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Simplification from TPV/RTV 500/200 BID to TPV/RTV 500/100 BID guided by therapeutic drug monitoring

Background

Tipranavir/ritonavir (TPV/r) is a potent protease inhibitor (PI), whose most frequent grade 3/4 toxicity is ALT, AST and lipids elevations. These alterations seem to be associated to TPV exposure, being lower with TPV/r 500/100 mg BID than using TPV/r 500/200 mg BID. Therefore, the tolerance of TPV/r could be improved by reducing ritonavir dose; however, this strategy could be adequate as long as the virological response is not compromised. In this regards, therapeutic drug monitoring (TDM) of TPV could be helpful.

Methods

A prospective study was initiated in HIV antiretroviral-experienced patients with plasma HIV-RNA <50 copies/mL under a TPV/r 500/200-based regimen for longer than 24 weeks. Patients were randomized to stay on the same TPV/r dosing or to switch to TPV/r 500/100 BID. TPV plasma trough concentrations had to be above the Cmin (≥20.5 ug/mL) before recruitment in the study. Lipids and liver enzymes were recorded at baseline and at week 12 of follow-up. TPV Ctrough was measured using a validated HPLC-UV.

Summary of results

A total of 10 patients were recruited in the study, five on TPV/r 500/200 BID and five on TPV/r 500/100 BID. All were male; mean [range] age, 45 [40–54] years; CD4 count, 550 [390–646] cells/μl; AST, 36 [20–83]; ALT, 29 [16–140]; total cholesterol, 205 [179–261]; triglycerides, 134 [104–384]. While TPV Ctrough at week 12 remained significantly unchanged in patients on stable TPV/r 500/200 BID, all patients switched to TPV/r 500/100 BID experienced a drop in TPV Ctrough ranging from 9 to 30%.

Four out of five patients switched to TPV/r 500/100 showed a decline in AST, ALT and total cholesterol (drop ranging from 5 to 45%, 15 to 49%, and 2 to 22%, respectively). In contrast, triglycerides only diminished in two patients (7% and 61%, respectively). In all five patients, plasma HIV-RNA remained undetectable at week 12. However, three patients showed sub-therapeutic TPV Ctrough and accordingly treatment was modified. The other two patients have maintained undetectable viral load with similar benefit in lipids and liver enzymes over 12 months of follow-up.

Conclusion

A subset of antiretroviral-experienced patients on successful TPV/r 500/200 BID based regimens could benefit from ritonavir dose reductions, which may be associated with improvements in liver enzymes and lipids. However, due to large inter-individual differences in TPV Ctrough, this strategy should only be performed using TDM. (Table 1.)

Table 1 Table 1

Author information

Correspondence to J Morello.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Keywords

  • Total Cholesterol
  • Viral Load
  • Liver Enzyme
  • Ritonavir
  • Therapeutic Drug Monitoring