Effect of viral nucleic acid testing on contamination frequency of manufacturing plasma pools

BACKGROUND: In Europe, all plasma pools used for manufacturing of plasma derivatives must be tested negative for hepatitis C virus (HCV) RNA by nucleic acid amplification techniques (NAT) with a defined minimal sensitivity. For a subset of pools, quantitative B19V DNA NAT is also mandatory. NAT for further viral targets was introduced by most of the manufacturers on a voluntary basis. The contamination frequency of plasma pools with HCV RNA, human immunodeficiency virus (HIV)-1 RNA, and hepatitis B virus (HBV) DNA was investigated with representative pools before and after introduction of NAT. STUDY DESIGN AND METHODS: A total of 873 pools from 1996 and 331 pools from 2006 were analyzed for the detection of HCV RNA, HIV RNA, and HBV DNA with an automated multiplex NAT system. The pools were obtained from different manufacturers and the source material was of European and US origin. RESULTS: HCV RNA, HIV-1 RNA, and HBV DNA were detectable in plasma pools from 1996 with the following frequencies: 17.8 percent (HCV RNA), 0.8 percent (HIV-1 RNA), and 0.5 percent (HBV DNA). Viral genome concentrations were up to 3 x 10(4) IU HCV RNA per mL and 7 x 10(3) IU HIV RNA per mL, whereas HBV DNA was below the quantitation limit of the quantitative NAT assay. Among the pools from 2006, one pool (0.3%) was found HCV RNA-positive at low titer (<10 IU/mL), whereas no HIV RNA or HBV DNA was detectable in any pool. CONCLUSION: The results imply that the introduction of NAT systems for the detection of viral genomes has largely reduced the contamination frequency and viral loads of manufacturing plasma pools and thereby improved the safety margin for human medicinal products manufactured from human plasma. Even with NAT, however, low-titer contamination may occur, which will be coped with by virus inactivation steps included into the manufacturing of plasma derivatives.     

Neopterin levels during the early phase of human immunodeficiency virus, hepatitis C virus, or hepatitis B virus infection

BACKGROUND: A study was conducted to assess the diagnostic sensitivity of neopterin screening of blood donors with regard to the detection of window-phase specimens of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) infection. STUDY DESIGN AND METHODS: In total, 1002 diagnostic window-phase specimens from 98 seroconversion panels (29 HIV-1, 52 HCV, and 17 HBV) were analyzed with viral antigen detection, viral nucleic acid amplification testing (NAT), and neopterin quantitation assays. The study was completed by the analysis of 92 anti-hepatitis B core antigen (HBc)-reactive and 103 alanine aminotransferase (ALT)-elevated blood donor specimens. RESULTS: A significant association between elevated neopterin concentrations and the very early phase of HIV-1 infection was found. No significant correlation could be observed between neopterin levels and the early phase of HCV or HBV infection. Neopterin concentration was not increased in specimens from blood donors with anti-HBc reactivity or ALT elevation. CONCLUSIONS: Neopterin screening of blood donors may identify window-phase cases of HIV, but not of HCV or HBV infection. The diagnostic sensitivity of neopterin screening during the HIV window phase is similar to that of the p24 antigen test. With the introduction of viral NATs in blood screening, there is no additional benefit of neopterin screening with regard to the three blood-borne viruses HIV, HCV, and HBV. Acute phases of other infectious agents, however, have been reported to be detected by neopterin enzyme-linked immunosorbent assays.     

扶正解毒汤辅治艾滋病合并乙型肝炎病毒感染的临床疗效观察

目的本研究旨在观察扶正解毒汤辅助治疗艾滋病合并乙型肝炎病毒感染的临床疗效。方法选取100例符合纳入标准的艾滋病合并乙型肝炎病毒感染患者,按照随机数表法随机分为两组,每组50例。其中对照组采用HAART疗法,观察组在HAART疗法基础上采用扶正解毒汤;治疗前后观察患者体液免疫功能(免疫球蛋白IgG、IgA及IgM)、细胞免疫功能(CD4^+T淋巴细胞数量)和病毒载量(HBV DNA载量和HIV RNA载量)。结果治疗后,两组患者体液免疫功能(免疫球蛋白IgG、IgA及IgM)明显升高(P<0.05);CD4^+T淋巴细胞数量明显升高(P<0.05);HBV DNA载量和HIV RNA载量均明显降低(P<0.05)。结论扶正解毒汤能提升艾滋病合并乙型肝炎病毒感染患者的体液免疫功能和细胞免疫功能,降低HBV DNA载量和HIV RNA载量,提高治疗效果。     

