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Synergistic Effect Resulting From Combinations of a Bifunctional HIV-1 Antagonist With Antiretroviral Drugs

Xu, Wei PhD*; Wang, Qian MS*; Yu, Fei PhD*; Lu, Lu PhD*; Jiang, Shibo MD, PhD*,†

JAIDS Journal of Acquired Immune Deficiency Syndromes: September 1st, 2014 - Volume 67 - Issue 1 - p 1–6
doi: 10.1097/QAI.0000000000000265
Rapid Communication

Abstract: Development of new anti-HIV therapeutics remains necessary for patients with HIV/AIDS who fail to respond to the current antiretroviral drugs. In this study, we investigated the potential cooperative effects of 2DLT, a bifunctional HIV-1 antagonist with viral inactivation and fusion inhibition activities, combined with different antiretroviral drugs, including HIV entry inhibitors, nucleoside and nonnucleoside reverse-transcriptase inhibitors (NRTIs and NNRTIs), and protease inhibitors. We found that combining 2DLT with these antiretroviral drugs resulted in synergism or strong synergism against infection by both X4 and R5 HIV-1 strains. Although 2DLT alone is highly effective against both NRTI- and NNRTI-resistant HIV-1 strains, combining 2DLT with zidovudine, stavudine, or nevirapine resulted in synergistic or strong synergistic antiviral effect against single or multiple RTI-resistant HIV-1 strains, suggesting that 2DLT can be further developed as a novel anti–HIV-1 drug for addition to the highly active antiretroviral therapy regimen for salvage therapy of patients with HIV/AIDS who are refractory to current antiretroviral drugs.

*Key Laboratory of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, Shanghai, China; and

Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY.

Correspondence to: Shibo Jiang, MD, PhD, Key Laboratory of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Road, Xuhui District, Shanghai 200032, China (e-mail: shibojiang@fudan.edu.cn).

Supported by Natural Science Foundation of China (NSFC, No.81102476, 81173098 and 81373456) and the NSFC-NIH Collaboration Project (No. 81361120378).

The authors have no conflicts of interest to disclose.

W.X. and Q.W. contributed equally to this study. S.J. and L.L. conceived the concept and designed the experiment. W.X., Q.W., and F.Y. performed experiments. S.J. and L.L. analyzed data and wrote the article. S.J. and L.L. contributed equally to this study and are co-first authors.

Received March 17, 2014

Accepted June 12, 2014

© 2014 by Lippincott Williams & Wilkins