HIV感染者免疫功能重建新视角:CD4/CD8比值

CD4+T淋巴细胞(简称CD4细胞)计数是衡量艾滋病病毒(HIV)感染者免疫状态的经典指标,但近年来的研究发现,仅用CD4细胞绝对计数难以精确反应艾滋病(AIDS)病人的免疫状态,特别是经过抗病毒治疗后CD4细胞500个/μL以上的患者。CD4/CD8比值在正确评价免疫功能中的价值逐渐受到关注。HIV感染后导致CD4/CD8比值倒置,经抗反转录病毒治疗(ART)后也难以恢复正常。基线状态、治疗方案、合并巨细胞病毒(CMV)感染等因素均影响CD4/CD8比值的恢复。CD4/CD8比值与HIV感染后异常免疫激活相平行,不仅作为艾滋病预后的预测因子,也与非AIDS相关事件的发生以及HIV储存库有关。CD4/CD8比值恢复正常有望作为评估HIV感染者免疫功能重建的新指标。     

92例灵芝联合高效抗反转录病毒治疗HIV/AIDS病人免疫重建不良的回顾性研究

目的初步观察灵芝联合高效抗反转录病毒治疗(HAART)艾滋病病毒(HIV)感染者/艾滋病(AIDS)病人(简称HIV/AIDS病人)免疫重建不良的疗效。方法采用回顾性研究方法,筛选门诊92例既往灵芝联合HAART的HIV/AIDS病人,95例单纯HAART的HIV/AIDS病人,比较两组治疗前与治疗后3、6、9、12个月CD4~+、CD8~+T淋巴细胞数(简称CD4、CD8细胞)及Th/Ts比值。结果对照组治疗3、6、9个月后CD4细胞数较治疗前升高(P 0.05);联合组各治疗周期CD4细胞数均较治疗前升高(P 0.01),尤其在3、12个月时CD4细胞数明显高于对照组(P 0.01)。对照组治疗至9、12个月后,CD8细胞数较治疗前升高(P 0.05);联合组治疗至3个月时,CD8细胞数较治疗前升高(P 0.05)。两组间各周期CD8细胞数比较差异均无统计学意义(P 0.05)。对照组各治疗周期Th/Ts比值较治疗前升高(P 0.05);联合组治疗至6、9、12个月后Th/Ts比值较治疗前升高(P 0.05),且于治疗12个月后高于对照组(P 0.05)。两组有效率、稳定率差异无统计学意义。结论灵芝可促进CD4细胞的增长,从而升高Th/Ts比值,对免疫重建不良有一定的治疗前景。     

艾可清颗粒联合HAART对免疫重建不良的HIV/AIDS病人CD4~+T淋巴细胞水平的影响

目的观察艾可清颗粒联合高效抗反转录病毒治疗(HAART),对艾滋病病毒(HIV)感染者/艾滋病(AIDS)病人(简称HIV/AIDS病人)中,免疫重建不良者CD4~+T淋巴细胞(简称CD4细胞)水平的影响。方法符合纳入标准的病人70例,随机分为治疗组和对照组各35例,治疗组在HAART基础上给予中药艾可清颗粒,对照组只进行HAART,评价5个时点(治疗前和治疗3、6、9、12个月)2组CD4细胞计数变化和免疫重建有效率。结果治疗9个月和12个月时,治疗组CD4细胞计数与对照组相比均显著升高(t=-2.664,P=0.011;t=-2.468,P=0.016),2个时点治疗组免疫重建有效率分别为58.06%(18/31)和48.39%(15/31),均高于对照组的31.25%(10/32)和21.88%(7/32),差异均有统计学意义(Z=-2.349,P=0.019;Z=-2.045,P=0.041)。结论艾可清颗粒联合HAART可一定程度提高免疫重建不良HIV/AIDS病人的CD4细胞计数,并且提高免疫重建有效率。     

