HIV/HCV共感染者抗逆转录病毒治疗后免疫恢复情况

由于具有相同的传播途径,人类免疫缺陷病毒(Human immunodeficiency virus,HIV)和丙型肝炎病毒(Hepatitis C virus,HCV)共感染非常普遍,但是关于合并感染的程度,两种病毒之间的相互关系,在艾滋病抗逆转录病毒治疗(Antiretroviral therapy,ART)前后,HCV合并感染对HIV患者免疫细胞恢复的影响仍不明确。为了通过分析CD4⁺和CD8⁺T淋巴细胞数的变化,以了解辽宁省HIV/HCV共感染者ART后免疫恢复的情况,本研究从辽宁省艾滋病抗病毒治疗数据库中筛选符合要求的HIV感染者和HIV/HCV共感染者,收集感染者基本人口学资料及HCV抗体检测结果、HIV/HCV共感染途径等资料。采用t检验或卡方检验进行组间比较,采用Kaplan-Meier乘积极限法绘制生存分析函数图。结果显示,本研究共纳入HIV感染者12742人,HIV/HCV共感染者340人。HIV感染者和HIV/HCV共感染者的不同人口学特征均差异显著(P<0.001)。HIV感染和HIV/HCV共感染者ART治疗后CD4⁺细胞数和CD4⁺/CD8⁺比值显著升高(P<0.05),CD8⁺细胞数比ART前显著下降(P<0.05)。HIV/HCV共感染者随着ART时长,CD4⁺T淋巴细胞数恢复情况始终显著低于HIV感染者(P<0.05)。生存分析曲线表明,HCV/HIV共感染者从艾滋病诊断开始随着ART的治疗CD4⁺细胞恢复情况显著低于HIV感染者,Log-Rank检验统计量为4.483(P=0.034)。本研究揭示,HCV感染对ART患者CD4⁺和CD8⁺T淋巴细胞的恢复有影响。ART后HIV/HCV共感染者中CD4⁺T淋巴细胞计数的改善低于HIV单一感染者,并且单一感染患者对ART的反应比合并感染患者更好。因此,建议在启动ART之前,对每个感染HIV的患者进行HCV抗体筛查。     

028 热变性P24抗原对人类免疫缺陷病毒1型感染早期疾病进展的预测

在人类免疫缺陷病毒1型(HIV-1)感染者中,CD4~+淋巴细胞计数HIV-1 RNA水平的检测是监测HIV感染者的临床疾病进展及治疗的重要指标。由于价格昂贵,这两项检查很难在发展中国家广泛采……     

人类免疫缺陷病毒1型同性恋感染者与健康人群Th17/Treg平衡状况的比较研究

通过探讨人类免疫缺陷病毒1型(HIV-1)同性恋感染者外周血中辅助性T细胞17(Th17)与CD4+CD25hiFoxp3+调节性T细胞(Treg)比例及Th17/Treg平衡状态与疾病进展的关系,初步阐明Th17/Treg失衡在HIV发病机制中的作用和意义。选取54例未经抗病毒治疗的HIV感染者,另有32名健康志愿者作为正常对照。分离外周血单核细胞后,利用流式细胞技术检测Th17和Treg水平。结果表明,在HIV感染者外周血中Th17比例明显低于正常对照组(0.68±0.35vs1.42±0.86,P<0.001),Treg比例明显高于正常对照(6.15±2.12vs4.50±0.76,P<0.001),导致HIV感染者中Th17/Treg比例较正常对照显著降低(0.12±0.07vs0.31±0.17,P<0.001)。研究还发现,Th17/CD4比例与CD4+T细胞计数正相关(r=0.371,P<0.05),与病毒载量不相关;Treg/CD4比例与CD4+T细胞计数负相关,与病毒载量正相关(r=-0.402,P<0.05;r=0.447,P<0.001)。此外,Th17/Treg比例与CD4+T细胞计数正相关,与病毒载量负相关(r=0.525,P<0.001;r=-0.318,P<0.05)。结果提示,HIV感染中存在Th17/Treg失衡现象,与疾病进程密切相关,可能在HIV进展中具有重要作用。     

