The triple combination of tenofovir DF (Viread), emtricitabine (Emtriva), and efavirenz (Sustiva) - the three drugs in the recently approved Atripla fixed-dose combination pill - is among the most widely used regimens for first-line antiretroviral therapy.

Atripla Tablets

Data to support approval of this regimen came from Gilead Study 934, which compared 2 dual nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) "backbones": tenofovir plus emtricitabine vs AZT plus 3TC (Combivir). Gilead Sciences manufactures tenofovir, emtricitabine, and the Truvada tenofovir/emtricitabine fixed-dose combination pill, and produces Atripla in partnership with Bristol-Myers Squibb. AZT, 3TC, and Combivir are manufactured by GlaxoSmithKline.

Study 934 is a multicenter, open-label Phase III trial that enrolled 517 HIV positive, treatment-naive patients in the United States and Europe. Participants were randomly assigned to receive either 300 mg tenofovir plus 200 mg emtricitabine once daily, or AZT/3TC (300/150 mg) twice daily. All subjects also received 600 mg efavirenz once daily.

As previously reported, tenofovir/emtricitabine/efavirenz demonstrated superior outcomes compared with AZT/3TC/efavirenz at 48 weeks, largely because more patients discontinued the latter regimen due to toxicity. Longer-term (96 week) data from the ongoing study were published in the December 15, 2006 Journal of Acquired Immune Deficiency Syndromes.

Results

• Through Week 96, significantly more patients receiving tenofovir/emtricitabine/efavirenz achieved and maintained HIV RNA levels below 400 copies/mL compared with those taking AZT/3TC/efavirenz (75% vs 62%; P = 0.004).

• There was a trend toward greater virological suppression below 50 copies/mL in the tenofovir/emtricitabine/efavirenz group, but the difference did not reach statistical significance (67% vs 61%; P = 0.16).

• Fewer patients in the tenofovir/emtricitabine/efavirenz arm experienced virological rebound (1% vs 5%).

• Subjects in the tenofovir/emtricitabine/efavirenz arm experienced a significantly greater increase in CD4 cell count (270 vs 237 cells/mm3; P = 0.036).

• Significantly more patients in the AZT/3TC/efavirenz group discontinued study drugs due to adverse events (11% vs 5%), largely driven by AZT-related anemia (6% vs 0%).

• No patients developed the K65R NRTI-resistance mutation.

• At Week 96, limb fat (measured by DEXA) was significantly greater in the tenofovir/emtricitabine/efavirenz arm compared with the AZT/3TC/efavirenz group (7.7 vs 5.5 kg; P < 0.001).

Conclusion

The authors concluded that, "Over 96 weeks, the combination of tenofovir, emtricitabine, and efavirenz was superior to fixed-dose [AZT/3TC] plus efavirenz for achieving and maintaining an HIV RNA level < 400 copies/mL and an increase in CD4 cells."

Study 934 will continue through 144 weeks.

Chelsea and Westminster Hospital, London, UK; Johns Hopkins University School of Medicine, Baltimore, MD; Orlando Immunology Center, Orlando, FL; Hospital de La Paz, Madrid, Spain; University of Miami, Miami, FL; Gilead Sciences, Foster City, CA.

1/09/07

Reference
A L Pozniak, J E Gallant, E DeJesus, and others. Tenofovir Disoproxil Fumarate, Emtricitabine, and Efavirenz Versus Fixed-Dose Zidovudine/Lamivudine and Efavirenz in Antiretroviral-Naive Patients: Virologic, Immunologic, and Morphologic Changes-A 96-Week Analysis. Journal of Acquired Immune Deficiency Syndromes 43(5): 535-540. December 15, 2006.