Incidence of Tuberculosis during Highly Active Antiretroviral Therapy in High-Income and Low-Income Countries

Abstract

Highly active antiretroviral therapy (HAART) has revolutionized the care of HIV-infected individuals, causing major reductions in HIV-associated morbidity and mortality. Once blood CD4⁺ cell counts have reached stable levels of >200 cells/µL, the risk of developing opportunistic disease due to cytomegalovirus, Pneumocystis jirovecii, Mycobacterium avium complex (MAC), Toxoplasma gondii, and Cryptococcus neoformans is generally very low [1]. This reflects the fact that partial restoration of the immune system is sufficient to suppress these low-virulence pathogens. In contrast, however, it is emerging that patients receiving HAART retain a chronically heightened risk of disease due to other, more virulent pathogens, such as tuberculosis (TB) and invasive pneumococcal disease [2–4]. In the case of TB, it might be hypothesized that this observation might relate to the coexistence of other risk factors for TB or possibly to nosocomial TB exposure at HIV treatment facilities. However, a principal underlying cause is undoubtedly the persistence of deficits in immune function during treatment [5]. Because the risk of TB is increased even among those with minor degrees of HIV-associated immunodeficiency, complete normalization of immune function during HAART would be required to reduce the risk of TB to background levels. Increasing evidence, however, shows that this goal is generally not attainable. Even among patients who have good responses to HAART, functional immunological deficits usually persist [5–7], including those specific to Mycobacterium tuberculosis [5, 8, 9].