大连市HIV感染者/艾滋病患者在抗病毒治疗过程中病毒载量及细胞免疫指标变化的相关性分析

目的研究大连市HIV感染者/艾滋病患者抗病毒治疗过程中,HIV病毒载量和细胞免疫指标的变化情况。方法选取2013年开始抗病毒治疗,治疗时间满一年的HIV/AIDS 60例,分别在进行抗病毒治疗过程中的0、6、12月用全自动病毒载量分析仪(COBAS AmpliPrep/COBAS TaqMan)检测HIV病毒载量,同时用流式细胞计数仪(FACSCalibur)检测CD4~+和CD8+T淋巴细胞数。结果60例HIV/AIDS中治疗前仅有9例患者有检测数据,都是高病毒载量(VL1 000),在治疗6个月后,病毒载量抑制比例为73.33%(44/60)、治疗12个月后,载量抑制比为81.67%(49/60)。两组治疗后比治疗前病毒载量抑制比显著升高(Z=12.85,P0.001;Z=16.35,P0.001)。随着治疗时间的推移,CD4~+T淋巴细胞数和CD4~+/CD8~+比值都有所上升,差异有显著性(F=72.73,P0.001;F=53.83,P0.001)。病毒载量越低,T淋巴细胞数及CD4~+/CD8~+比值越高,呈负相关,有显著性差异(F=21.66,P0.001;F=8.53,P0.001)。结论抗病毒治疗有助于提高CD4~+T淋巴细胞数,改善HIV/AIDS免疫状态。细胞免疫指标与病毒载量的相关性呈负相关。     

PLoS Comput Biol:患者和HIV遗传差异共同决定着HIV的感染进展

正根据一项新的研究,在HIV感染者之间观察到的疾病进展率差异当中,大约三分之一的差异是由HIV遗传差异和患者遗传差异一起导致的。这些发现提示着患者遗传差异通过触发HIV病毒基因组发生突变而影响疾病进展。相关研究结果发表在PLoS Computational Biology期刊上。HIV感染者经历着不同的疾病进展率。在具有更高病毒载量的HIV感染者体内,HIV进展得更快。HIV病毒载量指的是在一名感染者的血液     

43 例HIV/AIDS 患者抗病毒治疗情况分析

目的:研究来第四军医大学唐都医院传染科就诊的人类免疫缺陷病毒/艾滋病(Human immunodeficiency virus/Acquired immuno deficiency syndrome,HIV/AIDS)患者感染状况及抗病毒治疗效果。方法:采用前瞻性随访研究的方法,收集来我院就诊的HIV/AIDS患者的基本信息,并对其实验室检查结果、治疗方案及后续随访结果进行分析。结果:随访观察的43例HIV/AIDS患者治疗前平均基线CD4+T淋巴细胞计数为(330.74±176.35)cells/μL,CD8+T淋巴细胞计数为(1177.80±321.49)cells/μL,CD4+,CD8+T淋巴细胞比值为0.30±0.19;治疗一年后平均CD4+T淋巴细胞计数为(482.74±217.77)cells/μL,CD8+T淋巴细胞计数为(861.53±282.85)cells/μL,CD4+,CD8+T淋巴细胞比值为0.59±0.28。所有患者治疗一年后血浆HIV-RNA载量均达到检测限以下(500copies/m L)。结论:规范的抗病毒治疗对于改善HIV/AIDS患者预后至关重要;基线CD4+T淋巴细胞计数越低,抗病毒治疗效果越差。     

GBV-C与艾滋病毒的相互作用及其机制

GBV-C（GB Virus C)是20世纪90年代中期发现的一种单股正链RNA病毒,属黄病毒科Pegivirus属,全基因组长约9.4 kb,编码约2 900个氨基酸序列.早期认为,该病毒与肝炎有关,但随后的研究发现,该病毒对人类无致病作用.最近的研究表明,GBV-C与艾滋病毒（人类免疫缺陷病毒,human immunodeficiency virus,HIV）共感染情况下可抑制HIV的增殖、提高机体免疫、延缓HIV 患者疾病进程.进一步研究GBV-C与HIV的相互作用及其机制可能会为艾滋病（acquired immune deficiency syndrome,AIDS）治疗提供新思路. 本文就GBV-C与HIV-1相互作用的两种主要类型--间接和直接的作用以及其机制进行了综述.     

