| Objective:In this study,a comprehensive description of the HBV/HCV co-infection rate in HIV/AIDS patients in China was conducted through systematic review and meta-analysis to understand the current status of HBV/HCV co-infection in HIV/AIDS patients in China,and to explore influence factors of co-infection of HBV/HCV in this population,providing clues for the subsequent study of co-infection and scientific evidence for the development of co-infection prevention strategies and measures.Methods:In this study,systematic review was conducted to qualitatively synthesize HBV/HCV co-infection rates and influence factors in HIV/AIDS patients in China,and meta-analysis was conducted for quantitative integration if conditions permitted.The literature search used January 1,2017 as a deadline,and‘HIV/AIDS',‘HBV',‘HCV',and other related words were used as keywords to make up search strategy mainly in PubMed,China Knowledge Network and the Knowledge Service Platform of the Wanfang Data,and all retrieved literature were exported.According to the pre-established inclusion and exclusion criteria,the EndNote software was used for the initial screening of the literature(by reading the title and abstract),and the remaining literature were read through the full text for secondary screening.The pre-made data extraction form was used to extract the original research information,mainly collecting basic information,research objects,research methods,and research results.AHRQ research quality evaluation items and NOS literature quality assessment scale were used for the evaluation of literature quality,respectively for cross-sectional study,case-control study and cohort study.The screening of literature,data extraction and the literature quality evaluation were accomplished by two persons,and disputation was resolved through discussion.R 3.4.3 software was used to accomplish meta-analysis.The meta-analysis models were selected based on the heterogeneity test results——p<0.10 and I~2>50%was considered as high heterogeneity,and if I~2>50%then random-effect model should be used,otherwise the heterogeneity was small,fixed-effect model should be used to calculate the combined co-infection rates or the effect of influence factors.And Egger's test combined with funnel plot was used to determine whether there was publication bias.If the number of studies included exceeded10,the subgroup analysis was performed based on regional distribution and population sources.And sensitivity analysis was conducted to determine the stability of the results.Results:1.Inclusion of the basic situation of the study:The HIV/HBV/HCV co-infection rates systematic review and meta-analysis included a total of 103 articles,including 9English articles and 94 Chinese articles;co-infection influencing factors systematic review and meta-analysis included a total of 37 articles,including 3 English articles and 34Chinese articles.68,254 HIV/AIDS patients were included in the study,and the study population came from a total of 22 provinces and municipalities.The main population sources were:general population(28 articles),HIV/AIDS patients(50),drug users(15),MSM(8),and paid blood donors(2),and so on.2.Systematic review and meta-analysis of HBV/HCV co-infection rates in HIV/AIDS patients in China:2.1 HIV/HBV co-infection rateThe meta-analysis of HIV/HBV co-infection rate included 56 articles,51 Chinese and5 English.Because of the greater heterogeneity(p<0.01,I~2>50%),random effects model was chosen for consolidation.The HBV coinfection rate among HIV/AIDS patients in China was 12%(10%~14%).Funnel plot and Egger's test result indicated that there was no publication bias.HIV/AIDS patients in different regions had different rates of HBV co-infection,and the combined HIV/HBV infection rate in Central China was as high as 16%(95%CI:9%~27%),followed by East China and South China,and the lowest in Southwest China.The co-infection rate was 8%(95%CI:6%~11%).The rate of coinfection among HIV/AIDS patients who received antiviral therapy was almost the same as that of untreated patients.It was noteworthy that the HIV/HBV co-infection rate varies significantly among different populations,among which the HBV co-infection rate among HIV/AIDS patients in the MSM population was as high as 47%(95%CI:35%~63%),which was higher than that of the general population(8%,95%CI:5%~12%),and the coinfection rate of HIV/AIDS patients among drug users was lower(11%,95%CI:2%~48%).2.2 HIV/HCV co-infection rateThe systematic review and meta-analysis of HIV/HCV co-infection rate included 93articles,85 Chinese and 8 English.Because the heterogeneity was significant(p<0.01,I~2>50%),random-effect model was used to combine and the results showed that the HCV coinfection rate in HIV/AIDS patients in China was 33%(95%CI:30%~36%).Funnel plot and Egger's test result showed that there was publication bias,and studies with lower HIV/HCV co-infection rates were significantly more published than those with higher infection rates.The HIV/HCV co-infection rate in different regions was slightly different,with the combined infection rate in the northwest region as high as 45%(95%CI:35%~58%)and the lowest in Taiwan(20%,95%CI:3%~100%).The HIV/HCV co-infection rate of different populations was quite different.The rate of HCV co-infection among HIV/AIDS patients in drug users was as high as 93%(95%CI:91%~96%),and the HCV co-infection rate of HIV/AIDS patients with paid blood donation experience was 91%(95%CI:86%~95%).The co-infection rate of these two groups was significantly higher than that of other populations.In contrast,the HCV co-infection rate of HIV-infected MSM population was very low(2%,95%CI:1%~3%).2.3 HIV/HBV/HCV triple-infection rateThe HIV/HBV/HCV triple co-infection analysis section included 36 articles,33Chinese and 3 English.Due to the significant heterogeneity(p<0.01,I~2>50%),random effects model was selected.The results showed that the triple combined infection rate in HIV/AIDS patients in China was 5%(95%CI:3%~6%).There was no publication bias.The triple infection rate among HIV/AIDS patients varied in different regions,with the highest in Central China,which was 