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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have evaluated immunologic markers of disease progression in 79 children perinatally infected with HIV. Laboratory testing included T lymphocyte subsets and lymphoproliferative responses (LPR) to mitogens (PHA, Con A, and PWM), antigens (Candida, Tetanus), and alloantigens (MLC). Patients were graded into grades I, II, and III based on results of CD4 counts, and into grades A, B, and C based on results of LPR, with grades I and grades A being normal, III and C being the lowest, and II and B falling in-between. CD4 counts, CD4/CD8 ratio, and lymphoproliferative responses were markedly decreased in a majority of children. Grade III CD4 counts were almost always associated with decreased LPR. A majority of the children with grade I CD4 numbers, however, also had abnormal lymphoproliferative responses. Results of laboratory testing were analyzed in relation to clinical disease progression and survival. The first AIDS defining illnesses (ADI), especially opportunistic infections (OI), was usually associated with Grade III/C results in immunologic assays. Survival was significantly decreased in children with grade III CD4 cell counts, and grade C LPR, and was poorest if these abnormalities developed within the first year of life. In this latter age group, if the CD4 counts fell to grade III, the risk for dying was at least five times greater than those children with higher CD4 counts (grades II and I); if the proliferative responses to PHA and MLC were in Grade C, the survival was 22 months. Severe immune defects in the first year of life in children with HIV infection, as assessed by CD4 counts and a battery of functional tests, predicted rapid disease progression.
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PMID:Immunological characteristics of HIV-infected children: relationship to age, CD4 counts, disease progression, and survival. 857 77

This is the first time, to our knowledge, that evidence is presented showing that a polyantigenic immunomodulator (PAI), acting as a biological response modifier, can either induce or suppress HIV expression depending on the viral load of infected PBMC. PAI consists of a mixture of inactivated bacteria with influenza virus vaccine. PBMC from HIV-infected patients (asymptomatic, age 22-36, symptomatic, age 30-59 and pediatric, < 2 years old) were co-cultured with PHA-stimulated PBMC from uninfected individuals in medium containing IL-2 and PAI. Parallel co-cultures were carried out in a PAI-free medium. Cultures were fed with PHA-stimulated PBMC from uninfected donors on a weekly basis. HIV-p24 ag and cytokine profiles (IL-1 beta, IL-2, IL-4, IFN-gamma and TNF-alpha) were determined on supernatants on day 14. Peripheral blood samples from each patient were evaluated at the beginning of the experiment as to total CD3, total CD19, CD3/CD4, CD3/CD8, CD16/CD56, CD8/HLA-DR and CD8/CD38 markers through flow cytometry. PAI was able to induce viral expression (up to 11,881 pg/ml of p24 antigen) in cultures showing a low (less than 16 pg/ml) or no viral titer. In contrast, in those cultures with high viral titer (10(2)-10(5) pg/ml), a substantial reduction on the titer was observed upon exposure to PAI. PAI was able to induce the production of IFN-gamma and TNF-alpha while that of IL-4 and IL-1 beta was reduced. The predominant cell type detected in the blood samples of the studied subjects were CD8+, CD8+/CD38+ or CD8+/HLA-DR+.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in viral expression and cytokine profile induced by a polyantigenic immunomodulator in HIV-infected peripheral blood mononuclear cells. 857 53

We determined the anti-human immunodeficiency virus type 1 (anti-HIV-1) activities of various dideoxy-nucleoside analogs by using phytohemagglutinin-activated peripheral blood mononuclear cells (PHA-PBMs) and resting PBMs (R-PBMs) as target cells. The comparative order of anti-HIV-1 activity in PHA-PBMs was azidothymidine (AZT) > dideoxycytidine (ddC) > dideoxythymidinene (d4T) > dideoxyinosine (ddI) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) > 2'-beta-fluoro-dideoxyadenosine (F-ara-ddA), while that in R-PBMs was ddC > ddI, PMEA, and F-ara-ddA, >> AZT and d4T. A pronucleotide, bis-(S-acetylthioethanol)phosphotriester-ddAMP, which bypasses the anabolic monophosphorylation step for the intracellular delivery of ddAMP, was highly active both in PHA-PBMs and R-PBMs. These data may have basic and clinical relevance in the design of anti-HIV chemotherapy, particularly combination chemotherapy with dideoxynucleosides, and in the development of active pronucleotides.
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PMID:Comparative analysis of anti-human immunodeficiency virus type 1 activities of dideoxynucleoside analogs in resting and activated peripheral blood mononuclear cells. 858 44