Determination of HIV RNA concentration for evaluation of the efficacy of combined therapy of HIV infection

Plasma HIV RNA (viral load) and count of CD4+ T cells were evaluated in 23 patients with HIV infection treated with invirase (1800 mg/day), zidovudine (600 mg/day), and zalcitabine (2.25 mg/day) for 6 months in order to evaluate the efficiency of antiretroviral therapy. Viral load was measured by AMPLICOR HIV-1 Monitor test. The reproducibility of HIV RNA measurements was in line with reported data (CV 15-41%), allowing highly accurate (15%) evaluation of RNA in a standard control sample provided by National Institute for Biological Standards and Control, Great Britain. Plasma HIV RNA concentration decreased to an undetectable level (below 400 RNA copies/ml plasma) after 6 months of treatment in 52.2% patients. In 17.4% the therapy failed, and in 30.4% it resulted in a reduction of viral load to > 1 lg, although HIV RNA was still detected in the plasma after 6-month therapy. The count of CD4+ T cells increased by 9.5%. Changes in the viral load outstripped changes in CD4+ cells. Viral load was in high correlation with the count of CD4+ lymphocytes: -0.53, p = 0.01 before treatment and -0.61, p = 0.002 after 6-month treatment.     

140例成人人类免疫缺陷病毒感染与丙型肝炎病毒感染相互影响

目的 了解经输血或单采浆献血感染人类免疫缺陷病毒(HIV)的患者中丙型肝炎病毒(HCV)的感染率；分析HIV与HCV感染的相互影响。方法 对140例经输血或单采浆献血感染HIV的患者血清抗HCV、HBV—M、肝脏生化功能、CD4^ 和CD8^ 细胞计数、纤维胃镜、肝胆脾B超进行分析。结果 140例HIV感染和获得性免疫缺陷综合征(AIDS)患者中HCV抗体阳性者占91．5％(128／140)；HIV和HCV混合感染者肝功能损害较轻，与单纯HIV感染者比较，其肝功能、B超改变、CD4^ 细胞计数之间差异无统计学意义。结论 经输血或单采浆献血感染的HIV感染者中存在着极高的HCV感染(91．5％)。HIV和HCV混合感染者与单纯HIV感染者比较，肝功能损伤并不严重，提示HIV可能并不加速丙型肝炎的进展。     

Evaluation of two commercial procedures for quantification of human immunodeficiency virus type 1 RNA with respect to HIV-1 viral subtype and antiviral treatment

To determine the reliability of two commercial assays for quantifying the human immunodeficiency type 1 (HIV-1) RNA levels in patients infected with different HIV-1 subtypes and managed with various drug regimens, blind testing of 127 plasma samples from 57 patients infected with HIV-1 subtypes A, B, C and E was performed using the Amplicor HIV-1 Monitor Test (Roche) and Quantiplex HIV-1 RNA 3.0 Assay (Chiron). Included were time course studies in 7 patients in whom the virus load was correlated with CD4+ cell counts and therapy. Both assays were accurate and precise to measure standardized amounts of viral load and displayed high correlation coefficients that were independent of gender and treatment modality, even though some assay-specific differences may exist in the quantification of viral subtype RNA. Time course studies showed comparable inverse associations between the CD4+ count and viral load measured by the two assays. Hence, both the Amplicor HIV-1 Monitor Test and the Quantiplex HIV-1 RNA 3.0 Assay promise to be useful for the management of HIV-1 infected patients.     

Human immunodeficiency virus infection of the human thymus and disruption of the thymic microenvironment in the SCID-hu mouse

Infection with the human immunodeficiency virus (HIV) results in immunosuppression and depletion of circulating CD4+ T cells. Since the thymus is the primary organ in which T cells mature it is of interest to examine the effects of HIV infection in this tissue. HIV infection has been demonstrated in the thymuses of infected individuals and thymocytes have been previously demonstrated to be susceptible to HIV infection both in vivo, using the SCID-hu mouse, and in vitro. The present study sought to determine which subsets of thymocytes were infected in the SCID-hu mouse model and to evaluate HIV-related alterations in the thymic microenvironment. Using two different primary HIV isolates, infection was found in CD4+/CD8+ double positive thymocytes as well as in both the CD4+ and CD8+ single positive subsets of thymocytes. The kinetics of infection and resulting viral burden differed among the three thymocyte subsets and depended on which HIV isolate was used for infection. Thymic epithelial (TE) cells were also shown to endocytose virus and to often contain copious amounts of viral RNA in the cytoplasm by in situ hybridization, although productive infection of these cells could not be definitively shown. Furthermore, degenerating TE cells were observed even without detection of HIV in the degenerating cells. Two striking morphologic patterns of infection were seen, involving either predominantly thymocyte infection and depletion, or TE cell involvement with detectable cytoplasmic viral RNA and/or TE cell toxicity. Thus, a variety of cells in the human thymus is susceptible to HIV infection, and infection with HIV results in a marked disruption of the thymic microenvironment leading to depletion of thymocytes and degeneration of TE cells.     

