Occult hepatitis B virus infection in patients with leprosy

Leprosy patients may present with immune system impairment and have a higher hepatitis B virus (HBV) seroprevalence, justifying the investigation of occult HBV infection in these individuals. The aim of this study was to verify the frequency and the clinical factors associated with occult HBV infection in leprosy patients. Between 2015 and 2016, leprosy patients from a reference center in Brazil were interviewed to assess clinical data. Blood samples were collected for the screening of HBV serological markers using enzyme-linked immunosorbent assay. Patients with negative hepatitis B surface antigen (HBsAg) that had positive anti-HBc and/or anti-HBs were selected for HBV DNA detection using real-time polymerase chain reaction. SPSS was used for data analysis. Among 114 selected patients, six were identified with occult infection (5.3%) and five of them with multibacillary leprosy. Three patients with occult infection had a history of a type 2 reaction (P = 0.072; OR, 4.97; 95% CI, 0.87-28.52). Only two patients with occult infection had isolated anti-HBc, while three had isolated anti-HBs, including those with the highest HBV DNA titers. In conclusion, in leprosy patients with negative HBsAg and positive anti-HBc and/or anti-HBs, occult HBV infection occurs in 5.3% and can be found even in patients with isolated anti-HBs.     

中国北方地区隐源性肝炎及乙型肝炎表面抗原阴性肝癌患者中隐匿性HBV感染流行状况分析

目的调查中国北方地区隐源性肝炎及乙肝表面抗原（HBsAg）阴性肝癌患者中隐匿性乙型肝炎病毒（HBV）感染的流行状况。方法收集393个受试者的血清,其中包括隐源性慢性肝炎患者215名、HBsAg阴性肝癌患者178名。使用巢式PCR的方法检测血清中的HBV-DNA,同时使用实时定量PCR的方法检测HBV—DNA的载量。结果在隐源性慢性肝炎患者、HBsAg阴性肝癌患者中隐匿性HBV感染流行率分别为23．7％（51／215）和68．5％（122／178）。在IgGanti—HBc阳性者中,隐匿性HBV感染率较高。所有隐匿性感染者的病毒载量均较低（〈10^5拷贝／ml）。结论在中国北方隐源性肝炎及肝癌患者中,隐匿性HBV感染率较高。因此,对隐匿性HBV感染应给及足够的重视,避免因输血及器官移植造成HBV的传播。     

The prevalence and long term outcome of occult hepatitis B virus infections in community based populations

Features of occult hepatitis B infection in community‐based populations have yet to be described. In this study we documented: (1) the prevalence and demographics, (2) associated serology and viral loads, and (3) clinical outcomes of occult hepatitis B infection in community‐based populations. Hepatitis B surface antigen (HBsAg)‐negative sera collected from three Northern Canadian communities (HBsAg prevalences: 11–12%) in 1983–1985 were tested for HBV‐DNA by nested stage polymerase chain reaction. Of 706 HBsAg negative sera, 9 (1.3%) were HBV‐DNA positive. The median age of occult hepatitis B infected patients at the time of sampling was 9.8 years (range 3.1–50.4 years) and six (67%) were female. Two (22%) individuals were anti‐HBs positive (in the absence of prior vaccination). Viral loads were undetectable in all but two samples (2.40 and 2.86 log₁₀ IU/ml). Only one of the five (20%) patients who were assessed clinically, remained HBV‐DNA positive at 25–30 year follow‐up. There was no clinical, biochemical or radiologic evidence of chronic hepatitis, cirrhosis or hepatocellular carcinoma in these individuals or on review of the charts from the remaining four infected patients. The results of this study suggest that in community‐based populations: (1) occult hepatitis B infection is not as common as HBsAg positive infection, (2) the majority of infected subjects are young females, (3) a minority are anti‐HBs positive, (4) viral loads are either undetectable or low, and (5) in the absence of concurrent liver disease, occult hepatitis B infection does not appear to be associated with long term adverse clinical outcomes. J. Med. Virol. 84:1369–1375, 2012. © 2012 Wiley Periodicals, Inc.     

