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Abstract
EVOLUTION OF HIV-1 RESISTANCE MUTATIONS TO NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTI) FOLLOWING WITHDRAWAL
JOLY V, DESCAMPS D, ZENG F, TOUATI F, MENTRE F, YENI P, BRUN-VEZINET F
Objective : To study the evolution of NNRTI resistance mutations after withdrawal of this class of drugs, in patients (Pts) who experienced virological failure when receiving a NNRTI containing antiretroviral combination therapy.
Methods : Genotypic resistance was determined by sequencing the reverse transcriptase genome (ABI 377, PE Applied Biosystems) from plasma samples stored during follow-up in an observational cohort of 27 NNRTI-treated patients, who subsequently switched to salvage therapy without NNRTIs. The median time of follow-up after NNRTI withdrawal was 6 months (M6). Additionally, genotypic resistance data were available 12 months after NNRTI withdrawal (M12) in 20 out of the 27 studied patients.
Results : At baseline, just before NNRTI treatment was stopped, the median viral load was 5.13 log/ml and the median CD4 cell count was 143 cells/mm3. The median time of exposure to NNRTI was 7.0 months. 16 Pts had received nevirapine, 10 Pts delavirdine and 5 Pts efavirenz (preceded by nevirapine in 3 Pts and followed by nevirapine in 1 Pt). At baseline, 81% of Pts had > 2 AZT mutations and all Pts had NNRTI resistance mutations. The number of NNRTI mutations (mean +/- SD) decreased from 2.0 +/- 1.0 at baseline to 1.4 +/- 1.1 at M6 (p = 0.042) and to 1.1 +/- 1.1 at M12 (p = 0.31 between M6 and M12). K103N and Y181C/I were found in 59% and 63% of Pts at baseline, respectively. The percentage of Pts with at least one major resistance mutation conferring large cross-resistance to NNRTIs decreased from 100% at baseline to 78% (21/27 Pts) at M6 and 70% (14/20 Pts) at M12, p = 0.005. K103N persisted in 10/27 Pts (37%) at M6 and in 6/20 Pts (30%) at M12, p = 0.11. Y181C/I persisted in14/27 Pts (52%) at M6 and 9/20 Pts (45%) at M12, p = 0.31.
Conclusion : NNRTI resistance mutations may persist after NNRTI interruption, with 82% and 70% of Pts maintaining viruses with high level of resistance to this class 6 and 12 months after NNRTI withdrawal, respectively.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
123
Suggested Citation
"JOLYV, et al.
EVOLUTION OF HIV-1 RESISTANCE MUTATIONS TO NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTI) FOLLOWING WITHDRAWAL.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
123"
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