血浆microRNA与HIV感染及治疗关系的研究

本次研究分析了Ⅰ型艾滋病病毒(HIV-1)感染者血浆中miRNA表达特点,探讨了血浆miRNA作为HIV-1感染及治疗监测生物学标志物的潜在可行性。选取2017年7月-2018年7月期间在昆明市第三人民医院就诊的HIV-1感染未经抗病毒治疗患者50例作为未治疗组,HIV-1感染经抗病毒治疗患者50例作为治疗组,选取同期本院健康体检者50例作为对照组,应用qPCR技术检测三组对象血浆miR-29a、miR-122,miR-155的相对表达量。结果显示,与健康对照组相比HIV-1感染未经抗病毒治疗组血浆miR-29a、miR-155、miR-122表达均升高,差异有统计学意义(P<0.05);未治疗组与治疗组相比较血浆miR-29a、miR-155和miR-122表达均升高,差异有统计学意义(P<0.05)。对未治疗组的研究显示,血浆miR-29a、miR-155表达水平与HIV-1RNA病毒载量呈正相关(P<0.05),miR-122与HIV-1RNA病毒载量无显著相关(P>0.05),miR-29a、miR-155表达水平与CD4;T细胞计数呈负相关(P<0.05)。本研究提示HIV-1感染后血浆miRNA有变化,血浆miR-29a、miR-122,miR-155与HIV-1感染相关,可能是HIV-1感染的潜在生物学标志物。而抗病毒治疗可以诱导miR-29a、miR-155和miR-122表达降低,这些miRNA可能具有成为监测HIV-1感染抗病毒治疗效果观察指标的潜在价值。未治疗组血浆miR-29a、miR-155与HIV-1RNA呈正相关,表明其与HIV-1病毒复制相关。     

体内CD8^＋T细胞剔除对无症状期SHIV感染猴的影响

目的 CD8＋T细胞在一些病毒感染疾病的免疫反应中起着重要的作用,但CD8＋T细胞在HIV无症状期的作用尚不明确,本研究通过体内CD8＋T细胞剔除,研究CD8＋T细胞对SHIV感染猴的影响,进一步了解艾滋病的发病机制。方法选择8只SHIV病毒感染的恒河猴,均处于无症状期,随机分成两组,实验组4只恒河猴在0、3、7 d注射抗CD8＋T抗体cM-T807,不同的时间取外周血、腹股沟淋巴结。流式细胞术测定恒河猴外周血和淋巴结中CD8＋T细胞数目,Real-time RT-PCR法测定实验猴血浆病毒载量,并使用IFN-γElispot方法测定其对猴细胞免疫的影响。结果 CD8＋T细胞敲除后,4只猴的病毒载量都转阳,但反应性不一,HIV-1的靶细胞CD4＋T细胞有轻微下降,后反弹,与病毒载量无相关性;CD8敲除猴的感染情况（血浆病毒载量和CD4细胞）比SHIV病毒急性感染轻,这与ELIPOT结果一致。结论 CD8＋T细胞在HIV无症状期发挥重要的作用,但其作用具有个体差别。     

Frequency of HLA-A*03 associates with HIV-1 infection in a Chinese cohort

During the early mid-1990s, a number of rural farmers across central China were employed to the unregulated plasmaselling-activity and many of them were infected by HIV-1. However, AIDS progression in the former blood donors (FBDs) is various. The aim of this study is to assess human leukocyte antigen (HLA) class I allele distribution in FBDs and evaluate its association with HIV-1 infection and disease progression. A total of 353 FBDs were enrolled in the cohort including 294 ART naïve HIV-1 seropositive and 59 HIV-1 seronegative age-matched subjects. The viral load and CD4/CD8 T cell counts were assessed in all subjects. Compared with HIV-seropositive group, the frequency of HLA-A*03 in control was significantly higher. After classifying the HLA-B alleles of the subjects according to the presence of Bw4/Bw6 serological epitopes, detrimental effect of HLA Bw6/ Bw6 homozygosity was also confirmed in the HIV-seropositive subjects. This study provides novel evidence on HLA class I allele distribution and association of HLA-A*03 frequency with HIV-1 infection and viremia in the HIV-1 infected FBDs, which may throw light on intervention strategy for the HIV-1 infection and our understanding how host immunity and genetic background affect HIV infection and AIDS progression.     