Hepatitis C virus is frequently coinfected with serum marker-negative hepatitis B virus: Probable replication promotion of the former by the latter as demonstrated by in vitro cotransfection

Patients with hepatitis C have been reported occasionally to be coinfected with serum marker-negative (silent) hepatitis B virus (HBV). The frequency and significance of such coinfection were investigated. Thirty patients with hepatitis C virus (HCV) infections (10 acute, 10 chronic, 10 cirrhotic) were selected randomly; the acute cases were without serum hepatitis B surface antigen (HBsAg) and anti-hepatitis B core IgM, and the chronic cases were without HBsAg. A nested polymerase chain reaction for the X open reading frame was used to amplify HBV DNA in serum, and immunoperoxidase staining was carried out on liver biopsy specimens. Nucleotide sequencing was carried out to characterize the amplified HBV DNAs. In order to clarify the possibility that the silent HBV mutant promotes HCV replication in the liver, the full-length HCV RNA and the cloned silent HBV DNA dimer were cotransfected into an established cell line, HuH-7, and the amount of secreted HCV RNA was quantified serially. The target HBV DNA was amplified in 26 (86.7%) of the 30 patients. Subsequent direct nucleotide sequencing in 9 selected patients revealed an 8-nucleotide deletion, characteristic of a silent HBV mutant. Immunostaining revealed hepatitis B surface antigen in 15 (50.0%). Cotransfected silent HBV DNA augmented the secretion of HCV RNA by up to 5-fold in comparison with HCV RNA transfection alone. In conclusion, HCV is coinfected frequently with the silent HBV mutant and the latter probably promotes the replication of the former in the liver. J. Med. Virol. 52:399–405, 1997. © 1997 Wiley-Liss, Inc.     

Occult hepatitis B virus infection in Lebanese patients with chronic hepatitis C liver disease

Occult hepatitis B virus (HBV) infection, characterised by the presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg), was investigated in 98 Lebanese patients with chronic hepatitis C liver disease and 85 control subjects recruited from eight institutions in different parts of the country. The prevalence of occult HBV infection ranged from 11.9% to 44.4% in hepatitis C virus (HCV)-infected patients and it increased with increasing severity of the liver disease. The overall rate of HBV DNA in our 98 HCV-infected patients was 16.3%. On the other hand, the rate of HBV DNA was 41.0% in anti-HBc alone positive patients compared to only 7.1% in healthy controls who were also anti-HBc alone positive (p < 0.001). Moreover, the prevalence HBV DNA increased with increasing severity of the liver disease, but this increase was only marginally significant and, perhaps, could have been significant if more patients were involved in the study. Although Lebanon is an area of low endemicity for both HBV and HCV, occult HBV infection is common in HCV-infected patients. The presence of HBV DNA, therefore, presents a challenge for the effective laboratory diagnosis of hepatitis B, particularly if polymerase chain reaction (PCR)-based HBV detection methods are not used.     

Viral deletions among healthy young Chinese adults with occult hepatitis B virus infection

To investigate the mechanism and prognosis of occult hepatitis B virus (HBV) infection (OBI) at a molecular level among healthy young adults, the presence of HBV DNA in 1176 sera samples collected from healthy young people after neonatal vaccination was assessed by nested polymerase chain reaction (PCR) using specific primers designed for the X and S regions of the HBV genome. Full-length HBV DNA from 9 patients with OBI (OB1-OB9) was cloned and sequenced. Deletions in the pre-S, basal core promoter (BCP), core (C) and polymerase (P) regions were observed. The data indicate that there is still a substantial risk of OBI in China despite neonatal vaccination. All deletions that were observed in the pre-S, BCP, C and P regions play a direct or indirect role in OBI. The presence of a deletion mutation in the pre-S1 region was considered to play a pivotal role in hepatocarcinogenesis and was found to increase the risk of hepatocellular carcinoma in the cohorts studied.     

Occult hepatitis B virus infection in the setting of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co‐infection: Clinically relevant or a diagnostic problem?

