Effect of baseline protease genotype and phenotype on HIV response to atazanavir/ritonavir in treatment-experienced patients.
OBJECTIVE
To assess the virologic response rates of atazanavir/ritonavir and lopinavir/ritonavir based on baseline genotype and phenotype.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Naeger
Lisa K
LK
Division of Antiviral Products, Center for New Drug Evaluation, Food and Drug Administration, Silver Spring, Maryland 20993, USA. lisa.naeger@fda.hhs.gov
Struble
Kimberly A
KA
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate; D017277:Drug Approval / Q000379:methods; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009842:Oligopeptides / Q000627:therapeutic use; D010641:Phenotype; D011725:Pyridines / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D016333:HIV Protease; D019438:Ritonavir