| Autor: |
Zolopa, Andrew R., Shafer, Robert W., Zolopa, A R, Shafer, R W, Warford, A, Montoya, J G, Hsu, P, Katzenstein, D, Merigan, T C, Efron, B |
| Předmět: |
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| Zdroj: |
Annals of Internal Medicine; 12/07/99, Vol. 131 Issue 11, p813-821, 9p, 3 Charts, 2 Graphs |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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