Background: The ESS40013 study tested 4-drug induction followed by 3-drug maintenance as initial antiretroviral therapy (ART) to reduce HIV RNA rapidly and then to simplify to an effective yet more convenient and tolerable regimen.
Methods: Four hundred forty-eight antiretroviral-naive adults were treated with abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) and efavirenz (EFV) for the 48-week induction phase. Two hundred eighty-two patients were randomized in a 1:1 ratio to continue ABC/3TC/ZDV + EFV or to simplify to ABC/3TC/ZDV for the 48-week maintenance phase.
Results: The baseline median HIV RNA level and CD4 cell count were 5.08 log10 copies/mL (56% ≥100,000 copies/mL) and 210 cells/mm3 (48% <200 cells/mm3), respectively. No significant differences were noted between ABC/3TC/ZDV + EFV and ABC/3TC/ZDV for an HIV RNA level <50 copies/mL (79% vs. 77% [intent to treat (ITT), missing = failure]; P = 0.697) or time to treatment failure (P = 0.75) at week 96. Drug-related adverse events were more commonly reported for ABC/3TC/ZDV + EFV than for ABC/3TC/ZDV (15% vs. 6%). Improvements in total cholesterol, low-density lipoprotein cholesterol, and triglycerides were observed in the ABC/3TC/ZDV group. Virologic failure occurred in 22 patients during induction and in 24 patients (16 in ABC/3TC/ZDV group and 8 in ABC/3TC/ZDV + EFV group; P = 0.134) during maintenance. A greater proportion of patients receiving ABC/3TC/ZDV than ABC/3TC/ZDV + EFV reported perfect adherence at week 96 (88.8% vs. 79.6%; P = 0.057).
Conclusions: After induction with ABC/3TC/ZDV + EFV, simplification to ABC/3TC/ZDV alone maintained virologic control and immunologic response, reduced fasting lipids and ART-associated adverse events, and improved adherence.