Complex antiretroviral regimens can lead to multiple toxicities, poor adherence, and discontinuation of therapy.

As reported in the January 30, 2007 issue of AIDS, researchers with the Adult ACTG A5116 Study Team compared the efficacy and safety of switching from multi-drug regimens to 2 simplified, class-sparing combinations.

In this open-label study, 236 patients with virological suppression who were taking 3- or 4-drug protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens for at least 18 months were randomly assigned to switch to either 533/133 mg twice-daily lopinavir/ritonavir (Kaletra) plus 600 mg once-daily efavirenz (Sustiva), or else the same dose of efavirenz plus 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs).

Results

• After 2.1 years of follow up, patients receiving lopinavir/ritonavir + efavirenz discontinued treatment more often than those receiving efavirenz + NRTIs (P < 0.001).

• 21 patients developed virological failure: 14 receiving lopinavir/ritonavir + efavirenz and 7 receiving efavirenz + 2 NRTIs.

• 26 subjects discontinued therapy due to a drug-related toxicity: 20 receiving lopinavir/ritonavir + efavirenz and 6 receiving efavirenz + 2 NRTIs.

• Time to virological failure (HIV RNA > 200 copies/mL) or drug discontinuation due to toxicity was significantly shorter for patients taking lopinavir/ritonavir + efavirenz than for those one efavirenz + 2 NRTIs (P = 0.0015).

• Lopinavir/ritonavir + efavirenz was associated with a significantly higher risk of drug-related toxicity, mainly increased triglycerides (P = 0021).

• There was a trend toward a higher rate of virological failure with lopinavir/ritonavir + efavirenz in both intent-to-treat and as-treated analyses (P = 0.088 and 0.063, respectively).

Conclusion

In conclusion, the authors wrote, "Switching to efavirenz + NRTIs resulted in better outcomes, fewer drug-related toxicity discontinuations and a trend [toward] fewer virologic failures compared to switching to lopinavir/ritonavir + efavirenz."

University of Miami School of Medicine, Miami, FL; University of Washington School of Medicine, Seattle, WA; Harvard School of Public Heath, Boston, MA; University of Cincinnati College of Medicine, Cincinnati, OH; University of Rochester School of Medicine and Dentistry, Rochester, NY; University of Pennsylvania, Philadelphia, PA; Istituto Superiore di Sanita, Rome, Italy; National Institute of Allergy and Infectious Diseases, Bethesda, MD; Abbott Laboratories, Abbott Park, IL; Social and Scientific Systems, Inc., Silver Spring, MD.

02/02/07

Reference
M A Fischl, A C Collier, A L Mukherjee, and others (AACTG A5116 Study Team). Randomized open-label trial of two simplified, class-sparing regimens following a first suppressive three or four-drug regimen. AIDS 21(3): 325-333. January 30, 2007.