A small, nonrandomized simplification study recently evaluated the efficacy of raltegravir given once daily.
A group of 125 patients who were on a stable BID raltegravir-containing regimen with HIV RNA levels of <50 copies/mL was assigned to switch the raltegravir dosing to 800 mg QD (n = 63) or to continue raltegravir BID (n = 62), according to whether the antiretroviral (ARV) components of the subjects' individual background regimens required once- or twice-daily dosing. The two groups were adequately matched for baseline characteristics, and the median CD4 count was 536 cells/µL. All patients previously had been treated with regimens containing a protease inhibitor and had BID raltegravir substituted for a protease inhibitor before the initiation of the study.
Over a median follow-up period of 15 months, 1 patient in the once-daily raltegravir group developed virologic failure, compared with 4 patients in the twice-daily group; all 5 of these patients previously had experienced virologic failure on regimens containing nucleoside reverse transcriptase inhibitors (NRTIs). No details were given regarding the patients' previous ARV exposure or the resistance profiles of those experiencing virologic failure. Adherence rates were >90% in both groups. There were no significant differences between the groups in terms of CD4 cell counts or safety parameters.
| Clinical Bottom Line|
Given the long intranuclear half-life of raltegravir, there is great interest in exploring possibilities for once-daily dosing of this medication. This small pilot study presented few details about characteristics that may predict the success or failure of raltegravir-containing regimens (such as drug levels, patients' treatment histories, or HIV resistance test results), and further pharmacokinetic and clinical studies will be needed to evaluate the efficacy of once-daily raltegravir dosing. As in other raltegravir simplification studies, it appears that a potent ARV background is crucial to the success of a raltegravir-containing regimen, and that, regardless of the specific dosing strategy, raltegravir must be used in combination with other fully active agents (see for example, Raltegravir Substitution for Lopinavir/Ritonavir [SWITCHMRK Study] in the Spring 2009 installment of HIV Meds Quarterly). Fortunately, several studies of QD raltegravir are now under way and the results of these hopefully will be available in the coming months.
Mena A, Blanco F, Cordoba M, et al. A pilot study assessing raltegravir QD versus BID in HIV patients included in a simplification trial. In: Program and abstracts of the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2009); September 12-15, 2009; San Francisco. Abstract H-920.