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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This is the first report of natural killer cell enumeration and function in HIV-infected and high-risk uninfected adolescents. We examined the association of demographic characteristics of this cohort with three outcomes: CD16+ cell absolute count, lytic units per peripheral blood mononuclear cell (PBMC), and lytic units per natural killer (NK) cell. We also examined the association of CD4, CD38, and antiretroviral therapy (ART) use with these outcomes in the subset of HIV-infected adolescents. Adolescents participating in an on-going longitudinal study (the REACH study) were sampled for CD16+ cell count and NK function. This cross-sectional analysis was performed on 412 subjects with NK cell data available. HIV-positive males had higher numbers of CD3-/CD16+/CD56+ NK cells than HIV-positive females. However, for the HIV-negative subjects, we did not observe a gender-related effect for absolute NK cell numbers. Gender, however, was a significant covariate for the analysis, using lytic units per PBMC as the unit of measurement, with males showing higher values than females. Age was not a predictive covariate for any of the three assessments of NK cell number and function examined. Our observations concerning the HIV-positive individuals indicate that reduced CD4+ T cell counts were associated with decreased circulating CD3-/CD16+/CD56+ NK cells. We also observed an association between elevation of CD8+/CD38+/DR+ lymphocytes and lower NK lytic units per PBMC. The results of our multivariate models indicate that there is a reduced number of NK cells and reduced lytic units per PBMC in patients receiving single or multidrug antiretroviral therapy. There are changes in circulating NK cell number and function in HIV-infected adolescents, in comparison with high-risk HIV-negative adolescents. The data suggest that these changes may occur early in the course of HIV disease but that quantitative changes continue to occur with advancing depletion of the CD4+ T cell pool.
AIDS Res Hum Retroviruses 2001 Apr 10
PMID:Natural killer cell enumeration and function in HIV-infected and high-risk uninfected adolescents. 1135 Jun 68

Flow cytometry has played an invaluable role in recent advances made against HIV and AIDS, and there is every reason to expect it will continue to do so. Newer-generation machines, using three- and four-color panels, make measurements of lymphocyte subsets ever more accurate and potentially cost-effective. Similarly, recent single-platform techniques promise even more efficiencies, freeing CD4 enumeration from parallel determination of the CBC. In other developments, quantitative reporting of immunophenotype may well change the way subsets traditionally defined by qualitative determinations are viewed. The most promising initial candidates for such changes are surrogates of immune activation, such as CD38 expression on CD8 cells. But technical demonstration of reproducibility and reliability, and clinical trial evidence of utility--especially as measured against such established laboratory parameters as CD4 cell and HIV RNA determinations--are needed before a change from qualitative to quantitative immunophenotype measurement can be widely accepted. Although too soon to tell if they will emerge from the research arena into the clinical arena, tetramer binding, intracellular cytokine detection, and assays of cell division are rapidly advancing understanding of HIV-disease, and indeed understanding of all of human immunology. Some of these assays provide often subtly different information, and together they will help determine the most important surrogate measures of clinical immunity. Identifying such surrogates is critical to developing a rational HIV vaccine. The power of flow cytometry is its ability simultaneously to analyze data in four, five, six, or more dimensions. For longitudinal experiments, time adds yet another dimension. Humans struggle to think past three dimensions; interpreting results from experimental permutations and combinations that expand geometrically with each additional parameter studied requires considerable effort. Ultimately computer programs might come to our aid, but for now we have to live with the information overload if we hope to gain insight into the workings of complex biologic systems. In a world of limited resources, and with limited capacity to conceptualize in multiple dimensions, insight, inspiration, and perhaps a little luck are needed to ask the right questions and use the right assays if the recent string of advances against AIDS is to continue.
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PMID:An update on the use of flow cytometry in HIV infection and AIDS. 1177 Feb 91

