The Prevalence of Human Cytomegalovirus Viremia among HIV-1 Infected Individuals Undergoing Antiretroviral Therapy

HIV infection is an emerging health issue in Libya, particularly among young adults. Human cytomegalovirus (HCMV) is a prevalent infectious agent that presents with subclinical and fatal diseases in immunosuppressed individuals including HIV-infected individuals. Although the impact of HCMV infection in HIV-positive patients is well documented in several regions, epidemiologic estimates concerning HCMV co-infection among HIV-infected individuals remain limited in Libya. Hence, this cross-sectional study was undertaken to derive data regarding the prevalence of active HCMV viremia among HIV-infected individuals undergoing antiretroviral therapy (ART) from Libya. A total of 90 consented HIV-infected subjects followed by the National Center for Disease Control (NCDC) of Benghazi/Libya were recruited in this study and investigated for HCMV-IgG, HCMV-IgM specific antibodies, detection of HCMV lower matrix phosphoprotein (pp65) antigen, and detection of HCMV-DNA using qPCR to assess the prevalence of HCMV viremia. We determined that 77 (85.56%) of subjects were seropositive for HCMV-IgG antibodies, whereas the seropositivity for HCMV-IgM was 3.33% (3/90 subjects). Our results also revealed that 4.44% (4/90) of participants had viral antigenemia based on the laboratory diagnosis of HCMV-pp65. Regarding the PCR, we were able to detect the DNA of HCMV only in 3/90 subjects (3.33%) suggesting an active viremic condition. The detection of HCMV DNA along with the HCMV-pp65 in HIV-positive individuals highlights the necessity of early diagnosis to manage the progression of the disease. Furthermore, we highly recommend the use of anti-HCMV therapy in viremic individuals in combination with ART to reduce the burden of HCMV complications.

New therapeutic options for persistent low-level viremia in patients with chronic hepatitis B virus infection:Increase of entecavir dosage

Chronic hepatitis B virus(HBV)infection(CHB)is a public health concern worldwide.Current therapies utilizing nucleos(t)ide analogs(NA)have not resulted in a complete cure for CHB.Furthermore,patients on long-term NA treatment often develop low-level viremia(LLV).Persistent LLV,in addition to causing the progression of liver disease or hepatocellular carcinoma,may shed light on the current plight of NA therapy.Here,we review the literature on LLV,NA treatment,and various doses of entecavir to find a strategy for improving the efficacy of this antiviral agent.For LLV patients,three therapeutic options are available,switching to another antiviral monotherapy,interferon-αswitching therapy,and continuing monotherapy.In real-world clinical practice,entecavir overdose has been used in antiviral therapy for CHB patients with NA refractory and persistent LLV,which encouraged us to conduct further in-depth literature survey on dosage and duration related entecavir studies.The studies of pharmacodynamics and pharmacokinetics show that entecavir has the maximal selected index for safety,and has great potential in inhibiting HBV replication,in all of the NAs.In the particular section of the drug approval package published by the United States Food and Drug Administration,entecavir doses 2.5-20 mg/d do not increase adverse events,and entecavir doses higher than 1.0 mg/d might improve the antiviral efficacy.The literature survey led us to two suggestions:(1)Increasing entecavir dose to 1.0 mg/d for the treatment of NA naïve patients with HBV DNA>2×106 IU/mL is feasible and would provide better prognosis;and(2)Further research is needed to assess the long-term toxic effects of higher entecavir doses(2.5 and 5.0 mg/d),which may prove beneficial in treating patients with prior NA treatment,partial virological response,or LLV state.

HIV Drug Resistance Profiles and Clinical Outcomes in Patients with Viremia Maintained at Very Low Levels

