Methods We did a prospective, open, randomised, controlled study of HIV-1-infected patients in whom combination therapy was not successful. We randomly assigned patients standard care (control, n=43) or treatment according to the resistance mutations in protease and reverse-transcriptase genes (genotypic group, n=65). The major endpoint was the change in HIV-1 RNA viral load. Analysis was by intention to treat.
Findings 108 patients were enrolled. All patients were similar for risk factors, age, sex, previous treatment, CD4-cell count (214/μL [SD14]) and log HIV-1 RNA viral load at baseline (4·7 copies/mL [0·1]). At month 3, the mean change in HIV-1 RNA was −1·04 log (0·14) in the study group compared with −0·46 log (0·17) in the control group (mean difference 0·58 log [95 % CI 0·14–1·02], p=0·01). At month 6, changes were −1·15 (0·15) log copies/mL, and −0·67 (0·19) log copies/mL in the genotypic group and the control group, respectively (mean difference 0·48 log [0·01–0·97], p=0·05). Difference in the drop in viral load combined at 3 months and 6 months was significant (p=0·015). At month 3, HIV-1 RNA was lower than detection level (200 copies/mL) in 29 % (19/65) of patients in the genotypic group versus 14 % (6/43) in the control group (p=0·017). At month 6, the values were 32 % (21/65) and 14 % (6/43) (p=0·067) for the genotypic group and the control group, respectively. Therapy was generally well tolerated, with ten patients (six in the genotypic group, four in the control group) requiring toxic-effect-related drug modification.
Interpretation We found genotypic-resistance testing to have a significant benefit on the virological response when choosing a therapeutic alternative. Further study of the use of genotypic-resistance testing in assisting clinical decision-making is warranted.
- Ginsburg, Geoffrey S.; McCarthy, Jeanette J.,""Personalized medicine: revolutionizing drug discovery and patient care""Trends in Biotechnology2001pp. 491-496
Bibliographic PageFull Text - Merel1, Patrick; Pellegrin1, Isabelle; Garrigue, Isabele; Caumont, Anne; Schrive, Marie-Helene; Birac, Valerie; Bonot, Pascal; Fleury, Herve,""Comparison of capillary electrophoresis sequencing with the new CEQ 2000 DNA Analysis System to conventional gel based systems for HIV drug resistance analysis1""Journal of Virological Methods2001pp. 9-16
Bibliographic PageFull Text - Rey, D.; Schmitt, M.P.; Hess-Kempf, G.; Krantz, V.; Partisani, M.; Bernard-Henry, C.; Lang, J.M.,""Interruption therapeutique programmee chez des patients infectes par le VIH-1 en echec d'un traitement antiretroviral : resultats preliminaires""Pathologie Biologie2001pp. 559-566
Bibliographic PageFull Text - Garrait, V.; Molina, J.M.,""Nouvelles strategies de traitement antiretroviral chez les patients infectes par le VIH""Pathologie Biologie2001pp. 67-71
Bibliographic PageFull Text - Lerma, J. Gerardo Garcia; Heneine, Walid,""Resistance of human immunodeficiency virus type 1 to reverse transcriptase and protease inhibitors: genotypic and phenotypic testing""Journal of Clinical Virology2001pp. 197-212
Bibliographic PageFull Text - Sereni, Daniel; Lascoux, Caroline,""Recent developments in the treatment of HIV disease""European Journal of Internal Medicine2001pp. 322-326
Bibliographic PageFull Text - Koch, Nathalie; Tamalet, Catherine; Tivoli, Natacha; Fantini, Jacques; Yahi, Nouara,""Comparison of two commercial assays for the detection of insertion mutations of HIV-1 reverse transcriptase""Journal of Clinical Virology2001pp. 153-162
Bibliographic PageFull Text - Kijak, Gustavo H.; Carobene, Mauricio G.; Salomon, Horacio,""A highly prevalent polymorphism at codon 72 of HIV-1 reverse transcriptase in Argentina prevents hybridization reaction at codon 74 in the LiPA genotyping test""Journal of Virological Methods2001pp. 87-95
