Epidemiology of human T-lymphotropic virus type II (HTLV-II) infection in Spain

The human T-lymphotropic virus type II (HTLV-II) has recently been associated with the genesis of some subacute neurological syndromes and, rarely, with atypical T-lymphoid malignancies. The virus is endemic in some Amerindian and African tribes, and among intravenous drug users (IDUs) in North America and Europe. Given that HTLV-II is transmitted by the same routes as other human retroviruses, the screening of antibodies to HTLV-II in blood donors has became a matter of controversy in some countries. Herein, we describe the clinical, epidemiological and virological features of 113 individuals with HTLV-II infection identified in Spain up to September 1995. Most of them (94/113; 83%) were male, and all but seven were natives. Four were African immigrants living in Madrid and 3 had been born in other European countries. All but six subjects were IDUs, and sexual transmission of HTLV-II and transfusion were involved in five and one individual, respectively. Eighty-four percent of the IDUs infected with HTLV-II were co-infected by HIV-1 (93/107). Clinical manifestations potentially linked to HTLV-II were absent, although an IDU male co-infected by HIV-1 and HTLV-II developed a severe non-inflammatory proximal myopathy. In conclusion, HTLV-II infection is present in Spain, mainly among IDUs, with a growing incidence and a current overall prevalence of 2.0 percent.The members of the HTLV Spanish Study Group are listed in the Appendix.     

四川省2011－2015年4类高危人群HIV-1新发感染率及流行趋势分析

目的 在注射吸毒者、MSM、暗娼和性病门诊男性就诊者中开展HIV-1新发感染检测,估算新发感染率,了解艾滋病在4类人群中的流行趋势。方法 收集2011-2015年四川省注射吸毒者、MSM、暗娼和性病门诊男性就诊者监测哨点的确证阳性样本,排除既往感染后,采用BED-CEIA方法进行新发感染检测,估算4类人群的HIV-1新发感染率。结果 2011-2015年4类人群共计监测194 223例,检出HIV-1阳性5 297例,完成BED-CEIA检测4 640例,判为新发感染749例。MSM、暗娼、性病门诊男性就诊,凉山州3个吸毒哨点（主要为彝族聚居地）监测的注射吸毒者、凉山州外地区吸毒哨点监测的注射吸毒者HIV-1新发感染率分别为5.16%（95% CI：4.65~5.66）、0.22%（95% CI：0.16~0.28）、0.57%（95% CI：0.45~0.69）和7.53%（95% CI：6.06~9.01）、0.44%（95% CI：0.36~0.53）。经χ²检验,各年新发感染率差异均有统计学意义。结论 2011-2015年凉山州外地区的注射吸毒者、暗娼和性病门诊男性就诊者新发感染率均保持在较低的水平,防治工作取得一定成效。MSM的HIV-1新发感染率较高,且存在上升趋势,不排除HIV由MSM向其他高危人群扩散的可能。     

HIV-1, HIV-2, HTLV-I/II and STD among female prostitutes in Buenos Aires, Argentina

To determine the prevalence of HIV-1 and HTLV-I/II among female prostitutes from different areas of the city of Buenos Aires, we studied serum samples from 237 individuals (mean age: 25; range 17 to 39). Prostitutes were recruited from 16 different Buenos Aires locations with different economical status. Information on sexual behavior, health and socioeconomic conditions was collected through a questionnaire. HIV-1 and HTLV-I/II antibodies (ab) were tested by ELISA (Abbott) and Particle agglutination (Fujirebio, Tokyo) respectively. Positive results were confirmed by immunofluorescence assay. Samples that were positive for HIV-1 antibodies were also tested for p24 antigen (Abbott). VDRL for syphilis was performed in all samples. Fifteen (6.3%) out of the 237 individuals were positive for HIV-1 antibodies. Moreover, 2 (0.8%) HIV-1 seropositive prostitutes were also positive for HTLV-I/II antibodies and for HIV p24-Ag. Eventhough PCR for HTLV-I/II was not performed, titration by IFA in these two samples suggests HTLV-I. Our serologic results indicate a relatively high HIV-1 infection among prostitutes working in Buenos Aires. As we previously mentioned for other risk groups, we found an association between HTLV-I/III and HIV-1 infection in this particular group. Although we did not find any significant difference between HIV-1 seropositivity and the variables analyzed through the questionnaire, the prevalence of HIV-1 infection was higher in prostitutes working in mask brothels (sauna or massage houses) as compared with hotel or street prostitutes.     

