Efficacy of a 6-month versus 9-month intermittent treatment regimen in HIV-infected patients with tuberculosis. A randomized clinical trial.

Swaminathan, S.; Narendran, G.; Venkatesan, P.; Iliayas, S.; Ramesh, S.; Menon, P.A.; Padmapriyadarsini, C.; Ranjani, R.; Ponnuraja, C.; Suhadev, M.; Sakthivel, R.; Narayanan, P.R.

American Journal of Respiratory and Critical Care Medicine; 2010; 181; 743-751.

Rationale: The outcome of fully intermittent thrice-weekly anti-tuberculosis treatment of various durations in HIV-associated tuberculosis is unclear.

Objectives: To compare the efficacy of an intermittent 6-month regimen (Reg6M: 2EHRZ ₃ /4HR ₃ [ethambutol, 1,200 mg; isoniazid, 600mg; rifampicin, 450 or 600 mg depending on body weight <60 or ≥ 60 kg; and pyrazinamide, 1,500 mg for 2 mo; followed by 4 mo of isoniazid and rifampicin at the same doses]) versus a 9-month regimen (Reg9M: 2EHRZ₃/7HR₃ ) in HIV/tuberculosis (TB).

Methods: HIV-infected patients with newly diagnosed pulmonary or extrapulmonary TB were randomly assigned to Reg6M (n = 167) or Reg9M (n = 160) and monitored by determination of clinical, immunological, and bacteriological parameters for 36 months. Primary outcomes included favorable responses at the end of treatment and recurrences during follow-up, whereas the secondary outcome was death. Intent-to-treat and on-treatment analyses were performed. All patients were antiretroviral treatment–naive during treatment.

Measurements and Main Results: Of the patients, 70% had culture positive pulmonary TB; the median viral load was 155,000 copies/ml and the CD4 + cell count was 160 cells/mm 3 . Favorable response to antituberculosis treatmentwas similarby intent to treat (Reg6M, 83% and Reg9M, 76%; P = not significant). Bacteriological recurrences occurred significantly more often in Reg6Mthan in Reg9M(15 vs. 7%; P < 0.05) although overall recurrences were not significantly different (Reg6M, 19% vs. Reg9M, 13%). By 36 months, 36% of patients undergoing Reg6M and 35% undergoing Reg9M had died, with no significant difference between regimens. All 19 patients who failed treatment developed acquired rifamycin resistance (ARR), the main risk factor being baseline isoniazid resistance.

Conclusions: Among antiretroviral treatment–naive HIV-infected patients with TB, a 9-month regimen resulted in a similar outcome at the end of treatment but a significantly lower bacteriological recurrence rate compared with a 6-month thrice-weekly regimen. ARR was high with these intermittent regimens and neither mortality nor ARR was altered by lengthening TB treatment.

Keywords: tuberculosis; HIV; short-course chemotherapy; recurrence; acquired rifamycin resistance

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