Development and significance of resistance to protease inhibitors in HIV-1-infected adults under triple-drug therapy in clinical practice

✍ Scribed by Laura Romano; Giulietta Venturi; Saverio Giomi; Luigi Pippi; Pier E. Valensin; Maurizio Zazzi

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 110 KB
• Volume: 66
• Category: Article
• ISSN: 0146-6615
• DOI: 10.1002/jmv.2123

✦ Synopsis

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. J. Med. Virol. 66:143–150, 2002. © 2002 Wiley‐Liss, Inc.