There has been continuing interest in more effective use of the newer medications to improve efficacy and decrease toxicity in HIV patients. I went to an ART session on Monday where the main focus was on the potential use of Raltegravir in this role. The first 3 presentations focused on Raltegraivr, an integrase inhibitor which is a potent and well-tolerated ARV. The first study was the Progress study, an NNRTI sparing. Through 48 weeks, Lopinvir/ritonavir plus raltegravir was not inferior to Lopinavir/RTV plus tenofovir/FTC in ART naïve patients (85% suppression at 48 weeks) based on ITT. Both regimens were well tolerated with few study-related discontinuations (higher lipids in Raltegravir arm). The most common reason for stopping was loss to follow up, or LTFU. The study showed low resistance rates in both treatment arms and no new lop resistance, though there was more rapid suppression in nuke-sparing arm.
The next two presentations focused on simplification from a booster PI to Raltegraiver. Raltegravir is approved as BID (2x per day), but based on half life, it potentially could be used once a day (QD). The ODIS trial included patients suppressed on PI-containing regimen who were all switched and were randomized to BID to QD and followed for 6 months. They saw higher failure in QD arms and in patients with suboptimal regimen and prior nuke resistance, and in this group, failure was higher among the QD arms. Therefore, switch is not a good idea in patients with prior nuke resistance regardless of dosing. Study was prematurely stopped. These data were similar to the Switchmark-which was stopped in December 2008
The 3rd presentation looked at the same approach of simplification (SPIRAL study) with randomization of patients suppressed on boosted PIs for relatively long periods of time with endpoints of failure and other reasons for stopping at 48 weeks (itt). T405 had a history of prior exposure to suboptimal ART. See similar rates of virologic failure 4 in R arm, 6 in PI arm, and therefore non-inferiority, but with an improved lipid profile. There was a suggestion of increased risk of failure with Raltegraivir with NNRTi resistance. The speaker discussed the difference seen between this and the SWTICHMARK study. See similar performance of PI, but much better Raltegravir in SPIRAL versus SWITCHMARK; not sure why, but it may be due to longer duration of suppression required for entry into the study 924 weeks for SPIRAL. The bottom line is that for Raltegravir to work you need to have strong nuke backbone.