Variants in ZNRD1 Gene Predict HIV-1/AIDS Disease Progression in a Han Chinese Population in Taiwan

Patients demonstrate notable variations in disease progression following human immunodeficiency virus (HIV) infection. We aimed to identify ZNRD1 and RNF39 genetic variants linked to AIDS progression. We conducted a genetic association study in HIV-1-infected Han Chinese patients residing in Taiwan. The clinical characteristics of 143 HIV-1-infected patients were measured, and patients were split into 2 groups: AIDS progression and AIDS non-progression. Genotyping of ZNRD1 and RNF39 was performed in all participants. We found that patients in the AIDS progression group had higher HIV-1 viral loads and lower CD4 cell counts than did patients in the AIDS non-progression group. The frequency of the AA genotype of ZNRD1 (rs16896970) was lower in the AIDS progression group than in the AIDS non-progression group. Patients with AA genotypes had lower levels of HIV-1 viral loads and higher levels of CD4 cell counts than did patients with AG+GG genotypes. AIDS progression in patients with the AA group is significantly different from that in patients with the AG and GG groups by using Kaplan-Meier survival analysis. The hazard ratio for progression was lower in the AA group than in the AG and GG groups. We identified a SNP that contributes to AIDS progression in HIV-1-infected patients in this population. This SNP had a significant protective influence on AIDS progression, and polymorphisms of the ZNRD1 gene may play a role in the pathogenesis of HIV-1 infection.     

Intra-Host Diversity and Emergence of Unique GBV-C Viral Lineages in HIV Infected Subjects in Central China

GB virus C (GBV-C), which is highly prevalent among HIV/AIDS, seemed to slow the HIV disease progression. The HIV/GBV-C co-infected individuals may represent an interesting model for the investigation of the role played by HIV infection and/or the immune system in driving the evolution of the GBV-C viral populations. The present study investigated the prevalence and population dynamics of GB virus C in HIV infected individuals representing 13 geographic regions of Hubei Province of China. Approximately 37% of HIV-1 infected individuals were infected with GBV-C and genotype 3 is appeared to be predominant. Utilizing the 196 complete E2 nucleotide sequence data from 10 HIV/GBV-C infected individuals and employing coalescence based phylogenetic approaches; the present study has investigated the intra-host dynamics of GBV-C. The results revealed patient-specific unique GBV-C viral lineages and each viral lineage showed the evidence of rapid population expansion in respective HIV-1 infected patients, thus suggesting HIV-1 was unlikely to have been inhibiting effect on the GBV-C viral replication. GBV-C in all patients has experienced intense purifying selection, suggesting the GBV-C viral invasion and subsequent expansion within the HIV-1 infected hosts without any modification of the functional epitopes at their membrane protein. The finding of within host GBV-C recombinant sequences indicated recombination was one of the significant forces in the evolution and divergence of GBV-C.     

Characterization of GBV-C infection in HIV-1 infected patients

BACKGROUND: GB virus C, a positive-stranded RNA virus, is classified in the family Flaviviridae. It is currently believed that persistent infection occurs in 25-50% of infected individuals, however, it still remains an "orphan" virus in search of a role in human pathology. Molecular epidemiological studies have demonstrated that GBV-C infection is present in about 1-1.4% of the healthy population in developed countries, that it shares routes of transmission with HIV and HCV and that the prevalence of GBV-C in these populations is higher than in blood donors. On the basis of the sequence variation among the isolates, GBV-C is classified into at least four major genotypes. Preliminary evidence has suggested that GBV-C is a lymphotropic virus that replicates mainly in the spleen and bone marrow. Recently, several reports have investigated the possible beneficial effect of GBV-C co-infection on HIV disease progression to AIDS, reduced mortality in HIV infected individuals and lower HIV viral loads, not leading to a definitive conclusion yet. AIM: To investigate the role of GBV virus C co-infection in two different subsets of HIV-infected patients, and to evaluate the prevalence of GBV-C genotypes in Northern Italy. METHODS: A total of 86 HIV positive patients were examined for GBV-C viremia (years after HIV sera conversion: 12 +/- 5). Control population (Group A): 46 patients (mean age 42 years) with <200CD4/ml during the observation period. Longterm non progressor population (Group B): 40 patients, (mean age 40 years) with >500 CD4/ml for at least 8 years and never treated with HAART. After extraction of viral RNA from plasma samples, amplification of a highly conserved region of 5'UTR was performed by nested RT-PCR. All positive samples were genotyped by sequencing, alignment with published sequences and phylogenetic analysis. CD4 cell count, HIV plasma levels were also evaluated. RESULTS: 9 out of 46 (19.56%) in Group A and 15 out of 40 (37.5%) in Group B had detectable GBV-C viremia (p=0.064, OR 2.47, percent confidence interval 0.94 to 6.51). No statistical difference was observed when disease stage was evaluated between the two groups. In Group B, after regression analysis for CD4 cell count decrease over the period observed, no significant difference was detected between GBV-C positive and negative patients. No significant difference was observed in Group B in HIV viremia and CD4 cell count at time of GBV-C detection between GBV-C infected patients and GBV-C negative patients. All Italian patients were genotype 2, the only African patient carried GBV-C genotype 1. CONCLUSIONS: Although previous results suggest that GBV-C virus may be a favorable marker for long term non progression of HIV disease, whether it plays a direct anti-HIV role or just takes advantage of non progessors' higher CD4 cell count to replicate more efficiently, still remains to be answered. Follow up of untreated patients and further evaluation of virological interactions, between the viruses and the host immune system, will be helpful to shed some light on these observations, offering new prognostic and eventually therapeutical tools for the management of HIV patients.     

