Adherence to enfuvirtide and its impact on treatment efficacy.

High adherence rates to antiretroviral (ARV) therapy are associated with increased durability of viral suppression and decreased rates of drug resistance. The requirement of twice-daily subcutaneous self-administration of enfuvirtide (ENF) has raised concerns about adherence. This study assesses adherence to ENF and an optimized background (OB) of ARVs and its impact on virological and immunological responses during the TORO trials. Eighty-eight percent of patients in the OB arm reported > or = 85% adherence versus 87% of patients in the ENF + OB arm. Higher overall adherence was associated with improved virological and immunological response in both treatment arms at 48 weeks. In patients with > or = 85% adherence, 33% of patients in the ENF + OB arm achieved HIV-1 RNA < 400 copies/ml, versus 13% in the OB arm (p < 0.0001). Similarly, patients with > or = 85% adherence in the ENF + OB arm achieved a mean increase in CD4 cell count of 104 cells/mm(3) compared with 58 cells/mm(3) for patients in the OB arm (p < 0.001). None of the demographic factors explored (age, gender, race) or baseline characteristics (CD4 count, viral load, or baseline sensitivity score) was significant in predicting adherence to ENF when analyzed by multiple regression. Importantly, a history of intravenous drug use (IDU) was not associated with a significant decrease in adherence (mean adherence for IDU 96% versus mean adherence for non-IDU 96%; p = 0.825). Adherence was high in patients receiving the self-injectable ARV enfuvirtide. In addition, the inclusion of ENF did not negatively impact adherence to the ARV regimen as a whole.

Safety of enfuvirtide in combination with an optimized background of antiretrovirals in treatment-experienced HIV-1-infected adults over 48 weeks.

BACKGROUND: Antiretroviral tolerability is a critical factor contributing to treatment outcome. The T-20 Versus Optimized Background Regimen Only (TORO) studies assessed the safety and efficacy of enfuvirtide in treatment-experienced HIV-1-infected patients. METHODS: A total of 997 patients were randomized at a 2:1 ratio to an optimized background antiretroviral regimen plus enfuvirtide (n = 663) or an optimized background regimen alone (control group; n = 334). Control patients could switch to enfuvirtide on virologic failure. RESULTS: In total, 26.5% of patients randomized to enfuvirtide and 36.6% to the control group discontinued study treatment before week 48; the percentage of patients withdrawn for safety reasons (including adverse events [AEs], deaths, and laboratory abnormalities) was 14.0% in the enfuvirtide group and 11.6% in the control group. Injection site reactions (ISRs) occurred in 98% of enfuvirtide patients and led to treatment discontinuation in 4.4%. Treatment-related (defined as possibly, probably, or remotely) AE rates per 100 patient-years were lower with enfuvirtide (96.2) than in the control group (149.9); diarrhea, nausea, and fatigue, the most frequently reported AEs, were significantly less frequent with enfuvirtide than in the control group. Pneumonia was significantly more frequent in patients treated with enfuvirtide (6.7 vs. 0.6 events per 100 patient-years), although the incidence was within expected ranges for this population. Lymphadenopathy was also higher in enfuvirtide-treated patients (7.1 vs. 1.2 events per 100 patient-years) for control patients. CONCLUSION: The addition of enfuvirtide to an optimized background regimen does not exacerbate AEs commonly associated with antiretrovirals. ISRs limited treatment in <5% of patients.