The clinical relevance of occult hepatitis B virus (HBV) infection, defined as detectable HBV DNA serum/liver, in the absence of hepatitis B surface antigen (HBsAg), is unclear. We determined the prevalence of serum occult HBV infection in HIV/HCV co-infected patients enrolled in APRICOT, a randomized multinational trial that investigated the efficacy and safety of peginterferon alfa-2a (40 kDa) plus ribavirin for treatment of HCV. We also examined the effect of prior HBV exposure to liver histology at baseline. Only HBsAg-negative patients were eligible. At screening, serum HBV DNA was assessed by commercial assay (detection limit = 200 copies/mL). Patients were divided into four serological groups: anti-HBs+/anti-HBc+; anti-HBs-/anti-HBc+; anti-HBs+/ anti-HBc-; anti-HBs-/anti-HBc-. Baseline liver biopsy grade and stage were compared among groups. Serum HBV DNA was undetectable in all patients, (n = 866). Results of anti-HBs and anti-HBc was available for 176 patients: 60 (34.1%) anti-HBs+/anti-HBc+; 60 (34.1%) anti-HBs-/anti-HBc+; 11 (6.3%) anti-HBs+/anti-HBc-; 45 (25.6%) anti-HBs-/anti-HBc-. There were no differences among the groups in the histological grade or stage at baseline liver biopsies. Occult HBV infection in serum was not detected in this large immunocompetent cohort. Moreover, prior exposure to HBV did not appear to have any affect on baseline liver histology.     

深圳地区不同人群TTV感染情况的调查

目的了解深圳地区不同人群ＴＴＶ的感染情况。方法在ＴＴＶＯＲＦ１保守区设计两对套式引物，建立了检测ＴＴＶＤＮＡ的巢式聚合酶链反应（Ｎｅｓｔｅｄ－ＰＣＲ），用该法对深圳地区９０例一般人群、８８例职业献血员、７９例静脉毒瘾者及２９例非甲庚型肝炎病人进行ＴＴＶＤＮＡ的检测。结果ＴＴＶＤＮＡ在以上４种人群中的阳性率分别为７８％，９０％，４１７％与４４８％，前者与后两者比较差异均有显著性（Ｐ＜００５）。９０例一般人群与８８例职业献血员中，１４例ＴＴＶＤＮＡ阳性者丙氨酸转氨酶（ＡＬＴ）均正常。结论深圳地区一般人群与职业献血员中ＴＴＶ携带者较常见；静脉毒瘾者是ＴＴＶ感染的高危人群；部分非甲～庚型肝炎可能与ＴＴＶ相关     

Sequencing of human-viral DNA junctions in hepatocellular carcinoma from patients with HCV and occult HBV infection

DNA of free hepatitis B viruses (HBV) has been detected in the liver of patients infected with hepatitis C virus (HCV). It is unknown whether HBV DNA is integrated into such livers; if so, it may affect hepatocarcinogenesis. Hepatocellular carcinomas (HCCs) from 34 patients without HBV surface antigen (HBsAg) and with anti-HCV, and from 7 patients with HBsAg and without anti-HCV as controls, were examined, using the cassette-ligation-mediated polymerase chain reaction and primers based on HBV DNA sequence. In the controls, HBV DNA had been integrated into human DNA of all HCCs. On the basis of HBV DNA in tumor tissue, 23 of the 34 patients with anti-HCV had occult infection. Junctions between human DNA and HBV DNA were detected in 10 of the 34 patients without HBsAg and with anti-HCV. HBV DNA was integrated into chromosome 11q in 4 of the 10 HCCs with junctions. The DNA to either side of the human-viral junctions was sequenced. Clinically, the mean tumor size of these 10 HCCs was 39 mm; that of the 24 HCCs without integrated HBV was 25 mm. The surrounding tissue was cirrhotic in 2 of the 10 former HCCs and in 16 of the latter 24 HCCs. In conclusion, integrated HBV was detected in some patients with HCV infection; in these patients, the integrated DNA was associated with accelerated hepatocarcinogenesis.     

Prevalence and clinical implications of occult hepatitis B viral infection in hemophilia patients in Japan

The prevalence and clinical implications of occult hepatitis B virus (HBV) infection were investigated in the Japanese patients with hemophilia in whom a high prevalence of infection with transfusion-transmissible viruses has been reported. HBV DNA was detected in the sera of 22 of 43 (51.2%) patients with hemophilia who were negative for HBV surface antigen (HBs), indicating that these patients had occult HBV infection. No factor, including age, type or severity of hemophilia, presence of HBs or HBV core (HBc) antibody, or coinfection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV) was associated with occult HBV infection, except for high anti-HBc titer and/or coinfection with HCV genotype 1 (1a or 1b). In general, occult HBV infection did not appear to have significant clinical implications. However, in patients in whom HBV was detected by PCR specific for the surface (S)-region, higher alanine aminotransferase levels were observed. The genotype of the occult HBV in the present study was exclusively the domestic type indigenous to Japan (genotype C), suggesting a different route of transmission for HBV in comparison to HCV and HIV in this population.     

