Timing of Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus (HIV)-Associated Tuberculous Meningitis

Török, M. Estée; Yen, Nguyen Thi Bich; Chau, Tran Thi Hong; Hoang, Nguyen Thi; Phu, Nguyen Hoan; Phuong, Pham; Dung, Nguyễn Thị; Châu, Nguyễn Văn Vĩnh; Bang, Nguyen Duc; Tiến, Nguyễn Anh; Minh, Nguyen Hien; Hien, Nguyen Quang; Thai, Phan Vuong Khac; Anh, Do Thi Tuong; Thoa, Nguyen Thi Cam; Hải, Nguyễn Ngọc; Lan, Nguyễn Ngọc; Lan, Nguyễn Thị Ngọc; Quy, Hoang Thi; Dung, Nguyen Huy; Hien, Tran Tinh; Chinh, Nguyen Tran; Simmons, Cameron P.; Jong, Menno D. de; Wolbers, Marcel; Farrar, Jeremy

doi:10.1093/cid/cir230

Cited by 277 publications

(174 citation statements)

References 20 publications

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“…Here we report clinical outcomes among hospitalized Ugandans treated for TB meningitis over a 6.5-year period. In-hospital mortality was high in the cohort overall (44%), similar to other research settings with high HIV prevalence 7, 19, 22, 23 . The adjusted model on imputed data found odds of in-hospital mortality were almost two fold higher in the earliest cohort, tested by CSF smear microscopy only, than that of that of the most recent cohort in whom Xpert (and culture) are routinely performed.…”

Section: Discussionsupporting

confidence: 84%

“…However for pulmonary TB, Xpert has not been shown to decrease mortality 16– 18 . Yet, lessening diagnostic delay in persons with TBM may be more likely to lead to improved outcomes as compared to pulmonary TB given the high early mortality of TBM 19 . Whether routine use of Xpert for investigation of suspected TBM has made an impact on mortality has not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

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Can improved diagnostics reduce mortality from Tuberculous meningitis? Findings from a 6.5-year cohort in Uganda

Cresswell¹,

Bangdiwala²,

Bahr³

et al. 2018

Wellcome Open Res

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Background: Tuberculous meningitis (TBM) is the second most common cause of meningitis in sub-Saharan Africa and is notoriously difficult to diagnose. We describe the impact of improved TBM diagnostics over 6.5 years at two Ugandan referral hospitals. Methods: Cohort one received cerebrospinal fluid (CSF) smear microscopy only (2010-2013). Cohort two received smear microscopy and Xpert MTB/Rif (Xpert) on 1ml unprocessed CSF at physician discretion (2011-2013). Cohort three received smear microscopy, routine liquid-media culture and Xpert on large volume centrifuged CSF (2013-2017) for all meningitis suspects with a negative CSF cryptococcal antigen. We compared rates of microbiologically confirmed TBM and hospital outcomes over time. Results: 1672 HIV-infected adults presenting with suspected meningitis underwent lumbar puncture, of which 33% (558/1672) had negative CSF cryptococcal antigen and 12% (195/1672) were treated for TB meningitis. Over the study period, microbiological confirmation of TBM increased from 3% to 41% (P<0.01) and there was a decline in in-hospital mortality from 57% to 41% (P=0.27) amongst those with a known outcome. Adjusting for definite TBM diagnosis and antiretroviral therapy use, and using imputed data, assuming 50% of those with an unknown outcome died, the odds of dying were nearly twice as high in cohort one (adjusted odds ratio 1.7, 95% CI 0.7 to 4.4) compared to cohort three. Sensitivity of Xpert was 63% (38/60) and culture was 65% (39/60) against a composite reference standard. Conclusions: As TBM diagnostics have improved, microbiologically-confirmed TBM diagnoses have increased and in-hospital mortality has declined. Yet, mortality due to TB meningitis remains unacceptably high and further measures are needed to improve outcomes from TBM in Uganda.

