New Regimens to Prevent Tuberculosis in Adults with HIV Infection

Abstract

BACKGROUND Treatment of latent tuberculosis in patients infected with the human immunodeficiency virus (HIV) is efficacious, but few patients around the world receive such treatment. We evaluated three new regimens for latent tuberculosis that may be more potent and durable than standard isoniazid treatment. METHODS We randomly assigned South African adults with HIV infection and a positive tuberculin skin test who were not taking antiretroviral therapy to receive rifapentine (900 mg) plus isoniazid (900 mg) weekly for 12 weeks, rifampin (600 mg) plus isoniazid (900 mg) twice weekly for 12 weeks, isoniazid (300 mg) daily for up to 6 years (continuous isoniazid), or isoniazid (300 mg) daily for 6 months (control group). The primary end point was tuberculosis-free survival. RESULTS The 1148 patients had a median age of 30 years and a median CD4 cell count of 484 per cubic millimeter. Incidence rates of active tuberculosis or death were 3.1 per 100 person-years in the rifapentine–isoniazid group, 2.9 per 100 person-years in the rifampin–isoniazid group, and 2.7 per 100 person-years in the continuous-isoniazid group, as compared with 3.6 per 100 person-years in the control group (P>0.05 for all comparisons). Serious adverse reactions were more common in the continuous-isoniazid group (18.4 per 100 person-years) than in the other treatment groups (8.7 to 15.4 per 100 person-years). Two of 58 isolates of Mycobacterium tuberculosis (3.4%) were found to have multidrug resistance. CONCLUSIONS On the basis of the expected rates of tuberculosis in this population of HIV-infected adults, all secondary prophylactic regimens were effective. Neither a 3-month course of intermittent rifapentine or rifampin with isoniazid nor continuous isoniazid was superior to 6 months of isoniazid.

Rifapentine for latent tuberculosis infection treatment in the general population and human immunodeficiency virus-positive patients: summary of evidence

“…Safety -Martinson et al (11) reported that severe adverse events were less frequent with rifamycins like rifapentine, compared to the control (6 months with isoniazid), but this difference was not signifi cant. Similarly, no difference was observed between the rifamycins and control groups in terms of increasing the levels of liver transaminases (11) .…”

“…Effectiveness -In the study by Martinson et al (11) , the proposed regimen of 3 months of rifapentine (900mg) + isoniazid (900mg) combination administered once a week under directly observed therapy (DOT) did not reduce TB incidence or mortality in adults with LTBI and HIV compared to the actual standard regimen of 6 months of isoniazid (300mg) self-administered daily. Similar to the rifapentine + isoniazid combination, others proposed regimens for LTBI chemoprophylaxis were not superior to isoniazid 6-month monotherapy in reducing TB or death incidences [rifamycin + isoniazid for 3 months: relative ratio (RR) = 0.80, 95% confi dence interval (CI): 0.50-1.29, p = 0.34 and isoniazid monotherapy for up to 6 years: RR = 0.75, 95% CI: 0.38-1.38, p = 0.34].…”

“…Both the RCTs included defi ned antiretroviral therapy as an exclusion criterion. Martinson et al (11) designed an open-label RCT, but properly described randomization since the algorithm was computer generated. Follow-up losses were not clear; it was possible to identify how many subjects withdrew consent, but not the number of subjects who completed the follow-up time.…”

“…Both studies showed that adherence was higher in participants who received the combination of rifapentine + isoniazid, which was administered by DOT (11) (12) .…”

“…In total, 10 studies were included (Figure 1): 1 systematic review (10) , 2 randomized controlled trials (11) (12) , 1 American evidence-based synopsis (13) , and 6 clinical guidelines from different settings -United States of America (14) (15) , United Kingdom (16) (17) , Australia (18) , and WHO (4) . The results of Evidence -based synopsis = 1…”