青蒿琥酯片对HIV/AIDS患者ART后免疫功能重建不全影响的研究

目的观察比较青蒿琥酯片对HIV/AIDS患者ART后免疫功能重建不全人群的临床疗效和安全性。方法用多中心、前瞻性队列研究方法,将符合标准的患者分为单纯ART组(简称对照组),ART+青蒿琥酯片A组(青蒿琥酯片50 mg qd,简称A组)和ART+青蒿琥酯片B组(青蒿琥酯片50 mg bid,简称B组)。于治疗基线、治疗24周及48周评定比较分析免疫重建有效率、CD4细胞计数、CD45RA~+分子表达水平、CD45RO~+分子表达水平和安全性指标。结果治疗24周,与对照组、A组比较,B组CD4细胞计数水平明显升高(P_(adj)0.05);治疗48周,三组间CD4细胞计数水平差异无统计学意义(P0.05)。治疗24周、48周,对照组、A组及B组三组间比较免疫功能重建有效率方面差异无统计学意义(P0.05)。治疗24、48周,与对照组和A组比较,B组CD45RA~+分子表达水平差异具有统计学意义(P_(adj)0.05)。治疗24周、48周,与对照组相比,A组、B组CD45RO~+分子表达水平差异无统计学意义(P_(adj)0.05)。治疗24周、48周,与对照组相比,A组、B组在安全性指标方面差异无统计学意义(P_(adj)0.05)。结论青蒿琥酯片能够在一定程度上改善HIV/AIDS患者ART后免疫功能重建不全人群的CD4细胞计数水平,通过改善初始T细胞计数水平以促进患者重建免疫功能,HIV/AIDS患者ART后免疫功能重建不全人群在获得病毒学有效抑制后应尽早启动免疫抑制剂联合治疗方案,且其具备良好的用药安全性。     

中西医结合治疗对艾滋病免疫重建不全者CD4~+T淋巴细胞影响

目的分析云南省中西医结合治疗对高效抗反转录病毒治疗(HAART)后免疫重建不全患者CD4~+ T淋巴细胞(简称CD4细胞)的影响。方法收集2005年9月至2016年12月在云南省接受国家中医药治疗,并在入组前已接受HAART满2年的艾滋病病毒(HIV)感染者/艾滋病(AIDS)病人(简称HIV/AIDS病人)的CD4细胞数据。结果共有781例病人纳入研究,其中免疫重建不全组135例,对照组646例,接受中西医结合治疗后,两组病人CD4细胞计数上升或稳定。治疗后12个月时,免疫重建不全组有效占74.0%,稳定占22.0%,对照组有效占33.9%、稳定占57.4%;治疗24个月时,免疫重建不全组有效占78.0%、稳定占18.1%,对照组有效占39.1%、稳定占51.6%。结论中西医结合治疗可一定程度提高或稳定HIV/AIDS病人CD4细胞计数水平,且对免疫重建不全病人作用更具有优势。     

唐山市HIV/AIDS病人抗病毒治疗1年后CD4~+T淋巴细胞计数变化情况

正为了解唐山市艾滋病病毒(HIV)感染者抗病毒治疗(ART)的效果,促进医疗机构艾滋病病人规范、有效的治疗,对HIV感染者抗病毒治疗1年后CD4+T淋巴细胞(简称CD4细胞)计数变化情况进行分析,结果报告如下。1对象与方法1.1对象在唐山市首次接受国家免费ART,且基线CD4细胞计数和治疗1年后CD4细胞计数均有记录的HIV感染者。治疗随访时间截至2016年12     

中药艾灵颗粒对HIV/AIDS病人免疫细胞功能影响的初步探讨

目的通过用艾灵颗粒治疗艾滋病病毒感染者/艾滋病病人(HIV/AIDS),对CD4+、CD8+ T细胞数量及分泌γ-干扰素(IFN-γ)、白细胞介素4(IL-4)能力的影响,初步探讨中药艾灵颗粒对免疫细胞功能的作用。方法对45例HIV/AIDS病人给予艾灵颗粒治疗,平均治疗时间4个月,在疗前疗后分别检测T细胞亚群中的CD4+、CD8+、CD3+ T细胞计数,并采用流式细胞仪FACSCalibur检测CD4+、CD8+T细胞分泌IFN-γ、IL-4的能力。结果艾灵颗粒的短期治疗能够维持CD4+ T细胞数量的稳定,提高CD4+ T细胞分泌IFN-γ的能力(P0.05),并在一定程度上降低了CD8+T细胞分泌IL-4的能力(P0.05);CD4+ T淋巴细胞数量的变化与分泌IFN-γ能力存在中等正线性相关(P0.05)。结论中药艾灵颗粒可能通过恢复CD4+ T细胞数量,进而提高其分泌IFN-γ的能力,同时降低CD8+ T细胞分泌IL-4的能力来调整Th1与Th2类细胞因子的平衡,对艾滋病疾病进程产生影响;CD4+ T细胞数量的增加,可能对提高分泌IFN-γ能力具有一定的影响。中药的有效干预不仅对免疫细胞数量,更对免疫细胞能够产生积极的影响。     

