Bristol Myers Squibb today announced that its new protease inhibitor atazanavir (Reyataz) is now available on prescription in the United Kingdom.
Dr Margaret Johnson of the Royal Free Hospital in London said atazanavir, when boosted with ritonavir (another protease inhibitor used at a very low dose for its ability to raise drug levels), had proved just as effective as lopinavir/ritonavir in a 48 week study amongst treatment-experienced patients presented recently at the Eleventh Conference on Retroviruses and Opportunistic Infections in San Francisco. However patients treated with atazanavir experienced less diarrhoea and were less likely to experience rises in lipid levels in this trial, known as the 045 study.
Bristol Myers Squibb is keen to emphasise that its new product is convenient and well tolerated in comparison with other protease inhibitors, particularly the market leader Kaletra (lopinavir/ritonavir).
Atazanavir is the first once daily protease inhibitor to be licensed and is dosed as two capsules once daily with food together with a single ritonavir capsule (300/100mg). A European license for atazanavir unboosted by ritonavir in patients new to treatment has not yet been granted, although this formulation is already approved in the United States. Atazanavir is most likely to be used after the failure of first-line treatment that includes a non-nucleoside reverse transcriptase inhibitor, either nevirapine or efavirenz.
European medicines regulators want to see more follow-up information before they give approval for atazanavir to be dosed without ritonavir. In treatment-experienced patients they decided that atazanavir should be given with a boosting dose of ritonavir because of fears that people with a degree of resistance either to protease inhibitors or to other drugs in their regimen might be at risk of treatment failure due to the possibility of variations in blood levels of atazanavir between individuals. People with low blood levels of atazanavir would be at higher risk of treatment failure, and the European Agency for the Evaluation of Medicinal Products decided that the margin of error was too small with atazanavir for it to be used in treatment-experienced patients without boosting by ritonavir.
Whilst atazanavir seems to cause less diarrhoea than lopinavir/ritonavir, patients in the 045 comparative study reported last month were not altogether free of diarrhoea if they received atazanavir: 17% of atazanavir-treated patients reported diarrhoea, compared with 44% of the lopinavir/ritonavir-treated patients.
Atazanavir’s advantages in terms of lipids are clear-cut, however. Triglyceride levels that become elevated as HIV disease progresses tend to fall in atazanavir-treated patients when compared with people receiving other protease inhibitors, cholesterol levels do not rise, and people on atazanavir did not need lipid-lowering medication as often as people receiving lopinavir/ritonavir in the 045 study.
The chief side-effect noted with atazanavir is elevated levels of bilirubin, a waste product from the breakdown of old red blood cells. High and persistent levels of bilirubin caused by atazanavir (known as unconjugated hyperbilirubinemia) are not clinically harmful to the liver but can lead to the development of jaundice – yellowing of the skin and whites of the eyes. Although trials have shown that up to 45% of people who take atazanavir may develop elevated atazanavir levels, few people have needed to discontinue the drug as a result. Trials have typically shown that less than 1% of people who take atazanavir will decide to discontinue treatment as a result of jaundice.