title: Variability in the interpretation of transmitted genotypic HIV-1 drug resistance and prediction of virological outcomes of the initial HAART by distinct systems.
abstract: High level HIV-1 drug resistance in recently infected treatment-naive individuals correlates with sub-optimal virological responses to highly active antiretroviral therapy (HAART). To determine whether genotypic HIV-1 drug resistance in chronic naive patients, as interpreted by various systems, could predict the virological outcomes of HAART, isolates from patients enrolled in a prospective observational cohort (ICoNA) prior to treatment start were genotyped. Genotypic susceptibility scores (GSS) assigned to the initial HAART regimens using the interpretations of pre-therapy resistance mutations by 13 systems were related to virological outcomes. Of 415 patients, 42 (10%) had at least one major resistance mutation. According to the different interpretations, 1.9-20.5% of patients had some level of resistance to at least one drug in the initial regimen. In multivariable analysis, GSS from two systems significantly predicted the time to virological success: Rega 5.5, for each unit increase in GSS adjusted relative hazard (RH) 1.86 [95% confidence intervals (95% CI): 1.15-3.02] and hivresistanceWeb v3, RH 1.87 (95% CI: 1.00-3.48). With three other systems, GSS showed a trend towards a significant prediction of success: Retrogram 1.6, RH 2.33 (95% CI: 0.98-5.53), Menéndez 2002, RH 2.36 (95% CI: 0.97-5.72) and Stanford hivdb, RH 2.06 (95% CI: 0.94-4.49). Genotypic resistance testing coupled with adequate interpretation in chronic naive patients can usefully identify those at risk of sub-optimal virological response to HAART. This work was presented in part at the First European Workshop on HIV Drug Resistance. Luxembourg, 4-6 March 2003 (Abstract 44); and at the 9th European Conference on CIinical AIDS Therapy. Warsaw, 25-28 October 2003 (Abstract F6/7).
authors.affiliation: Institute of Clinical Infectious Diseases, Catholic University, Rome, Italy. andrea.deluca@rm.unicatt.it
authors.forename: Andrea
authors.initials: A
authors.lastname: De Luca
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.forename: Carlo-Federico
authors.initials: CF
authors.lastname: Perno
authors.forename: Claudia
authors.initials: C
authors.lastname: Balotta
authors.forename: Simona
authors.initials: S
authors.lastname: Di Giambenedetto
authors.forename: Antonio
authors.initials: A
authors.lastname: Poggio
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pagano
authors.forename: Giulia
authors.initials: G
authors.lastname: Tositti
authors.forename: Rita
authors.initials: R
authors.lastname: Piscopo
authors.forename: Antonio
authors.initials: A
authors.lastname: Del Forno
authors.forename: Francesco
authors.initials: F
authors.lastname: Chiodo
authors.forename: Giacomo
authors.initials: G
authors.lastname: Magnani
authors.forename: Antonella
authors.initials: A
authors.lastname: d'Arminio Monforte
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood
chemical_list: D012367:RNA, Viral; D054303:HIV Reverse Transcriptase; D016333:HIV Protease