序贯治疗中ART启动时间对TB/HIV患者的免疫学影响分析

目的 探讨抗反转录病毒治疗(antiretroviral therapy,ART)序贯抗结核治疗(antituberculosis therapy,ATT)中ART启动时间对结核病(tuberculosis,TB)/HIV患者CD4+T、CD8+T细胞计数及CD4/CD8比值的影响.方法 收集云南省传染病医院2014年1月—2017年12月间收治入院的TB/HIV患者病历资料.根据ART启动时间分为A组(ART基础上启动ATT)、B组(ATT 8周内启动ART)、C组(ATT 8周后启动ART).分析比较48周随访期内3组的免疫学指标差异.结果 共收集TB/HIV患者193例,分为A组90例、B组77例和C组26例.基线时B组的CD4+T细胞计数低于A组和C组(P均<0.05).3组患者在48周随访期内CD4+T细胞计数、CD4/CD8比值均呈不同程度上升趋势(P均<0.05).A组和B组的CD4+T细胞计数在序贯治疗后开始上升(P均<0.05),而C组则延迟至24周开始上升(P<0.05).24周、48周时3组的CD4+T细胞计数差异均无统计学意义(P均>0.05),B组的CD4+T细胞计数增幅高于A组和C组(P均<0.05).48周时,3组中仅少数患者的CD4+T细胞计数恢复至≥500 cells/μl,以B组恢复最为明显(12.99％).24周和48周时,CD4+T细胞计数≥500 cells/μl患者所占比例在3组之间差异均无统计学意义(P均>0.05).结论 尚未开始ART的TB/HIV患者应尽早接受ART,以恢复免疫功能,ATT 8周内启动ART,免疫重建效果最佳.     

序贯治疗中ART启动时间对TB/HIV患者的免疫学影响分析

目的 探讨抗反转录病毒治疗(antiretroviral therapy,ART)序贯抗结核治疗(antituberculosis therapy,ATT)中ART启动时间对结核病(tuberculosis,TB)/HIV患者CD4+T、CD8+T细胞计数及CD4/CD8比值的影响.方法 收集云南省传染病医院2014年1月—2017年12月间收治入院的TB/HIV患者病历资料.根据ART启动时间分为A组(ART基础上启动ATT)、B组(ATT 8周内启动ART)、C组(ATT 8周后启动ART).分析比较48周随访期内3组的免疫学指标差异.结果 共收集TB/HIV患者193例,分为A组90例、B组77例和C组26例.基线时B组的CD4+T细胞计数低于A组和C组(P均<0.05).3组患者在48周随访期内CD4+T细胞计数、CD4/CD8比值均呈不同程度上升趋势(P均<0.05).A组和B组的CD4+T细胞计数在序贯治疗后开始上升(P均<0.05),而C组则延迟至24周开始上升(P<0.05).24周、48周时3组的CD4+T细胞计数差异均无统计学意义(P均>0.05),B组的CD4+T细胞计数增幅高于A组和C组(P均<0.05).48周时,3组中仅少数患者的CD4+T细胞计数恢复至≥500 cells/μl,以B组恢复最为明显(12.99％).24周和48周时,CD4+T细胞计数≥500 cells/μl患者所占比例在3组之间差异均无统计学意义(P均>0.05).结论 尚未开始ART的TB/HIV患者应尽早接受ART,以恢复免疫功能,ATT 8周内启动ART,免疫重建效果最佳.     

