HIV/AIDS-associated Tuberculosis; A Global Health Catastrophe

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HIV/AIDS-associated Tuberculosis; A Global Health Catastrophe

 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

[1]. The HIV infection is commonly complicated by other infections; the most serious is Tuberculosis (TB) [2]. HIV and TB are so closely connected that the term “co-epidemic” or “dual epidemic” is often used to describe their relationship. The intersecting epidemic is often denoted as TB/HIV or HIV/TB. HIV affects the immune system and increases the likelihood of people acquiring new TB infection [3]. Tuberculosis (TB) is a disease that usually attacks the lungs but can affect almost any part of the body. A person infected with TB does not necessarily feel ill – and such cases are known as silent or “latent” infections. Tuberculosis has been known under a variety of names during the course of history. The actual name “Tuberculosis” was introduced during the first half of the nineteenth century and it refers to the diseased condition caused by infectious agent known as Mycobacterium tuberculosis [4].

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.


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12.  Reported Tuberculosis in the United States, 2009, CDC, October 2010

13.  Annual Report on Tuberculosis Surveillance in the UK 2010, HPA, November 2010

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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