Maryam Yousaf 1, Usman Waheed 2
1 Department of Biochemistry, PMAS Arid Agriculture University, Rawalpindi
2 Department of Molecular Biology, Quaid-i-Azam University, Islamabad
From its discovery in 1981, the Human Immunodeficiency Virus (HIV) has killed more than 25 million people and infects 0.6% world’s population These twin epidemics present a stark new global health threat and raise the prospect of a global pandemic of extensively-drug-resistant TB, which is extremely difficult to treat [5]. HIV infection has contributed to a significant increase in the worldwide incidence of tuberculosis. HIV is a major risk factor of causing death in tuberculosis patients. It not only increases the reactivation of latent TB infection but also increases progression rate of tuberculosis. People who are co-infected with both HIV and latent TB have an up to 800 times greater risk of developing active tuberculosis disease and becoming infectious compared to people not infected with HIV [6]. The World Health Organization (WHO) estimates that one-third of the world’s population is infected with M. tuberculosis and about 40 million from HIV [7, 8]. In 2009, 1.7 million people died of TB, 9.4 million new TB cases (including 3.3 million women) detected (mostly in Africa and Asia), including 1.1 million cases among people with HIV. 37% of HIV/TB coinfected patients were enrolled on antiretrovirals and 75% started on preventive treatment in 2009 [9]. HIV is acting as an important obstacle in the way to control TB and especially in developing country like Pakistan; it is becoming a major focus in TB preventive measures. Tuberculosis and HIV infection make each other’s control significantly more difficult. According to Tuberculosis statistics for “high burden” countries, 2009 there were 420,000 cases of tuberculosis in Pakistan [10]. TB-HIV co-infection is a growing concern in the country. In addition, the WHO data shows that drug-resistant TB is on the rise [11]. A global health catastrophe is unfolding. It is very important to note that TB is not only a problem in developing countries. For example, there were 11,545 new cases reported in the U.S.A. in 2009 [12]. In the UK, TB has been dubbed ‘the disease that has never went away’, with 9,040 new cases of tuberculosis reported in the UK in 2009 [13]. Previous studies on human immunodeficiency virus and tuberculosis revealed the impact of HIV in individuals having natural progression of TB, but the emerging studies in the field of immunology and virology indicates that host immune responses to M. tuberculosis increases replication rate of HIV [14]. It is estimated that HIV related TB occur in person’s ages from 15 to 49 years old because of lack of prevalence rate of HIV observed in older people [15]. M. tuberculosis is a facultative intracellular pathogen resides in the macrophages. It is believed that CD4+ as well as CD8+ T lymphocytes play important roles in developing the immunity against TB. On the other hand, HIV targets CD4 cells and reduces cellular immunity which is a major driving force to replicate M. tuberculosis. Th1 immune responses which are characterized as cell mediated immunity is the major area of defence against M. tuberculosis in body [16] and HIV infects these components of cellular immunity. The pathogenesis of TB can be altered by HIV either through reactivation of latent tuberculosis infection to active disease (more common) or by causing rapid progression from recent infection with M. tuberculosis to tuberculosis disease. The natural history of TB in a child infected with HIV depends on the stage of HIV disease. In the early stage of HIV infection, when immunity is good, the clinical features of TB are similar to those in a child without HIV infection. As HIV infection progresses and immunity declines, dissemination of TB and its occurrence in the form of tuberculous meningitis, miliary tuberculosis, and widespread tuberculous lymphadenopathy become more common [17]. The interaction between HIV and TB infection is bilateral interaction. The infectious rate of HIV is accelerated with the development of TB. Therefore this bilateral infection has important implications for the treatment as well as prevention of TB/HIV coinfected persons. The main area of infection of M. tuberculosis in host immune system is in alveolar macrophages which present M. tuberculosis antigens to antigen specific CD4+ T cells [18]. T cells are the cells which