湖州市HIV/AIDS病人ART后生存状况及相关影响因素分析

目的了解浙江省湖州市艾滋病病毒(HIV)感染者/艾滋病(AIDS)病人(简称HIV/AIDS病人)抗病毒治疗(ART)后的生存状况及相关影响因素,为科学防控艾滋病提供措施和依据。方法采用回顾性队列研究和现况调查等方法,查阅中国疾病预防控制信息系统的艾滋病防治基本信息系统中,有关HIV/AIDS病人ART后进行的随访记录以及现场流行病学问卷调查,资料录入数据库后进行相应的统计学分析。结果共调查≥16周岁接受ART的HIV/AIDS病人670例,其中男性574例(85.7%),已婚/同居345例(51.5%),平均年龄(39.90±13.42)岁。经多因素COX回归分析结果表明,在控制了患者的性别、年龄以及婚姻状况等相关潜在混杂因素之后,基线CD4+T淋巴细胞(简称CD4细胞)计数≥200个/μL组的死亡风险较基线CD4细胞计数200个/μL组低[风险比(HR)=0.112,95%可信区间(CI):0.028～0.455],最近一个月漏服药物(次数≥2次/月)组的死亡风险较未漏服组高(HR=8.991,95%CI:2.531～31.938),具有轻度以上焦虑组的死亡风险较无焦虑组高(HR=3.673,95%CI:1.244～10.849)。结论湖州市HIV/AIDS病人免费ART后能够提高其生存率,基线CD4细胞计数高、无焦虑症及未漏服抗病毒药物会降低死亡风险,建议针对HIV/AIDS病人早期加入ART、增强其服药后的心理干预和卫生服务、以及加强服药依从性的宣教,以提高其生活质量。     

Determinants of CD4+ T cell recovery during suppressive antiretroviral therapy: association of immune activation, T cell maturation markers, and cellular HIV-1 DNA

BACKGROUND: Suboptimal CD4+ T cell recovery during antiretroviral therapy (ART) is a common clinical dilemma. METHODS: We analyzed viral and immunologic predictors of CD4+ T cell recovery in 116 human immunodeficiency virus type 1 (HIV-1)-infected subjects who had suppressed viremia (< or = 50 copies/mL) while receiving ART. Successive measurements of T cell immunophenotypes and cellular HIV-1 DNA levels were obtained before and during receipt of ART. On the basis of increases in the CD4+ T cell count, subjects were classified as immunologically concordant (demonstrating an increase of > or = 100 CD4+ T cells/mm3) or discordant (demonstrating an increase of <100 CD4+ T cells/mm3) after 48 weeks of ART. RESULTS: In adjusted analyses, CD4+ and CD8+ T cell activation at baseline was negatively associated with immunologic concordance at week 48 of ART (odds ratio [OR], 0.80 [P = .04] and 0.67 [P = .02], respectively). High memory (CDRA(-)CD62L-) CD8+ T cell counts at baseline (OR, 0.33 [P = .05]) predicted less CD4+ T cell recovery, whereas increased naive CD4+ T cell counts were associated with higher increases in CD4+ T cells (OR, 1.19 [P = .052]). Neither the cell-associated HIV-1 DNA level at baseline (P = .32) nor the cell-associated HIV-1 DNA level at week 48 of ART (P = .42) was associated with immunologic concordance during ART. CONCLUSIONS: These results support the potential clinical usefulness of the baseline determination of immune activation and maturation subsets in the prediction of CD4+ T cell recovery during viral suppression. Furthermore, identification of individuals with reduced potential for CD4+ T cell recovery during ART may provide a rationale for the initiation of early therapy for some patients.     

Functionally competent antigen-specific CD127(hi) memory CD8+ T cells are preserved only in HIV-infected individuals receiving early treatment

The importance of functional CD4+ T cells and antigen control in the maintenance of CD127 expression on antigen-specific CD8+ T cells is poorly understood in humans. We compared CD127 expression on antigen-specific CD8+ T cells in 4 groups of human immunodeficiency virus (HIV)-infected patients. This analysis demonstrated that HIV-specific CD8+ CD127(hi) T cells are maintained as long-lived memory cells only in HIV-infected individuals treated early with antiretroviral therapy (ART). This population of CD127(hi) T cells fluctuates with viral load (VL) such that the antigen-specific T cell pool oscillates from a CD127(hi) memory to a CD127(lo) effector phenotype depending on the levels of plasma VL. In individuals with chronic infection, the CD127(hi) pool diminishes or is lost with time despite virologic control while receiving ART. These studies show that functionally competent subsets of antigen-specific memory CD8+ T cells in HIV-infected individuals are maintained but only if control of viremia is attained early during the course of infection.     

