Marked variability in plasma atazanavir levels: importance of ritonavir boosting and TDM

A retrospective analysis of requests for atazanavir (ATZ) therapeutic drug monitoring (TDM) was carried out by Sara Gibbons and colleagues at the University of Liverpool, who concluded that there was a marked variability in plasma ATZ concentrations in the clinical setting. The authors of this poster write that this was due to both a variety of dosing regimens and variability between patients on the same regimen. Their findings emphasise the usefulness of TD with this drug. [1]

They looked at data for 194 requests. Coadministered drugs included tenofovir in 115 cases, a second PI in 20 cases and/or an NNRTI in 24 cases. At the time of the first ATZ TDM request eight ATZ dosing regimens were identified.

Median ATZ trough concentrations in the three most frequently used regimens were 496 (range: <40-2149), 843 (89-2460) and 130 (40-925) ng/ml in the 300/100 mg, 400/100 mg, and un-boosted ATZ 400mg respectively. All regimens involved once-daily dosing. The proportions of trough concentrations that were below target of 100ng/ml were 9.8%, 2.9% and 46.2%.

There is a concern that almost 10% of patients using boosted atazanavir had suboptimal trough concentrations although this is clearly a great improvement on almost half patient with sub-optimal levels without ritonavir-boosting.

As with other boosted PIs, TDM appears to offer useful additional information to support individualised dose adjustments. Interpatient variability shows that some patients achieve higher levels will be able to safely use atazanavir with ritonavir, and are likely to have reduced side effects with this approach. For others, ritonavir is clearly essential if the combination is to produce a sustainable effect. Only TDM can differentiate between thewse two very different situations.

Gibbons S, Robinson L, Dickinson L et al. Therapeutic drug monitoring of atazanavir in routine clinical settings in the UK. 7th ICDTHI,14-18 Nov, 2004, Glasgow. Abstract P274.