Janssen-Cilag has launched Prezista (darunavir), licensed for use in combination with low-dose ritonavir, together with other antiretroviral agents, to treat HIV-1 infection in highly pre-treated patients who have failed more than one regimen containing a protease inhibitor

PHARMACOLOGY
Darunavir is a new HIV-1 protease inhibitor that has shown antiviral activity against wild-type and multidrug-resistant HIV-1 strains in vitro, including many viruses resistant to existing protease inhibitors.

CLINICAL STUDIES
Two randomised studies, POWER 1 and 2, evaluated the safety and efficacy of darunavir in combination with low-dose ritonavir in treatment-experienced HIV-1 infected patients. Treatment-experienced patients were randomised to optimised background regimens (comprising at least two nucleoside reverse transcriptase inhibitors with optional enfuvirtide) and one of four doses of darunavir (with ritonavir) or other control protease inhibitors.¹

After 24 weeks of dose-finding phases and primary efficacy analyses, the darunavir treatment groups demonstrated significantly greater viral suppression compared to the control group receiving other protease inhibitors. Of the four treatment groups, the darunavir 600mg/ritonavir 100mg twice daily dose regimen provided the best overall antiretroviral effect. This was selected as the treatment dose for the ongoing phases of POWER 1 and 2 and for the open-label, single-arm POWER 3 study.

A combined analysis of all the POWER studies² assessed the long-term safety and efficacy of darunavir 600mg/ritonavir 100mg twice daily compared to other protease inhibitors at 48 weeks. Response was measured by percentages of patients achieving >1 log10 reduction in viral load and those reaching undetectable viral load levels (<50 copies/ml). In the pooled analysis of POWER 1 and 2, 62 per cent of the darunavir/ritonavir group achieved >1 log10 reduction in viral load compared to 16 per cent of the control protease inhibitor group.

In addition, 45 per cent of the darunavir/ritonavir group achieved undetectable viral load compared to 11 per cent of the control group. These significant effects on virological response were comparable in the POWER 3 results where 61 per cent of the patients achieved >1 log10 reduction in viral load and 45 per cent reached undetectable viral load.

In all three POWER studies, over 90 per cent of the darunavir/ritonavir treatment group who reached undetectable viral load at week 24 sustained this response through week 48. Seventy-three per cent  of patients in the darunavir/ritonavir treatment group who achieved >1 log10 reduction in viral load, but did not achieve undetectable viral load at week 24, maintained or improved this response at week 48 in the POWER 1 and 2 studies. This figure was 82 per cent in the POWER 3 study.

The majority of adverse effects in the darunavir/ritonavir group were mild to moderate in severity and mostly lower than or similar to those in the control group when corrected for treatment exposure.

1. Katlama C, Carvalho M, Cooper D et al. Presented at the 3rd IAS conference on HIV pathogenesis and treatment; Rio de Janeiro, Brazil: July 24-27, 2005. Abstract WeOaLB0.102.
2. Ruane P, Gallant J, Tennenbeg A et al. Safety and efficacy of darunavir in combination with low dose ritonavir: 48 week results from the POWER studies. Presented at the Frontiers in Drug Development for Antiretroviral Therapies, 10-14 December 2006, Cancun, Mexico.

Further information: Janssen-Cilag 01494 567444