Clinical Significance Of Low Level Viremia In HIV-1 Infected Patients After Highly Active Antiretroviral Therapy

BackgroundAIDS is known as acquired immune deficiency syndrome(AIDS).It is a chronic infectious disease,which is mainly caused by the human immunodeficiency virus(HIV).HIV-1 and HIV-2 are two types of HIV,the former is the main epidemic strain in China.According to the report from WHO,there were approximately 36.9 million people living with HIV at the end of 2017 and 1.8 million people becoming newly infected in2017 globally.Meantime,59%adults and 52%children living with HIV were receiving highly active antiretroviral therapy(HAART),which is known as antiretroviral therapy.Though there are no vaccine to prevent and cure HIV/AIDS,the application of HAART can effectively inhibit virus replication and restore the level of CD4~+T lymphocytes(CD4cells)as well as immune system,maintain immune function as far as possible,improve the quality of life,and achieve the goal of reducing HIV-related morbidity and mortality by maximally and persistently reducing viral load in patients.One of the most important methods for judging the clinical condition and the effect of antiviral therapy is to detect the viral load(VL)in peripheral blood.Although HAART can inhibit the viral load below the detection level,it can be found clinically that a small number of patients can still be detected low levels of viral load and some patients will fail in virological treatment.According to foreign literature reports,low levels of viral load may be associated with virological failure,the higher levels of viral load,the longer the duration,the higher risk of drug resistance,finally,the possibility of subsequent treatment failure is also higher.Besides,virological failure is strongly related to the events and death of AIDS.Moreover,the potential harm from persistent low levels of viral load includes the increasing risk of HIV transmission,especially sexual transmission.Although the main international guidelines for viral inhibition are less than 50 copies/ml(cp/ml),there are differences in the standards for virological treatment failure.The WHO guidelines recommend that virological treatment failure is defined as viral load greater than 1000 cp/ml,while the US guidelines define virological treatment failure as greater than 200 cp/ml and European guidelines define as greater than 50cp/ml.Under actual conditions,when the viral load is greater than 1000cp/ml,the genotype resistance test can be carried out,then the targeted treatment should be carried out according to the results and the drug should be replaced if necessary.However,when the viral load is below 1000cp/ml,the successful rate of genotype resistance detection amplification is not high,and there is no clear treatment in the current guidelines,so there is a"gray area"in the clinical management of patients with viral load between 50-1000cp/ml after treatment,which is easy to be ignored.Therefore,the concept of low level viremia(LLV)has been proposed,which was first proposed by Cohen C.It usually refers to the persistence of viral load between 50-1000 cp/ml after treatment and it should appear at least two consecutive episodes.It is worth noting that the definition of LLV is not completely the same in different countries and regions due to different conditions.At present,the viral load between 50-1000cp/ml is described as low level viremia in most of studies,and the viral load greater than 1000cp/ml is described as virological treatment failure,so this study also defines LLV and virological treatment failure as this scope.The research results of Santoro MM et al.show that the proportion of LLV is increasing year by year.However,there is still a lack of epidemiological data in China.Considering the potential harm of LLV and it is on the rise,the LLV is attracting more and more attention from clinicians and relevant researchers.At present,the domestic researches on low level viremia are limited.The VL detected once a year after HAART is there any clinical significance?What is the incidence of LLV in our country?What are the relevant factors for LLV?Will it further affect the efficacy of antiviral therapy?Therefore,the people of this study are patients admitted to our hospital,meantime,we will adopt retrospective cohort analysis method to analyze the epidemiological characteristics of low level viremia and explore its influence and possible related factors in order to the improvement of clinical treatment level and provide certain reference value for relevant public health guidelines.ObjectiveIn this study,the clinical characteristics and possible related factors of low level viremia after highly effective antiretroviral therapy were analyzed,and its clinical significance was discussed to provide corresponding theoretical support for future clinical management and related research.ContentIn this study,the subjects are patients of the eighth people’s hospital in Guangzhou,their antiviral treatment is received more than 1 year and they are followed from January 1,2015 to December 31,2015.Retrospective cohort study was conducted.when the subjects began to receive antiviral therapy meanwhile they entered the study cohort.Before antiviral therapy and after 2015,patients were followed up one year at a time for 3 consecutive years.The deadline of follow up was December 31,2018.Epidemiological investigation and laboratory test indicators were collected at each follow up point.Among them,the epidemiological survey included the antiviral treatment plan,antiviral drugs were missed or not,whether the antiviral drugs were changed and the reasons.Laboratory indicators include viral genotype and drug resistance sites before HAART,the viral load,CD4 cells,CD8~+T lymphocytes(CD8 cells),CD4/CD8 ratio,blood routine examination and function of liver and kidney.The COBAS TaqMan automatic viral load detection system was used to detect HIV-1 RNA.Flow cytometry was used to detect the number of CD4 and CD8 cells.HIV-1 gene subtypes were identified by MEGA5 software to construct a phylogenetic tree,and the resistance sites were determined by online comparison of the HIV-1 drug resistance database at Stanford University.According to the above indicators,appropriate statistical methods were used to analyze the clinical characteristics and possible factors.Finally the corresponding treatment measures were proposed.All data were statistically analyzed using SPSS20.0,P<0.05 indicated statistically significant difference and GraphPad Prism 6 was used for drawing.Results1.In 2015,the incidence of LLV in HIV/AIDS patients in guang dong province was3.3%after antiviral treatment.2.Compared with those VL less than 20cp/ml,patients with the regimen of1NRTI+1PI and poor compliance are more likely to have low level viremia,besides,their treatment time were shorter(P<0.05).There was no significant correlation between the occurrence of LLV and the viral load,CD4、CD8 cell count,CD4/CD8 ratio and viral genotype before treatment(P>0.05).3.Compared with those VL less than 20cp/ml,the LLV group have a higher rate of virological treatment failure,the number of CD8 cells with low level viremia decreased slowly,the CD4/CD8 ratio recovered slowly and hypoproteinemia was more likely to occur in these patients,the difference was statistically significant(P<0.05).Conclusions1.In 2015,the incidence of LLV in HIV/AIDS patients in guang dong province was3.3%after antiviral treatment.2.The occurrence of LLV may be related to antiviral regimen、compliance and treatment time.3.Compared with those whose VL less than 20cp/ml,the LLV group have a higher rate of virological treatment failure,the recovery of immune function and the disorder of metabolism will be found in patients.