Marcelin AG, Cohen-Codar I, King M, Guillevic E, Lamotte C, Chauvin JP, Kempf D, Peytavin G, Calvez V; IAS Conference on HIV Pathogenesis and Treatment (2nd : 2003 : Paris, France).
Antivir Ther. 2003; 8 (Suppl.1): abstract no. 827.
Pitie-Salpetriere Hospital, Paris, France
OBJECTIVE: To combine virological and pharmacological parameters to predict the virological response to LPV/r. METHODS: For 116 protease inhibitor (PI)-experienced patients enrolled in an observational cohort of LPV/r, baseline genotype, LPV drug levels at months 1, 4, 5 and 6, and viral load (VL) data through 3 to 6 months were available. Response was defined as the change in VL from baseline to month 6 (value closest to month 6 used). Linear regression was used to assess the effects of baseline genotype (number of mutations from positions 10, 20, 24, 33, 36, 47, 48, 54, 82, 84 in protease), pharmacokinetics (median Cmin level), and genotypic inhibitory quotient (GIQ, Cmin divided by number of mutations). Two analyses were conducted: all patients, and patients with at least three mutations. RESULTS: Mean baseline VL was 4.9 log10 copies/ml, mean number of prior PIs was 3.2 and mean number of PI mutations was 2.9. Overall decrease in VL to month 6 was -1.55 log10 copies/ml. Among all 116 patients, number of mutations was significantly positively correlated with VL change from baseline through month 6 (P<0.001, lower number = larger VL decreases). Cmin (P=0.53) and GIQ (P=0.26) were not statistically significant. Among patients with three or more mutations (n=67), however, mutation number was no longer statistically significant (P=0.25), while Cmin had a marginally significant negative correlation with VL change (P=0.06) and GIQ was significantly negatively correlated (P=0.025, larger GIQ values and higher Cmin = larger VL decreases). CONCLUSIONS: Trough drug levels and GIQ were useful predictors of virologic response to LPV/r in patients with substantial PI resistance. In patients with few pre-existing mutations, response to LPV/r was independent of drug levels and GIQ.
Publication Types:
Keywords:
- Genotype
- Humans
- Linear Models
- Mutation
- Viral Load
- genetics
- pharmacology
- virology
Other ID:
UI: 102263106
From Meeting Abstracts