Long-term methadone treatment: effect on CD4+ lymphocyte counts and HIV-1 plasma RNA level in patients with HIV infection

The objective was to examine the effect of methadone on CD4+ lymphocyte counts and viral load and to expect to document the safety of methadone maintenance in patients with human immune deficiency syndrome. This is a retrospective chart analysis comparing the trends in CD4+ count and viral load in two populations of 21 human immunodeficiency virus (HIV) infected patients, one on methadone maintenance and a methadone non-using group. Each methadone user was matched with a control methadone non-user that had a similar CD4+ at the beginning of the study. For the CD4+ count we compared the slope of regression for each couple of patients. In 15 patients we also collected the viral load, which was measured at 4-6 monthly intervals. The mean length of follow-up was 811 days for the methadone group and 797 days in the control group. There was no statistical difference in the treatment received by the two groups of patients during the study. The slope of regression of CD4+ count showed a significantly steeper decline in the methadone-using patients compared with the methadone non-users (r= 0.487; p< 0.05). The evolution of the HIV-1 RNA levels was the same during the follow-up of mean 186 months in a few of the patients in each of the two groups. Long-term methadone use was associated with a significantly faster decrease of CD4+ count in HIV-1 affected patients compared with methadone non-users. HIV-1 RNA data were found in too few patients to enable any conclusions about the development of viral load in the two groups.     

多重定量PCR法同步检测HBV、HCV和HIV-1在血液筛查中的优化及应用

目的 初步探讨多重定量聚合酶链反应（PCR）同步检测乙型肝炎病毒（HBV） DNA,丙型肝炎病毒（HCV） RNA及人类免疫缺陷病毒（HIV）-1 RNA在血液筛查中的应用前景.方法 选择2012年8月至12月,于孝感市中心血站志愿献血的合格献血者血样中,经2次酶联免疫吸附法（ELISA）检测HBV表面抗原（HBsAg）、抗HCV及抗HIV-1,检测结果均呈阴性的4 800份血样为研究对象.采用全自动核酸混合提取仪对该4 800份血样进行核酸提取,然后利用多重定量PCR方法对血样中HBV、HCV及HIV-1进行同步扩增检测.采用中国药品和生物制品检定所提供的HBV DNA、HCV RNA及HIV-1 RNA标准参考品,检测多重定量PCR的灵敏度,并与单重定量PCR的灵敏度进行比较.在HBV、HCV及HIV-1 3者中任意1种病毒基因组浓度较高的条件下,对多重定量PCR检测另2种低浓度病毒基因组的能力进行评估.结果 增加多重定量PCR中c-MMLV逆转录酶和Hot Taq酶的用量,并适量加入单链结合蛋白（SSB）,可使其扩增效率提升至单重定量PCR扩增水平.本组4 800份血样中,经多重定量PCR检测出3份HBV DNA阳性样品,ELISA漏检率为0.062 5％,未发现HCV RNA和HIV-1 RNA阳性样品;多重定量PCR检测HBV DNA、HCV RNA及HIV-1 RNA在95％置信区间的灵敏度浓度分别为115 IU/mL、376 IU /mL和232 IU /mL;单重定量PCR检测HBV DNA、HCV RNA和HIV-1 RNA在95％置信区间的灵敏度浓度分别为51 IU /mL、94 IU /mL和78 IU/mL.结论 本研究初步建立了对献血者血液同时进行HBV DNA、HCV RNA及HIV-1 RNA检测的多重定量PCR检测方法;该检测体系经过进一步优化后,有望应用于临床大规模血液病毒筛查.     

