Once-daily
Boosted Fosamprenavir or Atazanavir in Treatment-naive Patients: The ALERT Study
Fosamprenavir
(Lexiva) and atazanavir
(Reyataz) are protease inhibitors that are FDA-approved for use in both treatment-naive
and treatment-experienced patients. However, combinations of ritonavir-boosted
fosamprenavir or atazanavir plus tenofovir/emtricitabine (Viread/Emtriva,
also available in the fixed-dose combination pill Truvada)
have not been well studied in as first-line therapy.
Data
from the ALERT trial, looking at such regimens
in treatment-naive patients, were presented at the recent 46th ICAAC in San Francisco.
ALERT is an
open-label, prospective study evaluating the efficacy and safety of 1400/100 mg
fosamprenavir/ritonavir or 300/100 mg atazanavir/ritonavir, both with tenofovir/emtricitabine
(300 mg/200 mg), administered once daily to patients with baseline HIV viral loads
greater than 1000 copies/mL.
The
study includes 106 participants (53 in each arm), most of whom were men (79%-89%).
The median baseline viral load was 4.9 log copies/mL, the median CD4 count was
161-188 cells/mm3, median cholesterol was about 160 mg/dL, and median triglyceride
level was about 120 mg/dL.
Results
A total of 7
patients discontinued the study by Week 24, 4 in the fosamprenavir arm and 3 in
the atazanavir arm
Reasons for discontinuation were: adverse events (1 in each arm), protocol violation
(1 in the fosamprenavir arm), virological failure (1 in the fosamprenavir arm),
and loss to follow-up (1 in the fosamprenavir arm, 2 in the atazanavir arm).
Protocol-defined
virological failure was observed in 2 patients in the fosamprenavir arm and 1
in the atazanavir arm.
1 patient with virological failure in the fosamprenavir arm exhibited baseline
resistance.
At Week 24, in an intent-to-treat/missing = failure analysis, 79% of patients
in the fosamprenavir arm (42 out of 53) achieved viral loads below 50 copies/mL,
compared with 83% (44 out of 53) in the atazanavir group.
For viral loads below 400 copies/mL, the corresponding rates were 89% (47 out
of 53) vs 89% (47 out of 53).
In an intent-to-treat observed analysis, 84% (42 out of 50) vs 88% (44 out of
50), respectively, had viral loads below 50 copies/mL; 94% (47 out of 50) in both
arms had viral loads below 400 copies/mL.
The median increase in CD4 cell count from baseline was 110 cells/mm3 in the fosamprenavir
arm and 134 cells/mm3 in the atazanavir arm.
Median cholesterol levels at Week 24 were 178 mg/dL (+11% from baseline) in the
fosamprenavir arm vs 182 mg/dL (+6%) in the atazanavir arm.
Median triglyceride levels were 165 mg/dL (+20%) vs 135 mg/dL (+10%), respectively.
Renal adverse
events occurred in 2% vs 9% of patients in the 2 arms, respectively.
Severe or Grade 3-4 adverse events occurred in 13% vs 49%, respectively.
These differences
were driven by hyperbilirubinemia in the atazanavir arm.
Conclusion
The
researchers concluded, "Both arms demonstrated a high rate of virologic suppression
through 24 wks. Lipid changes were similar."
Rush
Univ Med Ctr, Chicago, IL; Kaiser Permanente, Atlanta, GA; Orlando Immunology
Ctr, Orlando, FL; Univ Miami, Miami, FL; GlaxoSmithKline, Research Triangle Park,
NC.
A total of 7
patients discontinued the study by Week 24, 4 in the fosamprenavir arm and 3 in
the atazanavir arm