HIV/TB co-infection

HIV co-infection is the most powerful known risk factor for progression of LTBI to active disease. The risk of progression from LTBI to active TB in people with HIV infection is approximately 5 to 8% per year, in contrast to a 10% lifetime risk in HIV-negative people.[1] HIV has an impact on the host-pathogen (M. tuberculosis) relationship with a shift towards poor immune control, high bacillary numbers, and subsequent development of active infection and symptomatic disease.9 The risk of developing active TB increases 2-3 fold after HIV seroconversion due to an initial rapid depletion of CD4+ T cells[2] and continues to increase thereafter with ongoing decline in CD4+ T cell counts.[3] Re-infection with M. tuberculosis in endemic high prevalence settings is likely to contribute to the risk by further increasing bacillary numbers and increasing the likelihood of progression to disease.9 The development of TB in a person with HIV infection may accelerate HIV disease progression, probably related to prolonged immune activation.[4] Combination antiretroviral therapy (cART) and treatment of LTBI have been shown to have a significant impact in decreasing the incidence of TB in HIV-infected populations.[5],[6]

Clinical presentation of TB

TB may present with pulmonary disease, extrapulmonary disease (can involve almost any organ in the body including lymph nodes, central nervous system and blood/bone marrow) or disseminated disease. The typical presentation of TB (fever, weight loss, night sweats, constitutional symptoms with or without cough) has a wide differential diagnosis in patients with HIV infection. TB can occur at any CD4+ T cell count. Unlike most other opportunistic infections, the TB risk is increased irrespective of CD4+ T cell count, however is greater with increasing immunodeficiency, with a systematic review estimating a 1.4 fold increase in TB incidence for every 100 cells/mL decrease in CD4+ T cell counts. Pulmonary disease is present in most patients with both HIV and TB, as evidenced by autopsy studies and subclinical disease found during prevalence surveys or active case finding.  Extra pulmonary and disseminated  disease are more common in the setting of HIV infection, especially with advanced immunodeficiency. As a result, the World Health Organization (WHO) current staging system considers extrapulmonary TB as stage 4 (AIDS-defining) whereas pulmonary TB is stage 3.

The clinical manifestations of HIV-associated TB are influenced by the degree of immunodeficiency. When the CD4+ T cell count is greater than 350/μL, clinical manifestations are similar to persons without HIV infection. Advanced immunodeficiency impairs the host inflammatory response, resulting in lower rates of granuloma formation and pulmonary cavitation. This result accounts for more frequent sputum-smear negative disease and increased time to positivity of automated liquid mycobacterial cultures in HIV patients with TB.24 A second factor influencing clinical presentation in people with HIV infection, versus those without infection, is that TB progresses more rapidly in HIV patients, reflecting a subacute rather than chronic clinical course.