Highly Active Antiretroviral Therapies Are Effective against HIV-1 Cell-to-Cell Transmission

PLoS Pathogens

James Munro¹  Walther Mothes¹  Luis M. Agosto¹  Peng Zhong¹ 

[1] Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, United States of America

关键词: HIV-1;    Antiretroviral therapy;    T cells;    Antiretrovirals;    Drug therapy;    Highly-active antiretroviral therapy;    Apoptosis;    Drug screening;   

DOI  :  10.1371/journal.ppat.1003982

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

HIV-1 cell-to-cell transmission allows for 2–3 orders of magnitude more efficient viral spread than cell-free dissemination. The high local multiplicity of infection (MOI) observed at cell-cell contact sites may lower the efficacy of antiretroviral therapies (ART). Here we test the efficacy of commonly used antiretroviral inhibitors against cell-to-cell and cell-free HIV-1 transmission. We demonstrate that, while some nucleoside-analog reverse transcriptase inhibitors (NRTI) are less effective against HIV-1 cell-to-cell transmission, most non-nucleoside-analog reverse transcriptase inhibitors (NNRTI), entry inhibitors and protease inhibitors remain highly effective. Moreover, poor NRTIs become highly effective when applied in combinations explaining the effectiveness of ART in clinical settings. Investigating the underlying mechanism, we observe a strict correlation between the ability of individual drugs and combinations of drugs to interfere with HIV-1 cell-to-cell transmission, and their effectiveness against high viral MOIs. Our results suggest that the ability to suppress high viral MOI is a feature of effective ART regimens and this parameter should be considered when designing novel antiviral therapies.

【 授权许可】

CC BY