Despite the high prevalence of latent tuberculosis in HIV-positive patients in parts of South Africa, most don't receive preventive treatment for the disease. Factors contributing to public health programs' reluctance to provide prophylaxis include concerns that patients won't complete treatment, the possibility of reinfection, and fears of drug resistance. In the hope of finding a treatment regimen that will encourage the use of prophylaxis, researchers evaluated three new regimens along with a control regimen to determine which therapy is most effective.

The study population comprised HIV-positive patients who had a positive tuberculin skin test and weren't receiving antiretroviral therapy. A total of 1,148 patients completed the study. Subjects were randomized to receive one of four therapies: rifapentine plus isoniazid once weekly for three months, rifampin plus isoniazid twice weekly for three months, continuous isoniazid (daily use for a median 3.3 years), or isoniazid daily for six months (the control group). Eighty-three percent of the subjects were women and the median age was 30.4 years. Medication compliance (defined as taking more than 90% of prescribed doses) was strong among all four groups: the high was 95.7% in the rifapentine-isoniazid group and the low was 83.3% in the control group.

None of the new regimens was superior to the control. The tuberculosis incidence rates (cases per 100 person-years) were 2 in the rifapentine-isoniazid arm, 2 in the rifampin-isoniazid arm, 1.4 in the long-term isoniazid arm, and 1.9 in the six-month isoniazid arm. Similarly, the mortality-related incidence rates (deaths per 100 person-years) were 1.4, 1.3, 1.4, and 2.1 in the four groups, respectively. These differences weren't significantly different. Most of the serious adverse events, such as hepatotoxicity, occurred in the long-term isoniazid group (18.4 per 100 person-years); the lowest rate of serious adverse events (8.7 per 100 person-years) was in the rifapentine-isoniazid group. Multidrug-resistant tuberculosis was identified in two (3.4%) of the 58 Myobacterium tuberculosis specimens.

Although the new regimens weren't superior, the authors advocate the addition of the short-term rifamycin-based therapies as a way of increasing the number of patients receiving preventive treatment and of stemming the development of active tuberculosis in HIV-positive patients with latent disease.-AK

Reference