F2/1 - IMPACT OF NON NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIS) PLASMA CONCENTRATIONS ON VIROLOGICAL RESPONSE TO ANTIRETROVIRAL THERAPY IN HIV-1 INFECTED NNRTIS NAÏVE-PATIENTS (PTS) ENROLLED IN ANRS 088 TRIAL

9^TH EUROPEAN AIDS CONFERENCE (EACS)
1^st EACS RESISTANCE & PHARMACOLOGY WORKSHOP

October 25 - 29, 2003 Warsaw, Poland

4.2 Pharmacological Monitoring in Clinical Practice

F2/1 - IMPACT OF NON NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIS) PLASMA CONCENTRATIONS ON VIROLOGICAL RESPONSE TO ANTIRETROVIRAL THERAPY IN HIV-1 INFECTED NNRTIS NAÏVE-PATIENTS (PTS) ENROLLED IN ANRS 088 TRIAL

* Peytavin G.¹, Meynard J.L.², Lamotte C.¹, Vray M.³, Matheron S.¹, Morand-Joubert L.², Girard P.M.², Brun-Vézinet F.¹, Costagliola D.³, for the Narval Trial Group

(1) Hôpital Bichat Claude Bernard,² Hôpital Saint-Antoine,³ INSERM E 0214, Paris, France

Background: Although NNRTIs have proven highly efficacy in treatment of Pts with previous PI-containing regimen failure, the importance of TDM of these drugs in this setting has yet to be demonstrated.

Objective: To evaluate pharmacological parameters that could explain the strong virological impact of EFV in NNRTI-naïve Pts, contrasting with the low impact of NVP, as found in the multivariate analysis of the predictors of virological success (VS) at W12.

Methods: Among the 541 Pts, 42% and 24%, received EFV or NVP as part of their new regimen. Most of them were NNRTIs-naïve: 186 and 120 Pts received EFV and NVP. Virological success was defined as viral load (VL) <200 cps/mL at W12. At W2,W6 and W12, EFV and NVP Plasma concentrations (Cpl) were considered adequate if >1,100 and 4,000ng/mL, respectively. Statistical analysis was performed using Chi-square tests.

Results: 56% and 28% of Pts treated with EFV and NVP had VL <200 cps/mL at W12, respectively. Median (range;n) EFV and NVP Cpl were: 2,400ng/mL (10-14,300;288) and 4,500ng/mL (50-29,000;166). Adequate EFV and NVP Cpl were found in 90% and 54% of Pts, respectively (p<0.0001). This result could explain why EFV prescription to NNRTI-naïve Pts was associated with VS in multivariate analysis (OR=4.37; 95% IC 2.76-6.90), while NVP did not (OR=1.065; 95% IC 0.59-1.89).

Conclusion: In heavily pretreated but NNRTI-naïve Pts treated with NNRTI containing regimen, adequate EFV Cpl were predictive of VS. Surprisingly, NVP Cpl were subtherapeutic in half of Pts, suggesting the usefulness of TDM.

Presenting Author: Dr Gilles PEYTAVIN, Pharmacy Department Bichat-Cl.Bernard Hospital, 46 rue Henri Huchard, 75018, Paris, France, Phone: +33140258005

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