Laboratory markers that predict HIV-1 disease progression include plasma viral burden, CD4+ T-cell count, and CD38 expression on CD8 T cells. To better understand whether the predictive value of these markers is dependent on how long an individual has been infected, we analyzed data from the Multicenter AIDS Cohort Study early (median = 2.8 years) and late (median = 8.7 years) in the course of infection. Overall, we found that HIV RNA and CD38 levels were similarly predictive of AIDS early on compared with a relatively weaker CD4 cell count signal. Later in the course of infection, CD38 level remained the strongest predictive marker and CD4 cell count registered a marked increase in prognostic power. Among untreated individuals, there was little difference in prognosis (median time to AIDS) associated with given marker values regardless of infection duration. The prognosis given a specific viral load level tended to deteriorate late in the course of infection among those undergoing treatment with monotherapy or combination therapy, however. These data provide a unique historical look at the predictive value and prognostic significance of HIV-1 disease markers at different stages of infection in a large cohort, with direct relevance to current patients who are untreated or for whom treatment is ineffective.
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PMID:Predictive value of immunologic and virologic markers after long or short duration of HIV-1 infection. 1191 38

Plasma cell neoplasia occurs much less frequently than high-grade B-cell non-Hodgkins lymphoma in HIV-infected patients, but is nevertheless an AIDS-associated malignancy. In this report, we describe the fine-needle aspiration (FNA) findings of a mass in the left parotid region with plasmablastic features that occurred in a 41-yr-old HIV-infected homosexual man whom we diagnosed as having anaplastic myeloma. The patient had normochromic, normocytic anemia with a hematocrit of 21%, a white blood count of 2.2 x 10(9)/l with 76% neutrophils, and a CD4 count of 31%. He also had elevated levels of calcium (13.2 mg/dl), alkaline phosphatase (25,400 IU/l), blood urea nitrogen (2,600 mg/dl), and creatinine (2.5 mg/dl). Serum protein electrophoresis showed polyclonal hypergammaglobulinemia without any monoclonal component. A bone survey revealed multiple punched-out lytic lesions. FNA smears showed large plasmacytoid cells with eccentrically placed nuclei, prominent nucleoli, and moderate amounts of basophilic cytoplasm. By immunocytochemical staining, tumor cells were negative for CD19, CD20, and leukocyte-common antigen (LCA), but strongly positive for CD38 and kappa light chain. Anaplastic myeloma and plasmablastic lymphoma were considered in the differential diagnosis. Although the cytomorphologic and immunophenotypic findings of our case overlapped with those of plasmablastic lymphoma, the pattern of bone involvement with punched-out lytic lesions and absence of localization of the tumor to the mucosa of the oral cavity led us to a diagnosis of anaplastic myeloma. The patient initially received antiretroviral therapy followed by thalidomide and pulse dexamethasome therapy, but his response was poor. His HIV load increased, and his malignancy rapidly progressed with the development of multiple vertebral lesions, extraosseous extension, and eventually cord compression. He died of the disease less than 2 mo after presentation.
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PMID:Fine-needle aspiration cytology of a case of HIV-associated anaplastic myeloma. 1235 99

Immune activation associated with HIV infection declines after highly active antiretroviral therapy (HAART), but may persist or recur in some patients. It is not clear whether this reflects a resurgence of HIV replication or another cause of immune activation, such as inflammatory reactions to opportunistic pathogens (immune restoration disease [IRD]). Here, we studied plasma and cellular immune activation markers in adult HIV-1 patients who had received HAART for >12 months and maintained plasma HIV RNA levels of <400 copies/ml for >6 months. Plasma interleukin 1 receptor antagonist and tumor necrosis factor receptor I levels were similar in patients and HIV-negative control subjects, but the highest levels occurred mainly in patients with a history of IRD. In contrast, expression of HLA-DR and CD38 on monocytes and of HLA-DR on CD8(+) T cells was higher in patients than in control subjects. Thus, cellular markers of immune activation are abnormal in some patients with a good virological response to HAART, and abnormalities of plasma immune activation markers correlate with a history of IRD.
AIDS Res Hum Retroviruses 2002 Dec 10
PMID:Immune activation in patients infected with HIV type 1 and maintaining suppression of viral replication by highly active antiretroviral therapy. 1248 6