We describe an observational study of clinical, virologic and drug resistance profiles in HIV-positive antiretroviral adherent subjects with stable low level viremia (LLV) 50 - 1000 copies/mL for more than 12 months. Subjects were followed from time of first detectable viral load (VL). In total, 102 episodes of LLV were detected among 80 individuals. The median (mean, range) HIV copy number at genotyping was 250 (486, - 3900) copies/mL after 14 (17.9, 0 - 58) months of LLV. Few patients maintained LLV for the entire 9 years period of observation, with half (52%) experiencing viremic progression following a stable period of LLV either spontaneously or after treatment interruption or failed regimen intensification. In the setting of prolonged periods of sustained LLV, mean duration 22 (range 8 - 106) months, drug resistance (DR) was almost universal. Resistance to ≥1 on-treatment drugs was defined in 97% of specimens and DR to all drugs in the treatment regimen in over half of all patients. Evolution of DR mutations during the period of LLV was observed in 20/28 (71%) subjects with specimens available for follow-up testing. This evolution was associated with viremic progression to levels >1000 copies/mL (p = 0.03). Our data suggest that DR present in patients with LLV is likely to impact long term clinical outcomes, highlighting the importance of optimizing techniques to detect the presence of drug resistant HIV in the setting of LLV and the need for larger prospective studies to assess the emergence of DR in the setting of sustained LLV and the impact of this DR on treatment outcomes.

Effects of viremia and CD4 recovery on gut“microbiome-immunity”axis in treatment-na?ve HIV-1-infected patients undergoing antiretroviral therapy

BACKGROUND Human immunodeficiency virus type 1(HIV-1)infection is characterized by persistent systemic inflammation and immune activation,even in patients receiving effective antiretroviral therapy(ART).Converging data from many cross-sectional studies suggest that gut microbiota(GM)changes can occur throughout including human immunodeficiency virus(HIV)infection,treated by ART;however,the results are contrasting.For the first time,we compared the fecal microbial composition,serum and fecal microbial metabolites,and serum cytokine profile of treatment-na?ve patients before starting ART and after reaching virological suppression,after 24 wk of ART therapy.In addition,we compared the microbiota composition,microbial metabolites,and cytokine profile of patients with CD4/CD8 ratio<1(immunological non-responders[INRs])and CD4/CD8>1(immunological responders[IRs]),after 24 wk of ART therapy.AIM To compare for the first time the fecal microbial composition,serum and fecal microbial metabolites,and serum cytokine profile of treatment-na?ve patients before starting ART and after reaching virological suppression(HIV RNA<50 copies/m L)after 24 wk of ART.METHODS We enrolled 12 treatment-na?ve HIV-infected patients receiving ART(mainly based on integrase inhibitors).Fecal microbiota composition was assessed through next generation sequencing.In addition,a comprehensive analysis of a blood broad-spectrum cytokine panel was performed through a multiplex approach.At the same time,serum free fatty acid(FFA)and fecal short chain fatty acid levels were obtained through gas chromatography-mass spectrometry.RESULTS We first compared microbiota signatures,FFA levels,and cytokine profile before starting ART and after reaching virological suppression.Modest alterations were observed in microbiota composition,in particular in the viral suppression condition,we detected an increase of Ruminococcus and Succinivibrio and a decrease of Intestinibacter.Moreover,in the same condition,we also observed augmented levels of serum propionic and butyric acids.Contemporarily,a reduction of serum IP-10 and an increase of IL-8 levels were detected in the viral suppression condition.In addition,the same components were compared between IRs and INRs.Concerning the microflora population,we detected a reduction of Faecalibacterium and an increase of Alistipes in INRs.Simultaneously,fecal isobutyric,isovaleric,and 2-methylbutyric acids were also increased in INRs.CONCLUSION Our results provided an additional perspective about the impact of HIV infection,ART,and immune recovery on the"microbiome-immunity axis"at the metabolism level.These factors can act as indicators of the active processes occurring in the gastrointestinal tract.Individuals with HIV-1 infection,before ART and after reaching virological suppression with 24 wk of ART,displayed a microbiota with unchanged overall bacterial diversity;moreover,their systemic inflammatory status seems not to be completely restored.In addition,we confirmed the role of the GM metabolites in immune reconstitution.

