The Relationship Between The Variation Of Total HIV DNA Level In Peripheral Blood And Viral Rebound In HIV-Infected Individuals

Background and purposeHIV infection is a big global challenge.Despite a dramatic reduction in morbidity and mortality in HIV-infected individuals due to antiretroviral therapy(ART),life-long treatment is required due to the existence of viral reservoirs in infected cells.Among different markers of HIV reservoir,total HIV DNA is the most widely used one and has great clinical significance.Biomarkers used to evaluate patients’ status include CD4+T cell count and viral load in clinical practice.But we still need another new biomarker to provide more information when it comes to those who have achieved viral suppression and immune reconstitution.In addition,there is a critical need to find a useful predictive factor for viral rebound in treatment interruption which aims at finding interventions to achieve functional cure for HIV infection.Therefore,the purpose of this study is to explore the potential role of total HIV DNA in predicting viral rebound or blip.MethodsThis is a retrospective study.HIV-infected individuals who were treatment-naive and started ART during chronic HIV infection and have experienced viral rebound or blip during ART in previous study cohorts and Peking Union Medical College Hospital were selected.Viral rebound was defined as one plasma viral load(VL)>400 copies/ml or two continuous plasma VL>50 copies/ml in at least 30 days apart following initial viral suppression.Blips were defined as one transient VL>50 copies/mL,but less than 400 copies/mL,with return to<50 copies/mL without a change in therapy.The level of total HIV DNA,CD4+T cell count,CD4/CD8 ratio,and the percentage of CD8+T cells expressing CD38 or HLA-DR in peripheral blood at 5 time points(48,36,24,12,0 weeks before viral rebound or blip)were quantified.ResultsA total of 76 patients were selected from 2725 patients and 80%are male.31 patients experienced viral blip and 41 experienced viral rebound.Both of viral blip and rebound happened in 4 patients.Of all these patients,the median time of follow up,the time from ART initiation to viral suppression and the time from ART initiation to viral rebound or blip are 6.5 years,24 weeks and 72 weeks,respectively.The level of total HIV DNA decreased gradually during 48 weeks before both viral rebound and blip,and did not increase even at the time of viral rebound or blip.Significant difference was detected between 48 weeks and 24 weeks,48 weeks and 12 weeks before viral rebound in total HIV DNA level(P<0.05),but was not observed among other time points.To exclude the influence of natural decay of total HIV DNA during ART,the differences between the total HIV DNA level at the time of viral rebound/blip and the other 4 time points were calculated.When these differences were compared with 0,significant difference was only detected at 36 weeks before rebound and 48 weeks before blip(P<0.05).The levels of CD4+T cell count,CD4/CD8 ratio,and the percentage of CD8+T cells expressing CD38 or HLA-DR were stable during all 48 weeks before both viral rebound and blip.ConclusionsTotal HIV DNA level in peripheral blood does not change before viral rebound and blip,and it cannot help predict the occurrence of viral rebound or blip.