The Rise of Multidrug-Resistant Tuberculosis in HIV Patients

Multidrug-resistant tuberculosis (MDR-TB) was declared a public health crisis by the World Health Organization (WHO) in 2013 and each year continues to pose a serious threat to millions, especially to those infected with HIV. TB is one of the top 10 causes of death worldwide, and 15% of HIV-associated tuberculosis (TB) deaths were caused by MDR-TB in 2018. Furthermore, HIV patients are 20 times more likely to develop active TB than those without HIV.

In a systematic review and meta-analysis published in BMC Infectious Diseases, investigators provide an updated pooled risk estimate of the relationship of HIV infection and MDR-TB growth.

After initial screening and quality assessment scoring, study authors analyzed 54 studies, which included 430,534 TB patients, to find an unadjusted odds ratio (OR) that  displayed the relationship between HIV infection and MDR-TB.

The overall pooled OR was 1.42 (95% CI, 1.17-1.71), indicating that HIV patients have a 42% increased risk of developing MDR-TB compared with HIV-negative patients. This is a higher increased risk than reported in an earlier meta-analysis of fewer studies, and this result implies that HIV-infected individuals have become more likely to have MDR-TB over the last decade.

Researchers performed subgroup analyses to determine the pooled OR of each subgroup and searched for rationales for the heterogeneity. The WHO South-East Asia region had the highest OR of HIV patients developing MDR-TB (OR, 1.86; 95% CI, 1.30-2.67), followed by Europe (OR, 1.79; 95% CI, 1.42-2.27) and Africa (OR, 1.41; 95% CI, 1.06-1.89).

The South-East Asia region had the second-highest HIV prevalence with a 44% TB burden on its population. This region accounted for one-third of global MDR-TB patients.

Further subgroup analysis revealed that the odds of developing MDR-TB in HIV patients was higher for those 40 years of age and older (OR, 1.56; 95% CI, 1.17-2.06).

The pooled OR of MDR-TB was considerably higher for studies using culture-confirmed MDR-TB diagnosis compared with mixed or molecular methods. This diagnostic approach takes months to confirm via cultures, thus delaying treatment, increasing transmission, and ultimately leading to poor outcomes.

Other considerations to take into account when diagnosing TB include the following:

• Diagnosing patients with HIV is difficult due to decreased bacterial load and cavitation.
• HIV-associated superinfection may cause conversion to MDR-TB.
• Multiple TB strain infections may interfere in HIV patients.
• The spread of disease while waiting for culture-confirmation of MDR-TB can be deadly.

Limitations of the analysis are that most of the articles originated from Africa (25/54), and no studies originated from China.

Overall, this meta-analysis exhibits an increase in MDR-TB risk among patients with HIV. “Enhancement of the diagnosis and proper overall management of MDR-TB among HIV-positive individuals has become crucial in achieving WHO’s goals of ‘End TB’ by 2035,” the study authors concluded.

Reference

Sultana ZZ, Hoque FU, Beyene J, et al. HIV infection and multidrug resistant tuberculosis: a systematic review and meta-analysis. Published online January 11, 2021. BMC Infect Dis. doi:10.1186/s12879-020-05749-2.