Combatting the Double Jeopardy of Drug-Resistant Tuberculosis plus HIV

Despite our current focus on COVID-19, tuberculosis is still the number one cause of death from a single infection, according to the World Health Organization, which characterizes multidrug-resistant TB (MDR-TB) as a public health crisis. This in itself presents a challenge: “We have new and repurposed TB drugs that are known to be successful,” says Gregory Bisson, MD, MSCE, “but they’re not available in some locations. Of those MDR-TB patients who are started on treatment, only about half worldwide get treatment that is considered adequate.” And for TB patients who are also HIV-positive—about 9 percent—mortality risk is up to four times higher compared to HIV-negative patients.

How much can we improve HIV-positive patients’ chances of surviving if we treat their HIV with antiretroviral therapy (ART)—which often is not started until after treatment is completed—and their TB with the best possible TB drugs? Dr. Bisson recently led the first large multisite study to investigate this layered question. The team’s results, which appeared in The Lancet, show that HIV-positive patients’ risk of death decreases substantially as we take each of these steps, and their chances are best when we take both.

A Penn team, working in collaboration with the Centers for Disease Control and Prevention, McGill University, and other institutions internationally, conducted a meta-analysis of individual data from nearly 10,000 adult patients worldwide who have MDR-TB—which stems from infection with a strain of Mycobacterium tuberculosis that is resistant to at least isoniazid and rifampicin. They found that overall, the odds of death were about 2.5 times higher for HIV-positive individuals compared to those without HIV, and the odds were highest for those who were not on ART. However use of certain WHO preferred, or “Group A,” drugs—later-generation fluoroquinolones such as moxifloxacin and levofloxacin, as well as linezolid and bedaquiline—was significantly associated with substantially reduced risk of death among those with HIV. The study provides robust new evidence that ART use should be a core component of MDR-TB treatment in those with HIV infection and that use of WHO Group A MDR-TB drugs should urgently be made available for patients with both conditions.

In the U.S, patients generally do have access to the right MDR-TB drugs, Dr. Bisson says. As medical director for TB treatment in Philadelphia, where effective MDR-TB drugs are used, he is keenly aware of their value and says using the best drugs possible is worth the investment. “MDR-TB costs the system much more to treat: approximately $134K per patient versus $17K per patient if the TB is drug-sensitive. However, these patients need optimal therapies to survive, and death is the outcome we are preventing,” he says.

But even in Philadelphia, with its robust program, HIV is treated separately. Dr. Bisson has long worked on the intersection of HIV and TB and published another major study on the subject in 2016. Perhaps next on this list, he says, are the questions of how to best integrate the treatments into a single program and how to decrease the cost of the optimal TB regimens and ART.