Weekly rifapentine for 3 months safer than 9 months of INH in HIV+

Mark Mascolini
July 24, 2012, 9:30 p.m.

Three months of once-weekly observed rifapentine plus isoniazid (3HP) proved safer and more tolerable than 9 months of daily self-administered isoniazid (9H) in HIV-positive people from North America, South America, and Spain. HIV-positive people were less likely to stop 3HP than HIV-negative people enrolled in the same trial, TBTC Study 26/ACTG 5259.

HIV infection remains the strongest predictor of progression from latent Mycobacterium tuberculosis infection to tuberculosis. Although 9H effectively prevents TB, completion rates are low and the regimen may cause liver toxicity.

The PREVENT TB trial demonstrated that 3HP is at least as effective as 9H in warding off TB (Sterling TR, et al. N Engl J Med. 2011; 365: 2155-2166), but only 3% of study participants had HIV infection. Researchers extended enrollment of HIV-positive people to further assess tolerability.

The 3HP regimen consisted of once-weekly rifapentine at 900 mg plus once-weekly isoniazid at 900 mg for 3 months under direct observation. The 9H group took 300 mg of daily self-administered isoniazid for 9 months.

Study participants were at least 2 years old and had a positive tuberculin skin test or had close contacts with TB. No one took antiretroviral therapy for 90 days after enrollment. Researchers randomized participants from the United States, Canada, Brazil, Peru, and Spain to 3HP or 9H.

Of the 4128 trial participants with known HIV status who received at least one dose, 393 (9.5%) had HIV infection. A modified intention-to-treat analysis determined that 178 of 201 HIV-positive people (89%) completed 3HP compared with 125 of 193 HIV-positive people (65%) who completed 9H, a highly significant difference (P < 0.001).

Among trial participants with HIV taking 3HP versus 9H, significantly lower proportions had a serious adverse event (4% versus 11%, P = 0.006), one or more adverse events (22% versus 40%, P = 0.004), or liver toxicity (2% versus 6%, P = 0.03).

Compared with 1888 HIV-negative people treated with 3HP, HIV-positive people were significantly less likely to stop treatment permanently for any reason (11% versus 20%, P < 0.001) or to have possible drug hypersensitivity (1% versus 5%, P = 0.003). The HIV-positive and negative groups did not differ in proportions with serious adverse events, one or more adverse events, or liver toxicity.

The researchers conclude that, “among HIV-positive persons not receiving antiretroviral therapy, 3HP was better tolerated and had higher treatment completion rates than 9H for treatment of latent M. tuberculosis infection.”

Source: T. Sterling, C. Benson, N. Shang, J. Miro, B. Grinsztejn, R. Chaisson, A. Lucchetti, J. Sanchez, N. Scott, E. Villarino, AIDS Clinical Trials Group, Tuberculosis Trials Consortium. Tolerability among HIV-positive persons of three months of once-weekly rifapentine + INH (3HP) versus 9 months of daily INH (9H) for treatment of latent tuberculosis infection: the PREVENT TB Study (TBTC Study 26/ACTG 5259). XIX International AIDS Conference. 22-27 July 2012. Washington, DC. Abstract MOAB0302.