A series of 6-substituted amino analogs of 9-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl) purines (F-ddN) has been synthesized and characterized with the objective of finding compounds which might be superior to existing drugs for the treatment of HIV in the central nervous system. These compounds are intended to be more lipophilic than the currently approved anti-HIV drugs for better blood-brain barrier penetration. Subsequent adenosine deaminase (ADA)-catalyzed hydrolysis of these prodrugs in the brain is expected to produce the anti-HIV agent, 9-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl)hypoxanthine (F-ddI). The new compounds, synthesized from the corresponding 6-chloro analog, include F-ddN which contain methylamino, ethylamino, dimethylamino, hydroxylamino, methoxyamino, benzyloxyamino, hydrazino, and nitro substituents in the 6-position. The 6-nitro analog was isolated as an unexpected product during the preparation of the 6-chloro derivative. Among the analogs with anti-HIV activity, the ethylamino and dimethylamino compounds are ca. 100 times more lipophilic than ddI or F-ddI. As expected, 2'-fluoro substitution protects the compounds from acid-catalyzed glycosylic cleavage. Only the hydroxylamino and nitro analogs underwent any nonenzymatic hydrolysis at pH 1.0 or 7.4. This reaction, however, results in hydrolysis of the group in the 6-position rather than glycosylic bond cleavage. ADA catalyzes the hydrolysis of the 6-substituents at rates which vary from slightly slower (NO2, 1.7x) to much slower (NHEt, 5000x) than F-ddA. The 6-dimethylamino analog is the only compound which possesses anti-HIV activity (ED50 18 microM) without ADA hydrolysis. With the exception of the two inactive alkoxyamino compounds, the other prodrugs exhibited cellular protection in the HIV-1/PHA-PBM system with IC50 potencies of 7-40 microM.
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PMID:Lipophilic, acid-stable, adenosine deaminase-activated anti-HIV prodrugs for central nervous system delivery. 3. 6-Amino prodrugs of 2'-beta-fluoro-2',3'-dideoxyinosine. 864 1

This 4-year longitudinal study monitored the temporal association between the HIV-specific cytotoxic T lymphocyte (CTL) response and the control viremia in an individual infected with human immunodeficiency virus type (HIV-1). At the beginning of the study, this asymptomatic individual with a high CD4+ cell count showed no HIV-specific cytotoxic activity after polyclonal in vitro restimulation with autologous PHA-blasts, unlike most HIV-seropositive individuals. Anti-HIV CTLs were detected only in the last year of the study, both after in vitro restimulation and directly ex vivo. This was correlated with the inversion of the CD4+/CD8+ ratio, essentially due to increased numbers of CD8+CD28- T lymphocytes. The HIV-specific cytolytic activity was mediated by this CD28+CD28- subpopulation. The amount of HIV-1 provirus in peripheral blood mononuclear cells (PBMCs) did not change during the study, but the HIV RNA in plasma increased and virus was isolated from PBMCs only at the time when HIV-specific CTL activity was detected. This suggests overall that the HIV-1 replication was low in this individual, with a transient increase that could have reached the threshold for CTL reactivation, and was perhaps controlled thereby.
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PMID:Delayed virus-specific CD8+ cytotoxic T lymphocyte activity in an HIV-infected individual with high CD4+ cell counts: correlations with various parameters of disease progression. 867 5

Human cord blood (HuCB) can colonize a murine fetal thymus organ culture (FTOC) and generate phenotypically immature (CD4+ CD8+) and mature (CD4+ CD8-; CD4- CD8+) T cells. We have used this model system to demonstrate that the human T cells that develop in this culture system can be infected with HIV-1. A cytopathic and non-cytopathic patient isolate of HIV-1 were used to infect FTOC established using C.B-17 or NOD/LtSz.scid/scid strain fetal thymic lobes colonized with HuCB. At 13-15 days after infection, FTOC were placed in co-culture with human PHA-blasts. These co-cultures demonstrated the presence of replicating HIV-1. Few human CD45+ cells were detectable in the thymic lobes that were infected with HIV-1, while high numbers of human CD45+ T cells were present in the uninfected cultures. These results demonstrate the cytopathicity of HIV-1 on human T lymphocytes that have developed in a HuCB colonized FTOC system.
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PMID:HIV-1 infectivity of human T cells in a human/murine chimeric fetal thymic organ culture system. 872 9

The RANTES chemokine is a T cell-expressed, proinflammatory cytokine recently implicated as a suppressive agent of HIV replication. We have identified tandem kappaB-like sequences within the promoter for RANTES that are critical for RANTES promoter-reporter gene activity in both the T cell tumor line Hut78 and in PHA-activated PBL. This region binds not only Rel family members (including p50-p65 heterodimers and p50-p50 homodimers) but also non-Rel factors up-regulated in PBL 3 to 5 days following activation. The expression of these "late" expressed nuclear factors correlates with an up-regulation of RANTES message found at this point in T cell activation. These factors are also constitutively expressed in functionally mature CD8+ T cells. We hypothesize that these apparently novel proteins are responsible in part for the temporal regulation of RANTES seen in peripheral blood T cells and represent a component of transcriptional regulatory machinery newly expressed at this "late" stage of peripheral T cell development.
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PMID:Identification of a novel regulatory region critical for expression of the RANTES chemokine in activated T lymphocytes. 875 19

