July 14, 2003
The ACTG 5095 trial (for coverage of that trial, click here), a large, randomized, placebo-controlled trial, compared co-formulated abacavir (ABC, Ziagen) + AZT (zidovudine, Retrovir) + 3TC (lamivudine, Epivir) tablet (Trizivir) with efavirenz (EFV, Sustiva) plus co-formulated AZT + 3TC tablet (Combivir) with efavirenz plus Trizivir, and found that the efavirenz-containing arms were significantly superior to the Trizivir arm with regards to virologic success.
Another study presented at the conference, a retrospective analysis of patients treated at Parkland Hospital in Dallas, Texas, affirmed the validity of these data and indicated that they are applicable in the "real world" of clinical treatment of HIV patients.
In the Parkland study, the Parkland HIV database was queried for antiretroviral-naive patients treated with either abacavir + AZT + 3TC (herein referred to as Trizivir [TRZ] even though not all patients were on the co-formulated tablet) or efavirenz + AZT + 3TC (herein referred to as EFV).
According to the authors, the database includes prescription data, demographics, CD4 cell counts and HIV viral loads. The primary endpoint of the study was the time to virologic failure, defined as two consecutive viral loads more than 400 copies/mL as determined by Kaplan-Meier analysis. Additional analyses included time to failure in patients who successfully achieved a viral load less than 400 copies/mL and effects of baseline viral load on time to failure.
The database query identified 479 patients -- 250 on EFV and 229 on TRZ. There were no differences between the EFV and TRZ patients regarding baseline demographics, CD4 count or viral load.
Similar to the findings in ACTG 5095, this analysis revealed that compared to patients who received EFV, the TRZ-treated patients had a shorter time to virologic failure (EFV = 1,220 days, TRZ = 441 days, P<0.001). This shorter time to virologic failure in the TRZ-treated patients occurred regardless of whether the patients had a baseline viral load more than 100,000 copies/mL (EFV = 802 days, TRZ =148 days, P=0.001) or less than 100,000 copies/mL (EFV = 1,056 days, TRZ = 729 days, P=0.009).
Further, and again similar to the findings in ACTG 5095, the TRZ-treated patients failed more rapidly even if they had previously achieved a viral load less than 400 copies/mL (EFV = 1,526 days, TRZ = 942 days, P=0.02). The Cox proportional hazards model found a better time to treatment failure with EFV than with TRZ (odds ratio=0.42, P<0.001).
The authors conclude from these data that "efavirenz had better time to virologic failure than Trizivir. The result was not dependent on baseline viral load stratification or on initial response to therapy. This data suggest that [EFV] is superior to [TRZ] in antiretroviral-naive patients."
These findings are virtually the same as the findings of ACTG 5095, and should be considered as reinforcing the conclusion that Trizivir is not as effective as efavirenz-based HAART and should not be routinely used, regardless of the patient's baseline viral load or their temporarily achieving a viral load less than 400, less than 200 or less than 50 copies/mL on TRZ therapy.
|Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.|