| Objective:At present,the epidemic situation of Human immunodeficiency virus(HIV)in China is still severe,the epidemic characteristics of AIDS have also changed,sexual contact has become the most important route of transmission,and Men who have sex with Men(MSM)has become the main body of new HIV infection in China,and is on the rise.Not only the sexually active teenagers have become the focus of HIV infection prevention and control,but also the elderly people whose sexual needs are neglected and lead to high-risk behaviors are increasingly concerned.As one of the most common pathogens for sexual transmission,Herpes simples virus type 2(hsv-2)has the same route of transmission and clear epidemiological correlation with HIV.However,existing studies mainly focus on HIV-negative MSM high-risk groups,and there are few relevant studies on HIV infection complicated with HSV-2.In addition,there are relatively more studies focusing on HSV-2 infection in young people,while there are few reports on HSV-2 infection in elderly people with HIV.In the new situation of AIDS prevention and control in China,it is of great significance to identify the epidemiological characteristics and risk factors of elderly HIV patients with HSV-2,which will provide scientific data for targeting key populations and carrying out early AIDS prevention and control.There are great differences in disease progression among HIV individuals.It is now clear that co-infection,such as the combination of Hepatitis B virus(HBV)and Cytomegalovirus(CMV),accelerates the progression of HIV diseases.It has been reported that the infection rate of HIV infection with HSV-2 is as high as 42-87%,suggesting that HSV-2 infection is very common among HIV patients.However,the impact of HSV-2 combination on the progression of HIV infection has not received sufficient attention.At present,there are only a few international reports on whether HSV-2 can accelerate the disease progression of HIV,and the research results are still controversial.Therefore,the establishment of a prospective cohort of acute HIV patients through high-risk MSM follow-up to accurately assess the impact of HSV-2 on HIV disease progression will provide reference for guiding the early intervention of HSV-2and slowing down HIV disease progression.Although the antiviral treatment of AIDS is effective and significantly improves the survival rate and quality of life of the patients,there are still some patients who can not obtain good immune recovery and have a high risk of death and morbidity.The proportion of patients with poor immune recovery ranged from 9% to 45%.At present,advanced age and combined CMV infection are considered as important indexes affecting immune recovery.Given that both HSV-2 and CMV are human herpes viruses,we speculate that HSV-2 may have some negative effects on immune recovery and viral response after antiviral therapy,and ultimately affect the clinical prognosis of the disease,just like CMV.At present,there is still a lack of international research on the immune recovery and clinical prognosis of HSV-2 after antiviral treatment for HIV infection.Methods:1.Research subject:1.1 We carried out the baseline cross-sectional survey.We survey HIV patients during January 2003 to December 2018,in the China medical university first affiliated hospital and collected the patient's demographic,clinical and epidemiological information.We mainly analyzed and obtained the serum prevalence characteristics of HSV-2 in HIV-infected patients of different ages and different years of diagnosis,and identified the risk factors related to the serum status of HSV-2 through multivariate analysis.1.2 We established an HIV acute phase infection(AHI)cohort,prospectively assess the disease progression of HIV-infected individuals,and analyze the impact of HSV-2 serum status on HIV disease progression.After enrollment,we regularly followed up HIV-patients every 1-3 months and collected clinical information and blood samples for relevant laboratory tests.The predictive effects of demographic and clinical indicators such as HSV-2 on HIV disease progression were analyzed by multivariate.1.3 We established an antiviral treatment cohort for chronic HIV infection,and prospectively evaluate the effect of combined HSV-2 on immune recovery and clinical prognosis of HIV infection.Patients receiving antiviral therapy were enrolled between January 2009 and January 2017.Endpoint event definition:Definition good of immune recovery: CD4 count was lower than 350 /ul before treatment,and CD4 was greater than 350/ul twice in a row after 6 months of treatment.CD4/CD8<0.5 before treatment,and CD4/CD8>0.5 twice in a row after treatment for more than 6 months.Treatment failure definition: rebound of viral load greater than 1000 copies /ml or drug resistance after virus suppression occurs or death.2.Experimental methodsA)HSV-2 serum antibody detection: HSV-2,Herpe Select-2 ELISA-Ig G;Beijing Beier company)to detect HSV-2 specific immunoglobulin G(Ig G)antibody.B)Syphilis detection.Rapid plasma reactive protein(RPR)was used for serological screening of syphilis.The positive results of RPR were tested by treponema pallidum granule test(serum TPPA;Fujibashi(Tokyo,Japan)confirmed.Subjects who tested positive for plasma TPPA or RPR were considered to have syphilis infection.C)CD4 + T cell count was determined by flow cytometry(institute of biological sciences,San Diego,California,USA).D)Plasma hiv-1 viral load(VL)was measured using commercial hiv-rna quantification method cobas-ampliprep/cobas-taqman-HIV-1(mannheim,Germany)with a plasma limit of 20 copies/ml.E)All tests were carried out in accordance with the manufacturer's instructions.3.Statistical analysisSpss23.0 was used for statistical analysis.Data conforming to normal distribution were analyzed by independent sample t-test or paired t-test,while data not conforming to normal distribution were analyzed by non-parametric test.The risk factors of HSV-2infection were analyzed by using binary logistics regression and COX risk ratio regression model.P < 0.05 was considered statistically significant.Results:1.A total of 1449 infected persons were enrolled in our cross-sectional survey,among whom 542 were HSV-2 Ig G positive and the positive rate of HIV/HSV-2 serum was37.4%.Among the 542 HSV-2 Ig G-positive patients,411 completed intermediate hsv-2Ig M detection,and the positive rate of HSV-2 Ig M was 4.13%(17/411).In the multivariate analysis,after adjusting for age and sex,early diagnosis calendar and long diagnosis time were found to be risk factors for HSV-2 co-infection.2.400 patients with acute stage infection were enrolled,among whom 46.5% were rapidly progressing,35.1% were rapidly progressing at 12 months after infection,and63.9% were rapidly progressing at 24 months after infection.After adjusting for demographic characteristics such as age and sex,multivariate analysis showed that HSV-2 co-infection was a risk factor for rapid progression of HIV disease(P<0.001).3.We enrolled 991 patients with chronic HIV infection who received antiviral treatment.First,we selected 814 HIV-infected patients with CD4 count <350/ul before treatment,and assessed the occurrence of two consecutive CD4 count >350 /ul events.In multivariate analysis,HSV-2 negative was still found to be a protective factor for immune recovery,and young age,TDF+3TC+EFV or AZT+3TC+EFV regimen,high CD4/CD8 and low HIV viral load were protective factors for CD4 count recovery(all P values <0.05).We selected 905 HIV-infected patients with CD4/CD8 ratio <0.5 before treatment,and both univariate and multivariate analyses found that HSV-2 negative was an independent predictor of CD4/CD8>0.5 after treatment.We analyzed the risk factors for treatment failure and death in 991 HIV-infected patients.Multivariate analysis showed that HSV-2 positive,HBs Ag positive,low CD4 count(CD4 count <200 /ul)and high HIV viral load(>100000)Conclusion:1.The sero-prevalence of HSV-2 in HIV-infected persons is high,and the risk factors of HSV-2 infection are old age,early HIV diagnosis and long HIV diagnosis time.2.The disease progression of HIV-1 infected MSM is fast,HSV-2 significantly accelerates the HIV disease progression.3.HSV-2 significantly affects the immune recovery after treatment,significantly increasing the risk of treatment failure and death... |
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