湖南省HIV-1低病毒血症患者的生存质量及影响因素调查

目的 了解湖南省艾滋病低病毒血症(low-level viremia, LLV)患者生存质量的影响因素,为艾滋病防治策略的制定提供依据。方法 应用方便抽样的方式,采用自编的一般情况调查表和世界卫生组织生存质量测量简表(WHOQOL-HIV BREF)对44例LLV患者进行横断面调查,采用t检验、F检验、多元线性回归分析生存质量的影响因素。结果 44例LLV人群中,男性29例(65.91%),45~59岁年龄组16例(36.36%),37例(84.09%)服药依从性较好,7例(15.91%)服药依从性差,存在漏服药物的情况。LLV患者生存质量总均分为(68.58±6.04)分,生理领域均分为(10.77±1.49)分。单因素分析显示,不同生活居住地、职业、月收入水平、是否出现药物不良反应患者的生理领域得分比较,差异均有统计学意义(均P<0.05);多元线性回归分析显示不同文化程度(B_(心理)=0.449,P_(心理)=0.048;B_(环境)=0.851,P_(环境)=0.028)、月收入水平(B_(独立性)=1.072,P_(独立性)=0.006;B_(环境)=0.989,P_(环境)=0.026)、是否出现药物不良反应(B_(生理)=-1.665,P_(生理)=0.002)等是影响患者生存质量各领域的重要因素。结论 LLV患者的生存质量得分较低,应更加重视文化程度低、收入水平低、出现药物不良反应的患者,改善其生活质量。

HIV低病毒血症的影响因素及其临床意义研究

目的探讨HIV低病毒血症(low-level viremia,LLV)的影响因素及低病毒血症对病毒学失败(virological failure,VF)的影响。方法回顾性收集抗逆转录病毒治疗(antiretroviral therapy,ART)起始时间为2011年1月1日至2015年12月31日,并随访至2020年12月31日,且年龄大于等于18周岁的HIV感染者人口学特征和临床资料。研究对象分为长期抑制组和LLV组,就抑制组与LLV组的年龄、性别、基线病毒载量(viral load,VL)、基线CD_(4)^(+)T淋巴细胞计数、依从性、随访期间是否换药等指标进行比较分析。结果本研究共纳入3787名患者,年龄中位数为34(27,46)岁,男性占比为92.81%,其中抑制组3201例(84.53%)。其中年龄、基线VL≥1×10^(5) copies/ml、依从性较差、基线CD_(4)^(+)T淋巴细胞计数≥200cells/mm^(3)、起始ART方案中核心药物和有无合并症可能是LLV的影响因素。LLV组59.73%的患者出现LLV在开始ART后的1年内。当LLV患者的VL≥200copies/ml时,LLV是VF的危险因素。结论当HIV感染者ART出现影响LLV因素或LLV患者VL≥200copies/ml时,临床医师需高度关注该时期患者VL的变化,必要时增加患者检测VL的频率。

Characterization of Genotypic Mutations and Antiretroviral Resistance among Viremic HIV-Infected Patients in a High HIV Prevalence Area: Treatment Challenge and Transmission Risk

There have been few reports evaluating the prevalence of genotypic mutations and antiretroviral resistance among chronic HIV-infected Veterans within the United States. This retrospective cross-sectional study characterizes the rates and changes in HIV genotypic mutations and antiretroviral resistance among viremic patients from 2001 to 2006 at the VA Medical Center located in Washington, DC. The District of Columbia is the metropolitan area with the highest HIV prevalence within the United States. De-identified, linked HIV RNA, genotypic reverse transcriptase (RT) and protease (Pr) mutations and antiretroviral resistance results were assessed for changes during the 6-year period. Aggregated clinic and antiretroviral utilization, and HIV acquisition risk data were evaluated for patients in care during this time. Among 990 viremic samples, the rate of any detected RT or Pr mutation fell from 100% in 2001 to 95% in 2006. This was primarily attributable to the 15% - 20% decrease seen for RT gene mutations against nucleoside/nucleotide class and non-nucleoside class during this period. Resistance to didanosine, stavudine, zidovudine, nevirapine and efavirenz decreased, and tenofovir resistance increased. Despite stable rates of Pr gene mutations, atazanavir resistance increased by 22% from 2003 to 2006. Some but not all changes in genotypic mutations and resistance patterns reflected our patients’ antiretroviral drug utilization. As sexual contacts (77%) and injection drug use (22%) were the leading acquisition risks disclosed by our HIV-infected patients, the high prevalence and changing patterns of HIV genotypic mutations and drug resistance among these patients have had pivotal impacts not only on HIV treatment but potential transmission into our community.

