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Session 121 Poster Abstracts
Impact of Drug Resistance on Virologic Response and Clinical Outcomes
Friday, 1:30 - 3:30 pm
Hall A


710    
Successful Rescue Therapy in Patients Developing K65R on Tenofovir Containing Regimens: Long-term Follow-up
Roland Landman*1, D Descamps2, A Trylesinski3, A Benalycherif1, P Girard4, P Yeni2, M Bentata5, C Michelet6, P de Truchis7, B Bonnet8, C Katlama9, G Peytavin2, N Margot10, M Miller10, and F Brun Vezinet2
1Hosp Bichat-Claude Bernard, Paris, France; 2Hosp Bichat-Claude Bernard, Paris, France; 3Gilead Sci, Foster City, CA, USA; 4Hosp St-Antoine, Paris, France; 5Hosp Avicenne, Bobigny, France; 6Hosp Pontchaillou, Rennes, France; 7Hosp Raymond Poincaré, Garches, France; 8Hopital Hotel Dieu, Nantes, France; 9Hosp Pitie-Salpetriere, Paris, France; and 10Gilead Sci, Foster City, CA, USA

Background:  Few data are available regarding future treatment options in patients who developed the K65R mutation in HIV-1 RT. Despite good adherence, high rates of K65R have been observed in once-daily triple nucleoside regimens like tenofovir (TDF), abacavir (ABC), and lamivudine (3TC). In contrast, development of K65R was infrequent in the regimen containing TDF, 3TC and EFV. In either case, success of rescue therapy after potential development of K65R needs to be assessed.

Methods:  From the Tonus trial (TDF+3TC+ABC), 22 patients who developed K65R (n = 14) and from the GS 903 trial (TDF+3TC+EFV) (n = 8) were followed after a rescue second line regimen. Treatment and virologic outcome were evaluated.

Results:  At baseline before treatment modification, 14 patients developed K65R+M184V, 5 patients K65R+M184V+K103N, and 3 patients K65R+K103N. Median viral load and CD4 cell count were 6336 copies/mL (80 to 229,511) and 268 cells/mm3 (15 to 453), respectively, prior to new therapy. For nucleoside transcriptase inhibitors (NRTI) in the second line regimens, TDF and 3TC were not changed in 5 and 9 patients, respectively. Zidovudine (ZDV) and didanosine (ddI) were used in 14 and 11 patients, respectively. For third drug modification, a protease inhibitors (PI) was used in 16 patients (10 of 16 LPV/r) and non-NRTI (NNRTI) in 6 patients previously treated with TDF+3TC+ABC. Virologic outcome after rescue therapy:  19 of 22 patients have viral load < 50 copies/mL after a median follow-up of 48 weeks (14 to 177). One patient on ZDV/ddI/NFV responded with > 2 log10 viral load reduction to 423 copies/mL but was then lost to follow-up at week 68, 1 patient on ZDV/3TC/APV/r was considered non adherent with viral load of 1905 copies/mL and subsequent development of M184V, and 1 patient was lost to follow-up prior to new therapy. Interestingly, 2 patients remained on their previous failing triple nucleoside regimen and only added EFV and became undetectable despite failure viral load of 14,000 and 93,000 copies/mL.

Conclusions:  In this study, development of the K65R mutation had no negative effect on long-term rescue therapy with a variety of regimens even if viral load was high before regimen change. Phenotypic analyses and replication capacity of K65R mutant HIV should be further explored to understand the low impact of this mutation on future treatment options.

Keywords: K65R; Second treatment following virologic failure; Tenofovir