Raltegravir is a highly potent antiretroviral agent, with arguably one of the most favorable adverse event profiles in the HIV armamentarium. However, its standard twice-daily (BID) dosing schedule makes it less convenient than once-daily (QD) options. Although pharmacokinetic data suggest that QD raltegravir may provide adequate drug levels, the randomized phase III QDMRK trial (Eron, et al. Lancet Infect Dis. 2011;11:907-15) showed that 800 mg QD raltegravir failed to meet the criteria for non-inferiority when compared with 400 mg BID RAL in antiretroviral-naive HIV-infected individuals. 83% of patients in the QD arm achieved undetectable HIV viremia, in comparison with 89% in the BID arm. This was largely due to poorer efficacy among people with high baseline viral load (74 vs. 84%, respectively).