By Liz Highleyman

Two recent studies looked at the prevalence of resistance to the recently approved protease inhibitor (PI) darunavir (Prezista). Within this class of drugs, HIV mutations that confer resistance to one drug may also render other protease inhibitors less effective.

Study 1

As reported in the October 2007 Journal of Antimicrobial Chemotherapy, Spanish researchers examined all clinical specimens from HIV-infected patients on failing PI-based regimens who were referred for drug resistance testing between 1999 and 2007, looking for known darunavir-specific resistance mutations recently published by the International AIDS Society-USA.

Results

·         A total of 1021 HIV genotypes from patients failing treatment with the PIs lopinavir/ritonavir (Kaletra; 39.2%), nelfinavir (Viracept; 28.1%), saquinavir (Invirase; 14.5%), indinavir (Crixivan; 13.7%), atazanavir (Reyataz; 6.6%), fosamprenavir (Lexiva; 5.3%), and tipranavir (Aptivus; 1.1%) were identified.

·         The prevalence of major darunavir resistance mutations were:

o        I50V: 2.1%

o        I54M: 1.3%

o        L76V: 2.7%

o        I84V: 14.5%.

·         For minor darunavir resistance mutations, the rates were:

o        V11I: 3.3%

o        V32I: 3.9%

o        L33F: 11%

o        I47V: 2.1%

o        I54L: 2.3%

o        G73S: 12.8%

o        L89V: 2.4%.

·         Overall, 6.7% (n = 68) of the genotypes had 3 or more darunavir resistance mutations, which corresponded to a mean total number of PI resistance mutations of 12.3.

·         In a multivariate analysis, prior fosamprenavir failure, prior saquinavir failure, the total number of PI resistance mutations and the number of prior PIs used were all independently associated with having more darunavir resistance mutations.

“The prevalence of darunavir resistance mutations is low in patients failing other PI-based regimens, although prior failure to amprenavir and saquinavir might produce more cross-resistance to darunavir,” the authors concluded. “Thus, darunavir may be a good option for patients who have failed other PI-based regimens.”

Study 2

References

E Poveda, C de Mendoza, L Martin-Carbonero, and others. Prevalence of darunavir resistance mutations in HIV-1-infected patients failing other protease inhibitors. J Antimicrob Chemother 60(4):885-888. October 2007.

Y Mitsuya, TF Liu, S-Y Rhee, and others. Prevalence of Darunavir Resistance-Associated Mutations: Patterns of Occurrence and Association with Past Treatment. Journal of Infectious Diseases 196 (8): 1177–1179. October 15, 2007.