Importance of protease inhibitor plasma levels in patients treated with genotypic-guided therapy

A report published in the July issue of AIDS showed greater decline in viral load in subjects with optimal PI plasma concentrations (OC) compared to those with sub-optimal concentrations (SOC).

81 trial participants on failing therapy (defined as viral load over 10,000 copies/ml and at least 6 months of treatment with nucleosides and 3 months with protease inhibitors) in this PK sub-study were randomised to receive either standard (control group) or genotypic-guided therapy. Serial plasma levels were taken throughout the twelve-month study period. SOC was defined as at least two plasma levels below 2xIC95. Subjects fell into four categories: G1 (SOC/control); G2 (OC/control); G3 (SOC/genotype) and G4 (OC/genotype).

It was revealed that 67.9% of patients had OC and 32.1% SOC and this correlated significantly with reductions in HIV-1 RNA which fell by 1.4 log and O.36 log respectively by week 48.

There were also significant differences in the group treated with genotypic-guided therapy. At month 6 the mean changes in HIV-RNA from baseline were: G1 – 0.23+/0.29 log 10 copies/ml; G2 – 0.97+/-2.8; G3 – 0.68+/-0.37; G4 – 1.38+/0.20. In multivariate analyses optimal PI concentration, use of genotyping and presence of PI resistance were all implicated in viral load response.

The investigators concluded that other causes besides PI resistance contributed to therapeutic failure, and that ‘Sub-optimal concentrations of PI limit the response to antiretroviral therapy. Therapeutic drug monitoring of the PI plasma concentration may therefore prove useful in optimising antiretroviral therapy.’

Comment

Ritonavir boosted PI is now the rapidly developing standard of care to ensure adequate PK and dosing schedules/requirements that can be lived with. However, regular therapeutic drug monitoring should ensure those on single PI’s are maintaining adequate blood levels.

Importance of protease inhibitor plasma levels in HIV-infected patients treated with genotypic-guide therapy: pharmacological data from the Viradapt study. Durant et al AIDS 2000 July 7; 14 (10): 1333-9