Tenofovir + Efavirenz vs Tenofovir + Efavirenz + 3TC: The COOL Trial

There is increasing evidence that HIV positive patients are more adherent to therapy and therefore experience improved clinical outcomes when using simplified treatment regimens.

As presented at the 46th ICAAC last week in San Francisco, French researchers conducted a 48-week randomized open-label trial to assess the efficacy of a 2-drug maintenance regimen consisting of tenofovir (Viread) plus efavirenz (Sustiva/Stocrin), compared with a 3-drug regimen of tenofovir/efavirenz plus 3TC (Epivir).

The study included 143 patients on HAART with HIV viral loads below 50 copies/mL for longer than 6 months and no history of virological failure. Patients were monitored through Week 48 for CD4 cell count, viral load, clinical adverse events, and biochemical parameters. Treatment success was defined as maintaining a viral load below 50 copies/mL with no drug modification, and non-inferiority was defined as a 14% difference between the arms. Body fat distribution was assessed by CT scans and DEXA.

At baseline, the median age was 40 years (range 21-73), the median CD4 count was 473 cells/mm3 (range 78-1775), and 35% had CDC Class C HIV disease. Patients had been on HAART for a median duration of 3.7 years (range 0.5-7.7). Most used 2 NRTIs plus 1 NNRTI (43%) or PI (45%); AZT/3TC was the most common NRTI backbone, used by 71%.

Results

At Week 48, in an intent-to-treat (ITT) analysis, the treatment success rate in the 3-drug arm was 97.2%, compared with 81.7% in the 2-drug arm (delta 15.5%).

In an as-treated analysis, the respective success rates were 100% vs 90% (delta 10%).

At Week 48, 4 patients in the 2-drug arm showed evidence of NNRTI-associated resistance mutations, with viral load above 50 copies/mL in 3 patients.

The overall population ITT analysis showed a CD4 cell increase of 24 cells/mm3 (P = 0.007).

There were no changes in glomerular filtration rate or phosphatemia (markers of potential kidney dysfunction).

4 subjects in the 2-drug arm and none in the 3-drug arm discontinued drugs due to adverse events.

In the as-treated population, the Week 48 median change from baseline was -0.3 mmol/L for triglycerides (P < 0.001), -0.3 for total cholesterol (P < 0.001), and -0.02 for LDL cholesterol (P = 0.149).

There were no significant differences in lipids or fat distribution between the 2 arms.

Conclusion

Based on these results, the authors concluded that the 2-drug arm was inferior to the 3-drug arm. They added that, "Virological control was maintained with lipid parameter improvement" when switching from [twice-daily] HAART to [once-daily] tenofovir- based HAART.

Hop. St Antoine, Paris, France; Hop. Quitman, Fort de France, France; Hop. Pontchaillou, Rennes, France; Hop. Caen, Caen, France; Hop. Pitie Salpetriere, Paris, France; Hop. St Andre, Bordeaux, France; INSERM U593, Bordeaux, France; Gilead, Paris, France.

10/06/06

Reference
P M Girard, A Cabie, C Michelet, and others. Tenofovir DF + Efavirenz (TDF+EFV) vs Tenofovir DF+ Efavirenz + Lamivudine (TDF+EFV+3TC) Maintenance Regimen in Virologically Controlled Patients: COOL Trial. 46th ICAAC. San Francisco, CA. September 27-30, 2006. Abstract H-1383.

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