A Phase 3b, Randomized, Open-label Study of the Antiviral Activity and Safety of Dolutegravir Compared to Lopinavir/Ritonavir Both Administered With Dual Nucleoside Reverse Transcriptase Inhibitor Therapy in HIV-1 Infected Adult Subjects With Treatment Failure on First Line Therapy

For treatment of human immunodeficiency virus type 1(HIV-1), publicly funded programmes tend
to follow World Health Organization (WHO) guidelines to use a non-nucleoside reverse
transcriptase inhibitor (NNRTI) combined with two nucleoside reverse transcriptase inhibitors
(NRTIs) for first-line antiretroviral therapy (ART); however, there is a need for further
data on the best treatment options for people with HIV-1 who have virological failure with
this first-line regimen. The number of patients failing on their first-line regimen is
increasing thereby requiring a switch to second-line treatment to reduce accumulation of
drug-resistance mutations, disease progression, HIV transmission, and death. WHO guidelines
recommend second-line antiretroviral therapy for adults consisting of two NRTIs + a
ritonavir-boosted protease inhibitor (PI); atazanavir (ATV) plus ritonavir (RTV) or lopinavir
(LPV)/RTV are the preferred boosted PI options. This study is conducted to demonstrate
non-inferior antiviral activity at 48 weeks of a dolutegravir (DTG) containing regimen
compared to a WHO-recommended standard of care regimen for second line treatment, LPV/RTV +
two NRTIs, in HIV-1 infected patients failing first line therapy. This study comprises of a
Screening Phase (approximately 28 to 42 days), a Randomized Phase (Day 1 to Week 48 plus a
4-week treatment extension), and a Continuation Phase. Approximately 612 subjects will be
randomized 1:1 to receive DTG 50 milligram (mg) once daily or LPV/RTV (800/200 mg once daily
or 400/100 mg twice daily, in accordance with investigator decision and local label), each
added to an investigator selected background regimen of two NRTIs at least one of which needs
to be fully active based on viral resistance testing at Screening. Subjects randomized to the
LPV/RTV arm will either (i) continue receiving LPV/RTV and complete the study after the
4-week treatment extension at Week 52, or (ii) switch to the DTG arm prior to study
completion at Week 52 and continue to have access to DTG in the Continuation Phase. Subjects
randomized to receive DTG who successfully complete 52 weeks of treatment and subjects
originally randomized to receive LPV/RTV but switched to DTG prior to Week 52 will continue
to have access to DTG until it is either locally approved and commercial supplies are
available to patients or the patient no longer derives clinical benefit, or the patient meets
a protocol-defined reason for discontinuation.