Daily Treatment for HIV-Associated TB Is Still Best

There are many reasons to wish for a good alternative to daily treatment for HIV-associated tuberculosis, including minimizing pill burden, adverse effects, and drug interactions. However, suboptimal response rates and unusual drug resistance have been reported with intermittent regimens in coinfected patients.

To further assess the efficacy and safety of intermittent therapy in this setting, Indian researchers conducted an open-label, randomized, controlled trial between 2009 and 2016, in which 331 HIV-infected adults with newly diagnosed pulmonary tuberculosis (TB) received one of three treatment regimens:

• Standard daily treatment with isoniazid (INH), ethambutol (EMB), rifampicin (RIF), and pyrazinamide (PZA) for 2 months, followed by INH/RIF for 4 months;

• Two-phase treatment with daily INH/EMB/RIF/PZA for 2 months followed by thrice weekly INH/RIF for 4 months;

• Entirely thrice-weekly treatment with INH/EMB/RIF/PZA for 2 months and INH/RIF for 4 months.

All patients had culture-confirmed disease and were receiving effective antiretroviral therapy; those on protease inhibitors were excluded, as were those with baseline RIF resistance or substantial renal or liver failure.

At the end of the intensive 2-month, four-drug phase, sputum smears were negative for a similar percentage of patients in the entirely thrice-weekly group (58%) and both the standard daily group and the two-phase group (65%). However, culture results were negative for a significantly higher percentage of combined patients in the standard daily group and the two-phase group (97%) than in the entirely thrice-weekly group (87%). At the end of treatment, significantly more patients in the standard daily group had a good clinical and microbiologic response to treatment (91%) than did those in the two-phase group (80%) or the entirely thrice-weekly group (77%).

Grade 3 and 4 gastrointestinal and hepatic drug reactions were more common in both daily groups than in the thrice weekly group. All four cases of acquired rifampicin resistance occurred in the entirely thrice-weekly group. Low CD4-cell count at the end of treatment was predictive of a poor response. One year after the end of treatment, death rates and TB recurrence rates were similar in all groups.