9%(95%CI:5%~19%),followed by the Northwestern region(7%,95%CI:1%~62%),and the lowest in the East China.In addition,the triple combined infection rate among HIV/AIDS patients from different populations was significantly different.The HIV/AIDS patients in drug users were particularly worthy of attention whose triple combined infection rate of was 11%(95%CI:1%~100%).3.Systematic review and meta-analysis of related factors of HBV/HCV co-infection among HIV/AIDS patients in China:3.1 GenderThe heterogeneity in meta-analysis of the relationship between gender and the two kinds of co-infection was obvious(p=0.08,p<0.01,I~2>50%),so the results were combined using random-effect models.The results found that the risk of developing two types of coinfection in male patients was higher than that in female patients,and the risk of HIV/HBV coinfection in male patients was 1.38 times higher than that of female patients(OR=1.38,95%CI:1.18~1.62),the risk of HIV/HCV co-infection in male patients was2.06 times higher than that of women(OR=2.06,95%CI:1.37~3.10).Subgroup analysis results:except for drug users,the risk of HIV/HBV co-infection risk among male patients from the other two populations is higher than female,and HIV/HCV co-infection risk among male patients is higher than female in each subgroup.3.2 CD4~+T lymphocyte levelsThe heterogeneity of the meta-analysis of CD4~+T-lymphocyte levels and HIV/HBV co-infection was relatively small(p=0.89,I~2=0),thus fixed-effect model was chosen;while the heterogeneity in meta-analysis of HIV/HCV coinfection was significant(p<0.01,I~2>50%),so random-effect model was used.Patients with CD4~+T-lymphocyte levels?350cells/mm~3 had a lower risk of HIV/HCV co-infection than those with CD4~+T-lymphocyte cells<350 cells/mm~3.The former had a 26%lower risk of HCV coinfection than the latter(OR=0.74,95%CI:0.57~0.95).No significance was found between CD4~+T lymphocyte levels and the HIV/HBV co-infection(OR=1.16,95%CI:0.96~1.40).There were few relevant studies,and no subgroup analysis has been conducted.3.3 Sexual transmission and transmission by intravenous drug useThe heterogeneity of the meta-analysis of the relationship between transmission by intravenous drug use and sexually transmission and two types of co-infection(HIV/HBV and HIV/HCV)was significant(p<0.01,I~2>50%).Therefore,random-effect models were used for analysis.There was no significant difference in the risk of HBV co-infection between HIV-infected individuals with intravenous drug use and with sexual transmission(OR=1.32,95%CI:0.95~1.82).The risk of HCV coinfection was statistically significant.The risk of HCV co-infection in HIV-infected persons who received intravenous drug use was 30.68-fold higher than that of sexually transmitted patients(OR=30.68,95%CI:15.04~62.58).There was no statistically significant difference in the risk of HIV/HBV co-infection between the two routes of transmission in each subgroup,while the risk of HIV/HCV co-infection between the two routes in each subgroup all indicated that the HIV/HCV coinfection rates among the HIV-infected by intravenous drug use were higher than that of sexually transmitted patients,but the magnitude of the effect varied among the study populations.3.4 Homosexual transmission and heterosexual transmissionThe heterogeneity of the meta-analysis of the relationship between homosexual transmission and heterosexual transmission of HIV and two types of coinfections(HIV/HBV and HIV/HCV)was significant(p<0.10,I~2>50%),and random effect models were selected.The risk of HCV coinfection among the homosexual transmitted was 50%of the heterosexually transmitted patients(OR=0.50,95%CI:0.32~0.77).Given the relatively few studies,subgroup analysis was omitted.3.5 HIV/HBV/HCV Triple infection analysisThe only study of the factors affecting triple infection showed that the risk of triple infection in HIV-infected persons transmitted by intravenous drug use was 12.47 times(OR=12.47,95%CI:7.99~19.46)higher than that of sexually transmitted patients.There was no statistical difference in the risk of triple infection between the homosexually transmitted and the heterosexually transmitted.Conclusion:1.The HBV co-infection rate among HIV/AIDS patients in China was 12%(10 to14%),which was significantly higher than that of the general population in China.The HIV/HBV co-infection rate was relatively higher in East China,Central China,and South China.Therefore,the three regions should be the focus areas for prevention.MSM population may be the most concerned population for HIV/HBV co-infection prevention.2.The HCV co-infection rate in HIV/AIDS patients in China was 33%(30%to36%),which was significantly higher than the general population in China.Among the drug users,HIV/AIDS patients had the highest HCV coinfection rate,and this population should be the key high-risk population.3.The HIV/HBV/HCV triple infection rate in HIV/AIDS patients in China was 5%(3%~6%).Central China and the Northwest region should serve as the key prevention areas for triple infection.4.HIV transmission through intravenous drug use was an important risk factor for HCV co-infection in HIV/AIDS patients.There was also gender difference in HBV and HCV co-infection among HIV/AIDS patients,which also associated with intravenous drug use.5.Targeting HIV/AIDS patients in China,we should combine prevention and control of infection with antiviral therapy.We must also recognize the importance of intravenous drug use in the occurrence and spread of co-infection,and then carry out more comprehensive strategy of the HBV and HCV coinfection prevention,diagnosis and treatment among both HIV/AIDS patients and drug users for the purpose of helping maintain and improve the quality of life of patients,and control the HIV,HBV and HCV epidemic in China.6.The HBV and HCV co-infection of HIV/AIDS patients in two groups of special populations——drug users(especially intravenous drug users)and MSM population deserves urgently attention and much more study in order to provide study evidence for making better prevention strategy of HIV/HBV/HCV coinfection. |
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