艾滋病病毒血浆控制者外周血淋巴细胞亚群分析

目的目前对艾滋病病毒(HIV)血浆控制者机体免疫机制的研究仍然较少。文中旨在分析HIV血浆控制者外周血淋巴细胞亚群的分布及其相关性,了解其免疫功能状况,为研究其免疫机制提供参考。方法选取江苏省2016年1月至2018年12月29例HIV-1抗体确证5年以上的阳性患者。根据患者CD4细胞计数和病毒载量水平分为:血浆控制组[病毒载量<2000 copies/mL,平均病毒载量(991±887)copies/mL,n=6]、慢性感染组[病毒载量≥2000 copies/mL,平均病毒载量(52181±10180)copies/mL,n=23],另选取健康人群为对照组(n=70)。采用流式细胞仪对各组人群外周血淋巴细胞亚群进行检测,比较3组间CD4+ T淋巴细胞、CD8+ T淋巴细胞、NK细胞和B细胞的绝对计数,分析各组外周血淋巴细胞亚群的相关性。结果血浆控制组、慢性感染组CD4+T、CD8+T计数明显低于健康对照组(P<0.05),血浆控制组CD4+T计数明显高于慢性感染者组[(697.9±160.4)个/μL vs(399.3±118.7)个/μL,P<0.05]。慢性感染组NK细胞计数明显低于健康对照(P<0.05),血浆控制者组和健康对照组差异无统计学意义(P>0.05)。血浆控制组与健康对照组B细胞计数[(322.0±261.5)个/μL、(294.9±86.2)个/μL]明显高于慢性感染组[(127.1±98.7)个/μL],差异有统计学意义(P<0.05)。血浆控制组外周血CD4+、B和NK细胞计数之间两两呈正相关(P<0.05)。结论血浆控制者各淋巴细胞细胞亚群的数量高于慢性感染者,淋巴细胞亚群之间存在积极的相互促进关系,为进一步研究血浆控制者免疫作用机制提供了参考。

艾滋病低病毒血症的影响因素及临床意义研究进展

目前对于艾滋病低病毒血症的定义仍没有统一的共识,不同研究对于同一临床影响因素得到的结果也不完全相同。现将近年来国内外对低病毒血症的研究进行综述,总结与其有关的临床影响因素及其临床危害。通过现有论著结果表明抗病毒治疗前的CD_(4)^(+)T淋巴细胞水平、基线病毒载量、抗病毒治疗依从性可能是低病毒血症的影响因素。艾滋病低病毒血症也会增加病毒学治疗失败的风险,从而增加病毒传播的风险。临床医生必须密切关注低病毒血症的危害及其影响因素,对有相关危险因素的患者进行密切随访做到及时处理,以防止艾滋病低病毒血症的发生。

Low-level viremia in nucleoside analog-treated chronic hepatitis B patients

Low-level viremia(LLV)was defined as persistent or intermittent episodes of detectable hepatitis B virus(HBV)DNA(<2000 IU/mL,detection limit of 10 IU/mL)after 48 weeks of antiviral treatment.Effective antiviral therapies for chronic hepatitis B(CHB)patients,such as entecavir(ETV),tenofovir disoproxil fumarate(TDF),and tenofovir alafenamide(TAF),have been shown to inhibit the replication of HBV DNA and prevent liver-related complications.However,even with long-term antiviral therapy,there are still a number of patients with persistent or intermittent LLV.At present,the research on LLV to address whether adversely affect the clinical outcome is limited,and the follow-up treatment for these patients is open to question.At the same time,the mechanism of LLV is not clear.In this review,we summarize the incidence of LLV,the association between LLV and long-term outcomes,possible mechanisms,and management strategies in these patient populations.

Risk factors for very low-level viremia in patients with chronic hepatitis B virus infection: A single-center retrospective study