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Can improved diagnostics reduce mortality from Tuberculous meningitis? Findings from a 6.5-year cohort in Uganda

Cresswell¹,

Bangdiwala²,

Bahr³

et al. 2018

Wellcome Open Res

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“…In patients with pulmonary TB early ART initiation is associated with improvements in AIDS-free survival, particularly in patients with low baseline CD4 counts 27 . In patients with HIV-associated TBM, however, our previous study suggested that immediate ART did not result in a survival benefit, but was associated with an increase in severe adverse events 28 . The current study aimed to investigate the effect of ART initiation time upon drug exposures both in the systemic circulation and the CNS, and to assess if drug exposure correlated with clinical outcomes.…”

Section: Discussionmentioning

confidence: 89%

“…The study participants were HIV-infected adults (aged > 15 years) who fulfilled diagnostic criteria for TBM. Baseline demographic clinical and laboratory features of the study participants are reported elsewhere 28 . Rich pharmacokinetic data This article is protected by copyright.…”

Section: Study Design Setting and Participantsmentioning

confidence: 99%

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Suboptimal Exposure to Anti‐TB Drugs in a TBM/HIV+ Population Is Not Related to Antiretroviral Therapy

Török

Aljayyoussi

Waterhouse

et al. 2017

Clin Pharma and Therapeutics

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Six months therapy for tuberculous meningitis

Jullien¹,

Ryan

Modi

et al. 2016

Cochrane Database of Systematic Reviews

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BackgroundTuberculous meningitis (TBM) is the main form of tuberculosis that affects the central nervous system and is associated with high rates of death and disability. Most international guidelines recommend longer antituberculous treatment (ATT) regimens for TBM than for pulmonary tuberculosis disease to prevent relapse. However, longer regimens are associated with poor adherence, which could contribute to increased relapse, development of drug resistance, and increased costs to patients and healthcare systems.ObjectivesTo compare the effects of short-course (six months) regimens versus prolonged-course regimens for people with tuberculous meningitis (TBM).Search methodsWe searched the following databases up to 31 March 2016: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE; EMBASE; LILACS; INDMED; and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists and contacted researchers in the field.Selection criteriaWe included randomized controlled trials (RCTs) and prospective cohort studies of adults and children with TBM treated with antituberculous regimens that included rifampicin for six months or longer than six months. The primary outcome was relapse, and included studies required a minimum of six months follow-up after completion of treatment.Data collection and analysisTwo review authors (SJ and HR) independently assessed the literature search results for eligibility, and performed data extraction and 'Risk of bias' assessments of the included studies. We contacted study authors for additional information when necessary. Most data came from single arm cohort studies without a direct comparison so we pooled the findings for each group of cohorts and presented them separately using a complete-case analysis. We assessed the quality of the evidence narratively, as using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was inappropriate with no direct comparisons between short- and prolonged-course regimens.Main resultsFour RCTs and 12 prospective cohort studies met our inclusion criteria, and included a total of 1881 participants with TBM. None of the included RCTs directly compared six months versus longer regimens, so we analysed all data as individual cohorts to obtain relapse rates in each set of cohorts.We included seven cohorts of participants treated for six months, with a total of 458 participants. Three studies were conducted in Thailand, two in South Africa, and one each in Ecuador and Papua New Guinea between the 1980s and 2009. We included 12 cohorts of participants treated for longer than six months (ranging from eight to 16 months), with a total of 1423 participants. Four studies were conducted in India, three in Thailand and one each in China, South Africa,...

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Timing of Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus (HIV)-Associated Tuberculous Meningitis

Cited by 277 publications

References 20 publications

Can improved diagnostics reduce mortality from Tuberculous meningitis? Findings from a 6.5-year cohort in Uganda

Can improved diagnostics reduce mortality from Tuberculous meningitis? Findings from a 6.5-year cohort in Uganda

Suboptimal Exposure to Anti‐TB Drugs in a TBM/HIV+ Population Is Not Related to Antiretroviral Therapy

Six months therapy for tuberculous meningitis

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