Detection of lipoarabinomannan (LAM) in urine is an independent predictor of mortality risk in patients receiving treatment for HIV-associated tuberculosis in sub-Saharan Africa: a systematic review and meta-analysis

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dc.contributor.authorGupta-Wright, Ankur
dc.contributor.authorPeters, Jurgens A
dc.contributor.authorFlach, Clare
dc.contributor.authorLawn, Stephen D
dc.date.accessioned2021-10-08T06:54:42Z
dc.date.available2021-10-08T06:54:42Z
dc.date.issued2016
dc.description.abstractBackgroundSimple immune capture assays that detect mycobacterial lipoarabinomannan (LAM) antigen in urine are promising new tools for the diagnosis of HIV-associated tuberculosis (HIV-TB). In addition, however, recent prospective cohort studies of patients with HIV-TB have demonstrated associations between LAM in the urine and increased mortality risk during TB treatment, indicating an additional utility of urinary LAM as a prognostic marker. We conducted a systematic review and meta-analysis to summarise the evidence concerning the strength of this relationship in adults with HIV-TB in sub-Saharan Africa, thereby quantifying the assay’s prognostic value.MethodsWe searched MEDLINE and Embase databases using comprehensive search terms for ‘HIV’, ‘TB’, ‘LAM’ and ‘sub-Saharan Africa’. Identified studies were reviewed and selected according to predefined criteria.ResultsWe identified 10 studies eligible for inclusion in this systematic review, reporting on a total of 1172 HIV-TB cases. Of these, 512 patients (44%) tested positive for urinary LAM. After a variable duration of follow-up of between 2 and 6months, overall case fatality rates among HIV-TB cases varied between 7% and 53%. Pooled summary estimates generated by random-effects meta-analysis showed a two-fold increased risk of mortality for urinary LAM-positive HIV-TB cases compared to urinary LAM-negative HIV-TB cases (relative risk 2.3, 95% confidence interval 1.6–3.1). Some heterogeneity was explained by study setting and patient population in sub-group analyses. Five studies also reported multivariable analyses of risk factors for mortality, and pooled summary estimates demonstrated over two-fold increased mortality risk (odds ratio 2.5, 95% confidence interval 1.4–4.5) among urinary LAM-positive HIV-TB cases, even after adjustment for other risk factors for mortality, including CD4 cell count.ConclusionsWe have demonstrated that detectable LAM in urine is associated with increased risk of mortality during TB treatment, and that this relationship remains after adjusting for other risk factors for mortality. This may simply be due to a positive test for urinary LAM serving as a marker of higher mycobacterial load and greater disease dissemination and severity. Alternatively, LAM antigen may directly compromise host immune responses through its known immunomodulatory effects. Detectable LAM in the urine is an independent risk factor for mortality among patients receiving treatment for HIV-TB. Further research is warranted to elucidate the underlying mechanisms and to determine whether this vulnerable patient population may benefit from adjunctive interventions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0603-9) contains supplementary material, which is available to authorized users.
dc.identifier.apacitationGupta-Wright, A., Peters, J. A., Flach, C., & Lawn, S. D. (2016). Detection of lipoarabinomannan (LAM) in urine is an independent predictor of mortality risk in patients receiving treatment for HIV-associated tuberculosis in sub-Saharan Africa: a systematic review and meta-analysis. <i>BMC Medicine</i>, 14(1), 174 - 177. http://hdl.handle.net/11427/34316en_ZA
dc.identifier.chicagocitationGupta-Wright, Ankur, Jurgens A Peters, Clare Flach, and Stephen D Lawn "Detection of lipoarabinomannan (LAM) in urine is an independent predictor of mortality risk in patients receiving treatment for HIV-associated tuberculosis in sub-Saharan Africa: a systematic review and meta-analysis." <i>BMC Medicine</i> 14, 1. (2016): 174 - 177. http://hdl.handle.net/11427/34316en_ZA
dc.identifier.citationGupta-Wright, A., Peters, J.A., Flach, C. & Lawn, S.D. 2016. Detection of lipoarabinomannan (LAM) in urine is an independent predictor of mortality risk in patients receiving treatment for HIV-associated tuberculosis in sub-Saharan Africa: a systematic review and meta-analysis. <i>BMC Medicine.</i> 14(1):174 - 177. http://hdl.handle.net/11427/34316en_ZA
dc.identifier.issn1741-7015