Background and aim:Several effective antiviral drugs are now available;however,the risk of liver-related complications is still present.Low-level viremia(LLV),defined as a hepatitis B virus(HBV)deoxy-ribonucleic acid(DNA)load lower than 2000 IU/mL,is one of the major factors responsible for these complications.It has been reported that 22.7e43.1%of patients with HBV experience LLV.Herein,we aimed to explore the risk factors for very LLV(VLLV)during antiviral treatment.Methods:We collected data of patients with chronic hepatitis B(CHB)who received nucleos(t)ide analog treatment from October 2016 to April 2021.VLLV was defined as an HBV DNA load of 9e20 IU/mL.A total of 139 patients with LLV were matched with 139 patients with a sustained virological response at a 1:1 ratio according to age and gender.Results:Seropositivity rates for hepatitis B e antigen(HBeAg)(45.3%vs.17.3%,P<0.001)and hepatitis B surface antigen(HBsAg,3.11±0.68 lg IU/mL vs.2.54±1.04 lg IU/mL,P<0.001)and alanine amino-transferase levels(30.34±15.08 U/L vs.26.15±16.66 U/L,P¼0.040)in the two groups were significantly different.The multivariate analysis showed that both HBeAg seropositivity(adjusted odd ratio(aOR),3.63;95% confidence interval(CI):1.98±6.64;P<0.001)and HBsAg levels(aOR,2.21;95% CI:1.53±3.20;P<0.001)are independent risk factors for VLLV.During the multivariate analysis in the subgroup of HBeAg-positive patients,male gender(aOR,3.68;95% CI:1.23±10.76;P=0.017)and high HBsAg(aOR,4.86;95%CI:1.73e13.64;P¼0.003)levels were significantly correlated with VLLV.However,this was not the case in HBeAg-negative patients(P>0.050).HBeAg seropositivity(aOR,5.08;95% CI:2.15±12.02;P<0.001 vs.aOR,2.78;95% CI:1.16±7.00;P=0.022)and HBsAg levels(aOR,2.75;95% CI:1.41e5.37;P=0.003 vs.aOR,2.10;95% CI:1.27±3.46;P=0.004)significantly increased the risk of VLLV,irrespective of the age group.Both HBsAg(area under the receiver operating characteristic curve(AUC),0.681;95% CI:0.623±0.736;P<0.001)and HBeAg(AUC,0.640;95% CI:0.581±0.697;P<0.001)had certain pre-dictive value for VLLV.Conclusion:HBeAg seropositivity and higher HBsAg levels were not only risk factors for VLLV but also predicted its occurrence.When a patient with CHB remains HBeAg seropositive with high HBsAg levels after antiviral treatment for 48 weeks,emphasis should be placed on the potential occurrence of VLLV,warranting the use of highly sensitive HBV DNA detection methods.

2015-2021年湖南省HIV-1低病毒血症患者基本特征与发生耐药风险分析

目的分析湖南省艾滋病低病毒血症(low-level viremia,LLV)患者信息数据,探讨其发生耐药风险的影响因素。方法收集艾滋病综合防治数据信息管理系统中湖南省2015年1月1日-2021年12月31日艾滋病患者抗病毒治疗信息资料,对LLV患者基础特征进行描述性分析,采用χ^(2)检验分析持续性低病毒血症(persistent low-level viremia,pLLV)、间歇性低病毒血症(viral blip,Blip)患者分别与病毒学长期抑制(virologic suppression,VS)和病毒学失败(virological failure,VF)患者的特征差异性,使用logistic回归和限制性立方样条(restricted cubic spline,RCS)模型分析不同病毒载量的pLLV、Blip与耐药风险的关联性。结果2015—2021年湖南省发生pLLV、Blip、VS、VF的患者分别为233、3316、18682、7235例。单因素分析结果显示,pLLV、Blip患者分别与VS和VF患者比较,性别(χ_(1)^(2)=61.929,P_(1)<0.01;χ_(2)^(2)=25.872,P_(2)<0.01)、年龄(χ_(1)^(2)=11.312,P_(1)=0.023;χ_(2)^(2)=149.75,P 2<0.01)、感染途径(χ_(1)^(2)=116.207,P_(1)<0.01;χ_(2)^(2)=508.515,P_(2)<0.01)、WHO分期(χ_(1)^(2)=206.357,P_(1)<0.01;χ_(2)^(2)=52.948,P_(2)<0.01)、入组CD4+T淋巴细胞数(χ_(1)^(2)=177.715,P_(1)<0.01;χ_(2)^(2)=50.484,P_(2)<0.01)、治疗时长(χ_(1)^(2)=464.055,P_(1)<0.01;χ_(2)^(2)=685.623,P_(2)<0.01)、初始治疗方案(χ_(1)^(2)=87.935,P_(1)<0.01;χ_(2)^(2)=281.910,P_(2)<0.01)和是否耐药(χ_(1)^(2)=743.141,P_(1)<0.01;χ_(2)^(2)=125.616,P 2<0.01)等因素差异均有统计学意义,但2组患者与VF患者比较体质量指数(BMI)差异无统计学意义(χ_(2)^(2)=13.631,P_(2)=0.092),与VS患者比较婚姻状况差异无统计学意义(χ_(1)^(2)=5.710,P_(1)=0.434)。logistic回归分析结果提示,500~999拷贝/ml的pLLV与耐药发生有关(OR=7.427,95%CI:3.318~16.626),RCS模型显示pLLV和Blip的病毒载量水平变化与耐药发生风险呈线性剂量反应关系(整体关联性检验χ_(p)^(2)=19.22,P p=0.014;χ_( B)^(2)=107.08,P_(B)<0.01;非线性检验χ_(p)^(2)=1.30,P p=0.254;χ_(B)^(2)=1.47,P_(B)=0.225)。结论与VS和VF患者比较,pLLV和Blip患者的基本特征具有特异性,2类艾滋病患者的病毒载量水平越高则与耐药发生风险关联性越强,在抗病毒治疗过程中应该引起重视和关注。

