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Abstract
Sustained virological response despite K65R along with other resistance mutations in heavily pre-treated patients – a Radata subanalysis
C. Hoffmann1, T. Lorenzen2, A. Mutz3, T. Seidel4, D. Berzow5, B. Buchholz6, B. Kreft7, S. Staszewski8, C. Zamani9, B. Zinngrebe10, K. Graefe1, A. Stoehr1, A. Plettenberg1, for the Radata Study Group
Background: The K65R mutation represents a preferred pathway to tenofovir resistance and confers decreased sensitivity to all nucleoside reverse transcriptase inhibitors (NRTIs) except ZDV. Data on outcome of heavily pre-treated patients (pts) harbouring K65R are limited.
Methods: We screened all pts included in the Radata program for the presence of K65R. Radata offers free internet-based support for physicians planning an optimized antiretroviral therapy (ART), based on resistance analysis (RA), drug monitoring and expert advice (EA). Outcome of pts is evaluated prospectively every three months.
Results: Of 669 pts included, in 20 (3.0 %) K65R were found. Pts were heavily pre-treated (median number of prior ART-regimens 4.5, median time on ART 55 months). All had received NRTIs (3TC 100 %, ZDV 90 %, D4T 74 %, ABC 68 %, TDF 65 %, DDI 53 %) and NNRTIs (NVP 65 %, EFV 60 %) while 85 % had also received protease inhibitors. Among pts with K65R, most frequent RT mutations were K103N (75 %) and M184V (60 %). All pts had evidence for NNRTI resistance and at least one thymidine analogue mutation (TAM) was found in 35 %. ART was changed in 17/20 pts. Of pts being eligible for analysis, 8/14 (57 %) achieved a viral load of < 50 copies/ml at month 12. Except for 1 patient (who received T-20), none of these 8 pts displayed evidence for any TAM. Whereas 2/8 had the Q151M mutation, 7/8 had RA with virus mutants left sensitive for at least one PI.
Conclusions: The K65R mutation remains rare in this large cohort of heavily pre-treated patients. Despite evidence of K65R coincidental with multiple resistance mutations, sustained virological response was possible in most cases. This was particularly true in the absence of TAMs and in pts switching to a PI-based ART containing a thymidine analogue.
AIDS 2006 - XVI International AIDS Conference
Abstract no.
THPE0042
Suggested Citation
"C.Hoffmann, et al.
Sustained virological response despite K65R along with other resistance mutations in heavily pre-treated patients – a Radata subanalysis.
:
AIDS 2006 - XVI International AIDS Conference:
Abstract no.
THPE0042"
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