Abstract
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 of pol gene.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.
Highlights
Drug resistant human immunodeficiency virus (HIV)-1 variants were emergent more and more in AIDS individuals with highly active antiretroviral therapy (HAART) treatment
Characterization of HIV-1 variants 13 HIV-1 variants were isolated from AIDS patients (4 male and 9 female; average 40.3 years old) were recruited for this study. 4 patients received AZT + ddI + NVP, and 9 were treated with d4T + ddI+ NVP for 6 months or longer
Using GHOST cell line to determined the coreceptor usage, We found 5/13 viral variants were CCR5-tropic(R5) as determined by parallel infection of GHOST(3)-CXCR4 and GHOST(3)-CCR5 cells, 8/13 viral variants were CCR5 and CXCR4-tropic(R5X4)
Summary
Drug 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. Current therapies are not curative, and many treated patients develop resistance to one or more drugs, which is costly and may lead to complete treatment failure and death. The drug resistant HIV-1 variants emergent in HAART treatment individuals (page number not for citation purposes). By the end of 2007, it was estimated that there were 700,000 people living with HIV/AIDS in China. Most of these patients are being treated by antiretroviral treatment regimens.
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