HIV / AIDS

CROI 2010: ACTG 5202 Shows Abacavir/lamivudine and Tenofovir/emtricitabine Provide Similar HIV Suppression at Low Viral Loads

ACTG 5202 was a randomized Phase 3b clinical trial comparing the effectiveness of commonly used ART components. Two nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) "backbones" were tested in combination with both a non-nucleotide reverse transcriptase inhibitor (NNRTI) or a protease inhibitor.

A total of 1857 treatment-naive participants enrolled during 2005-2007 were randomly assigned to receive one of 4 combination regimens:

• Abacavir/lamivudine (the drugs in the Epzicom coformulation) + efavirenz;
• Abacavir/lamivudine + atazanavir/ritonavir;
• Tenofovir/emtricitabine (the drugs in the Truvada coformulation) + efavirenz;
• Tenofovir/emtricitabine + atazanavir/ritonavir.

Most participants (83%) were men, 40% were white, 33% were black, and 23% were Hispanic; the median age was 38 years. The mean baseline CD4 count was relatively low, at 230 cells/mm3. About 40% had high viral load (defined as >100,000 copies/mL) at study entry.

As previously reported, the study was modified in February 2008 after an independent Data and Safety Monitoring Board (DSMB) concluded based on an interim analysis that the regimens containing abacavir/lamivudine did not suppress HIV as well as tenofovir/emtricitabine in patients with high viral load. The high viral load group was therefore unblinded and offered the chance to switch therapy. Data from that group was presented at the International AIDS Conference in July 2008.

The study continued with the low viral load group. Participants were followed through September 2009, or 96 weeks after the last patient enrolled (median 138 weeks of follow-up). Eric Daar presented the final data from these participants at CROI.

Results

• At 96 weeks in the low viral load group, abacavir/lamivudine and tenofovir/emtricitabine combined with either atazanavir/ritonavir or efavirenz produced similar rates of viral suppression < 50 copies/mL:
• Abacavir/lamivudine: 83% with atazanavir/ritonavir vs 85% with efavirenz, HR for virological failure 1.13.
• Tenofovir/emtricitabine: 89% with atazanavir/ritonavir vs 90% with efavirenz, HR for virological failure 1.01.
• Atazanavir: 88% with abacavir/lamivudine vs 90% with tenofovir/emtricitabine, hazard ratio (HR) for virological failure 1.26,
• Efavirenz: 87% with abacavir/lamivudine vs 89% with tenofovir/emtricitabine, HR for virological failure 1.23.
• Looking at the other 2 drugs, rates of viral suppression were again similar:
• Atazanavir: 88% with abacavir/lamivudine vs 90% with tenofovir/emtricitabine, hazard ratio (HR) for virological failure 1.26,
• Efavirenz: 87% with abacavir/lamivudine vs 89% with tenofovir/emtricitabine, HR for virological failure 1.23.
• In the low viral load group, there was no significant difference in time to virological failure, while in the high viral load group the time to virological failure was shorter with abacavir/lamivudine than with tenofovir/emtricitabine.
• CD4 cell gains were as follows:
• Abacavir/lamivudine: 250 cells/mm3 with atazanavir/ritonavir vs 251 cells/mm3 with efavirenz.
• Tenofovir/emtricitabine: 252 with atazanavir/ritonavir vs 221 with efavirenz (a significant difference).
• Serious (grade 3-4) adverse events were reported more frequently and sooner with abacavir/lamivudine, likely related to abacavir hypersensitivity reactions (patients did not undergo HLA-B*5701 hypersensitivity screening):
• Total cholesterol, LDL (bad) cholesterol, and HDL (good) cholesterol levels were significantly higher with efavirenz than with atazanavir/ritonavir, with both NRTI backbones.
• All 3 cholesterol levels were also significantly higher with abacavir/lamivudine than with tenofovir/emtricitabine, again with both other drugs.
• Creatinine clearance (a potential indicator of kidney dysfunction) was significantly lower in patients taking tenofovir/emtricitabine with atazanavir/ritonavir (but not efavirenz).
• Among patients who experienced virological failure, there were more major drug resistance mutations with efavirenz (with either backbone) than with boosted atazanavir.

The overall number of virological failures was lower than expected, and the study did not meet its protocol endpoint of proving "equivalence." Nevertheless, Daar said that among people in the low viral load group, the regimens did not demonstrate a significant difference, and that overall -- regardless of viral load -- all studied regimens were highly successful.

A sub-study of ACTG 5202, also presented at CROI, found some significant differences between the regimens when looking at body fat and bone changes.

Los Angeles Biomed Res Inst at Harbor-UCLA, Torrance, CA; Harvard School of Public Health, Boston, MA; Univ of Miami Miller School of Med, Miami, FL; Harborview Medical Ctr, Univ of Washington, Seattle, WA; Division of AIDS, NIH, Bethesda, MD; Social & Sci Systems, Inc, Silver Spring, MD; Stanford Univ, Stanford, CA; Brigham and Women`s Hosp, Harvard Med Sch, Boston, MA.

3/2/10

Reference

E Daar, C Tierney, M Fischl, and others. ACTG 5202: Final Results of ABC/3TC or TDF/FTC with either EFV or ATV/r in Treatment-naive HIV-infected Patients. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. Abstract 59LB.

Other Source

Bristol-Myers Squibb. Bristol-Myers Squibb Media Statement on ACTG 5202. Press statement. February 17, 2010.