title: Latent and Active Tuberculosis Infection Increase Immune Activation in Individuals Co-Infected with HIV.
abstract: In recent years, chronic immune activation and systemic inflammation have emerged as hallmarks of HIV disease progression and mortality. Several studies indicate that soluble inflammatory biomarkers (sCD14, IL-6, IL-8, CRP and hyaluronic acid), as well as surface markers of T-cell activation (CD38, HLA-DR) independently predict progression to AIDS and mortality in HIV-infected individuals. While co-infections have been shown to contribute to immune activation, the impact of latent tuberculosis infection (LTBI), which is widely endemic in the areas most affected by the global AIDS epidemic, has not been evaluated. We hypothesized that both active and latent states ofMycobacterium tuberculosisco-infection contribute to elevated immune activation as measurable by these markers. In HIV-infected individuals with active, but not latent TB, we found elevated levels of soluble markers associated with monocyte activation. Interestingly, T-cell activation was elevated individuals with both latent and active TB. These results suggest that in the highly TB- and HIV-endemic settings of southern Africa, latent TB-associated T-cell activation may contribute to HIV disease progression and exacerbate the HIV epidemic. In addition, our findings indicate that aggressive campaigns to treat LTBI in HIV-infected individuals in high-burden countries will not only impact TB rates, but may also slow HIV progression.
authors.affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa ; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Zuri A
authors.initials: ZA
authors.lastname: Sullivan
authors.affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa ; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA.
authors.forename: Emily B
authors.initials: EB
authors.lastname: Wong
authors.affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa ; HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa ; The Ragon Institute of MGH, MIT, and Harvard, Harvard Medical School, Cambridge, MA ; Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
authors.affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa ; HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa ; The Ragon Institute of MGH, MIT, and Harvard, Harvard Medical School, Cambridge, MA.
authors.forename: Victoria O
authors.initials: VO
authors.lastname: Kasprowicz
authors.affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa ; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: William R
authors.initials: WR
authors.lastname: Bishai
keywords: HIV; immune activation; inflammation; tuberculosis