德宏州ART后HIV低病毒血症毒株基因亚型和耐药分析

目的探究接受抗病毒治疗的HIV/AIDS低病毒血症患者耐药情况和影响因素,基因亚型与耐药位点突变情况。方法纳入病毒载量50-999copies/mL的HIV/AIDS患者,巢式PCR扩增HIV-1的pol基因后进行耐药检测,根据世界卫生组织耐药标准和斯坦福大学耐药数据库判定耐药、确定突变位点以及毒株对ART药物的敏感性,Logistic回归分析耐药影响因素。结果896例低病毒血症患者中65.6%(588例)pol基因扩增成功。总耐药率为24.7%(145/588),NNRITs耐药率最高,为21.3%(125/588),部分患者存在多重耐药。588例HIV/AIDS低病毒血症患者中HIV-1毒株BC重组亚型占25.2%(148人),B亚型占24.5%(144人),C亚型占23.5%(138人),CRF 01_AE亚型占14.3%(84人)。Logistic回归分析发现,耐药与HIV-1病毒亚型有关。B亚型耐药率最高,为43.1%(62/144),CRFs、C亚型、URFs耐药率分别为22.7%(32/141)、18.8%(26/138)、15.2%(25/165)。所有亚型中K103 N、M184V/I突变频率最高,分别产生了对EFV/NVP、3TC/FTC的高度耐药。结论德宏州接受ART的HIV/AIDS低病毒血症患者耐药较为常见,不同毒株基因亚型耐药率不同,出现了常见的几种耐药突变,并产生对NNRTIs和NRTIs的耐药。应及时监测该人群的耐药情况,为更换ART药物、改善预后提供依据。

Transcriptome analysis of CD4^(+)T cells from HIV-infected individuals receiving ART with LLV revealed novel transcription factors regulating HIV-1 promoter activity

Some HIV-infected individuals receiving ART develop low-level viremia(LLV),with a plasma viral load of 50-1000 copies/mL.Persistent low-level viremia is associated with subsequent virologic failure.The peripheral blood CD4^(+)T cell pool is a source of LLV.However,the intrinsic characteristics of CD4^(+)T cells in LLV which may contribute to low-level viremia are largely unknown.We analyzed the transcriptome profiling of peripheral blood CD4^(+)T cells from healthy controls(HC)and HIV-infected patients receiving ART with either virologic sup-pression(VS)or LLV.To identify pathways potentially responding to increasing viral loads from HC to VS and to LLV,KEGG pathways of differentially expressed genes(DEGs)were acquired by comparing VS with HC(VS-HC group)and LLV with VS(LLV-VS group),and overlapped pathways were analyzed.Characterization of DEGs in key overlapping pathways showed that CD4^(+)T cells in LLV expressed higher levels of Th1 signature transcription factors(TBX21),toll-like receptors(TLR-4,-6,-7 and-8),anti-HIV entry chemokines(CCL3 and CCL4),and anti-IL-1βfactors(ILRN and IL1R2)compared to VS.Our results also indicated activation of the NF-κB and TNF signaling pathways that could promote HIV-1 transcription.Finally,we evaluated the effects of 4 and 17 tran-scription factors that were upregulated in the VS-HC and LLV-VS groups,respectively,on HIV-1 promoter activity.Functional studies revealed that CXXC5 significantly increased,while SOX5 markedly suppressed HIV-1 tran-scription.In summary,we found that CD4^(+)T cells in LLV displayed a distinct mRNA profiling compared to that in VS,which promoted HIV-1 replication and r+eactivation of viral latency and may eventually contribute to virologic failure in patients with persistent LLV.CXXC5 and SOX5 may serve as targets for the development of latency-reversing agents.

