http://www.nejm.org/doi/pdf/10.1056/NEJMoa1005136
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 continuousisoniazid
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. (Funded by the National Institute of Allergy and
Infectious Diseases and others; ClinicalTrials.gov number, NCT00057122.)