Proportions of circulating T cells with a regulatory cell phenotype increase with HIV-associated immune activation and remain high on antiretroviral therapy

OBJECTIVE: To examine the relationships between blood CD4 natural regulatory T (Treg) cells, plasma HIV RNA level, CD4 T-cell count and immune activation in untreated HIV-infected patients and immunodeficient patients beginning antiretroviral therapy (ART), using a novel phenotype to define Treg cells (CD25CD127CD4). Data were compared with established Treg cell markers (FoxP3, CTLA-4 and GITR). METHODS: Twenty-nine untreated HIV-infected patients with CD4 T-cell counts of < 300 or > 400/microl were compared in a cross-sectional study and 12 patients beginning combination ART with < 100 CD4 T cells/mul were followed for 1 year on therapy. Three- and four-colour flow cytometry was used to quantitate proportions of Treg cells. RESULTS: In control donors and patients with high CD4 T-cell counts, 28-89% (median 60%) of CD25CD127CD4 cells were FoxP3, but < 10% expressed GITR or CTLA-4. Immunodeficient patients also had CD4-negative lymphocytes with the phenotype FoxP3CD127. Proportions of CD25CD127 cells and activated (HLA-DR) cells in the CD4 T-cell population were increased in patients with low CD4 T cell counts. The proportion of CD25CD127CD4 T cells correlated positively with plasma HIV RNA level and CD4 T-cell activation, but inversely with CD4 T-cell count. Longitudinal studies of 12 patients receiving ART in two distinct cohorts (Western Australia and Malaysia) showed that the proportion of CD25CD127CD4 cells decreased slightly over time, but remained above levels seen in non-HIV controls. CONCLUSIONS: Proportions of circulating T cells with a regulatory cell phenotype increase with HIV-associated immune activation and remain high after 1 year on ART.     

IL-15 delays suppression and fails to promote immune reconstitution in virally suppressed chronically SIV-infected macaques

Human immunodeficiency virus (HIV) infection is characterized by a progressive loss of memory CD4(+) T cells in multiple tissues, especially at mucosal surfaces where most of these cells reside. Although antiretroviral therapy (ART) suppresses viral replication and promotes the recovery of peripheral CD4(+) T cells, HIV-infected patients fail to fully reconstitute the CD4(+) T-cell pool at mucosal sites. IL-15 has been shown to preferentially expand memory-phenotype T cells and promote their migration to nonlymphoid tissues. Here we examined IL-15 treatment in combination with highly active ART in chronically SIV-infected rhesus macaques and found that IL-15 delayed viral suppression and failed to enhance ART-induced total and antigen-specific CD4(+) T-cell reconstitution at mucosal and lymphoid sites. IL-15 was able to induce the transient proliferation of SIV-specific, CMV-specific, and total memory CD8(+) T cells, but not of SIV-specific or total CD4(+) T cells. Moreover, upon treatment interruption, macaques receiving combined IL-15+ART lost CD4(+) T cells faster than those receiving ART alone. These results suggest that the combination of IL-15 with highly active ART is not more efficient than ART alone in promoting CD4(+) T-cell recovery in HIV-infected individuals and may accelerate CD4+ T-cell loss after treatment interruption.     

Granulocyte colony-stimulating factor increases CD4+ T cell counts of human immunodeficiency virus-infected patients receiving stable, highly active antiretroviral therapy: results from a randomized, placebo-controlled trial