Geographical variation in prevalence of hepatitis B virus DNA in HBsAg negative patients.

AIMS--To study the geographical variation of the prevalence of hepatitis B virus (HBV) DNA in hepatitis B surface antigen (HBsAg) negative subjects. METHODS--A nested polymerase chain reaction (PCR) assay was used to amplify the core region of HBV. The assay was able to detect 10 molecules of a full length HBV plasmid. RESULTS--When applied to HBsAg negative paraffin wax embedded liver samples from Italy, Hong Kong, and the United Kingdom, a geographical variation in the prevalence of HBV-DNA positivity was noted. Two of 18 (11%) of Italian samples and 2/29 (6.9%) of Hong Kong samples were positive for HBV-DNA while none of the 70 cases from the United Kingdom was positive by nested PCR. Contamination by plasmid DNA was excluded using a novel method based on heteroduplex formation. One HBV-DNA positive case had idiopathic chronic active hepatitis, but the diagnoses in the other three HBV-DNA positive cases did not suggest any aetiological connection between HBV-DNA positivity and liver pathology. CONCLUSIONS--HBV-DNA could be detected in the liver tissues of a proportion of HBsAg negative subjects. The prevalence of such cases is related to the endemic rate of a geographical region. The use of HBV PCR on paraffin wax embedded tissues will be valuable for future studies on the molecular epidemiology of HBV.     

慢性乙型肝炎患者血清和肝组织中HBV DNA含量与庚型肝炎病毒感染的关系

目的：观察慢性乙型肝炎（CH－B）患者血清、肝组织中HBV DNA含量与庚型肝炎病毒（HGV）感染的关系，探讨HGV感染对CH－B患者乙型肝炎病毒（HBV）复制的影响。方法：应用逆转录－聚合酶链反应（RT－PCR）、免疫组织化学法、荧光定量PCR（FQ－PCR）技术方法对56份CH－B患者血清HGV RNA、肝组织HGV Ag、血清及肝组织中HBV DNA含量分别进行了检测，并将血清HGV RNA与肝组织HGV Ag的表达、HGV RNA、HGV Ag阳性与阴性患者HBV DNA含量分别进行了对比研究。结果：血清HGV RNA、肝组织HGV Ag阳性分别为10份（17．9％）、8份（14．3％）。血清HGV RNA阳性与肝组织HGV Ag表达显著相关（P＜0．01），但部分肝组织HGV Ag阴性患者亦有血清HGV RNA表达。血清HGV RNA、肝组织HGV Ag阳性与阴性患者血清及肝组织中HBV DNA含量差异无显著性（P＞0．05）。结论：HGV感染对CH－B患者HBV复制无影响。HGV可在肝脏中复制，但致病性可能较微弱。     

临床诊断为非甲～戊型肝炎患者的病原学研究

目的探讨临床诊断为非甲-戊型肝炎患者的病原学。方法 采用巢式PCR（nPCR)检测HBV、TTV、B19、和SENV DNA；用逆转录巢式PCR（RT-nPCR)检测HGV和HCV RNA。结果 60例临床诊断为非甲-戊型肝炎患者中，单独HBVDNA阳性30例（阳性率为50.0%)，HBV和TTVDNA阳性10例（16.7%)，HBV和B19DNA阳性6例（10.0%)，HCVRNA、HBV和SENVDNA阳性1例（1.7%)，单独HCVRNA阳性1例（1.7%)，HCVRNA和B19DNA阳性1例（1.7%),HGVRNA无一例阳性，单独B19DNA阳性2例（3.3%)。单独TTVDNA阳性1例（1.7%)，另8例（13.3%)上述病毒核酸均为阴性。HBV合并感染TTV或B19对其血清学生化指标无影响。结论HBV是临床诊断为非甲-戊型肝炎的主要病原，HGV、TTV、B19和SENV与非甲-戊型肝炎无关。     

