A Phase III Randomized, Double-blind Study of the Safety and Efficacy of GSK1349572 50 mg Once Daily Versus Raltegravir 400 mg Twice Daily, Both Administered with an Investigator-selected Background Regimen Over 48 Weeks in HIV-1 Infected, Integrase Inhibitor-Naïve, Antiretroviral Therapy-Experienced Adults.

Integrase inhibitors (INIs) are a new class of antiretroviral drugs designed to
block the action of the integrase viral enzyme, which catalyzes several key
steps in the HIV life cycle and is responsible for insertion of the viral
genome into the DNA of the host cell. The first INI for the treatment of HIV-1
infected subjects was raltegravir.
In ART-experienced subjects, the BENCHMRK studies demonstrated the superior
efficacy of raltegravir plus optimized background therapy compared to optimized
background alone over 48 weeks. Overall frequencies of drug-related adverse
events were similar in the raltegravir and placebo groups. Raltegravir will be
administered at the approved dose of 400 mg twice daily. Twice daily dosing is
a disadvantage when compared to multiple once daily options. In addition, RAL
may have a relatively low genetic barrier to resistance, given that
RAL-associated mutations readily develop in the setting of virologic failure.
Therefore, the development of new INIs with different resistance profiles, the
potential for higher barrier to resistance, and improved dosing administration
is desirable.
GSK1349572 is a next-generation INI that may deliver these attributes. Its
14-hour plasma half-life supports once daily dosing. It possesses potent
antiviral activity. The compound has no significant CYP P450 enzyme inhibition,
and thus has low drug-drug interaction liabilities.
This present study is designed to establish the safety and efficacy of
GSK1349572 50 mg once daily in adults infected with HIV-1 who are
ART-experienced and INI-naïve.

Primary: Antiviral efficacy after 48 weeks of treatment. Secundary: Antiviral
efficacy after 24 weeks, safety and tolerability, resistance development, PK,
incidence of HIV-associated conditions, gender-, race-, and/or HIV-1 subtype on
response to GSK1349572, quality of life.

Multicenter randomized doubleblind phase III non-inferiority parallel group
study.
Randomisation (1:1) to treatment with:
2. GSK1349572 50 mg once daily.
2. Raltegravir 400 mg twice daily.
Plus background therapy (not part of study treatment, on prescription), to be
chosen by investigator base don resistance tests.
Treatment duration 48 weeks.
Interim-analyse palnned after last subject completed 24 weeks of treatment and
after 60% have completed 48 weeks of treatment.
Approx 688 patients.
Patient who did receive GSK1349572 during the study may be eligible for a
follow-up study.

Treatment with GSK1349572 or raltegravir.

Risk: Adverse effects of study medication.
Burden: 11 visits in 48 weeks. Duration 1-4 uur.
Blood tests 11x approx. 10 ml/visit, pregnancy test (if relevant) every visit,
ECG 2x. Questionnaire (EQ 5D, 5 questions) 3x.