Is chewed raltegravir an option to care for HIV-infected patients with active tuberculosis?

TO THE EDITOR—Human immunodeficiency virus (HIV) and tuberculosis are closely intertwined, and the number of coinfected patients continues to grow rapidly [1]. Treating both infections can be a challenge owing to multiple drug interactions and risk of overlapping side effects [2]. The utilization of rifampicin as part of tuberculosis treatment limits the use of antiretroviral (ARV) drugs. Rifampicin induces cytochrome P450 enzymes, which results in reduced plasma concentrations of protease inhibitors and nonnucleoside reverse transcriptase inhibitors. Rifampicin also induces phase II enzymes including Uridine 5′diphospho-glucuronosyl transferase. The HIV integrase inhibitor raltegravir (RAL) is primarily metabolized by UGT1A1, and therefore there is the potential for a pharmacokinetic drug interaction with rifampicin. In fact, previous studies have shown a decrease in the RAL area under the concentration time curve (AUC), peak of maximum drug concentration, and trough concentrations when coadministered with daily rifampicin [3]. The recently updated recommendation for RAL now suggests a dose increase of RAL to 800 mg twice daily if coadministered with rifampicin [4]. According to 24-week results of the Agence Nationale de Recherche sur le Sida (ANRS) 12 180 REFLATE study [5], RAL 800 mg twice daily provided the highest success rate in HIV-infected patients receiving a rifampicin-based therapy for tuberculosis; in particular, 63% (95% confidence interval [CI], 46%–76%) in the efavirenz regimen group reached the primary endpoint of a viral load <50 copies per mL at 20 and 24 weeks, compared to 76% (95% CI, 65%–88%) in the 400 mg RAL group and 78% (95% CI, 67%–90%) in the 800 mg RAL group. Doubling the RAL dose to 800 mg when coadministered with rifampicin compensates for the effect of rifampicin on RAL exposure (AUC0–12) but does not overcome the effect of rifampicin on RAL trough concentrations (C12) [3]. On the other hand, doubling the RAL dose to 800 mg increased the cost of ARV regimens and, in a context of limited healthcare resources, pharmacoeconomic considerations are crucial. Recently, it was shown that HIV-infected patients taking RAL 400 mg twice daily by chewing the tablets have higher