Relationship Between HIV Reservoir And CD4+/CD8+T Lymphocyte Ratio In Chronic HIV Infected Patients

Background and Objectives:With emergence of HAART(Highly active antiretroviral therapy),HIV infection/AIDS has transformed from a fatal disease to a chronic disease which can be controlled in long term.However,current antiretroviral drugs are not able to cure infection/AIDS.HIV reservoir is the major obstacle to cure.Quiescent CD4+T cell integrated with viral DNA become latent HIV reservoir,leading to HIV replication and expression in low level,and infect other CD4+T cell.Persistent HIV replication and expression will promote immune activation;meanwhile,abnormal immune activation will stimulate HIV reservoir,resulting in new viral replication.CD4+/CD8+T lymphocyte ratio is a preferable marker for immune activation in HIV infected patients.This study is supposed to recruit chronic HIV infected patients,dividing them into two group by baseline HIV DNA,and compare the differences of virological factors and T lymphocyte subsets and their changes over time between two groups,to demonstrate the relationship between HIV reservoir and these factors.Methods:We recruited 61 patients from clinic in Peiking Union Medical College Hospital,and divided them into 2 groups.Group 1 includes patients with baseline HIV-1 DNA<3 log copies/106 PBMCs and group 2 includes patients with baseline HIV-1 DNA?3 log copies/106 PBMCs.Flow cytometry was conducted to detect T lymphocyte subsets.Fluorescence PCR was conducted in HIV-1 DNA qualification.Differences of CD4+/CD8+T lymphocyte ratio,CD8+T cell count,HLA-DR+CD8+T cell ratio and HLA-DR+CD8+T cell between two Group 1 and Group 2 were compared at every follow-up.Their changes over time were graphed and analyzed to show their changing trends.Results:1.Relationship between viral reservoir and CD4+/CD8+T cell ratioAt MO and M6,CD4+/CD8+T cell ratios of two group have significant differences.Group 2(DNA?3 log copies/106 PBMCs)has lower CD4+/CD8+T cell ratios than group 1.In the first 6 months of treatment,group 1(HIV-1 DNA<3 log copies/106 PBMCs)has higher CD4+/CD8+T cell ratios than group 2,while the differences narrow over time.2.Relationship between viral reservoir and CD8+T cell countAt MO and M6,CD8+T cell counts of two group have significant differences.Group 2(DNA?3 log copies/106 PBMCs)has higher CD8+T cell counts than group 1.In the first 6 months of treatment,group 1(HIV-1 DNA<3 log copies/106 PBMCs)has lower CD8+T cell counts than group 2,while the differences narrow over time.3.Relationship between viral reservoir and CD8+T cell functional subsetGroup 2(DNAS3 log copies/106 PBMCs)has higher HLA-DR+and CD38+CD8+T cell ratios than group 1,presenting higher immune activation.Conclusions:1.Higher baseline HIV-1 DNA level predicts lower CD4+/CD8+T cell ratio and higher CD8+T cell count in the first 6 months of treatment.The differences of CD4+/CD8+T cell ratio and CD8+T cell count associated with HIV-1 DNA level,will decline over treatment.2.Higher baseline HIV-1 DNA level predicts higher CD8+T cell functional subset ratio,which will not decline over treatment.