HIV–TB Coinfection and Therapeutic Challenges

HIV–TB coinfection represents a major public health concern, particularly in regions with high prevalence rates in developing countries (e.g. South-East Asia and South Africa). One major contributor for this high prevalence is due to lack of recognition of TB. Developing countries have less access to healthcare, therefore those with TB go undiagnosed and therefore the problem “doesn’t exist”. It wasn’t until recently that the gravity of TB’s serious effects have been exposed. Around a quarter of the world population is currently infected with TB, but only 5 ∼ 10 % of them will ever progress into active disease (American Lung Association, 2024). The rest of the population infected with TB that are not in active disease are considered “Latent” or asymptomatic. TB has gained a major prevalence over the past 20-30 years but has traces all the way to the early 1800s (CDC, 2000). Human immunodeficiency virus (HIV) compromises immune function, facilitating the progression of Mycobacterium tuberculosis (Mtb), the bacteria known to cause TB infection; from latent to active tuberculosis (TB), thereby establishing a highly effective symbiotic relationship between the two pathogens. To effectively manage drug–drug interactions (DDIs) between antiretroviral therapy (ART) for HIV and standard anti-TB medications, as well as the immunological interplay between these pathogens (Navasardyan et al., 2024), a comprehensive approach is essential.

HIV weakens the immune system by reducing the number of CD4+ T cells. These are a type of white blood cell that act like "helpers" in the immune system, coordinating the defense against infections. When HIV destroys these cells, it leaves the body less able to fight diseases, including TB. In a healthy person, the immune system forms granulomas to trap and contain TB bacteria (a kind of "prison" made of immune cells to stop Mtb bacteria from spreading). But when HIV reduces the CD4+ T cells, these granulomas fall apart. This breakdown allows Mycobacterium tuberculosis (Mtb), the bacteria that causes TB, to escape and cause an active TB infection. Therefore, the loss of CD4+ T cells makes it easier for TB bacteria to spread in the body, increasing the risk of severe illness (Navasardyan et al., 2024).

Standard HIV treatment involves Antiretroviral therapy (ART). It uses medicines to reduce the amount of HIV in the body, called the viral load, which helps keep the immune system working efficiently for longer. There are two main types of ART: NRTI’s and INSTI’s. NRTI’s or Nucleoside reverse transcriptase inhibitors use drugs to block HIV from a process of copying its genetic material (RNA) into DNA. Blocking this step prevents the reproduction of the virus and level’s off its amount in the body. INSTI’s or Integrase strand transfer inhibitors on the other hand, prevent the virus from inserting its DNA into the host cell. While these treatments do not eliminate HIV, they are vital in controlling the disease. ART comes with some potential negative side-effects: it is known to correlate with mitochondrial toxicity (improper mitochondria function) and weight fluctuations, the direct mechanisms behind this are still being studied (Luis Menéndez-Arias et al., 2021).  

TB treatment typically relies on the RIPE regimen: rifampin, isoniazid, pyrazinamide, and ethambutol.

Table 1

RIPE Regimen Functions

      (Shen et al., 2023)

However, rifampin, a critical anti-TB drug, interacts adversely with many ART components by inducing cytochrome P450 enzymes (proteins in the liver designed to break down many drugs such as ART), requiring dose adjustments or alternative therapies like rifabutin which has less DDI’s with ART (Centers for Disease Control and Prevention, 2023).

Managing HIV–TB coinfection involves balancing effective suppression of both pathogens while minimizing DDIs and toxicity. Shorter regimens, such as a 1-month course of rifapentine and isoniazid, have shown promise in improving treatment adherence and outcomes (Swindells et al., 2019). HIV–TB coinfection demands comprehensive treatment strategies that address immune suppression, DDIs, and patient compliance. Less developed countries often struggle to manage HIV–TB coinfection due to limited resources, inadequate healthcare infrastructure, and barriers to accessing comprehensive treatment. While current therapies improve survival rates, research into innovative dual-action drugs and metabolic interventions is essential for long-term management.

References:

Association, American Lung. “Learn about Tuberculosis.” American Lung Association, www.lung.org/lung-health-diseases/lung-disease-lookup/tuberculosis/learn-about-tuberculosis. Accessed 22 Nov. 2024. 

Core Curriculum on Tuberculosis: What the Clinician Should Know. U.S. Dept. of Health & Human Services, Centers for Disease Control and Prevention, National Center for HIV, STD, and TB Prevention, Division of Tuberculosis Elimination, 2000. 

Menéndez-Arias, Luis. “Update and Latest Advances in Antiretroviral Therapy.” Trends in Pharmacological Sciences, U.S. National Library of Medicine, pubmed.ncbi.nlm.nih.gov/34742581/. Accessed 22 Nov. 2024. 

Navasardyan I;Miwalian R;Petrosyan A;Yeganyan S;Venketaraman V;, Inesa. “HIV-TB Coinfection: Current Therapeutic Approaches and Drug Interactions.” Viruses, U.S. National Library of Medicine, pubmed.ncbi.nlm.nih.gov/38543687/. Accessed 22 Nov. 2024. 

S R Alsayed , Shahinda. “Tuberculosis: Pathogenesis, Current Treatment Regimens and New Drug Targets.” International Journal of Molecular Sciences, U.S. National Library of Medicine, pubmed.ncbi.nlm.nih.gov/36982277/. Accessed 22 Nov. 2024.