Protease-Sparing Regimens: Interim Study Results

Date of Report: 03/11/2003

Abacavir + Lamivudine + Zidovudine (Trizivir) Is Found to Be Inferior to Efavirenz-Containing Regimens in Initial Therapy

The National Institute of Allergy and Infectious Diseases (NIAID) has announced interim results of AACTG A5095, a study of three protease-sparing antiretroviral regimens used in initial treatment of HIV infection. In a planned interim analysis, the NIAID Data and Safety Monitoring Board (DSMB) determined that the fixed-dose combination of abacavir + lamivudine + zidovudine (Trizivir) was inferior to two efavirenz-containing regimens in terms of virologic efficacy and durability.

AACTG A5095 is a randomized, double-blind, placebo-matched study of three regimens in antiretroviral-naive patients: abacavir + lamivudine + zidovudine, lamivudine + zidovudine + efavirenz, and abacavir + lamivudine + zidovudine + efavirenz. Primary endpoints are reduction in HIV RNA to <200 copies/mL, and safety and tolerability. The study enrolled 1,147 subjects, with a median baseline viral load of 78,800 copies/mL and CD4 count of 238 cells/mm ³ .

At an average of 32 weeks on treatment, 21% of subjects in the abacavir + lamivudine + zidovudine arm had experienced virologic failure (HIV RNA >200 copies/mL at or after week 16) as compared with 10% of those in the efavirenz-containing arms combined (p < .001). Virologic failure occurred significantly earlier in the abacavir + lamivudine + zidovudine arm than in the combined efavirenz-containing arms; this was true in subjects with baseline HIV viral load <100,000 copies/mL and in those with baseline viral load >100,000 copies/mL (p <= .001 for both groups). At week 48, 74% of subjects on abacavir + lamivudine + zidovudine had viral loads of <200 copies/mL, compared with 89% of those in the combined efavirenz groups. No CD4 cell count results have been reported. There were no significant toxicity concerns in any of the treatment arms.

Based on these data, the DSMB recommended discontinuation of the abacavir + lamivudine + zidovudine study arm. Participants on this triple-nucleoside combination have been advised to change therapy. Participants receiving efavirenz-containing regimens will continue without change. All participants will be followed to the scheduled completion of the study.

Additional information about this study and the interim analysis are available on the NIAID Division of AIDS Web site at: http://www.niaid.nih.gov/daids/pdf/aactg_a5095.pdf .