S Lambert-Niclot1, E C George2, A Pozniak3, E White2, C Schwimmer4, H Jessen5, M Johnson6, D Dunn2, C F Perno7, B Clotet8, A Plettenberg9, A Blaxhult10, L Palmisano11, L Wittkop12, V Calvez13, A G Marcelin13, F Raffi14. 1. Sorbonne Universités, UPMC Univ Paris 06, Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, UMR_S 1136, AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, Paris, F-75013, France sidonie.lambert@psl.aphp.fr. 2. MRC Clinical Trials Unit at UCL, London, UK. 3. Chelsea and Westminster Hospital, London, UK. 4. INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France. 5. Gemeinschaftspraxis Jessen-Stein, Berlin, Germany. 6. Department of HIV Medicine, Royal Free Hospital, London, UK. 7. Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy. 8. HIV Unit and Retrovirology Laboratory 'Irsicaixa' Foundation, Hospital Universitari Germans Trias i Pujol, UAB, Badalona, Catalonia, Spain. 9. Ifi-institut, an der Asklepios-Klinik St Georg, Hamburg, Germany. 10. Department of Infectious Diseases, Venhaelsan-Sodersjukhuset, Stockholm, Sweden. 11. Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy. 12. INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France CHU de Bordeaux, Pôle de Santé Publique, Service d'Information Médicale, Bordeaux, France Université de Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France. 13. Sorbonne Universités, UPMC Univ Paris 06, Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, UMR_S 1136, AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, Paris, F-75013, France. 14. CMIT, 46 Rue Henri Huchard, 75018 Paris, France.
Abstract
OBJECTIVES: To describe the pattern of drug resistance at virological failure in the NEAT001/ANRS143 trial (first-line treatment with ritonavir-boosted darunavir plus either tenofovir/emtricitabine or raltegravir). METHODS: Genotypic testing was performed at baseline for reverse transcriptase (RT) and protease genes and for RT, protease and integrase (IN) genes for patients with a confirmed viral load (VL) >50 copies/mL or any single VL >500 copies/mL during or after week 32. RESULTS: A resistance test was obtained for 110/805 (13.7%) randomized participants qualifying for resistance analysis (61/401 of participants in the raltegravir arm and 49/404 of participants in the tenofovir/emtricitabine arm). No resistance-associated mutation (RAM) was observed in the tenofovir/emtricitabine plus darunavir/ritonavir arm, and all further analyses were limited to the raltegravir plus darunavir arm. In this group, 15/55 (27.3%) participants had viruses with IN RAMs (12 N155H alone, 1 N155H + Q148R, 1 F121Y and 1 Y143C), 2/53 (3.8%) with nucleotide analogue RT inhibitor RAMs (K65R, M41L) and 1/57 (1.8%) with primary protease RAM (L76V). The frequency of IN mutations at failure was significantly associated with baseline VL: 7.1% for a VL of <100,000 copies/mL, 25.0% for a VL of ≥100,000 copies/mL and <500,000 copies/mL and 53.8% for a VL of ≥500,000 copies/mL (PTREND = 0.007). Of note, 4/15 participants with IN RAM had a VL < 200 copies/mL at time of testing. CONCLUSIONS: In the NEAT001/ANRS143 trial, there was no RAM at virological failure in the standard tenofovir/emtricitabine plus darunavir/ritonavir regimen, contrasting with a rate of 29.5% (mostly IN mutations) in the raltegravir plus darunavir/ritonavir NRTI-sparing regimen. The cumulative risk of IN RAM after 96 weeks of follow-up in participants initiating ART with raltegravir plus darunavir/ritonavir was 3.9%.
OBJECTIVES: To describe the pattern of drug resistance at virological failure in the NEAT001/ANRS143 trial (first-line treatment with ritonavir-boosted darunavir plus either tenofovir/emtricitabine or raltegravir). METHODS: Genotypic testing was performed at baseline for reverse transcriptase (RT) and protease genes and for RT, protease and integrase (IN) genes for patients with a confirmed viral load (VL) >50 copies/mL or any single VL >500 copies/mL during or after week 32. RESULTS: A resistance test was obtained for 110/805 (13.7%) randomized participants qualifying for resistance analysis (61/401 of participants in the raltegravir arm and 49/404 of participants in the tenofovir/emtricitabine arm). No resistance-associated mutation (RAM) was observed in the tenofovir/emtricitabine plus darunavir/ritonavir arm, and all further analyses were limited to the raltegravir plus darunavir arm. In this group, 15/55 (27.3%) participants had viruses with IN RAMs (12 N155H alone, 1 N155H + Q148R, 1 F121Y and 1 Y143C), 2/53 (3.8%) with nucleotide analogue RT inhibitor RAMs (K65R, M41L) and 1/57 (1.8%) with primary protease RAM (L76V). The frequency of IN mutations at failure was significantly associated with baseline VL: 7.1% for a VL of <100,000 copies/mL, 25.0% for a VL of ≥100,000 copies/mL and <500,000 copies/mL and 53.8% for a VL of ≥500,000 copies/mL (PTREND = 0.007). Of note, 4/15 participants with IN RAM had a VL < 200 copies/mL at time of testing. CONCLUSIONS: In the NEAT001/ANRS143 trial, there was no RAM at virological failure in the standard tenofovir/emtricitabine plus darunavir/ritonavir regimen, contrasting with a rate of 29.5% (mostly IN mutations) in the raltegravir plus darunavir/ritonavir NRTI-sparing regimen. The cumulative risk of IN RAM after 96 weeks of follow-up in participants initiating ART with raltegravir plus darunavir/ritonavir was 3.9%.
Authors: Rohan Gurjar; Laura Dickinson; Daniel Carr; Wolfgang Stöhr; Stefano Bonora; Andrew Owen; Antonio D'Avolio; Adam Cursley; Nathalie De Castro; Gerd Fätkenheuer; Linos Vandekerckhove; Giovanni Di Perri; Anton Pozniak; Christine Schwimmer; François Raffi; Marta Boffito Journal: Pharmacogenomics J Date: 2022-10-20 Impact factor: 3.245
Authors: Michael S Saag; Constance A Benson; Rajesh T Gandhi; Jennifer F Hoy; Raphael J Landovitz; Michael J Mugavero; Paul E Sax; Davey M Smith; Melanie A Thompson; Susan P Buchbinder; Carlos Del Rio; Joseph J Eron; Gerd Fätkenheuer; Huldrych F Günthard; Jean-Michel Molina; Donna M Jacobsen; Paul A Volberding Journal: JAMA Date: 2018-07-24 Impact factor: 56.272
Authors: Olivier Ségéral; Eric Nerrienet; Sansothy Neth; Bruno Spire; Vohith Khol; Laurent Ferradini; Saramony Sarun; Chandara Mom; Sopheak Ngin; Charlotte Charpentier; Pagnaroat Men; Marion Mora; Vun Mean Chhi; Penhsun Ly; Vonthanak Saphonn Journal: Front Public Health Date: 2018-03-19