|
|
|
|
| Abstract |
|
|
|
|
Session 21
Symposium Controversies in Antiretroviral Therapy Session Time: Tuesday, 7 - 9 pm Room 4B |
Background: The goal is always to improve clinical outcome. We need to do this since a significant proportion of patients on HAART never achieve optimal viral suppression or may experience viral rebound within a short space of time. One approach to optimise therapy is therapeutic drug monitoring (TDM). This strategy can be applied to patient care if there is a well- defined relationship between the exposure to a drug and its efficacy or toxicity (PK-PD), a large inter-individual variability in drug exposure, and a relatively narrow therapeutic window. PIs and NNRTIs are candidates for TDM. Optimally we need to relate drug levels to virus phenotype (actual or virtual) and generate inhibitory quotients (IQs or virtual IQs or normalised IQs). However, a minimalist approach is to have a trough plasma concentration (Ctrough) above a critical value, which is based on a protein-corrected IC50 or EC50 of WT virus. Furthermore, the minimalist approach is to consider dose reduction in the face of drug-related toxicity. The ATHENA study has clearly shown that TDM of IDV and NFV in treatment-naïve patients improved outcome after 12 months’ follow-up. For IDV the difference was mainly driven by a lower rate of discontinuation for toxicity in the TDM group. For NFV, the difference was mainly due to a lower rate of discontinuation because of virological failure. Data from this study therefore give encouragement that TDM is a realistic approach. But again there is the need to stress that TDM in isolation from knowledge of resistance is only half a story. So the question then becomes, Can we use IQ to improve patient care? In one sense, IQ is still a research tool and there are numerous confounders in calculating the final number. However, the evidence of presentations at this meeting is that IQ (or vIQ or nIQ) is more predictive of virologic response than either resistance testing or drug exposure alone at least for some drugs. Conclusions: Numerous arguments against TDM have been put forward (i.e. low plasma levels simply reflect adherence problems; effect of protein binding not adequately understood; what is the in vivo therapeutic index of each drug; logistics—yet another test!; expert interpretation, etc.). But if, as the U.K. experience shows, patients benefit from a relatively straightforward, cheap test, then we should at least be open to consider implementation. |
|
©2002 9th Conference on Retroviruses and Opportunistic Infections |
