BACKGROUND: Tests for resistance to HIV drugs are available for clinical use; however, their predictive value has not been fully assessed. OBJECTIVES: To determine HIV-1 genotypic predictors of a virologic response to saquinavir-ritonavir therapy in patients in whom at least one previous protease inhibitor-containing regimen had failed and to compare the predictive value of baseline genotype with that of standard clinical evaluation. DESIGN: Retrospective clinical cohort study. SETTING: University-based HIV clinic. PATIENTS: 54 HIV-1-infected adults treated with saquinavir-ritonavir who had experienced virologic failure while receiving a protease inhibitor-containing regimen for at least 3 months. MEASUREMENTS: HIV-1 reverse transcriptase and protease gene sequences, CD4 cell counts, clinical characteristics, detailed antiretroviral treatment history, and plasma HIV-1 RNA levels at baseline and at three follow-up time points (median, 4, 12, and 26 weeks). Virologic failure was defined as a plasma HIV RNA level greater than 1000 copies/mL. RESULTS: In 22 patients (41%), a plasma HIV-1 RNA level less than 500 copies/mL was achieved by week 12; in 15 patients (28%), this response was maintained through week 26. Clinical characteristics predicting a poorer response included a diagnosis of AIDS, lower CD4 cell count, and higher plasma HIV RNA level (P<0.03). Number of previous nucleoside reverse transcriptase inhibitors, previous protease inhibitor therapy, and duration of previous protease inhibitor therapy were predictors of poorer response (P<0.01). Multivariate regression models revealed that protease mutations present at the initiation of saquinavir-ritonavir therapy were the strongest predictors of virologic response. A model of clinical features explained up to 45% of the variation in virologic outcomes by week 12, whereas the explained variance was 71% when genotypic predictors were included. CONCLUSIONS: In patients in whom protease inhibitor-containing antiretroviral therapy fails, HIV-1 genotype is predictive of virologic response to subsequent therapy. This predictive capacity adds to that of standard clinical evaluation.
BACKGROUND: Tests for resistance to HIV drugs are available for clinical use; however, their predictive value has not been fully assessed. OBJECTIVES: To determine HIV-1 genotypic predictors of a virologic response to saquinavir-ritonavir therapy in patients in whom at least one previous protease inhibitor-containing regimen had failed and to compare the predictive value of baseline genotype with that of standard clinical evaluation. DESIGN: Retrospective clinical cohort study. SETTING: University-based HIV clinic. PATIENTS: 54 HIV-1-infected adults treated with saquinavir-ritonavir who had experienced virologic failure while receiving a protease inhibitor-containing regimen for at least 3 months. MEASUREMENTS: HIV-1 reverse transcriptase and protease gene sequences, CD4 cell counts, clinical characteristics, detailed antiretroviral treatment history, and plasma HIV-1 RNA levels at baseline and at three follow-up time points (median, 4, 12, and 26 weeks). Virologic failure was defined as a plasma HIV RNA level greater than 1000 copies/mL. RESULTS: In 22 patients (41%), a plasma HIV-1 RNA level less than 500 copies/mL was achieved by week 12; in 15 patients (28%), this response was maintained through week 26. Clinical characteristics predicting a poorer response included a diagnosis of AIDS, lower CD4 cell count, and higher plasma HIV RNA level (P<0.03). Number of previous nucleoside reverse transcriptase inhibitors, previous protease inhibitor therapy, and duration of previous protease inhibitor therapy were predictors of poorer response (P<0.01). Multivariate regression models revealed that protease mutations present at the initiation of saquinavir-ritonavir therapy were the strongest predictors of virologic response. A model of clinical features explained up to 45% of the variation in virologic outcomes by week 12, whereas the explained variance was 71% when genotypic predictors were included. CONCLUSIONS: In patients in whom protease inhibitor-containing antiretroviral therapy fails, HIV-1 genotype is predictive of virologic response to subsequent therapy. This predictive capacity adds to that of standard clinical evaluation.
Authors: P R Harrigan; K Hertogs; W Verbiest; R Pauwels; B Larder; S Kemp; S Bloor; B Yip; R Hogg; C Alexander; J S Montaner Journal: AIDS Date: 1999-10-01 Impact factor: 4.177
Authors: J H Condra; W A Schleif; O M Blahy; L J Gabryelski; D J Graham; J C Quintero; A Rhodes; H L Robbins; E Roth; M Shivaprakash Journal: Nature Date: 1995-04-06 Impact factor: 49.962
Authors: R T D'Aquila; V A Johnson; S L Welles; A J Japour; D R Kuritzkes; V DeGruttola; P S Reichelderfer; R W Coombs; C S Crumpacker; J O Kahn; D D Richman Journal: Ann Intern Med Date: 1995-03-15 Impact factor: 25.391
Authors: M J Kozal; K Kroodsma; M A Winters; R W Shafer; B Efron; D A Katzenstein; T C Merigan Journal: Ann Intern Med Date: 1994-08-15 Impact factor: 25.391
Authors: J M Schapiro; M A Winters; F Stewart; B Efron; J Norris; M J Kozal; T C Merigan Journal: Ann Intern Med Date: 1996-06-15 Impact factor: 25.391
Authors: A J Japour; D L Mayers; V A Johnson; D R Kuritzkes; L A Beckett; J M Arduino; J Lane; R J Black; P S Reichelderfer; R T D'Aquila Journal: Antimicrob Agents Chemother Date: 1993-05 Impact factor: 5.191
Authors: Robert M Grant; Daniel R Kuritzkes; Victoria A Johnson; John W Mellors; John L Sullivan; Ronald Swanstrom; Richard T D'Aquila; Mark Van Gorder; Mark Holodniy; Robert M Lloyd; Caroline Reid; Gillian F Morgan; Dean L Winslow Journal: J Clin Microbiol Date: 2003-04 Impact factor: 5.948
Authors: Rami Kantor; Robert W Shafer; Stephen Follansbee; Jonathan Taylor; David Shilane; Leo Hurley; Dong-Phuong Nguyen; David Katzenstein; W Jeffrey Fessel Journal: AIDS Date: 2004-07-23 Impact factor: 4.177