Kalonji R. Collins, et al.: Tuberculosis and HIV A I D S REVIEWS 165 Impact of Tuberculosis on HIV-1 Replication, Diversity, and Disease Progression Kalonji R. Collins 1 , Miguel E. Quiñones-Mateu 2 , Zahra Toossi 3 and Eric J. Arts 1,3 1 Molecular Virology Program, Case Western Reserve University. 2 Department of Virology, Lerner Research Institute, Cleveland Clinic Foundation. 3 Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA Abstract HIV and Mycobacterium tuberculosis not only co-circulate throughout the developing world but each has contributed to prevalence and mortality caused by the other. Several reports have described how HIV-1 increases the incidence of new M. tuberculosis infections, exacerbates the severity of tuberculosis (TB), and re-activates latent M. tuberculosis. However, the converse relationship is more difficult to understand considering TB can emerge in asymptomatic individuals and as an opportunistic infection during AIDS. Development of TB in HIV infected individuals with higher CD4 cell counts (>200/mm 3 ) appears to increase the rate of disease progression and mortality. Higher viral loads, increased HIV-1 diversity, and changes in cytokine/chemokine levels in HIV- infected individuals with TB appear to be related to a localized immune stimulation. Specifically, increased levels of TNFα and MCP-1, induced by TB, may activate HIV replication in lymphocytes, monocytes, and macrophages that are resident or have migrated to M. tuberculosis infected organs (e.g. pleura or lung). The HIV-1 found in blood following this TB-mediated burst in load and diversity appear to be phylogenetically-related to HIV-1 clones that have evolved independently in the lung or pleural compartments, now infected by M. tuberculosis. AIDS Rev 2002;4:165-176 Correspondence to: Eric J. Arts Division of Infectious Diseases Department of Medicine Case Western Reserve University Biomedical Research Building 10th 2109 Adelbert rd Cleveland, OH, 44106-4984 USA Tel: (216) 368 8904 - Fax (216) 368 2034 Email: eja3@po.cwru.edu Key words HIV. Tuberculosis. Evolution. Genetic variability. in the world today. In December 2001, UNAIDS reported that AIDS was the world’s fourth biggest killer and gaining ground on the leaders, tubercu- losis (TB) and malaria. Of particular concern is the impact of HIV/AIDS in sub-Saharan Africa. In this region of the world, AIDS is the major cause of mortality with an estimated 2.3 million deaths in 2001 alone and three fourths of the 40 million HIV- 1 infected people in the world 1 . According to the United Nations, HIV/AIDS is the biggest threat to the development of the African economy because this disease is common in young teachers, farm- ers, health-workers, civil servants, and young pro- fessionals. The second leading cause of death in sub- Saharan Africa is TB. Unfortunately, these two Public health perspective on TB and HIV-1 Acquired immunodeficiency syndrome (AIDS) is one of the most destructive infectious diseases No part of this publication may be reproduced or photocopying without the prior written permission of the publisher © Permanyer Publications 2010