Antiretroviral-experienced HIV-positive patients taking lopinavir / ritonavir (Kaletra) at the same time as the nucleotide analogue tenofovir (Viread) may require increased doses of Kaletra to achieve adequate drug exposure, according to a poster presented today at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy in Washington, DC.
Although previous studies have shown that tenofovir only has a small effect on the blood levels of Kaletra, the present study was restricted to treatment-experienced HIV-positive patients, and found significant reductions in blood drug concentrations of lopinavir. The mechanism by which tenofovir may reduce lopinavir levels is not understood.
The investigators recruited 18 Caucasian patients for their pharmacokinetic study, with a mean age of 34 and weight of 70kg. Eleven of the participants were male.
They measured the levels of lopinavir and ritonavir in the blood during the ‘steady state’, and compared them with and without co-administration of tenofovir.
The minimum concentration (Cmin) of lopinavir was reduced by 34% when tenofovir was given (mean 4.61 vs. 3.06µg/ml, p = 0.04). Similarly, ritonavir’s Cmin was reduced by 44% (0.63 vs. 0.35µg/ml, p = 0.014).
In contrast, the maximum concentrations (Cmax) of both drugs were not affected by tenofovir (lopinavir: 10.7 vs. 9.7µg/ml, p = 0.27; ritonavir: 1.02 vs. 0.72µg/ml, p = 0.20).
The authors argue that the dose of Kaletra may have to be altered in antiretroviral-experienced patients also taking tenofovir. They concluded by suggesting that therapeutic drug monitoring may help to choose the appropriate dose adaptation for individual patients and highlighted a protocol for assessing whether dose adjustment of lopinavir might be needed:
- Lopinavir level greater than 4μg/ml: plasma Cmin predictive of treatment success, no dose adjustment necessary.
- Lopinavir level between 2.5 and 4μg/ml: measure intracellular lopinavir concentration; if not possible, and virological response is poor, increase Kaletra dose to 533/133mg.
- Lopinavir level below 2.5μg/ml: increase Kaletra dose to 533/133mg.
Breilh D et al. Pharmacokinetic drug interaction of lopinavir/ritonavir in combination with tenofovir in experienced HIV+ patients. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, abstract A-445, 2004.