Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro, recombinant soluble CD4 (rsCD4) attaches to and inactivates human immunodeficiency virus (HIV). To determine if prolonged therapy with high-dose intravenous rsCD4 provides an in vivo benefit, we gave three HIV-1-infected patients with AIDS, whose isolates were susceptible in vitro to rsCD4, 10 mg/kg of rsCD4 for 4 weeks, 5 mg/kg for 4 weeks, and 1 mg/kg for 2 weeks. Single-dose pharmacokinetic studies performed prior to this showed transient in vivo decreases of HIV-1 plasma viremia in all three subjects. Surrogate markers of HIV activity, clinical status, HIV-1 p24 antigen, plasma HIV-1 titers, and peripheral blood mononuclear cell (PBMC) intracellular titers of virus were measured at entry, and every other week after onset of therapy. All subjects demonstrated rsCD4 concentration-dependent reduction in plasma viremia, with two subjects having complete neutralization of cell-free virus. The third subject's isolate was relatively resistant to the in vivo effects of rsCD4 and only partial reduction in plasma virus titers was obtained, even at the highest dose of 10 mg/kg. There was no change in the PBMC intracellular viral titer or surrogate markers of HIV-1 activity (including CD4 cell count and beta 2-microglobulin). There was subjective improvement in clinical symptoms, and all subjects gained weight with the highest doses of rsCD4. rsCD4 exhibited linear pharmacokinetics over the dose range studied. We conclude that high-dose intravenous rsCD4 can be safely given for up to 10 weeks and that it has a stable pharmacokinetic profile.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I study of high-dose, intravenous rsCD4 in subjects with advanced HIV-1 infection. 774 91

In a phase I/II study, 7 levels of 3TC therapy (from 0.5 to 20.0 mg/kg/day) were studied in 104 asymptomatic and mildly symptomatic human immunodeficiency virus-infected patients with CD4 cell counts < or = 400 x 10(6)/L. Mild and transient episodes of diarrhea, headache, fatigue, nausea, and abdominal pain were the most frequent events reported. No dose-limiting toxicities were observed. Small and transient increases in CD4 cell counts were detected during the first 4 weeks of treatment. These were followed by progressive declines during prolonged therapy. Sustained decreases in beta 2-microglobulin, neopterin, and p24 antigen levels were seen over the 52-week study. There was no consistent dose-response correlation for any surrogate marker. Penetration of 3TC into cerebrospinal fluid (CSF) was in the same range as reported for ddC and ddI; the mean CSF-to-serum ratio was 0.06. These findings indicate that 3TC exhibits an excellent safety profile and has antiretroviral activity at the dosages studied.
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PMID:Evaluation of safety and efficacy of 3TC (lamivudine) in patients with asymptomatic or mildly symptomatic human immunodeficiency virus infection: a phase I/II study. 775 91

Inactivated simian immunodeficiency virus (SIV) grown in a human T-cell line induces protection from infection by the virus in macaques. However, observations that immunization with uninfected human T cells or with SIV-1 prepared in human T cells can also induce protection, has raised the possibility that protective antigens could be of human cellular origin. Sera from animals immunized with fixed infected and uninfected human T cells, as well as from animals immunized with partially purified cell-free SIV have been examined for their ability to bind to human and macaque peripheral blood mononuclear cells (PBMC) and to-components present in fetal calf serum (FCS) in which the cells were grown. Analysis by flow cytometry suggests that antibodies to human cell surface antigens can be elicited with both inactivated SIV grown in human T cells and by uninfected T cells. There was a significant association between the presence of anti-cell antibodies and protection from infection. However, anti-cell surface antibodies were not detected with macaque mononuclear cells by flow cytometry or by immunoprecipitation, unless these cells were first treated with FCS or activated by a mitogen. Immunoprecipitation of resting human PBMC with sera from immunized animals suggests the presence of antibodies to class I heavy and light chains [beta 2-microglobulin (beta 2 m)] and to bovine beta 2m, which may originate in FCS used to grow the cell line. Antibodies to CD4 were also found in sera from animals immunized with SIV grown in human T cells. We suggest that human cellular components augmented by FCS elicit anti-class I heavy chain, beta 2m, CD4 and FCS antibodies which may be responsible for protection against SIV infection in macaques.
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PMID:Antibodies to human and non-human primate cellular and culture medium components in macaques vaccinated with the simian immunodeficiency virus. 783 37

Several immunological and serological variables have become established in recent studies as valuable markers to identify human immunodeficiency virus (HIV)-positive individuals at the highest risk for rapid disease progression. These studies have been performed mainly in cohorts of homosexual men. In this study, we assessed the usefulness of CD4 lymphocyte count, serum beta 2-microglobulin concentration, and the presence of p24 antigen as predictors of AIDS in a cohort of 130 HIV-positive injection drug users (IDUs) followed-up for 1 to 67 months. Progression to AIDS was most strongly associated with reduced absolute numbers of CD4+ lymphocytes at baseline, but increases in beta 2-microglobulin levels at baseline were an independent predictor of outcome. After stratification by baseline CD4 count, beta 2-microglobulin concentration added significant prognostic information to CD4 count among IDUs with > 500/mm3 CD4 cells (Breslow statistic value, 5.84, p = 0.01). Thus among seropositive IDUs with normal CD4 counts, increases in beta 2-microglobulin may be used as an early marker of individuals with higher risk of progression to AIDS, who may benefit from more intensive laboratory monitoring or clinical management.
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PMID:Serum beta 2-microglobulin and prediction of progression to AIDS in HIV-infected injection drug users. 785 38