Thirty human immunodeficiency virus (HIV)-infected patients with CD4+ T cell counts <350 cells/mm3 who had received stable, highly active antiretroviral therapy (HAART) for at least 24 weeks were randomized to receive either placebo or granulocyte colony-stimulating factor (G-CSF; 0.3 mg/mL 3 times a week) for 12 weeks. Blood samples were collected at specified time points. G-CSF treatment enhanced the total lymphocyte count (P=.002) and increased CD3+ (P=.005), CD4+ (P=.03), and CD8+ (P=.004) T cell counts as well as numbers of CD3-CD16+CD56+ NK cells (P=.001). The increases in CD4+ and CD8+ cell counts resulted from increases in CD45RO+ memory T cells and cells expressing the CD38 activation marker. Lymphocyte proliferative responses to phytohemagglutinin and Candida antigen decreased, whereas NK cell activity and plasma HIV RNA did not change during G-CSF treatment. After 24 weeks, all immune parameters had returned to baseline values. This study suggests that G-CSF treatment of HIV-infected patients receiving stable HAART increases the concentration of CD4+, CD8+, and NK cells without inducing changes in the virus load.     

HIV-specific gag responses in early infancy correlate with clinical outcome and inversely with viral load

Many HIV-infected infants progress to AIDS during the first year of life when antiretroviral therapy (ART) is not given. The immune determinants of progression to AIDS are not known. We hypothesized that distinct HIV-specific T cell responses correlate with viral load and survival over the first year of life. Whole blood of infants at 3, 6, 9, and 12 months of age was incubated with HIV antigens Gag and Env. The frequency of specific T cells producing interferon (IFN)-γ was then measured by flow cytometry. Viral load and CD4% in HIV(+) infants were determined at each time point. ART was not available for this population at the time of sample collection. Those infants who survived to 12 months of age (n=12) had lower viral loads and higher Gag-specific CD8(+) T cell responses at 3 months, compared with infants who died (n=8). Furthermore, the frequency of Gag-specific CD4(+) T cells correlated inversely with viral load at 3 and 6 months of age. Together these data indicate that the early presence of quantitatively higher Gag-specific T cell responses in HIV-infected infants is associated with lower viral loads and decreased mortality in the first year of life. Our data support the design of a vaccine that preferentially elicits Gag responses, which may result in lower levels of viremia and possibly improve outcome.     

人类免疫缺陷病毒-1感染者胞嘧啶脱氨基酶家族表达水平分析

目的 定量研究HIV-1感染者外周血单个核细胞(PBMC)中胞嘧啶脱氨基酶家族成员hA3B、hA3F和hA3G的mRNA表达水平,并分析它们与CD4-T淋巴细胞计数的相关性.方法 采集各21例未接受和已接受抗病毒治疗的HIV-1感染者、10例HIV-1阴性健康对照者的外周静脉血,Ficoll密度梯度离心法分离PBMC,采用反转录一实时荧光定量PCR法检测其中hA3B、hA3F和hA3G mRNA水平,流式细胞术检测CD4~+ T淋巴细胞计数.数据行t、t'或Wilcoxon秩和检验.结果 未治疗及已治疗的HIV-1感染者、HIV-1阴性者hA3B mRNA的表达水平分别为208.4、365.2和563.6(P＜0.05),hA3F tuRNA分别为245.5、316.6和442.9(P＜0.05),hA3GmRNA分别为404.6、360.8和638.6.HIV-1感染者hA3G mRNA水平低于健康对照(Z=-2.451,Z=-2.493,均P＜0.05),但未治疗与已治疗HIV-1组间比较差异无统计学意义(Z=0.340,P=0.7342).HIV-1感染者hA3B、hA3F和hA3G mRNA表达水平与CD4+T淋巴细胞计数均无相关性(未治疗者:r=0.0104,r=-0.0545,r=0.1623,均P＞0.05;已治疗者:r=0.3220,r=0.2193,r=0.1455,均P＞0.05).hA3B、hA3F和hA3G三者mRNA水平在已治疗HIV-1感染者和健康对照者中呈正相关(P＜0.05),而在未治疗HIV-1感染者无相关性(P＞0.05).结论 hA3B、hA3F和hA3G基因表达水平与CD4~+ T淋巴细胞计数无直接相关性;HIV-1感染可导致PBMC中hA3B、hA3F和hA3G表达水平降低,抗病毒治疗可上调hA3B和hA3F的表达.     

