Gilead's
pivotal Study 934 is an ongoing international open-label Phase III trial in which
treatment-naive patients were randomly assigned to receive either once-daily tenofovir
DF (Viread) + emtricitabine (Emtriva) + efavirenz (Sustiva) or else twice-daily
AZT/3TC (Combivir) + efavirenz. The first regimen includes the 3 drugs in the
newly approved Atripla fixed-dose combination pill.
Participants
started the study with HIV viral loads greater than 10,000 copies/mL and any CD4
cell count. After 48 weeks, significantly more patients in the tenofovir/emtricitabine/efavirenz
arm reached the primary endpoint of HIV RNA below 400 copies/mL using the FDA's
"TLOVR" (Time to Loss of Virological Response) algorithm*.
At
the 8th Congress on Drug Therapy in HIV Infection, held earlier this month in
Glasgow, researchers presented data from an interim 96-week analysis.
Results
Baseline characteristics were similar in the 2 treatment arms (median age 37 years,
HIV RNA 5.0 log copies/mL, CD4 cell count 237 cells/mm3).
In the 96-week efficacy analysis, 75% of the 232 patients in the tenofovir/emtricitabine/efavirenz
arm achieved and maintained HIV RNA < 400 copies/mL, compared with 62% of the
231 subjects in the AZT/3TC/efavirenz arm (TLOVR 95% CI 4.3%-21.1%; P = 0.004).
67% of patients in the tenofovir/emtricitabine/efavirenz arm achieved HIV RNA
< 50 copies/mL, compared with 61% in the AZT/3TC/efavirenz arm (95% CI 2.3%-15.1%;
P = 0.16).
The mean increase from baseline in CD4 cell count was significantly greater in
the tenofovir/emtricitabine/efavirenz arm (270 vs 237 cells/mm3; P = 0.036).
No patients developed the K65R mutation associated with tenofovir resistance.
Significantly more patients taking AZT/3TC/efavirenz developed the M184V/I mutation
(9 vs 2; P = 0.036).
Adverse events leading to treatment discontinuation were less common in the tenofovir/emtricitabine/efavirenz
arm (5%) compared with the AZT/3TC/efavirenz arm (11%) (P < 0.001).
Both regimens were well-tolerated overall.
The renal safety (kidney toxicity) profile was similar in both arms.
2 patients in the AZT/3TC/efavirenz arm developed mild/moderate (Grade 1-2) creatinine
elevations, compared with none in the tenofovir/emtricitabine/efavirenz arm; no
subjects in either arm developed severe (Grade 3-4) elevations.
Median limb fat gain at Week 96 was greater in the tenofovir/emtricitabine/efavirenz
arm (7.7 vs 5.5 kg; P < 0.001).
Conclusion
"Through
Week 96, significantly more patients on [tenofovir/emtricitabine/efavirenz] achieved
HIV RNA < 400 copies/mL and had higher CD4 cell increase from baseline,"
the researchers concluded. "More patients in [the AZT/3TC/efavirenz] arm
discontinued study regimen due to adverse events. Limb fat was significantly higher
in [the tenofovir/emtricitabine/efavirenz] arm."
11/28/06
References
A
Pozniak, J Gallant, E DeJesus, and others. Efficacy and safety of tenofovir DF
(TDF), emtricitabine (FTC) and efavirenz (EFV) compared to fixed dose zidovudine/lamivudine
(CBV) and EFV through 96 weeks in antiretroviral treatment-naive patients. 8th
Congress on Drug Therapy in HIV Infection. Glasgow. November 12-16, 2006. Abstract
P6.
*J E Gallant,
E DeJesus, J R Arribas, and others. Tenofovir DF, emtricitabine and efavirenz
vs. zidovudine, lamivudine and efavirenz for HIV. N Engl J Med 354(3):
251-260. January 19, 2006.
Baseline characteristics were similar in the 2 treatment arms (median age 37 years,
HIV RNA 5.0 log copies/mL, CD4 cell count 237 cells/mm3).