The human immunodeficiency virus (HIV) is the acquired immunodeficiency syndrome (AIDS) caused by a lentivirus. The treatment of HIV/AIDS usually includes the use of multiple antiretroviral drugs to act on different viral targets, which is also known as highly active antiretroviral therapy (HAART). Nucleoside reverse transcriptase inhibitors (NRTIs), as the essential components in HAART, are able to compete with endogenous deoxynucleoside triphosphates (dNTPs) and then prevent the transcription of HIV-1.

However, long-term usage of anti-HIV drugs often results in the development of viral resistance or long-term toxicity. For example, in one of the most commonly used anti-HIV-1 treatment, the lamifudine (3TC) treatment, drug resistance has been detected in both cell culture and infected patients. Thus it is necessary to identify new agents with higher efficacy against the drug-resistant HIV-1 strains.

Currently, it has known that azvudine (FNC), a novel cystidine ananlogue, has antiviral activities on HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) and may serve as a better template of anti-HIV drugs than 3TC. Therefore, to address these questions, by collaborating with Prof. CHANG Junbian (Zhengzhou University), Prof. ZHENG Yongtang (Kunming Institute of Zoology, CAS) and his colleagues conducted a study to compare the anti-HIV activities of FNC and 3TC in parallel assays. The drug resistance of FNC was predicted via the in vitro dose escalation methods. Moreover, the clinical applications of FNC by combination assay with different target approved drugs were also evaluated.

In their study, FNC not only exerted highly potent inhibition on both HIV-1 and HIV-2, but also showed synergism in combination with other six approved anti-HIV drugs. The anti-HIV activities of ENC were higher than 3TC on lab-strains, clinical-strains and resistant-strains. Furthermore, in combination assay, the concentrations of FNC used were 1000 or 500 fold lower than other drugs. These results indicate that as a new NRTI, FNC is a promising drug to be used in therapy or served as replacement of 3TC for treating HIV-1 infection and can be considered as a new option for HIV infected patients.

The clinical research of FNC has received ratification from China Food and Drug Administration (CFDA) on April 2013 and the novel drug is currently under Phase I clinical studies. 　　

The main findings have been published on PLoS One (2014, 9(8):e105617).