Proliferation responses to HIVp24 during antiretroviral therapy do not reflect improved immune phenotype or function

OBJECTIVE: To ascertain whether lymphoproliferation (LP) responses to HIVp24 in chronically infected patients treated with antiretroviral therapy (ART) predict an improved cytolytic T-cell phenotype or better in vivo immune function as measured by immunization responses. METHODS: HIV-infected patients who started ART during chronic infection and who achieved viral suppression (HIV-RNA < 400 copies/ml for > 12 months) were grouped by the presence of strong [stimulation index (SI) > 10; n = 21] or absent (SI < 3; n = 18) LP to HIV-core antigen. The two groups were compared for functional immune responses to vaccination with diphtheria-toxoid, tetanus-toxoid and keyhole-limpet-hemocyanin, frequency of circulating naive and memory CD4+ and CD8+ T lymphocytes, maturation phenotype and expression of cytolytic molecules on total and HIV-specific CD8+ T cells, and frequency of memory CD4+ T cells with intracellular HIV-mRNA. Group comparisons were analyzed by non-parametric Mann-Whitney tests. Proportions were estimated by Pearson's chi analysis. RESULTS: There were no differences between the groups in immune responses to vaccination or in the numbers or phenotype of circulating T cells. In a subgroup of HLA-A2+ or B8+ patients, HIV-reactive CD8+ T cells in both groups had similar expression of perforin, granzyme A and T-cell maturation markers (CD27, CD28, CCR7, CD62L). However, patients with SI > 10 in response to HIVp24 tended to more often have high levels of circulating CD4+ T cells with intracellular HIV-1 mRNA than did patients with SI < 3. CONCLUSION: Following long-standing suppression of viral replication on ART, the presence of HIV-1 specific T-helper proliferation responses does not correlate with improved indices of immune phenotype or function but may reflect relatively higher levels of HIV-expression.     

Immune reconstitution in the first year of potent antiretroviral therapy and its relationship to virologic response

The effects of 1 year of zidovudine, lamivudine, and ritonavir treatment on immune reconstitution were evaluated in 34 human immunodeficiency virus (HIV)-infected individuals. After 48 weeks of therapy, 20 (59%) subjects had <100 copies HIV RNA/mL. CD4+ T cells increased from a median of 192/mm3 at baseline to 362/mm3 at week 48. Lymphocyte proliferative responses to Candida normalized within 12 weeks, but responses to HIV and tetanus remained depressed throughout therapy. Alloantigen responses increased within 12 weeks and then declined to baseline levels. Recovery of delayed-type hypersensitivity responses occurred after 12 weeks for Candida and after 48 weeks for mumps. The magnitude of virologic suppression was correlated with numeric increases in CD4+ T cells, but not with measures of functional immune reconstitution. Plasma virus suppression <100 copies/mL was not significantly correlated with increases in CD4+ T cells or functional immune reconstitution.     

Increase of haemoglobin levels by anti-retroviral therapy is associated with a decrease in immune activation

DESIGN: We evaluated whether an increase in haemoglobin levels in the first 6 months of effective anti-retroviral therapy (ART) is associated with a decrease in immune activation. To reduce confounding factors only men (n = 35) and patients not receiving agents known to enhance haematopoiesis or patients without diseases that might suppress haematopoiesis were included. Simultaneously parameters of iron metabolism and cofactors for haematopoiesis were analysed. RESULTS: A median baseline haemoglobin level of 139 g L-1 increased to 149 g L-1 at month 6 of ART (P < 0.001). At baseline low haemoglobin levels were strongly associated with high neopterin concentrations (r = - 0.64, P < 0.001), and much less correlated to high HIV-1 RNA levels (r = - 0.41, P < 0.05) and to a lower CD4+ cell count (r = 0.33, P < 0.05). The change of neopterin levels during the study period correlated with the relative change in haemoglobin levels, r = - 0.35, P = 0.03, whereas no such correlations were found for the change of HIV-1 RNA levels and the CD4 cell count. A logistic regression analysis revealed that the change of neopterin and soluble transferrin receptors concentrations are independently associated with an increase of haemoglobin levels of more than 15 g L-1. CONCLUSION: Our study supports a cause-effect relationship between immune activation and anaemia in HIV-infected patients. Treatment of patients with ART decreases virus load, which may thereby result in silencing of immune effector activity thus ameliorating anaemia by reversing the anti-proliferative effects of cytokines towards erythroid progenitors and the iron withdrawal strategy of the immune system.