ING117175: a Phase IIIb, Randomized, Open-label Study of the Safety and Efficacy of Dolutegravir or Efavirenz Each Administered With Two NRTIs in HIV-1-infected Antiretroviral Therapy-naïve Adults Starting Treatment for Rifampicin-sensitive Tuberculosis

HIV/Tuberculosis (TB) co-infection have profound effects on the host's immune system. TB is
the most common cause of death in patients with HIV worldwide. Rifamycins (such as rifampicin
[RIF]) are an important component of TB therapy because of their unique activity. The problem
is that most protease inhibitors (PI) and non-nucleoside reverse transcriptase inhibitors
(NNRTI) used to treat HIV have significant drug-drug interactions with RIF that can lead to
reduced concentrations of these agents with risk of treatment failure or resistance. The
non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV) does not present the
same significant drug interactions with RIF. EFV-based HIV treatment was tested in patients
concomitantly treated with RIF-containing TB therapy, demonstrating that their
co-administration can be used safely and effectively. However, the side effect profile of EFV
overlaps with the RIF-containing TB regimens and makes the management of treatment toxicities
very complex. Integrase inhibitors (INI), such as dolutegravir (DTG), may offer an important
alternative to EFV-based therapy in TB coinfected patients. A Phase I drug-drug interaction
study was conducted in healthy, HIV-seronegative subjects, and showed that DTG at 50 mg twice
daily given together with RIF was well-tolerated and resulted in DTG concentrations similar
to those of DTG 50 mg given once daily alone, which is the recommended dose for INI-naive
patients. Therefore, ART regimens using DTG 50 mg twice daily may represent a new treatment
option for TB-infected patients who require concurrent treatment for HIV infection. This is a
Phase III b, randomized, open-label study describing the efficacy and safety of DTG and
EFV-containing ART regimens in HIV/TB co-infected patients. This study is designed to assess
the antiviral activity of DTG or efavirenz (EFV) ART-containing regimens through 48 weeks. A
total of approximately 115 +/-5% subjects will be randomly assigned in a 3:2 ratio to DTG
(approximately 69 subjects) and EFV (approximately 46 subjects), respectively. This study
will include a Screening Period, a Randomized Phase (Day 1 to 48 weeks plus a 4-week
extension), and a DTG Open-label extension (OLE). During the DTG OLE, subjects will be
supplied with DTG until it is locally approved and commercially available, the subject no
longer derives clinical benefit, or the subject meets a protocol-defined reason for
discontinuation, which ever comes first.