Improved clinical outcome in 80% patients who modified an NNRTI or PI dose following therapeutic drug monitoring (TDM)

An analysis of the use of TDM interventions and clinical benefits at the Hospital Carlos III, Madrid during a three-year period, were published by Rendón and colleagues in the September 2005 issue of HIV Medicine.

The investigators retrospectively looked at 151 requests for TDM from 137 patients from October 2000 to August 2003.

Plasma samples were drawn at routine appointments prior to a morning dose, when levels were at steady-state, but without patients knowing that drug levels were going to be measured.

Almost sixty percent (89/151) of the requests were for suspected drug-related toxicity, and apart from three requests relating to drug interactions, the remainder related to virological failure. Suspected high drug levels relating to drug toxicity were more often requested for patients using NNTRIs (68% of NNRTI requests) and suspected suboptimal levels related to virological failure was more commonly requested for PIs (61% PI requests). TDM was requested more frequently for NNRTIs than PIs (73% vs 27%).

Around one third of the tests for toxicity (32/89) showed elevated plasma levels (this was slightly higher at 40% of the NNRTI-related toxicity tests). Sixty percent of patients with liver toxicity had elevated levels and 30% had suspected efavirenz toxicity (insomnia. dizziness). Only 2/12 patients with elevated triglycerides on lopinavir/r-containing regimens showed elevated drug levels.

Around half of the patients tested for toxicity had plasma levels within the normal range and eight percent were paradoxically below the reference range.

When TDM was requested in relation to virological failure, 37% of requests (22/59) showed suboptimal levels. This included 9/12 patients using lopinavir/r, 3/8 using amprenavir, 6/14 using efavirenz and 4/20 using nevirapine. Again though, around half of the requests showed levels within the therapeutic reference range.

Of more interest are the results reported following a dose modification in 20 of the patients at this clinic (8 efavirenz and 2 nevirapine-related dose reductions; 3 efavirenz, 4 lopinavir/r and 1 nevirapine-related dose increases; and 2 regimen changes). Following these dose-modifications, outcomes improved in 80% cases, and a similar percentage of patients whose drug-plasma levels were retested (11/14) were within the therapeutic range.

Individual results presented for the patients in this study are probably more important than pooled data. Follow-up in patients reducing efavirenz from 600mg to 400mg/day, or nevirapine from 400mg to 200mg once a day maintained virological suppression <50 copies/mL (one patient showed 65 copies/mL), though follow-up in these patients ranged from 1-8 months. Longer term confirmation is clearly important and required.

Viral suppression <50 copies/mL in 4/4 patients increasing efavirenz to 800/mg/day (follow-up range 3-8 months) but in only in 1/4 patients who increase the lopinavir/r dose to 533/133mg-twice-daily (follow-up 2-5 months).

Comment

Other studies looking at clinical benefits of TDM have reported a similarly low level of active dose modification after identifying either excess or sub-optimal levels.

The high rate of reported clinical benefits where the results of TDM were implemented in patients who were followed longitudinally, indicates that this is a resource that is still under-utilised on an individual patient level.

Rendón AL, Núñez M, Soriano V et al. Clinical benefit of interventions driven by therapeutic drug monitoring. HIV Medicine (September 2005), 6, 360-365