Efavirenz/tenofovir fails as 2-drug maintenance regimen
Mark Mascolini, natap.org
Efavirenz plus tenofovir given as a simplified maintenance regimen did not control HIV as well as the same two drugs plus 3TC in a 48-week French trial . Three people in the two-drug arm and none in the three-drug arm had to stop an antiretroviral because of treatment-related side effects.
Pierre-Marie Girard (St. Antoine Hospital, Paris) and colleagues across France recruited 143 people with a viral load below 50 copies/mL for at least 6 months on their current regimen, no history of virologic failure, and no significant lab or clinical abnormalities. Study participants were randomised to start efavirenz/tenofovir or those two drugs plus 3TC.
The group had a median age of 40 years (range 22 to 73) and a median CD4 count of 473 (range 78 to 1775); 35% had CDC stage C disease. They had taken antiretrovirals for a median of 3.7 years (range 0.5 to 7.7). While 45.5% were taking two nucleosides plus one protease inhibitor, 43.5% were taking a non-nucleoside with two nucleosides. Nearly three quarters (71%) were using AZT and 3TC as their nucleosides.
After 48 weeks, both intention-to-treat analysis and on-treatment analysis showed better virologic control in the three-drug group (Table 1). The 95% confidence interval for both comparisons stretched beyond the range set to establish non-inferiority of the two-drug regimen (14%).
Table 1: Two- versus three-drug maintenance for 48 weeks
|EFV/TDF||EFV+2 RTIs||Difference (upper bound 95% CI)|
|Intent-to-treat <50copies/mL||81.7%||97.2%||15.5% (23.7%)|
|On treatment <50copies/mL||90%||100%||10.0% (15.5%)|
Three people in the two-drug group had NNRTI-related resistance mutations by week 48, while no NNRTI mutations emerged in the triple-drug group. Ten people in the two-drug arm stopped one or more study drugs, 3 of them because of treatment-related side effects (2 transaminase elevations and 1 case of vertigo). No one in the three-drug arm stopped an antiretroviral because of side effects, though two stopped coming back for follow-up visits.
Median CD4 counts climbed by 35 cells/mm3 in the three-drug group and 14 cells in the two-drug group, but this difference lacked statistical significance (p=0.94). Median hemoglobin rose 0.80 g/dL in the triple-therapy arm and 0.45 g/dL in the double-therapy arm, a difference that also fell short of significance (P = 0.14). Creatinine clearance fell 3.3 mL/min in the three-drug arm and rose 1.7 mL/min in the two-drug arm, again a non-significant difference (p=0.17).
In the group as a whole, triglycerides fell 0.25 mmol/L (p<0.001) and total cholesterol fell 0.3 mmol/L (p<0.001). Dangerous low-density lipoprotein cholesterol dropped 0.2 mmol/L in the triple-therapy group (p=0.015 versus baseline) but rose (non-significantly) by 0.15 mmol/L in the two-drug group (p=0.5). The treatment groups did not differ in lipid changes or fat distribution. Subcutaneous abdominal fat rose significantly in the whole study group (9 cm2, p=0.017), while the visceral-to-subcutaneous adipose tissue ratio fell by 0.05 (p=0.06).
- Girard PM, Cabie A, Michelet C, et al. Tenofovir DF + efavirenz vs tenofovir DF + efavirenz + lamivudine maintenance regimen in virologically controlled patients: COOL trial. 46th ICAAC. September 27-30, 2006, San Francisco. Abstract H-1383.