Resistance
Profile After Treatment with Atazanavir-containing Regimens The
I50L substitution has been shown in previous studies to maintain or increase the
susceptibility of HIV-1 to other protease
inhibitors (PIs). At the time of virological
failure, 150L was observed in treatment-naive patients who developed resistance
on atazanavir (Reyataz)-containing
regimens. In
past studies, the evolution of primary PI resistance mutations was not observed
among treatment-naive patients receiving ritonavir-boosted
atazanavir. Resistance evolved through alternate pathways in treatment-experienced
patients. The
IMPACT study (BMS AI424-128) was conducted to expand upon these prior clinical
trial observations. IMPACT is a cross-sectional, observational study of patients
experiencing virological failure while on atazanavir-containing regimens. Virological
failure was defined as confirmed HIV RNA by PCR of at least 1000 copies/mL after
either: (1) viral load >/= 1000 copies/mL after achieving a confirmed viral
load below 400 copies/mL, or (2) viral load >/= 1000 copies/mL after 24 or
more weeks of atazanavir therapy. Data
were presented at the XVI International AIDS Conference
from a planned interim analysis that included patients enrolled from September
2004 through October 2005 at 230 U.S. centers. Results
•
Among 128 patients
enrolled, most had advanced disease:
- The median duration of HIV infection
was 13.1 years;
- The median CD4 cell count was 187 cells/mm3;
- 55% had
CDC stage C HIV disease.
•
The median duration
of atazanavir exposure was 16 months.
•
Overall, 12 patients
(9.4%) had the I50L substitution.
•
116 of 128 patients
(91%) were PI-experienced, including all 12 with the I50L mutation.
•
Among 12 patients
with virological failure on initial PI therapy with unboosted atazanavir or atazanavir/ritonavir,
no primary PI mutations developed, including I50L.
•
I50L prevalence was
3 of 24 patients (12.5%) taking unboosted atazanavir and 9 of 104 patients (8.7%)
taking atazanavir/ritonavir, regardless of prior treatment experience.
•
Ritonavir-boosted
PI use prior to atazanavir use was associated with a lower prevalence of the I50L
substitution (P = 0.033).
Conclusion The
authors concluded, "In this cohort, primary PI mutations, including I50L,
were not seen at virological failure in patients on initial PI-based therapy with
atazanavir/ritonavir. The prevalence of I50L in PI-experienced patients experiencing
virological failure on an atazanavir-containing regimen was 10%. Use of [a ritonavir-boosted
PI] prior to atazanavir/ritonavir appeared to reduce the prevalence of I50L." Stanford
University, Stanford Positive Care Clinic, Palo Alto, CA; Kaiser Permanente, Department
of Internal Medicine, Los Angeles, CA; Infectious Disease Solutions, Atlanta,
GA; Bristol-Myers Squibb Company, Virology Medical Affairs, Plainsboro, NJ. 09/08/06 Reference
A
Zolopa, W Towner, C Zurawski, and others. Resistance profile after treatment with
an atazanavir-containing regimen: first interim analysis results from the IMPACT
study (BMS AI424-128). XVI International AIDS Conference. Toronto, August 13-18,
2006. Abstract THPE0099.
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