 |
|
|
| |
Safety, Tolerability & Efficacy of Abacavir/Lamivudine/Zidovudine
vs.
Atazanavir & Lamivudine/Zidovudine
in Antiretroviral Naive Subjects
|
| |
| |
ESS100327: ACTION Study
Reported by Jules Levin
ICAAC Sept 27-30, 2006, San Francisco
There were criticisms of this study raised at ICAAC saying that the two arms of this study were alternative regimens therefore neither therapy provided in the study was the standard of care recommended by the guidelines for first choice in starting HAART. The critics asked if study enrollees were screened to see if they could or would tolerate the HHS recommended firstline therapies before giving them two alternative therapies.
Authors; Kumar PN, Salvato P, DeJesus E, LaMarca A, Patel P, Sutherland-Phillips D, McClernon D, Florance A, Sall J, Wannamaker P, and Shaefer M for the ACTION study group
Background
Abacavir/Lamivudine/Zidovudine (ABC/3TC/ZDV, Trizivir) & Atazanavir (ATV, Reyataz) are alternative options in ARV-naive patients
ABC/3TC/ZDV should be reserved for those who cannot receive an NNRTI or PI-based regimen1
ATV without ritonavir is an alternative to the preferred PI-based regimen, Lopinavir/ritonavir
Both regimens are used in clinical practice in select patient populations as they are well-tolerated and convenient therapies.
STUDY ENDPOINTS
Primary Endpoint
Proportion of subjects with HIV-1 RNA <50 c/mL at Week 48
--Subjects must not have met any definition of virologic failure
--ITT-E, Missing/Switch = Failure Analysis
Key Secondary Endpoints
Efficacy
--Proportion of subjects with HIV-1 RNA <50 c/mL, switch ≠ failure
--Change in HIV-1 RNA and CD4 cell counts from BL
--Treatment-emergent genotype mutations
Safety
--Drug-related adverse events (Grade 2-4) and serious adverse events
Changes in lipid parameters, insulin sensitivity and resistance
VIROLOGIC FAILURE CRITERIA
Virologic failure was defined as any of the following:
- Failure to have ≥ 1 log HIV-1 RNA drop by Week 12
- Failure to have HIV-1 RNA <400 by Week 24
- Confirmed HIV-1 RNA <50 then ≥ 400 confirmed prior to Week 24
- Confirmed HIV-1 RNA ≥ 400 after Week 24
- HIV-1 RNA ≥ 400 at Week 48 without confirmation
*Virologic responders could not have met any virologic failure criteria.
AUTHOR SUMMARY
In an ITT(E) M/S=F analysis, 62% vs. 59% of subjects achieved HIV-1 RNA <50 copies/ml in the overall population (ABC/3TC/ZDV vs. ATV+3TC/ZDV, respectively)
Protocol-defined virologic failure occurred in 13% of subjects and were balanced between arms
No treatment-emergent primary PI mutations in the ATV+3TC/ZDV arm were observed through 48 weeks and the majority of NRTI mutations were attributed to M184V
AUTHOR CONCLUSION
In this study, ABC/3TC/ZDV and ATV+3TC/ZDV were well-tolerated and had comparable efficacy
In select patients naive to therapy with HIV-1 RNA <100,000 c/mL, ABC/3TC/ZDV remains a viable option as an initial regimen
Phase IV, randomized, multicenter, open-label study evaluating the safety and efficacy of ABC/3TC/ZDV vs. ATV + 3TC/ZDV in ART-naive subjects over 48 weeks
279 subjects were enrolled from 46 sites in the U.S. & Mexico between May 2004 - March 2005.
-- 95% from U.S. sites.
Subjects experiencing toxicity from randomized treatment were permitted to switch medications
-- Suspected ABC HSR reaction to 3TC/ZDV + Tenofovir
-- Atazanavir-related jaundice or scleral icterus to Fosamprenavir + 3TC/ZDV
Virologic failure was based on multiple criteria
|
| |
|
|
|
|
|