聚合酶链反应检测乙型肝炎患者肾组织中的HBV DNA

应用巢式聚合酶链反应（ＰＣＲ）技术对１１例乙型肝炎患者石蜡包埋的肾、肝组织中的ＨＢＶＤＮＡ进行了检测，并与其免疫组化及原位杂交结果作了比较。二组引物检测的结果表明：在肝组织中均有ＨＢＶ的感染，其中５例存有ＨＢＶ的复制；倚组织中ＨＢＶＤＮＡ的检出率为８／１１（７２．７％），未检测出有ＨＢＶ的复制，包括２例有膜性肾炎和膜增生性肾炎病变的病例。ＨＢＶ可以感染肾组织但并不在肾组织中复制。这一实验结果较为支持乙型肝炎患者肾脏出现的病变可能系沉积于肾小球内的免疫复合物介导损伤的结果。     

单核细胞乙型肝炎病毒cccDNA检测方法及应用价值

目的 建立检测HBV共价闭合环状DNA（ cccDNA）的巢式-荧光定量PCR法,检测外周血单核细胞（ PBMC）及骨髓单核细胞（MMNC）中cccDNA。方法 根据HBV cccDNA与松弛结构DNA（rcDNA）结构上的差异,设计2对跨缺口的特异性引物及下游的特异性TaqMan探针。根据Mung Bean Nuclease对rcDNA与cccDNA作用的不同,使cccDNA扩增而使rcDNA降解,分别用外引物及内引物进行PCR反应,再用荧光探针进行实时荧光定量PCR,根据阳性参照物,计算出检测标本定量值。结果 成功建立了HBV cccDNA巢式-荧光定量PCR的检测方法,线性范围为5.0× 10２～3.9×107拷贝/ml。用上述方法检测25例慢乙肝及肝硬化血清HBV DNA阳性患者外周血单核细胞中cccDNA,7例骨髓单核细胞中cccDNA,21例健康献血者外周血单核细胞中cccDNA,骨髓标本中有3例cccDNA阳性,25例外周血标本中有9例cccDNA阳性。结论 巢式-荧光定量PCR法可检测乙肝患者PBMC及MMNC中的HBVcccDNA含量。PBMC及MMNC中可检测到HBVcccDNA.     

Increased detection of HBV DNA in HBsAg‐positive and HBsAg‐negative South African HIV/AIDS patients enrolling for highly active antiretroviral therapy at a Tertiary Hospital

This retrospective study investigated the prevalence of hepatitis B virus (HBV) in 192 stored sera from human immunodeficiency virus (HIV) positive South African patients initiating antiretroviral therapy (ART), and explored the implications of HBV–HIV co‐infection on laboratory diagnosis of HBV. HBV serology (HBsAg, anti‐HBs and anti‐HBc) and nested HBV PCR assays targeting the HBV polymerase gene were performed, with HBV DNA positive samples being quantified with Cobas Taqman HBV test 48 assay (Roche Diagnostics). The study found that 63% (121/192) of patients had past or present HBV infection, and 40.6% (78/192) had detectable HBV DNA. Also, 22.9% (44/192) of patients were HBsAg positive and HBV DNA positive, while 23% (34/148) of HBsAG negatives had occult HBV infections. Of the 78 HBV DNA positive samples, 62.8% had viral loads ranging from 10² to ≥10⁸ IU/ml, and 37.2% had HBV viral loads <200 IU/ml. There was a statistically significant positive association between HBsAg‐positivity and high viral loads, with 27% (12/44) of HBsAg positives having HBV viral loads between 10⁴ and ≥10⁸ IU/ml, compared to only 5.9% (2/34) of HBsAg negatives (relative risk: 4.64; 95% confidence interval: 1.11, 19.35; chi‐square P‐value = 0.015). The study shows that the majority of HIV/AIDS patients initiating ART have either acute or chronic HBV infections, and further confirms that HIV remains a risk factor for occult HBV infections in South African patients as previously shown. The findings strongly support HBV screening in all HIV‐positive patients initiating ART in South Africa, considering that current ART regimens include drugs with anti‐HBV activity (e.g., lamivudine). J. Med. Virol. 81:406–412, 2009. © 2009 Wiley‐Liss, Inc.     

