:10.1097/01.aids.0000391023.03037.1f

Cited by 98 publications

(103 citation statements)

References 40 publications

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“…IPT was safe and effective, with no additional adverse events or additional drug resistance observed during IPT. Barriers to providing IPT include lack of availability, provider concern about promoting resistance, lack of clarity about appropriate candidates, and viewing IPT as a low priority among competing healthcare needs 16, 17. The variability observed in this study related to TB symptom investigation and IPT provision highlight a need to reinforce clear, consistent policies to ensure TB symptoms are investigated, but that IPT is provided to patients when active TB is ruled out.…”

Section: Resultsmentioning

confidence: 99%

Completion of the tuberculosis care cascade in a community‐based HIV linkage‐to‐care study in South Africa and Uganda

et al. 2018

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IntroductionTuberculosis (TB) is the leading cause of HIV‐associated mortality in Africa. As HIV testing, linkage to care and antiretroviral treatment initiation intensify to meet UNAIDS targets, it is not known what effect these efforts will have on TB detection and prevention. We aimed to characterize the TB care cascade of screening, diagnostic testing, treatment and provision of isoniazid preventive therapy (IPT) in a study of community‐based HIV screening and linkage to care and determine whether symptom screening results affected progress along the cascade.MethodsBetween June 2013 and March 2015, HIV‐infected adults enrolled in the Linkages study, a multi‐site, community‐based, randomized HIV screening and linkage‐to‐care study in South Africa and Uganda. All participants were screened for TB symptoms at entry after testing positive for HIV and referred to local clinics for care. During the 9 month follow‐up, participants were periodically surveyed about clinic linkage and initiation of HIV care as well as subsequent TB testing, treatment, or IPT. We compared outcomes between persons with and without a positive symptom screen at baseline using descriptive statistics and Poisson regression to calculate relative risks of outcomes along the care cascade.Results and discussionOf the 1,325 HIV‐infected adults enrolled, 26% reported at least one TB symptom at the time of HIV diagnosis. Loss of appetite and fever were the most commonly reported symptoms on a TB symptom screen. Despite 92% HIV linkage success, corresponding TB linkage was incomplete. Baseline TB symptoms were associated with an increased risk of a TB diagnosis (relative risk 3.23, 95% CI 1.51 to 6.91), but only 34% of symptomatic persons had sputum TB testing. Fifty‐five percent of participants diagnosed with TB started TB treatment. In South Africa, only 18% of asymptomatic participants initiated IPT after linkage to HIV care, and presence of symptoms was not associated with IPT initiation (relative risk 0.86 95% CI 0.6 to 1.23).Conclusions HIV linkage to care interventions provide an opportunity to improve completion of the TB care cascade, but will require additional support to realize full benefits.

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Section: Resultsmentioning

confidence: 99%

Completion of the tuberculosis care cascade in a community‐based HIV linkage‐to‐care study in South Africa and Uganda

et al. 2018

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“…In those that have, the coverage remains low. 26,27 Previous evidence of IPT efficacy from randomized trials was derived mostly from studies conducted before the ART era. 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.…”

Section: Discussionmentioning

confidence: 99%

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

2015

N Engl J Med

1,034

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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“…Meta-analyses of randomized controlled trials have shown that IPT reduces the risk of active TB by 33% in people living with HIV, irrespective of skin test result, and by up to 64% in those with a positive tuberculin skin test [20,21]. Despite the substantial amount of clinical research that showed the benefits of IPT among people living with HIV, several barriers and operational challenges have hampered its roll out [22].…”

Section: Key Areas Of Operational Researchmentioning

confidence: 99%

Improving the prevention, diagnosis and treatment of TB among people living with HIV: the role of operational research

Sculier

Getahun

Lienhardt

2011

Journal of the International AIDS Society

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Operational research is necessary to improve the access to and delivery of tuberculosis prevention, diagnosis and treatment interventions for people living with HIV. We conducted an extensive review of the literature and reports from recent expert consultations and research-related meetings organized by the World Health Organization and the Stop TB Partnership to identify a TB/HIV operational research agenda. We present critical operational research questions in a series of key areas: optimizing TB prevention by enhancing the uptake of isoniazid preventive therapy and the implementation of infection control measures; assessing the effectiveness of existing diagnostic tools and scaling up new technologies; improving service delivery models; and reducing risk factors for mortality among TB patients living with HIV. We discuss the potential impact that addressing the operational research questions may have on improving programmes’ performance, assessing new strategies or interventions for TB control, or informing global or national policy formulation. Financial resources to implement these operational research questions should be mobilized from existing and new funding mechanisms. National TB and HIV/AIDS programmes should develop their operational research agendas based on these questions, and conduct the research that they consider crucial for improving TB and HIV control in their settings in collaboration with research stakeholders.

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Implementation of isoniazid preventive therapy for people living with HIV worldwide: barriers and solutions

Abstract: AIDS 2010, 24 (suppl 5):S57-S65

Cited by 98 publications

References 40 publications

Completion of the tuberculosis care cascade in a community‐based HIV linkage‐to‐care study in South Africa and Uganda

Completion of the tuberculosis care cascade in a community‐based HIV linkage‐to‐care study in South Africa and Uganda

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

Improving the prevention, diagnosis and treatment of TB among people living with HIV: the role of operational research

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