A report by Annie Luetkemeyer, MD, assistant clinical professor of medicine, UCSF Division of HIV/AIDS at San Francisco General Hospital and Trauma Center:
TB studies in Late Breaker Track B session: Raltegravir in HIV-TB coinfection (THLBB01) and the additive benefit of Isoniazid preventative therapy (IPT) in addition to ART for TB prevent (THLBB03)
Raltegravir may be an alternative to efavirenz for HIV treatment in HIV TB coinfection. ART must be given concomitantly with TB treatment but drug interactions limit what antiretrovirals can be given with rifampin-based TB treatment. In prior PK studies, rifampin reduced raltegravir concentrationd by about half, while doubling raltegravir to 800 mg BID restored the area under the curve (AUC )to pre-rifampin levels but the trough remains low.
To evaluate raltegravir use in HIV-TB, the ANRS 12180 study randomized 155 HIV-TB patients on rifampin to Efavirenz 600 mg QD, Raltegravir 400 mg BID or raltegravir 800 mg BID, each given with tenofovir and emtricitabine, while on rifampin. After 24 weeks of ART, suppression rates to <50 copies/ml were EFV 63%, Raltegravir 400 mg BID 76%, and Raltegravir 800 mg BID 78%. (modified intention to treat, TLOVR). The study was not designed to compare the arms directly so no test for significance was performed. Virologic failure occurred 15, 12, and 4 of the EFV, RAL 400 and RAL 800 arms, with drug resistance present in 4, 5 and 1 respectively in a subset available for resistance testing. Thus, while RAL 400 and 800 had similar suppression rates, there is a suggestion of more virologic failures and more drug resistance (including integrase resistance) in the standard RAL 400 dose. Raltegravir 800 mg bid appears to be a good alternative to EFV for HIV-TB treatment; 48 week data and PK analyses are forthcoming.
Turning to TB prevention, a South African study evaluated the effect of 12 months of isoniazid preventative therapy (IPT) versus placebo in addition to ART, which has been shown to reduce TB incidence by 60%. Active TB was excluded at baseline with AFB smear and culture, and IPT vs. placebo) was provided regardless of latent TB status. In four years of follow-up, one year of IPT reduced incidence TB by 37% compared to placebo, demonstrating an additional benefit to IPT above and beyond ART for TB prevention in a high incidence TB setting.
