First report of raltegravir (RAL, MK-0518) use after virologic rebound on elvitegravir (EVT, GS 9137)
Objectives: Data are limited about the clinical implications of resistance patterns and the possibility of sequencing integrase inhibitors (INI). We describe the clinical responses from 2 patients treated sequentially with INI.
Methods: After IRB approval and informed consent, 2 patients with virologic failure on elvitegravir were switched to raltegravir 400mg BID x7 days with the same background regimen (BR). At day-8, the regimen was re-optimized (OBR). Activity and safety labs, Phenosense-GT and samples for integrase sequence (IS) were collected at baseline(BL) and follow-up.
Results: Results are described for both patients 1 and 2; BL = transition from EVT to RAL, WK1 = RAL + BR, WK2 = RAL + OBR, WK4-24 = follow-up.
|WEEK 2|| ||1,039||TVD/ENF/RAL/DRV|| ||189||TVD/RAL/DRV|
|WEEK 4|| ||808|| ||457||<50|| |
|WEEK 8||203||2,137|| ||639||<50|| |
|WEEK 12||247||2,893|| ||592||<50|| |
|WEEK 24||DISCONTINUED|| ||<50|| |
IS at BL and WK1 for patient 1 showed similar patterns including K7R, S17N, V31I, V72I, T124N, T125A, I151V, V201I, V234L, A265A/V, and other mutations suspected to be associated with resistance to one or both INI: E138E/K, G140G/C, S147S/G and Q148R. IS for patient 2 was nonamplifiable. Regimens were well tolerated; no grade >1 adverse events reported. Further enrollment was halted given the lack of significant virologic activity observed.
Conclusions: These data support the possibility that at least some cross-resistance occurs between elvitegravir and raltegravir. Data with drug levels were not available to assess the possibility of a negative drug-drug interaction.
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention
"DeJesusE., et al.
First report of raltegravir (RAL, MK-0518) use after virologic rebound on elvitegravir (EVT, GS 9137).
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention: