The sensitivity of transmitted/founder HIV-1 to anti-HIV drugs / 药学学报

The majority of mucosal HIV-1 infection is initially established by a few HIV-1 viral variants, followed by the development of overt systemic infection, and these viral variants are known as transmitted/founder viruses (T/F viruses). Investigation of the sensitivity of T/F virus to different anti-HIV-1 drugs will provide the best strategies of pre-exposure prophylaxis (PrEP) for high-risk groups of HIV-infected patients. Herein we constructed for the first time, a luciferase reporter system for HIV-1 T/F viruses, and then compared the drug sensitivity between T/F viruses and chronic infection virus. The result showed that the 50% inhibitory concentration (IC50) of nucleoside reverse transcriptase inhibitors (NRTIs), integrase inhibitors (INIs) and protease inhibitors (PIs) were not significantly different between the T/F viruses and chronic infection viruses of the same subtype (P>0.05), while non-nucleoside reverse transcriptase inhibitors (NNRTIs) showed a moderate resistance to T/F viruses, with a significant increase in IC50 (P<0.05). The conclusion suggests that when patients are in high-risk or in the acute infection of HIV-1, NNRTIs should be avoided in the first-line antiretroviral therapy regimens.

Preparation and characterization of microspheres for controlled release of anti HIV drug.

A series of blend microspheres were developed from gelatin and hydroxypropyl cellulose (HPC) by emulsion crosslinking method employing glutaraldehyde (GA) as a crosslinker. Valganociclovir hydrochloride (VHCL), an anti HIV drug, was loaded in to these microspheres via insitu method. These microspheres were characterized by Fourier transform infrared spectroscopy (FTIR), to confirm the formation of crosslinking and absence of chemical interactions between drug, polymer and crosslinking agent. Further the microspheres were characterized by scanning electron microscopy to study the surface morphology of the microspheres and observed that the microspheres have smooth surface with spherical structure and no phase separation. The microspheres with the average particle sizes ranging from 614.5μm to 693.4μm were obtained. X-ray diffraction (X-RD) studies were performed to understand the crystalline nature of drug and its uniform distribution into blend microspheres. An in vitro release study was performed in phosphate buffer solution (pH-7.4) at 370C. The release rates were fitted to an emperical equation to understand the diffusion parameters, which indicate non-Fickian or anomalous trend release of VHCL. Further the results indicated that the release of drug was found for more than 12 h.