Effect of baseline protease genotype and phenotype on HIV response to atazanavir/ritonavir in treatment-experienced patients

• Published in: AIDS (London) Vol. 20; no. 6; pp. 847 - 853
• Main Authors: Naeger, Lisa K, Struble, Kimberly A
• Format: Journal Article
• Language: English
• Published: England 04.04.2006
• Subjects: Adult; AIDS/HIV; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Drug Approval - methods; Drug Resistance, Viral - genetics; Female; Genotype; HIV Infections - drug therapy; HIV Infections - virology; HIV Protease - genetics; HIV Protease Inhibitors - therapeutic use; HIV-1 - drug effects; HIV-1 - genetics; Human immunodeficiency virus; Humans; Male; Middle Aged; Mutation; Oligopeptides - therapeutic use; Phenotype; Pyridines - therapeutic use; Ritonavir - therapeutic use; Treatment Outcome; Viral Load
• ISSN: 0269-9370
• DOI: 10.1097/01.aids.0000218548.77457.76

To assess the virologic response rates of atazanavir/ritonavir and lopinavir/ritonavir based on baseline genotype and phenotype. Resistance analyses were performed on a Bristol-Myers Squibb-sponsored study comparing the safety and efficacy of atazanavir/ritonavir to lopinavir/ritonavir in treatment-experienced subjects at 48 weeks. Analyses evaluated virologic response based on the presence of baseline primary protease inhibitor mutations and baseline susceptibility. Less than 30% of atazanavir/ritonavir-treated patients were responders if substitutions at positions M46, G73, I84 or L90 were present in their HIV at baseline. In comparison, lopinavir/ritonavir response rates were less than 30% when protease substitutions at M46, I54, or I84 were present at baseline. The response rates were similar between atazanavir/ritonavir and lopinavir/ritonavir-treated subjects with zero to four baseline protease inhibitor mutations, but response rates were reduced if five or more baseline mutations were present: 0% for atazanavir/ritonavir compared with 28% for lopinavir/ritonavir. Baseline phenotype results showed that response rates were similar between atazanavir/ritonavir and lopinavir/ritonavir if shifts in susceptibility were zero to five, but response rates were lower if shifts were greater than five; 11% for atazanavir/ritonavir compared with 27% for lopinavir/ritonavir. Both type and number of baseline protease inhibitor mutations affected virologic response to atazanavir/ritonavir and lopinavir/ritonavir in treatment-experienced subjects. In addition, baseline phenotypic susceptibility could differentiate virologic response rates to the two drugs. These resistance analyses provide information on the likelihood of a virologic response to antiretroviral drugs based on baseline genotypic and phenotypic data, which is valuable to physicians and patients when choosing antiretroviral regimens.