Complement receptor 2 mediates enhancement of human immunodeficiency virus 1 infection in Epstein-Barr virus-carrying B cells

Although the CD4 glycoprotein is the primary receptor for HIV-1, recent reports have suggested that other molecules might be involved in the enhancement of HIV-1 infection. We investigated the possible role of the complement receptor 2 in enhancement of HIV-1 infection in CD4+ EBV-containing B cells by infecting such cells in the presence of sera from HIV sero-positive donors, with or without added human complement. A marked increase in production of viral p24 and infectious progeny virus was observed only when infection had been carried out in the presence of human complement. The addition of mAb to the human complement receptor 2 completely inhibited this enhancement. This mechanism was CD4 dependent, suggesting a cooperative effect between these two ligands in the potentiation of viral entry.     

First transmission of human immunodeficiency virus Type 1 by a cellular blood product after mandatory nucleic acid screening in Germany

BACKGROUND: In February 2007, a 63-year-old man underwent surgery. Retrospective testing with nucleic acid testing (NAT) showed that the patient was human immunodeficiency virus Type 1 (HIV-1) positive 10 days after transfusion. The transfusion-transmitted infection had been identified by a donor-related lookback started in April 2007 after anti-HIV seroconversion.
METHODS: Sequence analysis was performed in the gag-pol region as well as in the V3 loop env region. Archived plasma from the transmitting donation was investigated for the individual-donation NAT with the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 test (Roche CAP/CTM HIV-1 test) and for HIV antigen/antibody combination testing (Abbott Architect). Additional testing was done on the donor's follow-up sample and on the recipient's sample.
RESULTS: The Roche CAP/CTM HIV-1 test failed to detect viral RNA by minipool NAT in the index donation (April 2007) as well as in the donation that caused the infection (January 2007). Phylogenetic analysis showed a very high genetic similarity among viral sequences from both donor and recipient, proving the HIV-1 transmission by sequence data.
CONCLUSION: This case represents the first documented HIV-1 transmission by transfusion of red blood cells after mandatory introduction of HIV-1 NAT for blood screening in Germany. Low viral load and mismatches in the primer/probe region might explain the detection failure of the NAT screening assay. A certain risk remains that new virus variants contain mutations at positions critical for amplification or detection of viral genomes. An option to reduce the risk of a detection failure by NAT is the simultaneous use of several conserved regions as amplification targets.     

Laboratory markers of antiviral activity

Quantitative assays for viral nucleic acids have been instrumental in monitoring the response of patients to various antiviral therapies. The level of viraemia is predictive of clinical outcome in that a reduced risk of progression to AIDS or death was observed with lower plasma human immunodeficiency virus (HIV) RNA levels. Rebound in viral levels often signals therapeutic failures, some of which are associated with the development of drug resistance. Quantitative plasma assays for HIV, hepatitis C virus (HCV), cytomegalovirus (CMV) and hepatitis B virus (HBV) have been developed. Over time, modifications to these assays have been required to meet new demands. For example, as antiviral therapies have become more effective, HIV and HCV assays of greater sensitivity are required in order to follow patients for longer periods of time and to fully assess the extent of viral suppression. For HIV-1, a large percentage of patients treated with combination therapies had viral loads that were below the detection limit of the ultrasensitive assay (50 copies/ml). To assess the residual viral burden in this patient population an assay to quantify HIV-1 proviral DNA in peripheral blood mononuclear cells was developed. Studies to date indicate that proviral DNA remains easily detectable despite undetectable plasma RNA and may be useful in monitoring this patient population. To increase assay throughput, a new generation of quantitative assays that will provide real-time detection and a 6 log10 detection range from a single amplification is under development.     

Effect of weekly adefovir (PMEA) infusions on HIV-1 virus load: results of a phase I/II study

The compound 9-(2-phosphonylmethoxyethyl)adenine (adefovir; PMEA) is a potent inhibitor of a number of viruses in vitro, such as human immunodeficiency virus (HIV) type 1 and 2, herpes simplex virus (HSV) type 1 and 2, human papillomavirus virus (HBV) and Epstein-Barr virus (EBV). Adefovir also proved to be effective in vivo against feline immunodeficiency virus (FIV) in cats and simian immunodeficiency virus (SIV) in rhesus monkeys. In an open, non-placebo-controlled trial the antiviral activity of weekly doses of adefovir in nine patients with AIDS or AIDS-related complex was studied for a period of 11 weeks. CD4 cell counts at baseline were between 10 and 450 cells/mm3, HIV-1 RNA levels at baseline were between 24,210 copies/ml and 406,197 copies/ml. The drug was administered intravenously at a dose of 1000 mg every week and plasma viral load was assessed at multiple points during the study. Administration of adefovir was tolerated well and no severe side effects were seen. The response to adefovir treatment differed widely between patients. The increase in CD4 cell count at end point ranged from -40 to 120 cell/mm3. The lowest HIV RNA levels were measured after 3-5 days, showing an increase thereafter. The nadir in viral load was achieved after 2 weeks, with a mean viral load decline of 0.7 from baseline. The decrease of the HIV RNA level at end point ranged from -0.3 log10 to 1.8 log10 with a mean decrease of 0.4 log10. Our results indicate that adefovir given intravenously once weekly has a short-lasting initial antiviral effect. The effect of more frequent dosing requires further evaluation. If adefovir is to be useful clinically, it needs to be combined with other antiviral agents.     