HIV-1感染中第二受体与艾滋病进程的关系

第二受体在HIV_1感染及病程变化中有着重要作用,HIV_1所利用的第二受体由CCR5转换为CXCR4被认为是病程进展的标志,而X4型HIV_1也与较差的预后相联系。但是近几年的研究使人们对这种第二受体利用的转换有了新的认识,在近半数HIV_1感染者体内并不发生这种转换,但他们大多数会进展为艾滋病。本文就这一问题作了综述。     

Human T-cell leukemia virus type 1 molecular variants, Vanuatu, Melanesia

Four of 391 Ni-Vanuatu women were infected with variants of human T-cell leukemia virus type 1 (HTLV-1) Melanesian subtype C. These strains had env nucleotide sequences approximately 99% similar to each other and diverging from the main molecular subtypes of HTLV-1 by 6% to 9%. These strains were likely introduced during ancient human population movements in Melanesia.     

Selective pressures of human immunodeficiency virus type 1 (HIV-1) during pediatric infection

Pediatric HIV-1 infection presents remarkable features that are distinct from those observed in adult infection. In vertically HIV-1-infected children, the viral load declines more slowly, and the cytotoxic T-lymphocyte response emerges late, only after the sixth month of life. This response generally tends to be narrow and less intense than that seen in adults. While the nuances of immune response at the cellular level during pediatric HIV-1 infection have been addressed, there is a lack of studies focusing on the consequences of this delayed and narrowed immune response at the population level. To better explore these features, we evaluated the selection regimen in gag, pol and env gene fragments of HIV-1 during pediatric infection. We estimated the number of nonsynonymous substitutions (d(N)) and synonymous substitutions (d(S)) codon-by-codon, using the maximum likelihood method and a modified counting method. Notably, both methods indicated a similar intensity of selection (measure by mean d(N)/d(S) ratio) between children and adults. Additionally, sites under positive selection were equally distributed along HIV genes and the location of these sites was analogous between children and adults. Therefore, the selective regimen in HIV during pediatric infection is equally broad and intense likewise the observed in adults. Unexpectedly, our phylogenetic-based analysis enabled us to identify two regions in the env gene of HIV with distinct adaptive functions. The first region, located in the vicinity of V3 loop, contains sites that might increase viral fitness within-host during antibody attack and virus-cell interaction. The second region, restricted to amino acids 334-368 of Gp160, contains sites that might increase viral fitness during interhost transmission at the population level.     

同性和异性传播感染人群的HIV-1亚型分布和特征分析

目的了解河北省男男同性传播和异性传播人群HIV-1亚型分布和特征。方法从感染者的血浆样品中提取病毒RNA,逆转录后采用套式PCR扩增HIV-1 gag和env基因的部分片段,对PCR产物直接进行核苷酸序列测定,所获序列与各亚型国际参考株序列比对,确定基因型并进行系统进化树分析。结果同性传播的52例HIV-1感染者中,发现了3种HIV-1亚型和重组型,以CRF01-AE为主,占65.4%(34/52),其次为B亚型占30.8%(16/52);异性传播的60例HIV-1感染者中,存在6种亚型和重组型,以B亚型为主占43.3%(26/60),其次是CRF01-AE占30.0%(18/60),CRF07-BC占15%(9/60);两类人群的亚型分布差异有统计学意义(P<0.001)。异性感染人群的各亚型组内基因距离均大于同性感染人群。结论在河北省同性传播人群和异性传播人群中HIV-1亚型分布不均衡。     

采用集合RNA检测方法估计高危人群的HIV感染发病率

目的 及时发现艾滋病自愿咨询检测(VCT)人群和男男性行为人群(MSM)HIV抗体窗口期感染者,并估计发病率.方法 收集2012年1-10月云南省疾病预防控制中心VCT门诊和MSM活动室HIV抗体筛查阴性样本,以50∶1和10∶1二级集合方式进行HIV-1 RNA检测,并随访HIV-1 RNA阳性者,最后以Ron Brookmeyer方法估计VCT和MSM人群的HIV感染年发病率.结果 1400份VCT门诊HIV抗体筛查阴性样本中,发现2名HIV-1 RNA阳性窗口期感染者,HIV感染年发病率为1.87％(95％CI:1.23％-2.65％).MSM 500份HIV抗体筛查阴性样本中,发现2名HIV-1 RNA阳性窗口期感染者,HIV感染年发病率为5.31％(95％CI:3.52％ - 7.45％).结论 集合RNA检测为及时发现VCT和MSM的HIV窗口期感染者提供有效方法,建议通过提高集合RNA检测频率等方式,加强MSM及其他高危人群HIV感染窗口期的筛查.     