HCV Coinfection Associated with Slower Disease Progression in HIV-Infected Former Plasma Donors Na?ve to ART

Background

It remains controversial how HCV coinfection influences the disease progression during HIV-1 infection. This study aims to define the influence of HCV infection on the replication of HIV-1 and the disease progression in HIV-infected former plasma donors (FPDs) naïve to ART.

Methodology/Principal Findings

168 HIV-1-infected FPDs were enrolled into a cohort study from Anhui province in central China, and thereafter monitored at month 3, 9, 15, 21 and 33. Fresh whole blood samples were used for CD4+ T-cell counting. Their plasma samples were collected and stored for quantification of HIV-1 viral loads and for determination of HCV and Toxoplasma. Out of 168 HIV-infected FBDs, 11.9% (20 cases), 80.4% (135 cases) and 7.7% (13 cases) were infected with HIV-1 alone, HIV-1/HCV and HIV/HCV/Toxoplasma, respectively. During the 33-month follow-up, only 35% (7 out of 20 cases) HIV-1 mono-infected subjects remained their CD4+ T-cell counts above 200 cells/µl and retained on the cohort study, which was significantly lower than 56% (75 out of 135 cases) for HIV/HCV group and 69% (9 out of 13 cases) for HIV/HCV/Toxoplasma group (p<0.05). CD4+ T cells in HIV mono infection group were consistently lower than that in HIV/HCV group (p = 0.04, 0.18, 0.03 and 0.04 for baseline, month 9, month 21 and month 33 visit, respectively). In accordance with those observations, HIV viral loads in HIV mono-infection group were consistently higher than that in HIV/HCV group though statistical significances were only reached at baseline (p = 0.04).

Conclusions/Significance

These data indicated HCV coinfection with HIV-1 is associated with the slower disease progression at the very late stage when comparing with HIV-1 mono-infection. The coinfection of Toxoplasma with HIV and HCV did not exert additional influence on the disease progression. It will be highly interesting to further explore the underlying mechanism for this observation in the future.     

Plasma concentrations of transforming growth factor beta 1 in non-progressive HIV-1 infection correlates with markers of disease progression

The human immunodeficiency virus (HIV) infection shows variable rate of disease progression. The underlying biological and molecular mechanisms involved in determining progression of HIV infection are not fully understood. The aims of this study were to determine plasma concentrations of active TGF β 1, Th1 and Th2 cytokines in patients with non-progressive and those with progressive HIV-1 infection, as well as to determine if there is an association of these cytokines to disease progression. In a cross-sectional study of 61 HIV-1 infected individuals categorized according to disease progression as having non-progressive HIV-1 infection (n = 14) and progressive infection (n = 47), plasma levels of active TGF β 1, INF-γ, TNF-α, IL-10, IL-1β, IL-12p70 and IL-13 were compared with HIV uninfected healthy controls (n = 12). Plasma concentration of these cytokines was measured using a highly sensitive luminex200 XMAP assay. Pearson correlation test was used to assess the correlation of cytokines with CD4+ and CD8+ T cells, CD4:CD8 ratio and plasma HIV-1 RNA in the different study groups. Plasma concentrations of TGF β 1 and IL-10 were significantly decreased while IL-1β, IL-12p70 and TNF-α were increased in patients with non-progressive HIV-1 infection compared to patients with progressive infection. Plasma levels of TGF β 1 and IL-10 showed an inverse correlation with CD8+ T cell counts and CD4:CD8 ratios in patients with non-progressive HIV-1 infection, while plasma HIV-1 RNA positively correlated with CD4+ T cell counts. Plasma levels of TNF-α, IL-1β, IL-12p70 and IL-13 positively correlated with CD4+ T cell counts and inversely correlated with plasma HIV-1 RNA, CD8+ T cell count and CD4:CD8 ratio in patients with non-progressive infection. The correlation of cytokines to the state of T-lymphocyte and plasma HIV-1 RNA found in this study may provide insight into the role of cytokines in both progressive and non-progressive HIV-1 infection. Additionally, these findings may have implications for systemic cytokine-based therapies in HIV-1 infection.     