We investigated cytokine production and accessory cell function in human macrophage hybridoma cell lines and primary monocytes after infection with HIV-1. HIV-1 infection induced IL-10 production in the macrophage hybridoma cell line with loss of IL-12 1 wk after infection. There were also significant increases in production of IL-10 (537 +/- 521 vs 687 +/- 625 pg/ml) while there was a reduction in IL-12 (6.3 +/- 3.1 vs 1.2 +/- 1.0 pg/ml, p = 0.021) in the primary monocytes 5 days after HIV-1 infection. In addition, the hybridoma cell lines and primary monocytes failed to support PHA, Con A, PWM, or anti-CD3- induced T cell proliferation 1 wk after infection. The viability of the T cells cocultured with the HIV-1-infected macrophage cell lines or the primary monocytes as determined by propidium iodide staining was unaltered and there was no increase in apoptosis-specific DNA strand breaks or increased expression of Bcl-2 in the T cells. No soluble suppressor factor was present, since UV-inactivated supernatants from the hybridoma cell line and primary monocytes failed to inhibit mitogen- and anti-CD3-induced T cell proliferation. Early events in T cell activation, including calcium flux and phosphotyrosine kinase activity, were intact in the T cells cocultured with the HIV-1- infected hybridomas and monocytes but there was reduced IL-2 production. Addition of exogenous IL-2 restored the proliferative responses. Taken together, these data suggest that alteration of cytokine production and accessory cell function for mitogens and anti-CD3-induced T cell proliferation independent of induction of apoptosis, suppressor factor production, or inhibition of T cell signaling occurs very early after HIV-1 infection and may contribute to the global immunosuppression observed in AIDS.
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PMID:Altered cytokine production and accessory cell function after HIV-1 infection. 875 40

Production of cytokines by immunocompetent cells in vitro may be assessed after stimulation with polyclonal activators. Because it mimics the natural environment, diluted whole blood (WB) culture may be the most appropriate milieu in which to study cytokine production in vitro. We tested TNF alpha production by small volume of whole blood (25 microliters) from HIV-1 positive patients by using a one-step procedure that combines WB stimulation with LPS and PHA and cytokine measurement. We studied 30 patients without secondary infection or at distance of secondary infection staged according to the classification proposed by the CDC and 12 healthy seronegative subjects. The mean values of TNF alpha from patients were not statistically different from those from normal controls however in certain patients at different stages of the disease higher values than the mean +2 SD of controls and lower values than the mean -2 SD of controls were obtained. Heparinized blood from 5 control subjects had been collected sequentially during a period of 5 months. The individual variation of TNF alpha production were limited for all these individuals. For each of 6 HIV-1 patients, whole blood samples were collected sequentially during a period of 5 months and in most of patients large variations of levels of TNF alpha were observed from one sample to another one. Our method can detect abnormal cytokine production in HIV-1 positive individuals and can become a useful tool to investigate the role of cytokines in the outcome of HIV-1 infection.
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PMID:TNF alpha production by whole blood from HIV-1 infected patients. 875 83

The study of epidemiological, virological and immunological parameters in HIV+ patients defined as long-term non-progressors (LTnP) could be the key to knowledge of the natural history of HIV disease and its therapeutical approach. The aim of this study was to identify the factors that delay the onset of HIV related symptoms in patients with HIV disease with low rate of progression. We studied several individuals defined as LTnP according to the following criteria. The patients were asymptomatic with HIV infection documented for at least 8 years, they had never received antiretroviral treatment and their CD4 levels were always above 500/cmm. They were studied every 6 months for the following tests: viral isolation, characterization of viral strain; quantitative DNA-PCR; serum p24 HIV antigen, plasma viremia, neutralizing antibodies versus primary autologous and heterologous isolates. The immunological study includes a large panel of monoclonal antibodies to characterize lymphocyte phenotype, cellular proliferation with mitogen and antigens (tetanus toxoid; GMP of C. Albicans, p24 and gp160 of HIV), specific cytoxicity for HIV (env and gag) and spontaneous cellular mortality rate. Surnatants from lymphocyte cultures (stimulated with PHA) are collected to measure cytokines (IL2; IL4; IL10; gamma IFN) and T cell clones are grown to characterize the phenotype and cytokine pattern. Here we report only a summary of immunological data collected.
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PMID:Immunologic and virologic studies in long-term non-progressor HIV infected individuals. NOPHROCO Study Group. Non progressors HIV + Roman cohort. 878 12


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