Bibliographic PageFull Text - Zollner, Bernhard; Feucht, Heinz-Hubert; Weitner, Lutwin; Adam, Axel; Schroter, Matthias; Schafer, Peter; Laufs, Rainer,""Application of HIV-1 genotypic-resistance testing prevents the evolution of further resistance mutations in heavily pretreated patients""Journal of Clinical Virology2001pp. 37-45
Bibliographic PageFull Text - Shi, Michael M.,""Diagnostics meets therapeutics: the impact of pharmacogenetics ""Drug Discovery Today2002pp. 1161-1162
Bibliographic PageFull Text - Versalovic, James; Lupski, James R.,""Molecular detection and genotyping of pathogens: more accurate and rapid answers""Trends in Microbiology2002pp. s15-s21
Bibliographic PageFull Text - Iga, Mutsunori; Matsuda, Zene; Okayama, Akihiko; Sugiura, Wataru; Hashida, Seiichi; Morishita, Kazuhiro; Nagai, Yoshiyuki; Tsubouchi, Hirohito,""Rapid phenotypic assay for human immunodeficiency virus type 1 protease using in vitro translation""Journal of Virological Methods2002pp. 25-37
Bibliographic PageFull Text - Loemba, Hugues; Brenner, Bluma; Parniak, Michael A.; Ma'ayan, Shlomo; Spira, Bonnie; Moisi, Daniela; Oliveira, Maureen; Detorio, Mervi; Essex, Max; Wainberg, Mark A.,""Polymorphisms of cytotoxic T-lymphocyte (CTL) and T-helper epitopes within reverse transcriptase (RT) of HIV-1 subtype C from Ethiopia and Botswana following selection of antiretroviral drug resistance""Antiviral Research2002pp. 129-142
Bibliographic PageFull Text - Ross, Jeffrey S.; Ginsburg, Geoffrey S.,""Integrating diagnostics and therapeutics: revolutionizing drug discovery and patient care""Drug Discovery Today2002pp. 859-864
Bibliographic PageFull Text - Peduzzi, C.; Pierotti, P.; Venturi, G.; Romano, L.; Mazzotta, F.; Zazzi, M.,""Performance of an in-house genotypic antiretroviral resistance assay in patients pretreated with multiple human immunodeficiency virus type 1 protease and reverse transcriptase inhibitors""Journal of Clinical Virology2002pp. 57-62
Bibliographic PageFull Text - Pillay, D.; Emery, V.C.; Mutimer, D.; Ogilvie, M.M.; Carman, W.; Mutton, K.; Wreghitt, T.; Westmoreland, D.; Breuer, J.; Zuckerman, M.,""Guidelines for laboratory monitoring of treatment of persistent virus infections""Journal of Clinical Virology2002pp. 73-92
Bibliographic PageFull Text - Sturmer, Martin; Morgenstern, Birgit; Staszewski, Schlomo; Doerr, Hans Wilhelm,""Evaluation of the LiPA HIV-1 RT assay version 1: comparison of sequence and hybridization based genotyping systems""Journal of Clinical Virology2002pp. 65-72
Bibliographic PageFull Text - Minkoff, Howard,""Human Immunodeficiency Virus Infection in Pregnancy""Obstetrics and Gynecology2003pp. 797-810
Bibliographic PageFull Text - Hachiya, Atsuko; Matsuoka-Aizawa, Saori; Tsuchiya, Kiyoto; Gatanaga, Hiroyuki; Kimura, Satoshi; Tatsumi, Masashi; Oka, Shinichi,""""All-in-One Assay"", a direct phenotypic anti-human immunodeficiency virus type 1 drug resistance assay for three-drug combination therapies that takes into consideration in vivo drug concentrations""Journal of Virological Methods2003pp. 43-53
Bibliographic PageFull Text - Mocroft, A; Ledergerber, B; Katlama, C; Kirk, O; Reiss, P; d'Arminio Monforte, A; Knysz, B; Dietrich, M; Phillips, A N; Lundgren, J D,""Decline in the AIDS and death rates in the EuroSIDA study: an observational study""The Lancet2003pp. 22-29
Bibliographic PageFull Text - Rusconi, Stefano; Moroni, Mauro,""Clinical impact of anti retroviral resistance testing: current problems and future directions""International Journal of Antimicrobial Agents2000pp. 425-427
Bibliographic PageFull Text - Rosina, M.; Micheli, V.; Besana, S.; Toia, C.; Gismondo, M.R.; Cargnel, A.,""Genotyping in HIV drug resistance mutations: epidemiology in 145 patients""International Journal of Antimicrobial Agents2000pp. 435-440
Bibliographic PageFull Text - Joly, Veronique; Yeni, Patrick,""New trends in antiretroviral therapy for HIV infection""European Journal of Internal Medicine2000pp. 301-308
Bibliographic PageFull Text
Footnotes: