136 Use of Antiretroviral Therapy During Treatment of Active Tuberculosis with a Rifabutin-based Regimen W. Burman*1, D. Benator2, A. Vernon3, A. Khan3, W. El-Sadr4, C. Silva5, C. Lahart6, S. Weis7, B. Mangura8, B. King7, M. Weiner9, B. Jones5 1Denver Publ Hlth and Univ of Colorado Hlth Sci Ctr; 2Veterans Admin Med Ctr, Washington, DC; 3CDC, Atlanta, GA; 4Harlem Hosp Ctr and Columbia Univ Coll of Physicians and Surgeons, New York, NY; 5Los Angeles County-Univ Southern California Med Ctr, CA; 6Thomas Street Clin, Houston, TX; 7Univ of North Texas Hlth Sci Ctr, Ft Worth; 8Natl Tuberculosis Ctr and New Jersey Med Sch, Newark, NJ; and 9Audie L Murphy VA Hosp, San Antonio, TX
Background: Rifabutin has been recommended for treatment of HIV-related tuberculosis (TB) because rifabutin has fewer drug interactions with antiretroviral drugs than does rifampin, thus facilitating use of highly active antiretroviral therapy (HAART). We evaluated use of HAART and its outcomes among patients (pts) enrolled in a study of rifabutin-based therapy for active TB.
Methods: TBTC Study 23 is a prospective trial of largely twice-weekly rifabutin plus isoniazid (with pyrazinamide and ethambutol during the first 2 mos) for treatment of HIV-related TB. The regimen was active against TB, with a 5% rate of treatment failure or relapse. The use and timing of HAART were not limited, other than prohibiting delavirdine. CD4 cell counts were measured at local laboratories; HIV RNA levels were measured using Bayer VERSANT 3.0 assay (bDNA). We compared the mortality rate among pts in TBTC Study 23 to that of pts in a pre-HAART trial of treatment of HIV-related TB in the U.S. (CPCRA 019/ACTG 222).
Results: A total 169 pts enrolled in TBTC Study 23, with median CD4 cell count at TB diagnosis of 90 cells/mul (interquartile range [IQR] 37-175; n = 137) and median HIV RNA level of 5.3 log10 copies/ml (IQR 4.8, 5.7; n = 107). Sixty-three (63) pts (37%) were on HAART at the time of TB diagnosis. Seventy (70) pts (41%) started HAART during TB treatment; most (n = 47) within 4 mos of the start of TB treatment. The most common regimens were 2 nucleosides plus nelfinavir (n = 52) and 2 nucleosides plus efavirenz (n = 59). Among pts with values available at start and end of TB therapy, HIV RNA levels fell (median decrease of 1.8 log10 copies/ml [IQR 0.5-3.5]; n = 62) and CD4 cell counts rose (median increase of 61 cells/µl [IQR 17-127]; n = 108) during TB treatment. Despite similar baseline CD4 cell counts (90 cells/mul in TBTC Study 23 vs 70 cells/mul in CPCRA 019/ACTG 222), pts in TBTC Study 23 had a markedly lower death rate during the 12 mos after TB diagnosis, compared to the pts in the pre-HAART trial (5% vs 15%).
Conclusions: Despite the complexities of antiretroviral therapy during TB treatment (overlapping side effect profiles, drug interactions, etc.), AIDS pts with TB can be successfully treated with HAART while receiving rifabutin-based TB therapy. Use of HAART was associated with improved survival after TB diagnosis
