Objective: To compare the long-term efficacy and tolerability of two efavirenz-containing regimens with those of an indinavir-containing regimen in the initial use of HAART.
Method: HIV-1-infected patients (N = 1266) were randomly assigned to receive one of three regimens: efavirenz, zidovudine plus lamivudine, n = 422; efavirenz plus indinavir, n = 429; or indinavir, zidovudine plus lamivudine, n = 415. Entrance criteria included baseline viral load greater than 10 000 copies/ml HIV-1 RNA, CD4 cell count 50 cells/μl or greater, and no previous use of lamivudine, any non-nucleoside reverse-transcriptase inhibitor or protease inhibitor. The primary endpoint was the proportion of patients (response rate) in each regimen with a viral load under 400 copies/ml at 168 weeks of treatment.
Results: Response rates at 168 weeks were 30% in the indinavir, zidovudine, lamivudine group, 48% in the efavirenz, zidovudine, lamivudine group (P < 0.0001, difference estimate; 97.5% confidence interval (CI) 18.5; 10.9, 26), and 40% in the efavirenz plus indinavir group (P = 0.0018, difference estimate; 97.5% CI 10.2; 2.9, 17.6). Median CD4 cell counts increased above respective baselines by 292 cells/μl (efavirenz, zidovudine, lamivudine and indinavir, zidovudine, lamivudine) and 300 cells/μl (efavirenz plus indinavir). Total discontinuations were 54% (efavirenz, zidovudine, lamivudine), 63% (efavirenz plus indinavir), and 69% (indinavir, zidovudine, lamivudine) of which 13, 12 and 26%, respectively, were caused by adverse events. No new or unexpected increases in the rates or severity of adverse events occurred from long-term treatment with efavirenz-containing regimens.
Conclusion: Long-term HIV therapy with efavirenz-containing regimens, particularly efavirenz, zidovudine, lamivudine, provides significantly greater antiviral activity and tolerability than a regimen of indinavir, zidovudine plus lamivudine.
From the aMiriam Hospital, Providence, Rhode Island, USA
bGoethe University, Frankfurt, Germany
cChelsea and Westminster Hospital, London, UK
dSunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada
eBaystate Medical Center, Springfield, Massachusetts, USA
fTower I.D. Medical Associates, Los Angeles, California, USA
gBristol-Myers Squibb Company, Princeton, New Jersey, USA
hBristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut, USA.
Received 4 August, 2007
Revised 21 August, 2007
Accepted 12 September, 2007
Correspondence to Karen Tashima, MD, Brown University, The Miriam Hospital, 164 Summit Avenue, Providence, RI 02906, USA. Tel: +1 401 793 4089; fax: +1 401 793 4323; e-mail: email@example.com