Influence of GB virus C on IFN-γ and IL-2 production and CD38 expression in T lymphocytes from chronically HIV-infected and HIV-HCV-co-infected patients

This study was designed to assess the effect of GB virus (GBV)-C on the immune response to human immunodeficiency virus (HIV) in chronically HIV-infected and HIV- hepatitis C virus (HCV)-co-infected patients undergoing antiretroviral therapy. A cohort of 159 HIV-seropositive patients, of whom 52 were HCV-co-infected, was included. Epidemiological data were collected and virological and immunological markers, including the production of interferon gamma (IFN-γ) and interleukin (IL)-2 by CD4, CD8 and Tγδ cells and the expression of the activation marker, CD38, were assessed. A total of 65 patients (40.8%) presented markers of GBV-C infection. The presence of GBV-C did not influence HIV and HCV replication or TCD4 and TCD8 cell counts. Immune responses, defined by IFN-γ and IL-2 production and CD38 expression did not differ among the groups. Our results suggest that neither GBV-C viremia nor the presence of E2 antibodies influence HIV and HCV viral replication or CD4 T cell counts in chronically infected patients. Furthermore, GBV-C did not influence cytokine production or CD38-driven immune activation among these patients. Although our results do not exclude a protective effect of GBV-C in early HIV disease, they demonstrate that this effect may not be present in chronically infected patients, who represent the majority of patients in outpatient clinics.     

Role for plasmacytoid dendritic cells in anti-HIV innate immunity

The role of plasmacytoid dendritic cells (pDC) in anti-HIV immunity is mostly represented by the production of type I IFN in response to HIV infection in vitro and in vivo. This production is decreased in HIV-1 infected patients at the time of primary infection and during chronic disease in association with progression of disease. Circulating pDC counts are decreased concomitantly with type I IFN, and both factors correlate inversely overall with viral loads and positively with CD4+ T-cell counts. These parameters might be used in clinical immunology to monitor treatment and as predictive factors of immune control of HIV-1 replication to help decide whether to interrupt antiretroviral treatment. They may be related to control of HIV replication as well as to pathogenesis of infection, perhaps in setting the balance between immunity or tolerance to the virus. A better understanding of these parameters is required while attempts to use IFN-alpha or ligands of Toll-like receptors found on pDC are being made.     

Broad, intense anti-human immunodeficiency virus (HIV) ex vivo CD8(+) responses in HIV type 1-infected patients: comparison with anti-Epstein-Barr virus responses and changes during antiretroviral therapy.

The ex vivo antiviral CD8(+) repertoires of 34 human immunodeficiency virus (HIV)-seropositive patients with various CD4(+) T-cell counts and virus loads were analyzed by gamma interferon enzyme-linked immunospot assay, using peptides derived from HIV type 1 and Epstein-Barr virus (EBV). Most patients recognized many HIV peptides, with markedly high frequencies, in association with all the HLA class I molecules tested. We found no correlation between the intensity of anti-HIV CD8(+) responses and the CD4(+) counts or virus load. In contrast, the polyclonality of anti-HIV CD8(+) responses was positively correlated with the CD4(+) counts. The anti-EBV responses were significantly less intense than the anti-HIV responses and were positively correlated with the CD4(+) counts. Longitudinal follow-up of several patients revealed the remarkable stability of the anti-HIV and anti-EBV CD8(+) responses in two patients with stable CD4(+) counts, while both antiviral responses decreased in two patients with obvious progression toward disease. Last, highly active antiretroviral therapy induced marked decreases in the number of anti-HIV CD8(+) T cells, while the anti-EBV responses increased. These findings emphasize the magnitude of the ex vivo HIV-specific CD8(+) responses at all stages of HIV infection and suggest that the CD8(+) hyperlymphocytosis commonly observed in HIV infection is driven mainly by virus replication, through intense, continuous activation of HIV-specific CD8(+) T cells until ultimate progression toward disease. Nevertheless, highly polyclonal anti-HIV CD8(+) responses may be associated with a better clinical status. Our data also suggest that a decrease of anti-EBV CD8(+) responses may occur with depletion of CD4(+) T cells, but this could be restored by highly active antiretroviral treatment.