Abstract

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First report of raltegravir (RAL, MK-0518) use after virologic rebound on elvitegravir (EVT, GS 9137)

Presented by Edwin DeJesus, United States.

DeJesus E.¹, Cohen C.², Elion R.³, Ortiz R.¹, Maroldo L.⁴, Franson S.⁴, Pesano R.⁴

¹Orlando Immunology Center, Orlando, United States, ²CRI New England, Boston, United States, ³George Washington University, Washington DC, United States, ⁴Monogram Biosciences, San Francisco, United States

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.

	1			2
	CD4	VL	ARV	CD4	VL	ARV
BASELINE	204	10,700	TVD/ENF/EVT	459	840	TVD/EVT
WEEK 1	194	7,254	TVD/ENF/RAL	499	427	TVD/RAL
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.

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