14th International HIV Drug Resistance Workshop


7-11 June 2005, Québec City, Canada

GENOTYPIC PROTEASE EVOLUTION IN ANTIRETROVIRAL-EXPERIENCED PATIENTS RECEIVING LOPINAVIR/R-CONTAINING REGIMENS

Antivir Ther. 10, Suppl 1:S32 (abstract no. 30)

D Costagliola1, D Descamps2, L Bocket3, C Tamalet4, M Wirden5, B Montès6, J Izopet7, P Palmer8, V Schneider9, A Ruffault10, V Ferré11, G Peytavin2, H Fleury12, F Brun-Vézinet2, B Masquelier12 and the ANRS AC11 Resistance Study Group
1INSERM U720, Paris, France 2Laboratoire de Virologie, Hôpital Bichat Claude Bernard, Paris, France 3Laboratoire de Virologie, CHU de Lille, France 4Laboratoire de Virologie, CHU La Timone, Marseille, France 5Laboratoire de Virologie, Hôpital Pitié Salpêtrière, Paris, France; 6Laboratoire de Virologie, CHU de Montpellier, France 7Laboratoire de Virologie, CHU de Toulouse, France 8Laboratoire de Virologie, Hôpital St Louis, Paris, France 9Laboratoire de Virologie, Hôpital Tenon, Paris, France 10Laboratoire de Virologie, CHU de Rennes, France 11Laboratoire de Virologie, CHU Nantes, France 12Département de Virologie et Immunologie Biologique, CHU de Bordeaux, France

OBJECTIVE: We studied the genotypic evolution of HIV-1 protease gene and the progression towards LPV resistance in protease inhibitor (PI)-experienced patients receiving tenofovir disoproxil fumarate (TDF) and lopinavir (LPV)-containing regimens.

METHODS: ARV-experienced patients were followed for 6 months on LPV-including regimens. Genotypic resistance analysis was processed from plasma sampled at baseline (M0) and at M6 in patients with plasma HIV-1 RNA >1000 copies/ml. The prevalence of LPV resistance mutations, at baseline and at M6, according to the IAS-USA list, and the evolution of the ANRS algorithm interpretation were compared using the McNemar test. The progression in the number LPV mutations included the ANRS algorithm was assessed using the Wilcoxon signed rank test.

RESULTS: Sixty-two patients with virological failure and an available genotype at M6 were included. At M0, the median plasma HIV-1 RNA was 5.14 log10 copies/ml and the median CD4 cell count 185 cells/µl. Patients had been exposed to a median number of 11 antiretroviral drugs (interquartile range (IQR):9–12) including four PI (IQR:3–5) over a period of 7 years (IQR:6.1–8.7). The median number of primary PI mutations was two (IQR:2–3) and the mean number of LPV mutations 5.8±2.5. The median change in plasma viral load at M6 was –0.2 log10 copies/ml. Only three LPV mutations were significantly more frequent at M6 than at M0: 33F (40% vs 29%, P=0.016), 63P (86% vs 76%, P=0.031) and 82A (55% vs 44%, P=0.039). At M6, the mean number of LPV mutations was increased to 6.5±2.5 (P=0.019 versus M0). At M0, 36% of viruses were classified as sensitive to LPV, 37% as possibly resistant to LPV and 27% as resistant to LPV, while at M6 the corresponding figures were 24%, 34% and 42%, evidencing the increased frequency of resistance to LPV (P=0.027).

CONCLUSION: In contrast with the very rare selection of mutations observed in naïve patients receiving a failing LPV-containing regimen, we observed a rapid increase of resistance to LPV after 6 months of a failing regimen in ARV-experienced patients, mainly explained by the increased frequency of mutations 33F, 63P and 82A.

PRESENTING AUTHOR: D Costagliola

Acrobat ReaderDownload PDF of this abstract.

2005-06-07
30

Copyright © 2005 - International Medical Press Ltd. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the International Medical Press Ltd. 2-4 Idol Lane, London EC3R 5DD UK.