Clinical Significance Of Nucleic Acid Detection With High Accuracy In HIV/AIDS Patients

Background and Purpose:Nowadays HIV-positive patients’death rate has already been lowered through HAART regimens,however,their life spans are still not up to normal.The underlying reason is low-level viremia(LLV).In addition,HIV could not be totally eradicated from body because of the HIV reservoir.The purpose of the study is to explore the relationship between LLV and clinical events,the dynamic change trend of HIV reservoir and the connection with immune checkpoint molecules,providing basis for optimization of HAART regimens.Methods:The first part:We enrolled 165 HIV-positive patients from September 2013 to January 2018 in infectious department of the first affiliated hospital,Zhejiang University,96 patients of which are the ones whose HIV RNA are undetectable,69 patients of which are the ones whose HIV RNA are between 20 copies/ml to 1000 copies/ml.Then we obtained clinical information,AIDS-related malignant tumors and laboratory index including HIVRNA、absolute counts of CD4+T lymphocytes、calcium、phosphate、glomerular filtration rate and so on.The second part:We enrolled 21 HIV-positive patients from September 2013 to January 2017 in infectious department of the first affiliated hospital,Zhejiang University.These patients are all on more than 2 years’s treatment with undetectable HIV RNA and whose CD4+ T lymphocytes are more than 350/mm3.The antivirus regimen of the first group is 2NRTIs plus 1 protease inhibitor(PI),the second group is 2NRTIs plus 1 integrase inhibitor(IN).They were followed for 3 times totally about 6 months.We collected the whole blood and PBMC.The level of total HIV RNA was measured by polymerase chain reaction.The subsets of CD4+ T lymphocytes and the immune checkpoint molecules expressed on the surface of cells were measured by flowcytometry.Statistical analysis was performed using SPSS version 20.0 version and Graphpad Prism version 6.0 software.Results:The first part:the results of immunological indicators are that there were no difference between the undetectable group and LLV group about CD4+ T lymphocytes prior to treatment and in the process(p>0.05).There was difference between groups about opportunistic infections(p<0.05)especially tuberculosis,the group 200 copies/ml≤HIV RNA<1000 copies/ml are prone to opportunistic infections.There was difference between groups about AIDS-related malignant tumors(p<0.05),the group 20 copies/ml≤HIV RNA<199 copies/ml with the highest incidence.About biochemical indexes,the level of serum phosphate is different between groups(p<0.05).The second part:We found central memory T lymphocytes(Tcm)and effector memory T lymphocytes(Tem)consititute the majority of HIV reservoir.Tcm subsets decline in the treatment of integrase inhibitor(p<0.05),there are no differences among other subsets(p>0.05).There is no significant change about HIV total DNA within the group and between two groups(p>0.05).We do not see correlations between CD4+ T lymphocytes and HIV reservoirs(p>0.05).CTLA-4 expressed on the surface of Tem and terminal differentiated T lymphocytes(Ttd)declines significantly in two groups(p<0.05).Other two immune checkpoint molecules show no trends(p<0.05).Conclusions:1.There is a high proportion about LLV in Zhejiang Province.2.The patients of LLV group are prone to opportunistic infections and AIDS-related malignant tumors.3.HIV reservoir shows no significant changes among completely virologically suppressed patients in their short-term anti-viral treatments.4.The percentage of Tcm subset declines between two groups,especially in the group of integrase inhibitor.5.Immune checkpoint molecules especially CTL,A-4 expressed on the central memory T lymphocytes and effector memory T lymphocytes could reflect the change of HIV reservoirs.