Proliferation within T lymphocyte subsets of HIV-infected adolescents was quantified by detection of Ki-67, a nuclear antigen found in cells in late G(1), S, or G(2) phases of the cell cycle. Median percentages and absolute counts of Ki-67(+) cells for all subsets tested (CD4 naive and memory, CD8 naive and memory) were significantly higher for HIV-infected adolescents compared to uninfected controls. CD8 naive cells of HIV-infected adolescents had the greatest increase in rate of proliferation and number of proliferating cells compared to uninfected controls. In HIV-infected adolescents, the percentage and absolute number of proliferating CD4 naive cells were considerably lower than corresponding values for the other subsets. CD4 percent correlated inversely with Ki-67 expression in CD4 memory, CD8 naive, and CD8 memory cells, while Ki-67 expression in CD4 and CD8 memory cells correlated directly with average CD38 molecules/CD8 cell and absolute number of CD8/CD38/HLA-DR cells, consistent with T cell activation. These results indicate that in adolescents, HIV infection is associated with increased proliferation within CD4 and CD8 naive and memory subsets. Proliferation within the CD8 naive subset was higher than that observed previously for HIV-infected adults, suggesting that adolescents have a greater ability to regenerate and/or expand CD8 naive cells. CD4 naive cells of HIV-infected adolescents had a low rate of proliferation, and the total number of CD4 naive cells was low, suggesting that regeneration and/or peripheral expansion are limited and may contribute to the reduced size of this subset. The Ki-67 assay provided new and useful information on in vivo lymphocyte proliferation in HIV-infected adolescents.
AIDS Res Hum Retroviruses 2002 Nov 20
PMID:Increased proliferation within T lymphocyte subsets of HIV-infected adolescents. 1248 18

Infection by human immunodeficiency virus (HIV) causes persistent chronic inflammation. Viral Tat protein plays a role in the intracellular increase of reactive oxygen species (ROS) thus increasing apoptotic index, mostly the one mediated by FAS/CD95, and depleting CD4+ T lymphocytes. The aim of this study was to investigate whether there is a relationship between an extensive array of redox status indices (glutathione (GSH), malondialdehyde (MDA), peroxidation potential, total antioxidant status, glutathione peroxidase (GPx), superoxide dismutase (SOD), total hydroperoxide (TH), DNA fragmentation) and relative CD4, CD95, CD38/CD8 T lymphocyte counts in HIV/AIDS patients compared to healthy subjects. Blood samples from 85 HIV/AIDS patients and 40 healthy subjects were tested by spectrophotometric techniques in order to measure oxidative stress indices, and by flow cytometry to quantify T cell subsets. Patients were divided in two groups according to CDC 1993 guidelines. CD95 and CD38 increase paralleled the severity of HIV infection. Both a reduction of GSH levels and an increase in MDA and TH levels were detected in the plasma of HIV+ patients. These patients also showed an increase of DNA fragmentation in lymphocytes as well as a significant (P<0.05) reduction of GPx and an increase in SOD activity in erythrocytes. Relatively to the control group, HIV-infected patients had significantly differences in global indices of total antioxidant status. These results corroborate that substantial oxidative stress occurs during HIV infection. To our knowledge this study is the first relating oxidative stress indices with both CD38/CD8 and CD95 lymphocytes subsets.
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PMID:Contribution to characterization of oxidative stress in HIV/AIDS patients. 1259 Oct 17

