[HIV genotypic mutation selectively induced by the protease inhibitor nelfinavir at codon 30. Case series and consequences for antiretroviral management].
In a survey of 247 HIV-infected patients which received at least six months of combined antiretroviral therapy including the protease inhibitor nelfinavir during the last two years (2000-2001), the specific primary genotypic mutation D30N (with or without the minor mutation N88D), was detected in only four of the 149 (2.7%) subjects who received genotypization after virological failure. Three of these cases of primary nelfinavir resistance occurred among the 84 patients who were protease inhibitor- and/or non-nucleoside reverse transcriptase inhibitor-na ve, while the last episode was registered in a female patient treated since five years, who received an indinavir-based therapy of nearly 12-month duration (interrupted because of untoward kidney effects). During the subsequent follow-up, the substitution of nelfinavir had a favourable laboratory and clinical outcome in all reported patients who continued a different highly active anti-HIV treatment, while a significantly less positive virological and immunological response was seen in all the remaining subjects, and especially in those who experienced virological failure after undergoing at least two prior changes of combined antiretroviral therapy, and were borne by a broad spectrum of protease gene mutations (save those regarding codons 30 and 88). Due to its exclusive resistance pattern, nelfinavir may represent a favorable first-line choice among protease inhibitor-based regimens, since it may spare further treatment options even in the same pharmacological class. In fact, cross-resistance with other protease inhibitors may be limited also in patients experiencing prior long-term antiretroviral therapy, from second-line to rescue regimens, provided that they were pre-treated with drugs other than nelfinavir.
Manfredi
Roberto
R
Dipartimento di Medicina Clinica Specialistica e Sperimentale, Sezione di Malattie Infettive, Università degli Studi "Alma Mater Studiorum", Azienda Ospedaliera di Bologna, Policlinico S. Orsola-Malpighi, Bologna, Italy.
Calza
Leonardo
L
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D003062:Codon / Q000235:genetics*; D024921:Drug Resistance, Multiple, Viral / Q000187:drug effects / Q000235:genetics; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D019469:Indinavir / Q000494:pharmacology / Q000627:therapeutic use; D007558:Italy; D008297:Male; D009154:Mutation / Q000187:drug effects*; D019888:Nelfinavir / Q000494:pharmacology* / Q000627:therapeutic use; D012367:RNA, Viral / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D016879:Salvage Therapy
D019380:Anti-HIV Agents; D003062:Codon; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019469:Indinavir; D016333:HIV Protease; D019888:Nelfinavir
Mutazione genotipica del virus HIV indotta selettivamente dall'inibitore delle proteasi nelfinavir a livello del codon 30. Casistica personale e riflessi sulla condotta terapeutica antiretrovirale.