Novel Developments in the Epidemic of Human Immunodeficiency Virus and Tuberculosis Coinfection

Abstract

Tuberculosis (TB) disease remains one of the highest causes of mortality in HIV-infected individuals, and HIV-TB coinfection continues to grow at alarming rates, especially in sub-Saharan Africa. Surprisingly, a number of important areas regarding coinfection remain unclear. For example, increased risk of TB disease begins early in the course of HIV infection; however, the mechanism by which HIV increases this risk is not well understood. In addition, there is lack of consensus on the optimal way to diagnose latent TB infection and to manage active disease in those who are HIV infected. Furthermore, effective point-of-care testing for TB disease remains elusive. This review discusses key areas in the epidemiology, pathogenesis, diagnosis, and management of active and latent TB in those infected with HIV, focusing attention on issues related to high-and low-burden areas. Particular emphasis is placed on controversial areas where there are gaps in knowledge and on future directions of study.

Doxycycline and HIV Infection Suppress Tuberculosis-induced Matrix Metalloproteinases

“…A characteristic hallmark of TB is tissue destruction, causing morbidity, mortality, and transmission of infection. However, the mediators of this immunopathology are incompletely understood (7,8), preventing the design of rational therapies to reduce immunemediated host damage and improve outcomes in TB.TB is primarily a disease of the lung (9, 10). In advanced HIV infection, with severely reduced CD4 cell counts, TB infection is common, but there is reduced tissue destruction and cavitation rarely occurs (11).…”

“…A characteristic hallmark of TB is tissue destruction, causing morbidity, mortality, and transmission of infection. However, the mediators of this immunopathology are incompletely understood (7,8), preventing the design of rational therapies to reduce immunemediated host damage and improve outcomes in TB.…”

Vitamin D Rescues Impaired Mycobacterium tuberculosis-Mediated Tumor Necrosis Factor Release in Macrophages of HIV-Seropositive Individuals through an Enhanced Toll-Like Receptor Signaling PathwayIn Vitro

“…ycobacterium tuberculosis infection in HIV-seropositive (HIV ϩ ) persons represents an enormous global health problem, frequently occurs in persons in early stages of HIV disease, and is associated with exceptional morbidity and mortality, especially with multidrug-resistant (MDR) or extensively drug-resistant (XDR) tuberculosis (1,2). However, the underlying predisposing mechanisms, particularly in HIV ϩ persons with relatively preserved CD4 ϩ T-lymphocyte counts, remain incompletely understood (3)(4)(5).…”

Impact of tuberculosis treatment and antiretroviral therapy on serial RD-1-specific quantitative T-cell readouts (QuantiFERON-TB Gold In-Tube), and relationship to treatment-related outcomes and bacterial burden

“…This is likely due to ART-related immune reconstitution and the redistribution of effector memory T-cells back into the blood compartment. 53 Similarly, ART can cause apparent conversion of the TST whereby TST-negative persons become TST-positive on ART. 54,55 These data have important implications for the interpretation of immunodiagnostic tests in the context of isoniazid preventive therapy (IPT) provision in high-burden settings, as current data suggest that only TSTpositive persons are likely to benefit from IPT.…”