Increased Antiretroviral Potency by the Addition of Enfuvirtide to a Four-Drug Regimen in Antiretroviral-Naive,HIV-Infected Patients

Abstract

Objective

To assess if enfuvirtide (ENF) increases antiviral activity of a highly active four-drug antiretroviral (ARV) regimen containing lopinavir/ritonavir, efavirenz, lamivudine and tenofovir in ARV-naive, HIV-infected patients.

Methods

Pilot study in ARV-naive, HIV-infected patients with viral load (VL) >10,000 copies/ml and no documented resistance to any of the study drugs. Patients were randomized to receive ENF (ENF Group) or not (Control Group) in combination with lopinavir/ritonavir, efavirenz, lamivudine and tenofovir as a backbone. The primary endpoint was to assess differences in the HIV-1 RNA decay rate during the first phase of viral decay. VL and treatment adherence were measured at baseline, every 6 h during the first 3 days, and once daily from day 3 to 6. Individual HIV-1 RNA decay rates were obtained using a non-linear least squares regression model.

Results

Eight subjects were included in each study group. Mean (sd) baseline VL was 4.98 (0.38) log₁₀ copies/ml in the ENF Group and 5.10 (0.49) log₁₀ copies/ml in the Control Group (P=0.607). Baseline CD4⁺ cell count was 463 (306) and 362 (225) cells/mm³ in the ENF and the Control Group, respectively (P=0.484). First phase HIV-1 RNA decay rate was 0.802 (0.127) d-¹ in the ENF Group and 0.624 (0.182) d^-1 in the Control Group (P=0.045). By day 6, VL was 3.55 (0.40) and 3.92 (0.36) log₁₀ copies/ml in the ENF and the Control Group, respectively (P=0.079).

Conclusion

The addition of ENF increased the antiviral potency of a highly active four-drug ARV regimen by 28.5% in ARV-naive, HIV-infected patients. The clinical impact of this finding should be assessed.