Comparison of lymphocyte subpopulations in the peripheral blood of patients with infectious mononucleosis and human immunodeficiency virus infection: a preliminary report.

The aim of this study was to analyse the lymphocyte subpopulations in the peripheral blood of HIV-1-infected adults to compare them with four patients with acute EBV infection. Lymphocyte subsets in 15 healthy controls, 40 HIV-1-infected adults and 4 EBV-infected patients with infectious mononucleosis were analysed by flow cytometry. The immunophenotyping of HIV-1-infected patients in different stages of disease showed a significant reduction in the percentage and absolute count of CD4+ T-lymphocytes, significantly increased percentage of CD8+ T-lymphocytes, inverted CD4/CD8 ratio and an increase in the expression of activation marker HLA-DR compared to controls. The immuno-phenotyping profiles of HIV and EBV infection share some similarities as they both result in the decreased percentage of CD4+ T-lymphocytes, increased CD8+ T-lymphocytes and an inverted CD4/CD8 ratio. Patients with HIV infection could be distinguished from patients with EBV infection by the absolute lymphocytosis and increased expression of HLA-DR seen in the patients with infectious mononucleosis. In conclusion, both HIV-1 and EBV profoundly change the distribution of lymphocyte subpopulations in the peripheral blood. It is our opinion that flow cytometry could be an aid in the rapid distinguishing of patients with suspected primary HIV-1 infection from those with infectious mononucleosis (before serology data are available).     

大理市HIV感染者中HCV感染状况的研究

目的探讨人类免疫缺陷病毒(HIV)-1感染者中丙型肝炎病毒(HCV)的混合感染率,并了解HCV对HIV-1感染者CD4+T细胞计数的影响。方法采用横断面研究方法,在云南大理市招募HIV-1感染者,分别采用血清学和核酸方法检测HCV混合感染。结果在526例HIV-1感染者中,静脉吸毒者占94.3%,其余为性途径感染。86.9%(457/526)为HCV血清学检测抗体阳性,其中HCV核酸阳性者占78.3%。在HCV血清学阴性的69例中,24例HCV RNA>1 000 IU/mL。由于引入HCV核酸检测方法,现场HCV混合感染的发现率增加了4.6%(24/526),所调查的HIV-1感染者中HCV混合感染率为91.4%。HCV混合感染者的CD4+T细胞计数明显低于HIV-1单纯感染者。结论在HCV感染的高流行区或髙危人群中,HCV与HIV-1共感染率较高。筛查HIV-1感染时应加强对HCV的检测,有助于对HCV感染进行早期诊断并开展HCV的早期治疗,减少HCV对HIV-1感染者的不利影响。     

Inhibition of human immunodeficiency virus replication and growth advantage of CD4+ T cells and monocytes derived from CD34+ cells transduced with an intracellular antibody directed against human immunodeficiency virus type 1 Tat.

Current clinical gene therapy protocols for the treatment of human immunodeficiency virus type 1 (HIV-1) infection involve the ex vivo transduction and expansion of CD4+ T cells derived from HIV-positive patients at a late stage in their disease (CD4+ cell count <400 cells/mm3). We examined the efficiency of transduction and transgene expression in adult bone marrow (BM)- and umbilical cord blood (UCB)-derived CD34+ cells induced to differentiate into T cells and monocytes in vitro with an MuLV-based vector encoding the neomycin resistance gene and an intracellular antibody directed against the Tat protein of HIV-1 (sFvtat1-Ckappa). The expression of the marker gene and the effects of antiviral construct on subsequent challenge with monocytotropic and T cell-tropic HIV-1 isolates were monitored in vitro in purified T cells and monocytes generated in culture from the transduced CD34+ cells. Transduction efficiencies of CD34+ cells ranged between 22 and 27%. Differentiation of CD34+ cells into T cells or monocytes was not significantly altered by the transduction process. HIV-1 replication in monocytes and CD4+ T cells derived from CD34+ cells transduced with the intracellular antibody gene was significantly reduced in comparison with the degree of HIV replication seen in monocytes and CD4+ T cells derived from CD34+ cells transduced with the neomycin resistance gene alone. Further, T cells and monocytes derived from CD34+ cells transduced with the intracellular antibody gene were demonstrated to express the sFvtat1-Ckappa transgene by RT-PCR and had a selective growth advantage in cultures that had been challenged with HIV-1. These data demonstrate that sFvtat1-Ckappa inhibits HIV-1 replication in T cells and monocytes developing from CD34+ cells and supports the continuing development of a stem cell gene therapy for the treatment of HIV-1 infection.     

