| Antiretroviral therapy(ART)is turning AIDS from a daunting terminal illness to a chronic disease that can be prevented and controlled.However,current drugs can only suppress viral replication rather than eliminate pathogens,so more effective methods of diagnosis and treatment have always been research hotspots.Gene therapies such as miRNA-targeted therapy and CRISPR/Cas9 gene editing have made it possible to cure the diseases.In addition,the guarantee of efficacy is based on the timely diagnosis and standard administration.In order to confirm the possibility of long-term survival of AIDS patients,we analyzed the follow-up records of AIDS patients on ART for a long time to understand the efficacy and compliance,with a view to Summarize experience,optimize strategies,and improve the quality of life of patients.Therefore,this study starts from two aspects of exploration methods and new strategies,and strives to provide new scientific basis and comprehensive treatment strategies for optimizing HIV treatment.In the first part of the study,we found new therapeutic targets from the basic level.Micro ribonucleic acid(miRNA),as an important host factor,can interact with HIV during the process of HIV infection:highly expressed anti-HIV miRNAs in cells are not conducive to HIV replication in cells,while HIV also affects miRNA expression in turn to resist inhibition,so miRNAs may become biomarkers or potential therapeutic targets for HIV infection.We used microarray to analyze the miRNA profiles in PBMCs of HIV-infected patients(both treated and untreated)and healthy people,and found significant differences among the three groups(P<0.05).Compared with healthy people,the expression levels of 3 miRNAs including hsa-miR-433-5p in HIV-infected people were increased;7 miRNAs including hsa-miR-3667-5p were down-regulated;while hsa-miR-937 decreased in the treated group and increased in the untreated group relative to the healthy group(Table.1.3).In general,miRNAs showed a downregulation trend after HIV infection.Subsequently,we verified the differentially expressed miRNAs by quantitative PCR after expanding the sample size(150 cases in total).Among them,hsa-miR-191-5p was significantly different between HIV patients and healthy controls(P<0.05),and the expression trends were consistent in the results of microarray,that was,the expression was significantly downregulated among HIV-infected people.Further validation in vitro models showed an inhibitory effect of hsa-miR-191-5p on HIV replication.In order to explore mechanisms of action,we predicted the targets through bioinformatics databases and literature retrieval methods.Hsa-miR-191-5p may achieve the inhibitory effect on HIV by inhibiting CCR1 and/or NUP50 by q-PCR and construction of the reporter gene,providing a scientific basis for exploring biomarkers or potential therapeutic targets for HIV infection.In the second part of the study,we analyzed the effectiveness of current treatments to minimized side effects and improved the quality of life of HIV-infected patients by analyzing 6 precious German cases that were on ART for about 30 years and followed up to date.These patients are male at an average age of 58.33 years old now and infected by MSM.At the time of the first diagnosis of HIV infection,they're 28.83 years old with an average CD4 level of 226.67/?L and the average viral load as high as 1.3 105 copies/mL.In addition to HIV infection,there were also various opportunistic infections,cardiovascular disease and metabolic abnormality.As soon as they were diagnosed,they immediately received ART and insisted on follow-ups every 3 months in the hospital.We summarized the results of the follow-ups every 5 years and compiled them into charts.With the help of ART for around 30 years,the number of CD4+T cells had reached normal levels,an average level of 778.67/?L and the viral load was under the detection value(<20 copies/mL).Besides,opportunity infections and other diseases had been treated or controlled.Most laboratory test indicators over the years gradually were approaching or had reached normal levels,only a few indicators were still abnormal.Current CD4/CD8 ratio was 1.17 indicating a continued immune activation.These patients all had metabolic diseases at first.The average blood glucose before ART was 5.83 mmol·L-1,but 4.97 mmol·L-1 currently.With the help of treatment,blood lipids of patients 1 and 4 have been controlled but not adjusted to normal while the other patients have an average cholesterol of 4.5 mmol·L-1 and triglycerides of 1.09 mmol·L-1.In the course of treatment,almost every patient had suffered from mental illnesses,like depression,sleep disorders,migraine,etc.Doctors combined drugs and psychological counseling together to help them reduce misery and change in better mood.In total,their physical condition improved significantly through active treatment.Results mentioned above suggest that as long as patients are willing to communication with doctors,have timely treatment of HIV,complications,secondary disease,even they have been diagnosed with AIDS,patients can still survive for a long time.As long as AIDS patients can be treated timely with close follow-ups,they ultimately can achieve the same living conditions as normal people,achieving improvements both in physical condition and quality of life.In summary,this study can draw the following conclusions:(1)HIV-infected can cause significant down-regulation of hsa-miR-191-5p in PBMC;hsa-miR-191-5p can inhibit HIV replication,possibly by inhibiting CCR1 and/or NUP50.These provide a scientific basis for further investigation of potential therapeutic targets.(2)As long as HIV-infected patients are treated as soon as possible,timely symptomatic treatment and active follow-up,even if they have AIDS,they can survive for a long time and even achieve the same living conditions as normal people,achieving improvements both in physical condition and quality of life. |
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