New TB therapy works for HIV-positive patients
New TB therapy works for HIV-positive patients
Regimen could ease protease inhibitor conflict
A five-year international study has concluded that two months of therapy for preventing tuberculosis in HIV-positive patients is an effective alternative to the year-long regimen that has been recommended. The new regimen could improve drug compliance for co-infected patients and ease the dilemma of having to delay protease inhibitor therapy while treating for TB, experts say.
The study, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) and the Centers for Disease Control and Prevention, holds strong promise for reducing HIV-related TB disease and death, particularly in the United States where it is widespread, say CDC officials.
The finding, reported at the 5th Conference on Retroviruses and Opportunistic Infections, is significant because TB and HIV are synergistic infections, says Anthony Fauci, MD, director of NIAID. "HIV infection speeds the progression of TB disease and increases the activation of latent TB infection. TB appears to increase HIV replication in HIV-infected individuals."
The mechanics of that synergy were illustrated in another study presented at the conference showing that HIV viral load increases six- to sevenfold during the course of TB treatment.1
The short-course study followed nearly 1,600 HIV-infected patients randomized to take either two months of daily rifampin and pyrazinamide or 12 months of daily isoniazid. After 36 months of follow-up, the number of TB cases was the same in both treatment arms. Fewer deaths were found in the two-drug arm, but the difference was not statistically significant, the researchers noted.
Moreover, researchers found a significantly greater number of patients complied with the two-drug regimen. While 80% of patients in the two-drug group completed their treatment, fewer than half completed the year-long regimen, says Fred Gordin, MD, NIAID's principal investigator for the study.
Patient compliance with TB regimens is a serious problem, particularly those who are HIV-positive. A study of co-infected patients attending New York City HIV clinics showed a substantial number were lost to follow-up at the clinic. Of patients who received all or part of their preventive therapy after their first visit at the clinic, only 46% completed at least 12 months of therapy, and 43% were lost to follow-up.2
While the NIAID short course included only HIV-positive patients, Gordon points out that the short-course two-drug regimen (rifampin and pyrazinamide) could be successful for preventing active disease in patients who don't have HIV but have latent TB infection. The CDC currently recommends six to 12 months of daily isoniazid therapy for skin-test-positive patents at high risk for TB disease.
The CDC plans to evaluate the new data and to review existing preventive therapy guidelines in a meeting later this year that will be co-hosted with the American Thoracic Society and possibly the Infectious Diseases Society of America, says Kenneth Castro, MD, director of the CDC's division of TB elimination. Until then, the CDC cannot make recommendations about use of the two-drug, two-month regimen, he says.
"Because these trials have not shown superior efficacy to what is available, I think we will be at a minimum obligated to offer it as an alternative option," he says. "However, we first need to look at toxicity data with the multidrug regimen to make sure we are not increasing the potential for toxicity before the recommendation is issued. I would suspect that after the discussion, debate, and looking at the data, the outcome is likely to be that this is an alternative that may be very reasonable."
Addressing rifampin interactionsThe possibility of a preventive therapy regimen that is only two months instead of six or 12 months would make it easier to ask HIV-positive patients to delay or temporarily discontinue taking protease inhibitors, which have strong interactions with rifampin, Reichman notes. Although some clinicians are replacing rifampin with rifabutin because of studies showing less severe interaction with protease inhibitors, there are no prospective studies proving the switch to be an effective option, he adds.
A two-drug, two-month regimen also makes it more feasible to provide directly observed preventive therapy for HIV-positive patients, says Joan Otten, RN, director of the tuberculosis control program at Jackson Memorial Hospital in Miami.
References1. Ellner J. Interaction between HIV and TB. Presented at the 5th Conference on Retroviruses and Opportunistic Infection. Chicago; 1998.
2. Sackoff J, Torian L, Vavagiakis P, et al. TB preventive therapy in HIV-infected patients. Presented at the 5th Conference on Retroviruses and Opportunistic Infection. Chicago; 1998.
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