抗病毒治疗后低病毒血症患者HIV-1基因型耐药特征分析

目的 分析北京佑安医院ART后发生低病毒血症(LLV)的HIV/AIDS患者病毒亚型及耐药特征。方法收集2020年1月至2021年6月期间在北京佑安医院性病艾滋病门诊常规接受ART≥6个月且发生LLV的HIV/AIDS患者随访3个月后的外周静脉血,通过对分离的血浆进行超速离心后提取HIV RNA,利用反转录-巢式荧光定量聚合酶链反应(RT-PCR)技术扩增pol基因区,测序成功后进行基因亚型和耐药突变分析。结果 共筛查了10 693例患者,LLV患者225例,LLV发生率2.1%。纳入研究期间成功留血液样本的患者134例,成功收集73份VL在50~999拷贝/mL的血浆样本。扩增得到51条序列,扩增成功率69.9%。51条序列来自41例患者,CRF01_AE亚型最常见(43.9%,18/41),其次为CRF07_BC亚型(19.5%,8/41),B亚型(19.5%,8/41)和C亚型(7.3%,3/41)。19例患者发现了耐药突变,整体耐药突变率为46.3%(19/41)。其中,以NNRTIs相关耐药突变为主,占36.6%(15/41),最常见的耐药突变位点为V106I/M和V179D/E;其次为NRTIs和PIs相关突变,分别占34.1%(14/41)和19.5%(8/41),最常见的突变位点M184V/I和M46I。结论 ART后LLV患者耐药突变较常见。VL较低的情况下也可以检测到耐药突变。对出现LLV的患者进行耐药检测将有助于优化治疗方案、改善临床结果。

HIV感染者巨细胞病毒血症现患率Meta分析

目的运用Meta分析了解HIV感染者巨细胞病毒(CMV)血症的流行情况及相关因素。方法系统检索2011-2020年PubMed、中国知网、万方数据知识服务平台、维普数据库中关于HIV感染者CMV血症现患率的文献,文献筛选和数据提取后进行Meta分析。结果共纳入15篇文献,总样本量为5076例。Meta随机效应模型显示,HIV感染者CMV血症合并现患率为26.2%(95%CI:16.8%~35.6%,I 2=99%);亚组分析和Meta回归结果显示,不同研究间异质性来源可能为:研究样本中>30岁人群比例、同性性传播比例、HIV病毒载量>104拷贝数/ml比例、CD4+T淋巴细胞计数<200个/μl比例。结论HIV感染者CMV血症现患率较高,现患CMV血症可能与HIV感染者的年龄、HIV感染途径、艾滋病病程进展密切相关。

台州市2017-2018年新报告HIV/AIDS巨细胞病毒血症现患率及影响因素研究

目的了解2017-2018年台州市新报告且未接受抗病毒治疗(ART)的HIV/AIDS血浆巨细胞病毒血症现患率及其影响因素。方法收集台州市新报告且未接受ART的成年HIV/AIDS血浆样本,提取核酸后采用荧光定量PCR检测巨细胞病毒DNA水平,采用单因素与多因素logistic回归分析其影响因素。结果研究对象612例HIV/AIDS中,男性480例(78.4%),年龄>60岁125例(20.4%),同性性传播者177例(28.9%),异性性传播者430例(70.3%)。巨细胞病毒血症现患率为13.4%(82/612)。多因素logistic回归分析结果显示,CD_(4)^(+)T淋巴细胞计数(CD4)≤200个/μl者现患巨细胞病毒血症的风险显著高于CD4>500个/μl者(OR=5.10,95%CI:1.74~14.96,P=0.003);82例现患巨细胞病毒血症者的血浆巨细胞病毒DNA载量(log10)中位数为1.57(P_(25),P_(75):1.04,2.13),CD4≤200个/μl者的巨细胞病毒载量最高(P<0.01)。结论2017-2018年台州市新报告未接受ART的HIV/AIDS中,巨细胞病毒血症现患率与免疫缺陷状态显著关联,巨细胞病毒血症对HIV/AIDS病程的影响有待进一步研究。

