Rifampin-resistant TB associated with HIV, increased mortality

An analysis of 17 years of national surveillance data showed that all forms of rifampin resistance in patients with tuberculosis were positively associated with HIV infection, delayed culture conversion and increased mortality, researchers reported.

According to Suzanne M. Marks, MPH, MA, an epidemiologist in the CDC’s Division of Tuberculosis Elimination, and colleagues, it was the largest identified study of rifampin resistance performed in the United States.

The researchers found that people with HIV were at greatest risk for rifampin-monoresistant (RMR) and acquired rifampin-resistant (ARR) TB.

“Drug-resistant TB poses significant barriers to identification of appropriate treatment, treatment completion, and to the achievement of CDC’s goal of TB elimination. Previous studies have shown that Mycobacterium tuberculosis resistance to rifampin, the principal TB bactericidal medication, resulted in fewer and more expensive therapeutic options, prolonged treatment, greater toxicity, and poorer clinical outcomes,” Suzanne Marks, MPH, MA, epidemiologist in the CDC’s Division of Tuberculosis Elimination, told Infectious Disease News.

“Rifampin resistance has also been found to be more common in persons with HIV infection. Previous studies of the National Tuberculosis Surveillance System had examined isoniazid- and multidrug-resistant TB but had not studied RMR TB, which occurs less frequently than either of the forementioned conditions. We decided to investigate factors associated with RMR TB using national surveillance data to help further characterize RMR and ARR TB in the United States.”

Marks and colleagues analyzed 126,431 M. tuberculosis culture-positive cases reported to the National Tuberculosis Surveillance System between 1998 and 2014 and reported the following results:

• 359 patients had RMR TB;
• the percentage of RMR TB patients with HIV declined 4% annually during the study period;
• patients with HIV and prior TB (adjusted RR = 25.9; 95% CI, 17.6-38.1) or no prior TB (aRR = 3.1; 95% CI, 2.4-4.1) were both more likely to have RMR TB compared with patients without either characteristic;
• patients with RMR TB experienced greater mortality (aRR = 1.4; 95% CI, 1.04-1.8), controlling for HIV and other variables;
• patients with HIV were at greater risk for ARR TB than persons without HIV (aRR = 9.6; 95% CI, 6.9–13.3);
• ARR was also associated with increased mortality, controlling for HIV and other variables.

Marks said that although the prevalence of rifampin-resistant TB was lower than that of isoniazid-resistant TB, the mortality rate for patients with RMR TB was greater than that for isoniazid-monoresistant TB, and comparable to that of multidrug-resistant TB cases.

“Despite the overall decline in the percentage of TB cases with HIV because of improved HIV treatment and treatment for latent TB infection, HIV is still a risk for RMR TB at TB diagnosis. HIV and TB clinicians should consider rifampin resistance when TB is first diagnosed in persons with HIV. Primary prevention of TB and HIV [is] also important,” Marks said.

“CDC is committed to the goal of TB elimination in the United States and is exploring new approaches to identify drug-resistant TB through whole-genome sequencing, and researching shorter, effective TB treatment regimens through the TB Trials Consortium.”

Sharling L, et al. Clin Infect Dis. 2019;doi:10.1093/cid/ciz491.

Source: Healio