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Session 64 Poster Session Therapeutic Drug Monitoring Session Time: 4:30-6:30 pm Room 4E-F

454-W. Attainment of Higher Efavirenz Plasma Levels Allow to Regain Complete Virus Suppression in Patients Carrying NNRTI Resistance D. González de Requena*, O. Gallego, C. Briones, I. Jiménez-Nácher, and V. Soriano Inst. de Salud Carlos III, Madrid, Spain Background: NNRTIs exert a potent activity against HIV-1, although the development of single mutations at critical sites within the RT gene can reduce or even annul their activity. In this regard, the genetic barrier for efavirenz (EFV) seem to be greater than for nevirapine (NVP). Response to EFV-based regimens has been linked to the attainment of plasma drug concentrations > 1 ug/ml. We have examined whether the response to EFV could be preserved in patients experiencing an early virological failure under NVP-containing regimens, and the influence of EFV plasma levels in response. Methods: 40 subjects who showed their first confirmed detectable plasma viral load (VL) > 50 HIV-RNA cop/ml after being undetectable for at least 3 months under a NVP-triple combination were selected. NVP was replaced by EFV keeping the same two-nucleoside backbone. Genotyping and plasma drug concentrations at the time of failure and the virological outcome at 3 months were examined. Results: Overall, 17/40 (43%) subjects regained undetectable VL or showed VL reductions > 1 log after replacing NVP by EFV. Mutations associated to NNRTI resistance (at least at codons 103, 181, or 190) were found at baseline in 25 of 31 subjects for whom genetic material could be amplified. As expected, most subjects (5/6) lacking NNRTI-resistant mutations reached undetectable VL with EFV. Moreover, virological response to EFV was also seen in subjects carrying NNRTI mutations but limited to those with high EFV plasma levels. Overall 33% of subjects with EFV levels >2 ug/ml showed virological response even in the presence of NNRTI mutations. Conclusions: More than 40% of subjects experiencing early virological failure with NVP can be rescued with EFV. The genotypic profile at the time of virus rebound can help to predict which patients may benefit from this intervention. Moreover, therapeutic drug monitoring of EFV plasma concentrations may permit to adapt therapy, and obtain response in one third of subjects harbouring viruses with NNRTI resistance genotypes.

©2002 9th Conference on Retroviruses and Opportunistic Infections