HIV-1 Drug Resistance Mutations Among Antiretroviral-Naïve HIV-1–Infected Patients in Asia: Results From the TREAT Asia Studies to Evaluate Resistance-Monitoring Study

Of 682 antiretroviral-na_ve patients initiating antiretroviral therapy in a prospective, multicenter HIV-1 drug resistance monitoring study involving eight sites in Hong Kong, Malaysia, and Thailand, the prevalence of patients with ≥1 drug resistance mutation(s) was 13.8%. Primary HIV drug resistance is emerging after rapid scaling-up of antiretroviral therapy in Asia

Chemical targeting of the innate antiviral response by histone deacetylase inhibitors renders refractory cancers sensitive to viral oncolysis

Intratumoral innate immunity can play a significant role in blocking the effective therapeutic spread of a number of oncolytic viruses (OVs). Histone deacetylase inhibitors (HDIs) are known to influence epigenetic modifications of chromatin and can blunt the cellular antiviral response. We reasoned that pretreatment of tumors with HDIs could enhance the replication and spread of OVs within malignancies. Here, we show that HDIs markedly enhance the spread of vesicular stomatitis virus (VSV) in a variety of cancer cells in vitro, in primary tumor tissue explants and in multiple animal models. This increased oncolytic activity correlated with a dampening of cellular IFN responses and augmentation of virus-induced apoptosis. These results illustrate the general utility of HDIs as chemical switches to regulate cellular innate antiviral responses and to provide controlled growth of therapeutic viruses within malignancies. HDIs could have a profoundly positive impact on the clinical implementation of OV therapeutics