title: HIV-1 and the Mycobacterium tuberculosis granuloma: A systematic review and meta-analysis.
abstract: Infection with HIV-1 greatly increases the risk of active tuberculosis (TB). Although hypotheses suggest HIV-1 disrupts Mycobacterium tuberculosis (Mtb) granuloma function, few studies have examined this directly. The objective of this study was to determine what evidence exists about the effect HIV-1 co-infection has upon Mtb granulomas. A systematic search of PubMed, Web of Science, and Medline up to 20 March 2015 was conducted, to identify studies comparing Mtb-infected tissue from HIV-1 infected and uninfected persons, or HIV-1 infected persons with stratified peripheral CD4 T cell (pCD4) counts. We summarized findings that focused on how HIV-1 changes granuloma formation, bacterial presence, cellular composition, and cytokine production. Nineteen studies with a combined sample size of 899 persons were included. Although studies frequently were limited by variable or inadequately described definitions of outcomes and analytical methods, HIV-1 was found to be associated with increased bacillary load within Mtb-infected tissue. Reductions in pCD4 counts within co-infected persons associated with both poorer granuloma formation and higher bacterial load. The high degree of heterogeneity among studies combined with experimental limitations made it difficult to conclusively support previously published and prevalent hypotheses about HIV-1/Mtb co-infection granulomas. To elucidate the validity of these hypotheses we have described areas that can be improved in future studies in order to clarify the influence HIV-1 co-infection has upon the Mtb granuloma.
authors.affiliation: Clinical Infectious Diseases Research Initiative Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa. Electronic address: CRDiedrich.Publications@gmail.com.
authors.forename: C R
authors.initials: CR
authors.lastname: Diedrich
authors.affiliation: Clinical Infectious Diseases Research Initiative Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa; Royal Hobart Hospital, Tasmania, Australia.
authors.forename: J
authors.initials: J
authors.lastname: O'Hern
authors.affiliation: Clinical Infectious Diseases Research Initiative Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa; Department of Medicine, University of Cape Town, South Africa; Francis Crick Institute Mill Hill Laboratory, London, United Kingdom; Department of Medicine, Imperial College London, W21PG, United Kingdom.
authors.forename: R J
authors.initials: RJ
authors.lastname: Wilkinson
mesh_terms: D016009:Chi-Square Distribution; D060085:Coinfection; D016207:Cytokines / Q000276:immunology; D006099:Granuloma / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology*; D015658:HIV Infections / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity*; D016017:Odds Ratio; D011379:Prognosis; D012307:Risk Factors; D014376:Tuberculosis / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology*
chemical_list: D016207:Cytokines
keywords: AIDS; Granuloma; HIV; Histology; Mycobacterium tuberculosis; Tissue; Tuberculosis