An “ultra”-sensitive test, and a proactive use of prednisone show promise, require monitoring
SEATTLE – In the halting progress against tuberculosis in people living with HIV, advances in both diagnosis and effective treatment have come with gaps and caveats, highlighted, and then answered with research presented last week in sessions and press conferences dedicated to tuberculosis.
The arrival of diagnostic Xpert RIF technology in 2010 increased the chances of prompt and appropriate treatment, Timothy Rodwell of FIND said, but as the test still continues to miss harder to diagnose cases, which include tuberculosis in people living with HIV, an upgrade to the test has been eagerly awaited. That came with the Xpert Ultra. More sensitive, and set to be launched at the same price as the original Xpert, it offers greater sensitivity — that is the ability to detect true numbers of tuberculosis cases among samples from patients who are sick. Recently compared to the original Xpert in tests on samples from more than 1500 patients — a quarter of whom were living with HIV — at 10 sites across 10 countries, it showed a 12 percent higher rate of sensitivity for detecting TB in HIV-infected patients over the older technology. But, Rodwell noted, that improved sensitivity comes at its own price — the Xpert Ultra is less good at detecting the true number of negative samples, or those from people who are not sick with TB. That’s because in its improved sensitivity, it detects old evidence from people once sick with tuberculosis as active infection. As that, in turn, can lead to further unnecessary tests and treatment, it will require careful, and discerning use, in settings where it still may offer the best chance of correct diagnosis, Rodwell said.
And while a goal of early detection is early treatment, that too can bring its own risks. Early antiretroviral treatment for TB patients living with HIV lowers their risk of dying, but increases the risks of an inflammatory response to treatment that can intensify TB symptoms and frequently requires patients to be hospitalized — causing clinicians, particularly where hospital beds are in short supply to proceed cautiously. Now, research from the University of Cape Town has shown that proactive use of prednisone, a steroid that reduces immune responses, can lower the risk of that response — TB-immune Reconstitution Inflammatory Syndrome (TB-IRIS) by 30 percent. And although concern existed that prednisone could suppress infection-fighting ability, researchers saw no increased rates of infections.