Cytotoxic T lymphocytes (CTL) are key players to suppress viral load (VL) but CTL responses become compromised with progression of HIV-infection/AIDS. Some progressors develop MHC-unrestricted CTL with anti-CD4+ cytocidal activity. Immune activation status of these CTL and its significance in disease progression are unknown. To determine the relationship between VL and T cell activation, a cross-sectional study was carried out using blood samples from 13 HIV-1-infected/AIDS patients at various stages of progression and seven age-matched seronegative controls. We examined expression of HLA-DR and CD38 activation markers on purified CTL. MHC-unrestricted killing by these CTL was also evaluated against uninfected, allogeneic CD4+ T cells as well as several human cell lines. The expression of activation markers correlated inversely (rs = - 0.91, P < 0.0001) with VL of the subjects. CTL effectors of these patients killed targets expressing or lacking CD4+, independently of MHC class I recognition. Interestingly, the patients with higher VL showed an increased number of gammadeltaTCR-bearing CTL in blood and their MHC-unrestricted killing activity was blocked significantly (P < 0.01) by gammadeltaTCR-specific monoclonal antibody. CD3+ T counts of these patients were also consistently subnormal. Inverse correlation between VL and CD8+ T cell activation markers seems to be an indicator of CTL-associated immunopathogenesis in HIV patients with elevated gammadeltaCTL in the peripheral blood.
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PMID:Virus load correlates inversely with the expression of cytotoxic T lymphocyte activation markers in HIV-1-infected/AIDS patients showing MHC-unrestricted CTL-mediated lysis. 1265 46

HIV infection may be modified by CD8(+) T cells by the production of nonlytic antiviral factors. To determine subpopulations that mediate nonlytic, antiviral activity, we examined the production of beta chemokines and of CD8 antiviral factor (CAF) by different subsets, using CD8(+) cells derived from 24 HIV-1-infected and 25 uninfected individuals. Subjects with CD8(+) cell counts greater than 200/microl produced increased levels of MIP-1alpha by CD8(+)CD28(+), CD8(+)CD38(-), and CD8(+)HLA-DR(+) subsets as compared with uninfected controls. CD8(+)CD38(-) cells produced higher levels of MIP-1beta and RANTES. CAF production was increased by CD8(+)CD38(+) and CD8(+)HLA-DR(+) cells of HIV-infected individuals as compared with uninfected controls. Chemokine production was increased by cells that do not express activation markers, whereas CAF activity was increased by cells expressing CD38 or HLA-DR. These findings shed light on CD8(+) T cell noncytotoxic antiviral factor production during HIV infection.
AIDS Res Hum Retroviruses 2003 Jun
PMID:Production of CD8+ T cell nonlytic suppressive factors by CD28, CD38, and HLA-DR subpopulations. 1288 59

To investigate HIV-1-related B cell disorders, the quantity of CD27 positive (CD27+) B cells and their CD38, CD95, and bcl-2 intensities were examined by flow cytometry analysis in 16 drug-naive patients, 27 highly active antiretroviral therapy (HAART)-treated patients, and 20 uninfected controls. CD27+ B cells have been recognized as memory B cells. The mean percentage of CD27+ B cells was significantly lower in drug-naive patients (11.9%) and in HAART-treated patients (16.1%) than in controls (31.4%) (p < 0.01). The intensities of CD38 and CD95 on CD27+ B cells were higher in drug-naive patients than in controls (p < 0.01 in CD95). The intensity of CD95 on CD27+ B cells in HAART-treated patients was lower than that of drug-naive patients, but significantly higher than that of controls (p < 0.01). The intensity of bcl-2 on CD27+ B cells was equivalent among the three groups. These findings suggest that disturbance of peripheral B cell composition, exemplified by CD27+ B cell reduction, exists in both drug-naive and HAART-treated HIV-1-infected patients. In addition, the augmented apoptotic state of CD27+ B cells found in HAART-treated patients with undetectable viral loads, indicated by CD95 elevation, suggests that some HIV-1-related B cell disorders last for years after effective antiviral therapy.
AIDS Res Hum Retroviruses 2004 Feb
PMID:Selective CD27+ (memory) B cell reduction and characteristic B cell alteration in drug-naive and HAART-treated HIV type 1-infected patients. 1501 10


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