HIV及HBV重叠感染患者生化免疫指标的检测价值

[目的] 探讨人类免疫缺陷病毒(HIV)与乙型肝炎病毒(HBV)重叠感染患者生化免疫指标的变化特点.[方法] 比较30例HIV感染、32例HBV感染及20例HIV、HBV重叠感染患者(HIV/HBV组)肝功能、免疫功能、血生化常规指标的差异.[结果] ①HBV组CD3+、CD4+、CD4+/CD8+高于HIV组、HIV/HBV组(P<0.05),HIV、HIV/HBV组组间比较差异无显著性(P>0.05);②HBV组谷草转氨酶(AST)、谷丙转氨酶(ALT)、总胆红素(TBil)均高于其他两组(P<0.05),HIV组与HIV/HBV组组间比较差异无显著性(P>0.05);③HIV/HBV组HIV RNA、HBV DNA病毒载量均高于HIV组(P<0.05);④HBV组血红蛋白(Hb)水平高于(P<0.05),其血小板计数(PLT)、红细胞(RBC)水平均低于HIV组与HIV/HBV组(P<0.05),而HIV组、HIV/HBV组Hb、PLT、RBC组间比较差异无显著性(P>0.05).[结论] HIV/HBV重叠感染后,机体免疫功能进一步降低,可促进两者病情的进展,但其可能减轻HBV感染患者肝脏炎性损伤,但对HIV所引起贫血无明显影响.     

Activation of virus replication after vaccination of HIV-1-infected individuals

Little is known about the factors that govern the level of HIV-1 replication in infected individuals. Recent studies (using potent antiviral drugs) of the kinetics of HIV-1 replication in vivo have demonstrated that steady-state levels of viremia are sustained by continuous rounds of de novo infection and the associated rapid turnover of CD4+ T lymphocytes. However, no information is available concerning the biologic variables that determine the size of the pool of T cells that are susceptible to virus infection or the amount of virus produced from infected cells. Furthermore, it is not known whether all CD4+ T lymphocytes are equally susceptible to HIV-1 infection at a given time or whether the infection is focused on cells of a particular state of activation or antigenic specificity. Although HIV-1 replication in culture is known to be greatly facilitated by T cell activation, the ability of specific antigenic stimulation to augment HIV-1 replication in vivo has not been studied. We sought to determine whether vaccination of HIV-1-infected adults leads to activation of virus replication and the targeting of vaccine antigen- responsive T cells for virus infection and destruction. Should T cell activation resulting from exposure to environmental antigens prove to be an important determinant of the steady-state levels of HIV-1 replication in vivo and lead to the preferential loss of specific populations of CD4+ T lymphocytes, it would have significant implications for our understanding of and therapeutic strategies for HIV-1 disease. To begin to address these issues, HIV-1-infected individuals and uninfected controls were studied by measurement of immune responses to influenza antigens and quantitation of virion- associated plasma HIV-1 RNA levels at baseline and at intervals after immunization with the trivalent influenza vaccine. Influenza vaccination resulted in readily demonstrable but transient increases in plasma HIV-1 RNA levels, indicative of activation of viral replication, in HIV-1-infected individuals with preserved ability to immunologically respond to vaccine antigens. Activation of HIV-1 replication by vaccination was more often seen and of greater magnitude in individuals who displayed a T cell proliferative response to vaccine antigens at baseline and in those who mounted a significant serologic response after vaccination. The fold increase in viremia, as well as the rates of increase of HIV-1 in plasma after vaccination and rates of viral decline after peak viremia, were higher in individuals with higher CD4+ T cell counts.(ABSTRACT TRUNCATED AT 400 WORDS)