title: Development and significance of resistance to protease inhibitors in HIV-1-infected adults under triple-drug therapy in clinical practice.
abstract: Development of drug resistance is considered a major cause for failure of antiretroviral therapy in human immunodeficiency virus type 1 (HIV-1)-infected patients adherent to treatment. However, the rate of emergence and the significance of HIV-1 drug resistance in clinical practice have been not investigated thoroughly. Selection of HIV-1 variants that are genotypically resistant to protease inhibitors was studied in all the patients (n = 169) who completed at least 18 months of treatment with a protease inhibitor plus two nucleoside reverse transcriptase inhibitors at two urban Italian hospitals. HIV-1 carrying primary protease inhibitor resistance mutations was detected in 70 (41.4%) patients. The estimated proportion of patients developing genotypic resistance to protease inhibitors at 12 and 24 months was 18.3% (95% CI, 12.5-24.2%) and 33.9% (95% CI, 26.4-41.5%), respectively. Independent predictors of development of resistance to protease inhibitors were higher HIV-1 RNA levels at the nadir (P < 0.0001) and inclusion of ritonavir or saquinavir versus indinavir in the starting regimen (P = 0.0313). Resistance to protease inhibitors was strongly associated with a lower response to treatment, as shown by HIV-1 RNA load (P = 0.0001) and CD4 cell counts (P = 0.005). However, a linear increase in CD4 cell counts was maintained up to the end of follow-up even in the protease inhibitor-resistant population. Resistance to protease inhibitors develops in a relevant proportion of patients under long-term triple-drug therapy in clinical practice and is associated with virological treatment failure and limitation of CD4 cell increase.
authors.affiliation: Sezione di Microbiologia, Dipartimento di Biologia Molecolare, Università di Siena, Siena, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Romano
authors.forename: Giulietta
authors.initials: G
authors.lastname: Venturi
authors.forename: Saverio
authors.initials: S
authors.lastname: Giomi
authors.forename: Luigi
authors.initials: L
authors.lastname: Pippi
authors.forename: Pier E
authors.initials: PE
authors.lastname: Valensin
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zazzi
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D016333:HIV Protease