非甲-非戊型慢性病毒性肝炎患者隐匿性HBV感染的研究

目的 观察非甲-非戊型慢性病毒性肝炎患者隐匿性HBV感染的状况,探讨荧光定量聚合酶链反应(FQ-PCR)技术对隐匿性HBV感染的诊断价值.方法 应用FQ-PCR技术对57例非甲-非戊型慢性病毒性肝炎患者进行了血清、肝组织HBV-DNA定量检测,并将肝组织HBV DNA定量水平与肝脏炎症活动度的关系进行了分析.结果 血清、肝组织HBV DrqA定量阳性分别为13例(22.81%)、22例(38.60%).13例血清HBV DNA定量阳性患者其肝组织定量亦均阳性,但9例肝组织HBV DrqA定量阳性患者其血清定量为阴性,差异有统计学意义(P<0.01);同时13例血清与肝组织定量均阳性患者比较.显示肝组织HBV DNA定量水平显著高于血清定量水平[(6.62±1.21)拷贝,gvs.(4.03±1.06)拷贝/ml,(P<0.01)].肝组织HBV DNA水平与肝脏炎症活动度并无相关性,10例G2,7例G3,5例G4患者HB'q DNA定量分别为(6.13±1.65)拷贝/g、(5.92±1.81)拷贝,g、(5.83±1.89)拷贝/g,(P0.05),但HBV DNA定量阳性患者均为活动性肝脏病变.结论 HBV隐匿性感染是部分非甲-非戊型慢性病毒性肝炎患者的病因.单纯检测血清免疫学标志物对HBV感染诊断存在漏诊,对非甲-非戊型慢性病毒性肝炎患者应用FQ-PCR技术开展血清定量尤其是肝组织中HBV DNA定量检测可提高HBV感染的诊断.对隐匿性HBV感染的慢性病毒性肝炎亦应给予有效的抗病毒治疗.     

贵州地区不同人群TTV核酸检测及部分核苷酸序列分析

目的 了解贵州地区TTV感染状况，分析TTV贵州株的基因特点。方法 以公布的TTV第1读码区序列设计两对寡核苷酸引物，用套式聚合酶链反应法(nested—PCR)检测贵州地区不同人群血清中TTV核酸(TTV DNA)，并对3份TTV DNA阳性血清的PcR产物，用直接测序法测定核苷酸序列。结果 62例正常人，37例志愿献血员，50例血液透析患者，107例静脉药瘾者及139例肝病患者血清中TTV DNA阳性率分别为6．45％(4／62)，8．1％(3／37)，26.0％(13／50)，25.23％(27／107)和16.55％(23／139)。在肝病组中，重型肝炎、肝硬化、肝癌患者的TTV DNA阳性率分别为35.71％(5／14)，14．15％(15／106)和15．79(3／19)。测定的282个核苷酸中，3株贵州株的同源性均高于99％，与日本株N22相比，同源性都为98％。结论 贵州存在TTV感染，血透患者中有较高的TTV感染率，TTV可能是重型肝炎的病原因子，3株贵州株可能为同一基因型。     

Occult hepatitis B in HIV-infected patients

Prevalence of hepatitis B virus (HBV) markers, including occult HBV, has not been described in diverse cohorts among HIV-infected patients. The objective of this study was to assess prevalence and significance of active and occult HBV infection in an HIV-positive US cohort. A random sample was taken from 2 prospective multicenter treatment intervention cohorts. The sample population (n = 240) was HIV-1 infected and highly active antiretroviral therapy-naive. Prevalence of HBV serologic markers and quantitative HBV DNA were determined. Serum alanine aminotransferase (ALT) levels were measured to evaluate correlates of hepatocyte injury. A total of 64.6% of subjects demonstrated reactivity for any marker of current or past HBV infection or prior vaccination. Chronic HBV infection characterized by hepatitis B surface antigen (HBsAg) reactivity was present in 7.1% while 15.8% exhibited HB anticore IgG only. Approximately 10% of the latter group was HBV DNA positive by a polymerase chain reaction-based assay. Only patients with a serologic pattern of HBsAg or HB anticore alone reactivity had HBV DNA. Occult HBV was observed in approximately 10% of HIV-infected patients with HB anticore IgG antibody in a geographically representative national cohort. Though viral titers and serum ALT levels were low, screening of this subset of HIV-infected patients may have implications in terms of antiretroviral therapy and risk of immune reconstitution-associated flares.