人免疫缺陷病毒1型潜伏感染激活剂研究现状

高效抗逆转录病毒治疗(HAART)对控制HIV-1进展效果显著,但病毒潜伏库的存在导致病毒无法完全清除.HIV-1感染后,潜伏库建立早,半衰期长,长期处于静息状态,是根治HIV-1感染的主要障碍之一.目前清除病毒潜伏库的方法有潜伏感染激活剂、免疫治疗和基因治疗等.此文主要讨论了HIV-1潜伏感染激活剂相关内容.     

福建省3市男男性行为者HIV-1感染率与新发感染率初探

目的了解福建省男男性行为（MSM）人群HIV-1感染的流行状况,为制定防治策略提供依据。方法对2010—2012年福州、泉州和厦门市哨点监测MSM人群进行问卷调查和HIV-1抗体筛查和确证,计算感染率;用BED HIV-1捕获酶联法对HIV抗体阳性样本进行检测,估算HIV-1血清阳转时间在168d内的新发感染率。结果 2010、2011和2012年福州、泉州和厦门市MSM人群HIV-1感染率分别为7.1%（39/553）、8.7%（94/1 078）和9.3%（95/1026）;在HIV抗体阳性者中,新发感染率分别为5.8%、2.2%和10.9%。结论 2010—2012年福建省3地市MSM人群HIV的感染率与新发感染率均达到较高水平,且有上升的趋势。     

Sexual transmission of hepatitis C virus and HIV-1 infection in female intravenous drug users

We examined the relationship between the presence of antibody to HCV and sexually transmitted diseases in 151 female, intravenous drug users aged 17–43 years. Anti-HCV was present in 49 of 66 HIV-1-negative women (74.2%), and 63 of 85 HIV-1-positive women (74.1%). Anti-HCV seropositivity was significantly related to sexually transmitted infections (Ureaplasma urealyticum infections excluded) in HIV-1-seronegative women, but not in HIV-1-positive women. Also, in HIV-1-negative subjects, Trichomonas vaginalis infections (and infections with M. hominis) were significantly related to anti-HCV seropositivity, and a positive relation between the number of sexual partners and the presence of anti-HCV was demonstrated. In HIV-1-positive subjects a shared use of needles and syringes was more likely, and an increased parenteral exposure to HCV may decrease the relative contribution by sexual transmission. However, in HIV-1-negative subjects, sexual transmission of HCV appears to be both a possible and important means of transmission.     

Cell-associated infectious HIV-1 viral load as a predictor of clinical progression and survival among HIV-1 infected injection drug users and homosexual men

Cell-associated infectious HIV-1 viral load was measured using semi-quantitative microculture techniques to determine its predictive capability for progression to AIDS or survival among HIV-1 infected injecting drug users (IDU) and homosexual men (HM). The authors followed 296 IDU and 240 HM from February 1992 through September 1995 for: (i) death, (ii) AIDS, and (iii) AIDS or bacterial infection. At baseline, viral load was quantified using microculture techniques to determine infectious units per million peripheral blood mononuclear cells (IUPM). Data were analyzed using standard statistical methods for survival analysis. Of the 536 total participants, 106 died (20%), and 98 of the 481 AIDS-free participants developed AIDS (20%). The relative hazard of AIDS for a viral load of 100 IUPM, relative to a negative culture (0 IUPM), was 6.73 (95% CI: 2.23–20.3) after adjusting for risk group, initial CD4+ count, and other covariates. The adjusted relative hazard of death for a viral load of 100 IUPM vs. 0 IUPM was 2.57 (95% CI: 0.97–6.80). Viral load predicted time to death within the <200 cells/l CD4+ stratum. The predictive value of viral load on HIV-1 progression did not vary by risk group. These data show that cell associated infectious HIV-1 viral load was significantly predictive of progression across risk groups for AIDS and death among those severely immune compromised.     

东莞市HIV-1主要毒株基因分型及其对耐药影响的研究

目的 了解东莞市人类免疫缺陷病毒Ⅰ型（HIV-1）感染者流行毒株基因亚型的分布特征及耐药情况。方法 收集2015年10月至2016年2月东莞市疾病预防控制中心未经抗病毒治疗的50例HIV感染者血浆,提取病毒RNA,采用实时荧光定量逆转录聚合酶链反应（RT-PCR）法扩增pol基因序列并测序,应用BioEdit、Genotyping和MEGA等生物学软件对pol基因进行HIV-1基因亚型分析,并将获得的核酸序列提至美国斯坦福大学HIV耐药数据库（http：//hivdb.stanford.edu）进行耐药位点分析。结果 50例样本最终成功扩增得到35份样本的pol基因序列,在这35例研究对象中,88.6%（31/35）为男性,65.7%（23/35）为经性接触感染。35条pol基因序列中,CRF01_AE亚型占37.1%（13/35）,CRF07_BC亚型占37.1%（13/35）,B亚型占14.3%（5/35）,CRF55_01B亚型占11.4%（4/35）。在35条基因序列中检测到11条（占31.4%）含有耐药相关突变,以CRF01_AE和CRF55_01B重组亚型为主,原发性耐药率为11.4%（4/35）。结论 东莞市HIV-1感染者存在着多种基因亚型,以CRF01_AE和CRF07_BC重组亚型为主,基因序列发生原发耐药性,应引起重视。     