dc.identifier.ris TY - Journal Article AU - Gupta-Wright, Ankur AU - Peters, Jurgens A AU - Flach, Clare AU - Lawn, Stephen D AB - BackgroundSimple immune capture assays that detect mycobacterial lipoarabinomannan (LAM) antigen in urine are promising new tools for the diagnosis of HIV-associated tuberculosis (HIV-TB). In addition, however, recent prospective cohort studies of patients with HIV-TB have demonstrated associations between LAM in the urine and increased mortality risk during TB treatment, indicating an additional utility of urinary LAM as a prognostic marker. We conducted a systematic review and meta-analysis to summarise the evidence concerning the strength of this relationship in adults with HIV-TB in sub-Saharan Africa, thereby quantifying the assay’s prognostic value.MethodsWe searched MEDLINE and Embase databases using comprehensive search terms for ‘HIV’, ‘TB’, ‘LAM’ and ‘sub-Saharan Africa’. Identified studies were reviewed and selected according to predefined criteria.ResultsWe identified 10 studies eligible for inclusion in this systematic review, reporting on a total of 1172 HIV-TB cases. Of these, 512 patients (44%) tested positive for urinary LAM. After a variable duration of follow-up of between 2 and 6months, overall case fatality rates among HIV-TB cases varied between 7% and 53%. Pooled summary estimates generated by random-effects meta-analysis showed a two-fold increased risk of mortality for urinary LAM-positive HIV-TB cases compared to urinary LAM-negative HIV-TB cases (relative risk 2.3, 95% confidence interval 1.6–3.1). Some heterogeneity was explained by study setting and patient population in sub-group analyses. Five studies also reported multivariable analyses of risk factors for mortality, and pooled summary estimates demonstrated over two-fold increased mortality risk (odds ratio 2.5, 95% confidence interval 1.4–4.5) among urinary LAM-positive HIV-TB cases, even after adjustment for other risk factors for mortality, including CD4 cell count.ConclusionsWe have demonstrated that detectable LAM in urine is associated with increased risk of mortality during TB treatment, and that this relationship remains after adjusting for other risk factors for mortality. This may simply be due to a positive test for urinary LAM serving as a marker of higher mycobacterial load and greater disease dissemination and severity. Alternatively, LAM antigen may directly compromise host immune responses through its known immunomodulatory effects. Detectable LAM in the urine is an independent risk factor for mortality among patients receiving treatment for HIV-TB. Further research is warranted to elucidate the underlying mechanisms and to determine whether this vulnerable patient population may benefit from adjunctive interventions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0603-9) contains supplementary material, which is available to authorized users. DA - 2016 DB - OpenUCT DP - University of Cape Town IS - 1 J1 - BMC Medicine LK - https://open.uct.ac.za PY - 2016 SM - 1741-7015 T1 - Detection of lipoarabinomannan (LAM) in urine is an independent predictor of mortality risk in patients receiving treatment for HIV-associated tuberculosis in sub-Saharan Africa: a systematic review and meta-analysis TI - Detection of lipoarabinomannan (LAM) in urine is an independent predictor of mortality risk in patients receiving treatment for HIV-associated tuberculosis in sub-Saharan Africa: a systematic review and meta-analysis UR - http://hdl.handle.net/11427/34316 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/34316
dc.identifier.vancouvercitationGupta-Wright A, Peters JA, Flach C, Lawn SD. Detection of lipoarabinomannan (LAM) in urine is an independent predictor of mortality risk in patients receiving treatment for HIV-associated tuberculosis in sub-Saharan Africa: a systematic review and meta-analysis. BMC Medicine. 2016;14(1):174 - 177. http://hdl.handle.net/11427/34316.en_ZA
dc.language.isoeng
dc.publisher.departmentDesmond Tutu HIV Centre
dc.publisher.facultyFaculty of Health Sciences
dc.sourceBMC Medicine
dc.source.journalissue1
dc.source.journalvolume14
dc.source.pagination174 - 177
dc.source.urihttps://dx.doi.org/10.1186/s12916-016-0603-9
dc.subject.otherHIV
dc.subject.otherLAM
dc.subject.otherLipoarabinomannan
dc.subject.otherMortality
dc.subject.otherSystematic review
dc.subject.otherTuberculosis
dc.subject.otherAdult
dc.subject.otherAfrica South of the Sahara
dc.subject.otherBiomarkers
dc.subject.otherFemale
dc.subject.otherHIV Infections
dc.subject.otherHumans
dc.subject.otherLipopolysaccharides
dc.subject.otherMale
dc.subject.otherPrognosis
dc.subject.otherProspective Studies
dc.subject.otherRisk Factors
dc.subject.otherTuberculosis
dc.subject.otherBiomarkers
dc.subject.otherLipopolysaccharides
dc.subject.otherlipoarabinomannan
dc.titleDetection of lipoarabinomannan (LAM) in urine is an independent predictor of mortality risk in patients receiving treatment for HIV-associated tuberculosis in sub-Saharan Africa: a systematic review and meta-analysis
dc.typeJournal Article
uct.type.publicationResearch
uct.type.resourceJournal Article
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