responsible for the release of interferon-gamma, a cytokine that activates macrophages. These activated macrophages also release pro-inflammatory cytokines like TNF and interleukin (IL)-1, which enhance viral replication in monocyte cell lines in vitro [19-22]. Researchers also demonstrated that immune activation by M. tuberculosis enhances systemic as well as local HIV replication. Increased level of HIV RNA also observed in some patients of TB before the diagnosis of tuberculosis. Moreover, it is also observed that TB treatment alone can reduce viral load in these patients [23]. These findings suggest that pulmonary tuberculosis might act as a stimulus for the replication of HIV at cellular level. These findings also help us to understand the way of HIV replication and its effects on natural progression of TB and also support preventive measures as well as the way of recognition and treatments for both diseases. Taking treatment for both HIV and TB together is more complicated but it is often necessary because if we wait to start ARVs after TB treatment is finished then it might be too late. Therefore prevention and treatment of TB in people living with HIV is an urgent priority for both HIV/AIDS and TB programmes. The Three ‘I‘s, Isoniazid preventive treatment, Intensified case finding for active TB, and TB Infection control, are key public health strategies to decrease the impact of TB on people living with HIV. The treatment of HIV-related tuberculosis requires close monitoring because of frequent drug toxicities, possible drug-drug interactions, and paradoxical reactions. HIV-seropositive patients with tuberculosis respond well to antituberculosis therapy, as long as the regimen contains Isoniazid and a rifamycin [24]. To conclude, it is very essential that everyone infected with HIV should be tested for TB and everyone infected with TB should complete preventive therapy as soon as possible to prevent progression to TB disease. TB and HIV prevention and care interventions are mutually reinforcing and should be aimed to improve performance and coverage, increase testing and counselling facility, provide community home based care for people living with HIV/AIDS and provide antiretroviral treatment. Well-directed funding and commitment to clear-sighted public health policies are the key to fight this catastrophe which is growing bigger and bigger. References: 10. http://www.avert.org/tuberculosis.htm 11. http://www.sciencedaily.com/releases/2009/03/090324131600.htm 12. Reported Tuberculosis in the United States, 2009, CDC, October 2010 13. Annual Report on Tuberculosis Surveillance in the UK 2010, HPA, November 2010 14. Whalen, C. Copathogenicity of tuberculosis and human immunodeficiency virus disease. Clin. Infect. Dis. 15. Coovadia HM, Jeena P, Wilkinson D. Childhood human immunodeficiency virus and tuberculosis co-infections: reconciling conflicting data. Int J Tuberc Lung Dis. 1998;2:844-851. 16. Schluger NW, Rom WN. The host immune response to tuberculosis. Am J Respir Crit Care Med 1998; 157: 679-91. 17. http://www.searo.who.int/en/Section10/Section18/Section356/Section421_1626.htm 18. Toossi Z. Cytokine circuits in tuberculosis. Infectious Agents and Disease 1996; 5:98-107). 19. Duh EJ, Maury WJ, Folks TM, Fauci AS, Rabson AB. Tumor necrosis factor alpha activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-kappaB sites in the long terminal repeat. Proc Natl Acad Sci USA 1989;86:5974-8. 20. Poli G, Bressler P, Kinter A, et al. Interleukin 6 induces human immunodeficiency virus expression in infected monocytic cells alone and in synergy with tumor necrosis factor alpha by transcriptional and post-transcriptional mechanisms. J Exp Med 1990;172:151-8. 21. Folks TM, Justement J, Kinter A, Dinarello CA, Fauci AS. Cytokine-induced expression of HIV-1 in a chronically infected promonocyte cell line. Science 1987;238:800-2. 22. Osborn L, Kunkel S, Nabel GJ. Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kB. Proc Natl Acad Sci USA 1989;86:2336-40. 23. Goletti D, Weissman D, Jackson RW, et al. Effect of Mycobacterium tuberculosis on HIV replication. Role of immune activation. J Immunol 1996;157:1271-8 24. AIDS Control and Prevention (AIDSCAP) Project of Family Health Internal, The Francois-Xavier Bagnoud Center for Public Health and Human Rights Of the Harvard School of Public Health, UNAIDS. The Status and Trends of the Global HIV/AIDS Pandemic. Final Report July 5-6, 1996