HTLV-I and HTLV-II infections among HIV-1 seropositive patients in Sao Paulo,Brazil

To estimate the presence of, and the risk factors for HTLV-I and HTLV-II infections among HIV-1 infected subjects in Sao Paulo, Brazil, a serosurvey was performed in 471 HIV-1 infected patients, including 216 intravenous drug addicts (IVDA), 229 homosexual/bisexual men, and 26 with other risk factors. Serum samples were screened for HTLV seroreactivity by ELISA; reactive samples were analyzed by Western Blot (WB), using whole HTLV-I lysate as antigen. To confirm and discriminate HTLV-I and HTLV-II infections, sera presenting any bands on WB were further analyzed by a WB containing recombinant HTLV-I and HTLV-II proteins (WB 2.3), and by enzyme immunoassays using synthetic peptides specific for envelope proteins (Synth-EIA). In 22 cases, cell samples were available for polymerase chain reaction (PCR) studies. On WB, 114 sera were reactive and, of these, 37 and 25 were concordantly positive on both WB 2.3 and Synth-EIA procedures for HTLV-I and HTLV-II specific antibodies, respectively; 37 specimens were negative on both assays, and 15 gave discordant or indeterminate results. PCR findings confirmed concordant results obtained in the discriminatory serological assays. The prevalence rates of HTLV-I and HTLV-II infections were 15.3% and 11.1% in IVDA, and 0.9% and 0.4% in homosexual/bisexual men, respectively. No case of HTLV-I/HTLV-II co-infection was found.     

Therapeutic immunisation plus cytokine and hormone therapy improves CD4 T-cell counts,restores anti-HIV-1 responses and reduces immune activation in treated chronic HIV-1 infection

BackgroundThis randomised, open label, phase I, immunotherapeutic study investigated the effects of interleukin (IL)-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), recombinant human growth hormone (rhGH), and therapeutic immunisation (a Clade B DNA vaccine) on combination antiretroviral therapy (cART)-treated HIV-1-infected individuals, with the objective to reverse residual T-cell dysfunction.MethodsTwelve HIV-1⁺ patients on suppressive cART with baseline CD4 T-cell counts >400 cells/mm³ blood were randomised into one of three groups: (1) vaccine, IL-2, GM-CSF and rhGH (n = 3); (2) vaccine alone (n = 4); or (3) IL-2, GM-CSF and rhGH (n = 5). Samples were collected at weeks 0, 1, 2, 4, 6, 8, 12, 16, 24 and 48. Interferon (IFN)-γ, IL-2, IL-4 and perforin ELISpot assays performed at each time point quantified functional responses to Gag p17/p24, Nef, Rev, and Tat peptides; and detailed T-cell immunophenotyping was undertaken by flow cytometry. Proviral DNA was also measured.ResultsMedian baseline CD4 T-cell count was 757 cells/mm³ (interquartile range [IQR] 567–886 cells/mm³), median age 48 years (IQR 42–51 years), and plasma HIV-1-RNA <50 copies/ml for all subjects. Patients who received vaccine plus IL-2, GM-CSF and rhGH (group 1) showed the most marked changes. Assessing mean changes from baseline to week 48 revealed significantly elevated numbers of CD4 T cells (p = 0.0083) and improved CD4/CD8 T-cell ratios (p = 0.0033). This was accompanied by a significant reduction in expression of CD38 on CD4 T cells (p = 0.0194), significantly increased IFN-γ and IL-2 production in response to Gag (p = 0.0122) and elevated IFN-γ production in response to Tat (p = 0.041) at week 48 compared to baseline. Subjects in all treatment groups showed significantly reduced PD-1 expression at week 48 compared to baseline, with some reductions in proviral DNA.ConclusionsMultifarious immunotherapeutic approaches in the context of fully suppressive cART further reduce immune activation, and improve both CD4 T-lymphocyte counts and HIV-1-specific T-cell responses (NCT01130376).     

