HIV Not Involved in Drug-Resistant Tuberculosis Development

Although the HIV pandemic heightens tuberculosis (TB) outbreaks, it does not drive the development and transmission of multidrug resistance in Mycobacterium tuberculosis (Mtb), as was previously thought.

In a study published in eLife, researchers sought to investigate the impact of HIV co-infection on Mtb drug resistance.

“It is already known that a parallel HIV pandemic amplifies the TB epidemic, with ongoing efforts around the world to tackle these potentially fatal diseases,” said lead study author Vegard Eldholm. “Among the estimated 1.5 million people who died from TB in 2015, about 200,000 cases involved in multidrug-resistant TB and 400,000 were HIV co-infected. However, it is not clear exactly how much of an effect HIV has had on drug resistance in the most common form of TB, Mycobacterium tuberculosis.”

For the study, researchers analyzed the genomes of 252 TB isolates from patients in South America, which has the largest outbreak of multidrug-resistant TB to date. The collected isolates came from patients with known HIV status from the mid-1990s until 2009.

The genomes were used to create a diagram called time-labeled phylogenic tree that shows the inferred evolutionary relationships among mutations within the sampled patients. A new mathematical model optimized for TB was then applied to reconstruct how the disease spreads among people.

Researchers combined the results of both methods to estimate the length of the time from TB infection to infectiousness (latency period), and identified the patients whose TB strains evolved drug-resistance mutations.

“We saw no significant differences in the rate at which mutations occur in the genomes of strains in HIV-positive and negative patients,” said co-corresponding study author Francois Balloux. “This suggests that drug resistance is not more likely to evolve in HIV-positive patients.”

The findings did not show a significant impact of HIV coinfection on a patient’s ability to transmit TB, but the estimates of TB latency confirmed that HIV coinfection accelerates the development of active TB.

“HIV prevents some cells from doing their job in the immune system, meaning the body is unable to fight off a large number of infections,” Eldholm said. “The disease therefore provides TB with a pool of susceptible hosts, amplifying the rate of co-infection. Indeed, for this reason, HIV patients at a major hospital in Buenos Aires, Argentina, played a central role in fueling South America’s largest multidrug-resistant TB epidemic in the early 1990s.”