Relative anti-HIV-1 efficacy of lamivudine and emtricitabine in vitro is dependent on cell type

Objective: To assess the relative in vitro potency of the antiviral agents emtricitabine (FTC), lamivudine (3TC), and zidovudine (ZDV) in peripheral blood mononuclear cells (PBMCs), monocyte-derived macrophages, and MT-4 cells infected with HIV-1. Design: In vitro evaluation of the test compounds against M-tropic or T-tropic laboratory strains of HIV-1 and against clinical HIV-1 isolates from antiretroviral therapy-naive subjects using PBMCs, monocyte-derived macrophages, and MT-4 cells. Methods: Standard methods for assessing antiviral potency based on 50% inhibitory concentrations using propidium iodide staining of host cell DNA to assess cytopathic effects or measurement of HIV-1 reverse transcriptase activity to assess inhibition of viral replication. Results: There were no significant differences in potency between 3TC and FTC in assays with HIV-1(IIIB)-infected PBMCs or HIV-1(Ba-L)-infected monocyte-derived macrophages, which are primary cell types for HIV-1 infection in vivo. In agreement with earlier reports, FTC was approximately fourfold more active than 3TC in assays in the transformed T-cell line MT-4 infected with HIV-1(IIIB), whereas ZDV was more active than FTC. 3TC, FTC, and ZDV were equally active against a panel of eight primary HIV-1 isolates from antiretroviral-naive subjects in PBMCs. These results demonstrate the in vitro similarity of 3TC and FTC activity in primary cells. The variability in potency depending on cell types and viral strains underscores our observation that antiviral effects in vitro are not reliable predictors of in vivo clinical activity.