云南边境地区HIV-1型和HIV-2型混合感染的流行病学分析

〔目的〕了解云南边境地区和口岸艾滋病流行情况,为边境地区和口岸艾滋病防治工作提供科学依据。〔方法〕对2004～2007年7月间检出的20例HIV-1型和HIV-2型混合感染者的资料进行回顾性流行病学分析。〔结果〕云南边境检出的HIV-1型和HIV-2型混合感染者都是在缅甸和中缅边境地区感染的,云南省边境地区和口岸的HIV-2型是由缅甸传入。〔结论〕中缅边境地区的缅甸籍HIV感染者依然是云南边境地区和口岸艾滋病传播的重要传染源。     

A high prevalence of HIV-1 infection among pregnant women living in a rural district of north Uganda severely affected by civil strife

This study aims at estimating the recent trends in HIV-1 prevalence and the factors associated with infection among pregnant women in the Gulu District of north Uganda, a rural area severely affected by civil strife. In 2000-2003, a total of 4459 antenatal clinic attendees of Lacor Hospital were anonymously tested for HIV-1 infection. The overall and age-specific prevalence did not show any significant trend over time. The age-standardized prevalence slightly declined, from 12.1% in 2000 to 11.3% in 2003. Increased age [20-24 years: adjusted odds ratio (AOR) 1.63; 95% CI 1.18-2.25; >or=25 years: AOR 2.56; 95% CI 1.91-3.44], residence in urban areas (AOR 1.76; 95% CI 1.41-2.18), being unmarried (AOR 1.60; 95% CI 1.27-2.01), increased age of partner (25-34 years: AOR 1.87; 95% CI 1.29-2.73; >or=35 years: AOR 2.68; 95% CI 1.72-4.16), modern occupation of partner (AOR 1.98; 95% CI 1.53-2.58), and short time of residence at the current address (AOR 1.36; 95% CI 1.05-1.76) were associated with infection. The HIV-1 prevalence in this rural district is high and similar to that observed in urban antenatal clinics, probably reflecting the effect of the last 18 years of civil strife.     

Gene polymorphisms in CCR5, CCR2, SDF1 and RANTES among Chinese Han population with HIV-1 infection

Chemokines and chemokine receptors are crucial for immune response in HIV-1 infection. Although many studies have been done to investigate the relationship between chemokines and chemokine receptor gene polymorphisms and host’s susceptibility to HIV-1 infection, the conclusions are under debate. In the present study, a cohort of 287 HIV-1 seropositive patients, 388 ethnically age-matched healthy controls and 49 intravenous drug users (IDUs) HIV-1 exposed seronegative individuals (HESN) from Chinese Han population were enrolled in order to determine the influence of host genetic factors on HIV-1 infection. Seven polymorphisms on four known chemokines/chemokine receptor genes (CCR5Δ32, CCR5 m303, CCR5 59029A/G, CCR2 64I, RANTES −403A/G, RANTES −28C/G and SDF1 3′-A) were screened. CCR5Δ32 and CCR5 m303 were absent or infrequent in Chinese Han population, which may not be hosts’ genetic protective factors for HIV-1 infection. Our results showed the CCR5 59029A/G, CCR2 64I and SDF1 3′-A were not associated with host’s resistance to HIV-1 infection. The frequency of RANTES −403A allele was significantly lower in HIV-1 patients than in healthy blood donors (p = 0.0005) and HESN group (p = 0.035), which implied the association between A allele and reduced HIV-1 infection risk. Different genetic models were assessed to investigate this association (AA vs. GG + AG, OR = 0.38 95% CI, 0.22–0.65 p = 0.0004; A vs. G, OR = 0.66 95% CI, 0.52–0.84 p = 0.0006), which supported this association, either. The genotype and allele distribution of RANTES −28 between HIV-1 patients and healthy controls (genotype profile: p = 0.072; allele profile: p = 0.027) or HIV-1 seronegative group (genotype profile: p = 0.036; allele profile: p = 0.383) were both at the marginal level of significance, which were not observed after Bonferroni correction. All these results suggest the RANTES −403A may be associated with reduced susceptibility to HIV-1 infection, while the RANTES −28 locus not. By lack of the patients’ clinical information, whether these polymorphisms affect AIDS disease progression and their role in different HIV-1 infection routes could not performed in present study and needs to be assessed in ongoing studies.     

艾滋病病毒1型与乙型肝炎病毒X蛋白的相关性

最近研究显示,HIV和HBV具有部分相同生物活性,在艾滋病病程中相互协同作用。文中对HIV_1和HBx及其编码产物特点、相互作用及作用机制进行综述。