Darunavir looking promising as companion for agents in new HIV drug classes

Further data from the POWER 1 & 2 studies of darunavir (Prezista) / ritonavir show that almost half of patients who received the new protease inhibitor with an optimised background regimen were able to maintain a viral load below 50 copies/ml after 48 weeks, despite extensive experience of treatment failure with other regimens.

The findings, electronically published in The Lancet today, have already been presented at several scientific conferences and covered in the following news reports:

• After 48 weeks of study, and 24 weeks in the real world, darunavir continues to show staying power
• Darunavir response did not differ by prior PI in POWER studies
• Darunavir/ritonavir superior virologically and immunologically to comparator drugs over one year.

Many highly treatment-experienced patients may have difficulty in assembling a background regimen of active drugs when a new class of HIV drug is introduced. Within the next year it is likely that drugs from two new classes - integrase inhibitors and chemokine antagonists - will be licensed in Europe and the United States.

Darunavir, which was designed to bind more tightly to the HIV protease `pocket` than other drugs in its class, is thought to have a much higher resistance barrier than other protease inhibitors, and so may be active in the face of high-level resistance to other drugs in its class.

This makes it an important potential partner for drugs in new classes, such as the imminent integrase and chemokine inhibitors, but also other classes in the pipeline such as maturation inhibitors.

Recent data presented at the European HIV Drug Resistance workshop in Cascais, Portugal, showed that among 91,932 isolates with reduced susceptibility to at least one protease inhibitor submitted to Virco for virtual phenotyping, only 7% were judged to be resistant to darunavir. Furthermore a Spanish cohort study of 1021 patients with PI failure showed that the risk of cross-resistance to darunavir was highest after the failure of tipranavir/ritonavir or fosamprenavir/ritonavir.

These findings suggest that highly treatment-experienced patients still stand to benefit from darunavir, especially when it is combined with a new drug class.

In the POWER 1 & 2 studies individuals who had no prior exposure to the fusion inhibitor enfuvirtide (Fuzeon), and who included the drug in their optimised background regimen, were significantly more likely to experience a viral load reduction of at least 1 log₁₀ by week 48 (n=36, 81% vs 23%, p

Subgroup analysis of the BENCHMRK study of the new integrase inhibitor raltegravir, reported in February at the Fourteenth Conference on Retroviruses and Opportunistic Infections in Los Angeles, showed that 90% of patients who received raltegravir with darunavir or enfuvirtide achieved a viral load below 400 copies/ml after 16 weeks, compared with 74% who received neither darunavir or enfuvirtide (T-20).

Longer-term follow-up from the BENCHMRK study will be reported at scientific conferences later this year.

Results of a subgroup analysis of the MOTIVATE 1 & 2 trials of maraviroc in treatment-experienced patients looking at the effects of combining the experimental chemokine antagonist with darunavir are still awaited.