Chronic Hepatitis B Infection with Low Level Viremia Correlates with the Progression of the Liver Disease

Background and Aims:Currently,insufficient clinical data are available to address whether low-level viremia(LLV)observed during antiviral treatment will adversely affect the clinical outcome or whether treatment strategies should be altered if LLV occurs.This study compared the clinical out-comes of patients with a maintained virological response(MVR)and patients who experienced LLV and their treatment strategies.Methods:A retrospective cohort of 674 patients with chronic hepatitis B virus(HBV)infection who received antiviral treatment for more than 12 months was analyzed for the development of end-stage liver disease and treatment strategies during the follow-up period.End-stage liver disease included decompensated liver cirrhosis and hepatocellular carcinoma(HCC).Results:During a median 42-month follow-up,end-stage liver disease developed more frequently in patients who experienced LLV than in those who experienced MVR(7.73%and 15.85%vs.0.77%and 5.52%at 5 and 10 years,respectively;p=0.000).The trend was consistent after propensity score matching.In the high-risk group of four HCC risk models,LLV patients had a higher risk of HCC development(p<0.05).By Cox proportional hazard model analysis,LLV was an independent risk factor for end-stage liver disease and HCC(hazard ratio[HR]=6.280,confidence interval[CI]=2.081-18.951,p=0.001;HR=5.108,CI=1.392-18.737,respectively;p=0.014).Patients achieved a lower rate of end-stage liver disease by adjusting treatment compared to continuing the original treatment once LLV occurred(p<0.05).Conclusions:LLV is an independent risk factor for end-stage liver disease and HCC,and treatment adjustments can be considered.

Factors Associated with the Size of HIV DNA Reservoir

Objective： To review the recent literatures related to the factors associated with the size of the HIV reservoir and their clinical significance. Data Sources： Literatures related to the size of HIV DNA was collected from PubMed published from 1999 to June 2016. Study Selection： All relevant articles on the HIV DNA and reservoir were collected and reviewed, with no limitation of study design. Results： The composition and development of the HIV- 1 DNA reservoir in either treated or untreated patients is determined by integrated mechanism comprising viral characteristics, immune system, and treatment strategies. The HIV DNA reservoir is a combination of latency and activity. The residual viremia from the stochastic activation of the reservoir acts as the fuse, continuing to stimulate the immune system to maintain the activated microenvironment for the rebound of competent virus once treatment with antiretroviral therapy is discontinued. Conclusion： The size of the HIV-1 DNA pool and its composition has great significance in clinical treatment and disease progression.

社区HIV病毒载量可作为人群病毒载量最优替代指标

目的探讨适用于评估新疆伊宁市HIV传播潜力的人群病毒载量(PVL)最优替代指标。方法建立动态队列研究,监测伊宁市2017—2019年所有HIV/AIDS的病毒载量(VL),计算不同PVL替代指标值,并评估不同PVL替代指标、病毒血症流行率与HIV新发感染率、抗逆转录病毒治疗(ART)覆盖率、病毒抑制率的关联强度。结果新疆伊宁市2017—2019年HIV感染者的不同PVL指标值均呈逐年下降趋势(P<0.05),社区病毒载量(CVL)的减少与HIV新发感染率的增加之间显著相关(r=0.999,P=0.028),CVL与ART覆盖率(r=-1.000,P=0.001)、病毒抑制率(r=-1.000,P=0.010)均呈负相关。以不同VL值为界限的敏感性分析中的病毒血症流行率2(VL>400 copies/mL)和病毒血症流行率3(VL>1000 copies/mL)与HIV新发感染率呈正相关(r^(2)=0.997,P^(2)=0.048;r^(3)=0.998,P^(3)=0.041),与ART覆盖率(r^(2)=-1.000,P^(2)=0.019;r^(3)=-1.000,P^(3)=0.012)、病毒抑制率(r^(2)=-1.000,P^(2)=0.010;r^(3)=-1.000,P^(3)=0.003)均呈负相关。结论CVL为PVL最优替代指标,可与病毒血症流行率共同评估新疆伊宁市HIV传播潜力。