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BackgroundDrug resistant HIV-1 variants were emergent more and more in AIDS individuals with highly active antiretroviral therapy (HAART) treatment. Understanding the replication and drug resistant mutation of HIV-1 variants isolated from HAART treatment individuals of China could help to design appropriate therapeutic strategies for these individuals.MethodsUse GHOST cell lines to analysis the coreceptor usage of HIV-1 variants. Coculture with PBMCs to analysis the replication capacity. Use RT-PCR to analysis the drug resistant mutation ofpolgene.Results13 HIV-1 variants experienced HAART were included in this study. 5 HIV-1 variants used CCR5 coreceptor (R5), while 8 use both CCR5 and CXCR4 coreceptor (R5X4). The replication capacity of R5X4 variants was no difference with R5 variants in vitro without antiretroviral drugs. Compare the drug resistant mutation between first HIV-1 variants and fourth variants; there were 37 drug resistant mutations in first variants and 32 drug resistant mutations in fourth variants. Only 7 drug resistance mutations were lost after coculture for 4 weeks, and 2 drug resistance mutations were emerged.ConclusionThese data suggested that the drug resistant level could not reduce in vitro in absence of antiretroviral drugs in few weeks. And maybe helpful for these HAART experienced individuals when change antiretroviral drugs.

Background This study explored co-receptor usage and prediction of V3 genotyping algorithms in HIV-1 subtype B' from paid blood donors experienced anti-retroviral therapy in Chinese central province in order to design effectively therapeutic regimen. Methods HIV-1 strains were isolated in treatment HIV-1 infections and treatment-naïve HIV-1 infections, then co-receptor usage of HIV-1 strains was identified based on Ghost cell lines using flow cytometry. HIV-1 V3 region was amplified and submitted into web-server (WebPSSM and geno2pheno) to predict HIV-1 co-receptor usage. The feasibility of prediction HIV-1 usage with Web-server assay was analyzed by comparing prediction of V3 genotyping algorithms with HIV phenotype assay based on Ghost cell line. Results 45 HIV-1 strains and 114 HIV-1 strains were isolated from HIV-1 infections exposed anti-retroviral therapy and treatment-naïve, respectively. 41% clinical viruses from ART patients and 18% from treatment-naïve patients used CXCR4 as co-receptor. The net charge in the V3 loop was significantly difference in both groups. The sensitivity and specificity for predicting co-receptor capacity is 54.6% and 90.0% on 11/25 rule, 50.0% and 90% on Web-PSSMx4r5, 68.2% and 40.0% on Geno2pheno[co-receptor]. Conclusion Dual/mixed/X4 co-receptor utilization was higher in ART patients than treatment-naïve patients. It is should paid attention to predicting HIV-1 co-receptor usage based on V3 genotyping algorithms in HIV-1 subtype B' from paid blood donors experienced anti-retroviral therapy in Chinese central province.

Background The non-nucleoside reverse transcriptase inhibitor (NNRTI), as a major component of the highly active antiretroviral therapy (HAART) to HIV-1 (human immunodeficiency virus type 1) infected patients, required the development of new NNRTIs with improved resistance profile and decreased toxicity. Therefore, a series of novel compounds, 9-phenylcyclohepta[d]pyrimidinedione derivatives (PCPs), were designed based on the chemical structure of TNK-651, to detect anti-HIV-1 activity. Results 1-[(benzyloxy)methyl]-9-phenyl-cyclohepta[d] pyrimidinedione (BmPCP) among four PCPs has antiviral activity on laboratory-adapted HIV strains (HIV-1 SF33). The results showed 50% inhibition concentrations (IC50s) of BmPCP were 0.34 μM, 1.72 μM and 1.96 μM on TZM-bl, peripheral blood mononuclear cells (PBMCs) and MT4, respectively. It was also effective against infection by the predominant HIV-1 isolates in China, with IC50s at low μM levels. Its selectivity index (SI) ranged from 67 to 266 in different cells. The results of time-of-addition assay demonstrated that BmPCP inhibited HIV-1 infection by targeting the post entry of the HIV-1 replication cycle. For inhibition of HIV-1 reverse transcriptase activity, the IC50 values of BmPCP and NVP were 1.51 and 3.67 μM, respectively. Conclusions BmPCP with a novel structure acts as a NNRTI to inhibit HIV-1 replication and can serve as a lead compound for further development of new anti-HIV-1 drugs.