AEGiS-13IAC: Concurrent use of rifabutin and HAART: Evidence for reduced efficacy.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Concurrent use of rifabutin and HAART: Evidence for reduced efficacy.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. TuOrB277)

Spradling P, McLaughlin S, Drociuk D, Ridzon R, Pozsik C, Onorato I;;; P. Spradling, Centers for Disease Control & Prevention, 1600 Clifton RD, Mailstop E-10, Atlanta, GA 30333, United States, Tel.: +1 404 639 53 10, Fax: +1 404 639 89 59, E-mail: pps9@cdc.gov

BACKGROUND: Use of rifamycins is limited by drug interactions in those receiving highly active antiretroviral therapy (HAART). Substitution of rifabutin (Rfb) for rifampin is recommended for treatment of active tuberculosis (TB) and when using a 2-month rifamycin/pyrazinamide (2RZ) regimen for latent M. tuberculosis infection. Limited data on Rfb use with HAART exist. In Sept 1999, following an outbreak at a prison for HIV-infected men, Rfb was used to treat 255 men (30 cases and 225 contacts).

METHODS: Before treatment, Rfb and protease inhibitor (PI) doses were adjusted for men on interacting (1 PI or efavirenz [EFV]) and complex interacting (>1 PI or 1 PI/EFV) HAART. Steady state peak Rfb levels were obtained after dose adjustments for all men on interacting and complex interacting HAART, and for a group on non-interacting HAART ( é 1 nucleoside analogue or no ART) without dose adjustments. Viral loads (VL) and CD4 counts were obtained.

RESULTS: Of 255 cases and contacts, 123 had Rfb levels (35 non-interacting [NI], 67 interacting [I], 21 complex interacting [CI]). Rfb doses were adjusted for 88/255 (35%) men; 47/56 (84%) PI doses were adjusted. Low Rfb levels (>0.1 mcg/ml) occurred in 9% on NI vs. 19% on I vs. 29% on CI HAART (Chi square trend = 3.76; p = 0.05). Neither VL nor CD4 was associated with low Rfb levels. A é 2 log increase in VL occurred in none on NI vs. 3.2% on I vs. 17.6% on CI HAART (Chi-square trend = 4.41; p = 0.04). Of 225 contacts receiving 2RfbZ, 162 (72%) completed while incarcerated, 18 (8%) were released before completion; and 20 (9%) were changed to isoniazid because of low Rfb levels. 2RfbZ was discontinued in 25 (11%), including 18 for LFTs > 5 ó Ç Ö normal.

CONCLUSIONS: Use of Rfb with complex interacting HAART may adversely affect treatment of both M. tuberculosis and HIV infection. 2RfbZ was difficult to implement due to the need for dose adjustments and expert clinical management, however, most men completed 2RfbZ while incarcerated. More data are needed on optimal treatment of HIV and M. tuberculosis coinfection.

Keywords: AEGIS, Antiretroviral Therapy, Highly Active, Rifabutin, CD4 Lymphocyte Count, HIV Infections, Viral Load, Tuberculosis, Oxazines, Prisoners, Disease Outbreaks, Antigens, CD4, efavirenz, Human, Male, immunology
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TuOrB277