Glasgow, UK, 23 October, 2000 - Roche has announced the results of in vitro laboratory experiments showing that the Roche HIV protease inhibitor (PI) saquinavir is more potent than the new PI, lopinavir. The study, presented at the 5th International Congress on Drug Therapy in HIV Infection in Glasgow, tested the potency of the two drugs side by side in the laboratory in the presence of the key blood plasma protein alpha 1 acid glycoprotein. Both saquinavir and lopinavir were tested against a number of different HIV mutants, characteristic of viruses found in patients for whom protease therapy has failed, as well as the wild-type virus. The purpose of the experiments was to determine which drug had the higher potency against each viral strain. The results showed saquinavir to be more potent than lopinavir against wild-type HIV and also a range of drug-resistant viral strains with the exception of one virus containing both the G48V and L90M mutations.1 "This study is the first step towards making direct comparisons between two protease inhibitors in the same laboratory across a variety of conditions," said Dr. Cammack, Roche Research’s HIV Disease Area Head, Welwyn, UK. "Whilst these laboratory data are extremely encouraging, we know that other variables also have an impact on a drug’s activity in a clinical setting, therefore we now need to move closer to the real world by conducting head-to-head clinical trials in patients infected with HIV.” The results reported by the Roche
team are important as they come at a time of revolution for the HIV
protease inhibitors - the drugs that changed the face of HIV treatment.
Results from a number of studies reported over the last couple of years
show that plasma levels of the protease inhibitors can be elevated by the
addition of a small amount of ritonavir - itself a protease
inhibitor.2,3,4 "Our results fill in part of a puzzle," commented Dr. Cammack, Roche Research’s HIV Disease Area Head, Welwyn, UK. "The five years since the PIs were launched have taught us many things. Perhaps the most sobering is that the virus is unforgiving. If there is an opportunity for it to mutate and escape - then it will. We need to use the most potent drugs possible and use them at concentrations that overwhelm the virus without causing undue toxicity. The data we are seeing with saquinavir both in the laboratory, where we try to mimic the protein binding effects that the drug would meet in human plasma, and in our clinical studies where it is combined with low-doses of ritonavir, indicate that saquinavir is challenging the virus on both fronts." 1. Craig, C et al. Antiviral
efficacy and effects of protein binding on HIV proteinase (PR) inhibitors
(PI). Abstract 290. 5th International Congress on Drug Therapy in HIV
Infection, Glasgow, UK, 22-26 October 2000.
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