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The surprising combination of HIV and tuberculosis: Why they are the world's deadliest combination.
Among the current global health challenges, the co-epidemic of tuberculosis (TB) and human immunodeficiency virus (HIV) is a problem that cannot be underestimated. According to the World Health Organization (WHO), tuberculosis remains one of the leading causes of death among people living with HIV.
In 2019, TB was responsible for 30% of the 690,000 HIV/AIDS-related deaths worldwide.
In addition, 15% of the 1.4 million TB deaths worldwide are among people living with HIV or AIDS. The combination of these two diseases results in a decrease in immunity caused by HIV, and the progression of tuberculosis is also aggravated by the defective immune status. If a person's CD4 T cell count falls below 200 (usually due to untreated HIV), their risk of contracting TB increases 25-fold. The situation is even more serious when faced with multidrug-resistant tuberculosis (MDRTB) and extensively drug-resistant tuberculosis (XDRTB), which is not only difficult to treat but also leads to an increase in mortality.
TB can develop at any stage of HIV infection. The risk and severity of TB disease increase soon after HIV infection. Although TB can be a relatively early sign of HIV infection, the risk of TB increases as the CD4 cell count decreases. Even while receiving antiretroviral therapy, the risk of tuberculosis in HIV-infected patients generally remains higher than the background risk in the general population.
From 2000 to 2021, the incidence of tuberculosis fell by 60% after initiation of highly active antiretroviral therapy (HAART) in resource-limited settings.
The tuberculosis mortality rate dropped by 72%. HAART reduces the risk of TB infection in HIV-infected individuals by 67% to 84%. Classical tuberculosis usually affects the upper lobes of the lungs with cavitary lesions, but in patients with HIV, presentation may be atypical. In those patients with HIV who are immunosuppressed, noncavitary nodular consolidation of the lower lobes may be seen, and even in advanced HIV/AIDS, the chest X-ray may appear normal.
HIV patients are more likely to spread tuberculosis after being infected with tuberculosis. The most common extrapulmonary tuberculosis sites are lymph nodes, liver, spleen and central nervous system (tuberculous meningitis). However, the mortality rate of tuberculous meningitis is as high as 40%. Even in HIV patients, TB can present as sepsis, with some studies showing that approximately 50% of hospitalized HIV patients have tuberculosis bacteremia (Mycobacterium tuberculosis in the blood).
If active TB is not properly treated, the mortality rate is about 50%.
The root cause of tuberculosis is the failure of the immune response to prevent the growth of mycobacteria. Normally, CD4+ helper T cells secrete the cytokine IFN-γ, which recruits macrophages and stimulates them to destroy tuberculosis bacteria, forming granulomas to prevent the spread of infection. However, in HIV patients, particularly those with low CD4+ helper T cell counts, granuloma formation is poorly organized, leading to dissemination of TB in the lungs and throughout the body.
In terms of treatment, if HIV-infected people develop tuberculosis, it is recommended that they receive comprehensive treatment for both diseases at the same time, regardless of the CD4+ cell count. The standard of care is a six-month rifampicin-based treatment plan. For people with drug-resistant TB, bedaquiline, pretomanid, linezolid, or moxifloxacin may be needed.
Early initiation of antiretroviral therapy reduces early mortality, decreases relapses, and prevents the development of drug-resistant TB.
However, initiation of ART in HIV-infected individuals may increase the risk of immune reconstitution inflammatory syndrome (IRIS). This usually develops within three months of starting ART and is associated with new or worsening symptoms of TB. When dealing with this condition, steroids are often used.
Currently, diagnosing TB in HIV-infected people is often difficult because typical symptoms may not be obvious. Traditional methods for TB diagnosis, such as sputum culture and microscopic examination, are not very sensitive. In contrast, GeneXpert MTB/RIF is a PCR-based test that can detect tuberculosis and its resistance to rifampicin in just two hours.
Early detection of TB in HIV patients is crucial, and only by fully understanding these conditions can we more effectively curb these two crises.
How to prevent and effectively treat co-infection of HIV and tuberculosis remains a major challenge facing health workers around the world. More research and appropriate policies will be needed in the future to address this issue.
