Tuberculosis remains the most common cause of HIV-related deaths worldwide. There is proven clinical benefit to concurrently treating patients for TB and with ART. However, there are concerns regarding drug-drug interactions, overlapping toxicities and immune reconstitution inflammatory syndrome (IRIS) when treating both infections. Plasma concentrations of protease inhibitors and some nonnucleoside reverse transcriptase inhibitors (NNRTIs) are reduced when co-administered with rifampicin and thus cannot be used. Rifampicin also significantly decreases levels of dolutegravir but data from health volunteers showed this interaction can be overcome if the DTG dose is doubled. This study (INSPIRING) randomized 113 patients age >18 years with HIV infection and culture-proven Mycobacterium tuberculosis to receive 600mg of Efavirenz or 50mg of dolutegravir twice daily (both with 2 NRTIs) while also receiving rifampicin-based TB treatment. The median CD4+ count was 206 cells/mm3 and about 60% had HIV-RNA levels of > 100,000 copies/mL. At week 48, by intention-to-treat analysis, 75% of the DTG patients and 82% of the EFV patients had an HIV-RNA level of < 50 copies/ml. Most of the DTG failures were not treatment-related but mainly due to loss of follow-up. There was a total of 4 IRIS events in the DTG arm but no discontinuations or deaths. Also noted was that the TG treatment success rate was 88% in the DTG arm and 91% in the EFV arm – although the trial was not powered to assess differences between  arms. This study supports the use of 100mg of DTG in patients with HIV requiring rifampicin-based TB therapy.

Author’s Commentary:

Although TB is uncommon in the U.S., this data is very important for treating patients in resource-limited settings as well as other geographic locations. The World Health Organization now recommends DTG as a first-line therapy when initiating ART due to increasing levels of NNRTI resistance seen in low and middle-income countries. This study provides evidence for effectively using DTG in patients with TB. Further data is needed to determine if DTG can be given as 100mg once daily as opposed to twice-daily to improve the likelihood of adherence.