Objectives: 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.
From the Division of Antiviral Products, Center for New Drug Evaluation, Food and Drug Administration, Silver Spring, Maryland, USA.
Received 6 September, 2005
Revised 20 October, 2005
Accepted 19 January, 2006
Correspondence to Lisa K. Naeger, PhD, FDA/CDER/OND/DAVP, 10903 New Hampshire Avenue, Building #22, Room 6367, Silver Spring, MD 20993, USA. E-mail: firstname.lastname@example.org
These views represent the authors' opinion and not necessarily the views of the Food and Drug Administration.