Forty-four asymptomatic patients infected with human immunodeficiency virus type 1 (HIV-1), who had 200-799 CD4 cells/microL, received oral prednisolone (0.5 mg/kg for 6 months; 0.3 mg/kg thereafter). After 1 year of treatment, no major side effect or AIDS events had occurred. The percentage of DR+ and CD25+ phenotypes in CD4 T cells decreased significantly as did levels of serum IgG, IgA, and beta 2-microglobulin. Serum p24 antigen and HIV RNA levels remained stable. CD4 cell counts increased significantly at all time points (median increase at 1 year, 119 cells/microL). Peripheral blood mononuclear cell apoptosis after overnight stimulation with anti-CD3 monoclonal antibodies was strongly inhibited at all times. In asymptomatic seropositive patients, immunotherapy for 1 year with glucocorticoids was safe and led to sustained increases in CD4 cell counts and to improvement or stabilization of other biologic markers of disease activity.
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PMID:Sustained increases in CD4 cell counts in asymptomatic human immunodeficiency virus type 1-seropositive patients treated with prednisolone for 1 year. 787 96

The association between isolation of the syncytium-inducing (SI) phenotype of human immunodeficiency virus (HIV) and unfavorable clinical and immune status was evaluated in a cross-sectional study. Data on HIV phenotype were available for 341 of 878 persons entering clinical trials of antiretroviral therapies. Patients with SI virus were demographically similar to those with non-SI (NSI) virus but were more likely to have a diagnosis of AIDS and detectable circulating HIV p24 antigen. Patients with SI virus also had a lower CD4+ cell count and a higher serum level of beta 2-microglobulin. The association between phenotype and present status was explained statistically by CD4+ cell count. Phenotype, serum level of beta 2-microglobulin, and the presence of detectable p24 antigen were all independent predictors of present CD4+ cell count. The likelihood of finding SI virus increased with unfavorable virologic and immunologic parameters and varied with the amount of prior antiretroviral therapy.
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PMID:A cross-sectional comparison of persons with syncytium- and non-syncytium-inducing human immunodeficiency virus. 793 Jul 3

Breast milk specimens from human immunodeficiency virus type 1 (HIV-1)-seropositive and HIV-1-seronegative women were examined for the presence of HIV-1 p24 antigen by the antigen capture method and for viral DNA using the polymerase chain reaction. HIV-1 DNA was present in 70% of milk specimens collected from 47 HIV-seropositive women 0-4 days after delivery and in approximately 50% of specimens collected 6 and 12 months postpartum. p24 antigen, present in 24% of milk specimens collected from 37 seropositive women within the first 4 days postpartum, was not detected in any of the subsequent specimens. The presence of HIV-1 DNA or p24 antigen in milk was not significantly associated with maternal CD4 lymphocyte count, beta 2-microglobulin level, or fulfillment of the AIDS clinical case definition. Although the correlation of either HIV-1 proviral DNA or p24 antigen with the presence of infectious virus is not known, these data indicate the need for additional studies examining the role of breastfeeding in maternal-infant transmission of HIV-1.
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PMID:Prevalence of HIV-1 DNA and p24 antigen in breast milk and correlation with maternal factors. 790 81

Serum concentrations of soluble tumor necrosis factor receptors (sTNF-Rs) were measured in 61 human immunodeficiency virus (HIV)-infected individuals. Thirty-five percent of these had increased serum concentrations of sTNF-R type I (p55) (sTNF-R55) and 82% had increased concentrations of sTNF-R type II (p75) (sTNF-R75). The extent of the increase of sTNF-R75 was greater in more advanced HIV infection (p = 0.046) as it was measured by dividing the 61 individuals into two groups according to the median of the CD4+ T-cell count. However, the increase in concentrations of sTNF-R55 in the group with a CD4+ T-cell count below the median was only moderate and did not reach statistical significance. A strong correlation was found between sTNF-R75 and the soluble immune activation markers beta 2-microglobulin (rs = 0.74, p < 0.0001) and urinary neopterin (rs = 0.67, p < 0.0001), and a less strong correlation was found with interferon-gamma (rs = 0.51, p = 0.0001). The correlations observed for sTNF-R55 were also significant but were always weaker than that of sTNF-R75. A weak inverse correlation was found between the number of CD4+ T cells and sTNF-R75 (rs = -0.33, p = 0.012), but no such correlation was observed with sTNF-R55. Our findings suggest that increased concentrations of serum sTNF-Rs in HIV infection are linked to immune activation, in which synergistic actions of interferon-gamma and the TNF-alpha system are likely to play an important role.
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PMID:Increased serum concentrations of soluble tumor necrosis factor receptors in HIV-infected individuals are associated with immune activation. 790 82

Serum concentrations of soluble receptors for tumor necrosis factor-alpha (sTNF alpha R) types I and II, beta 2-microglobulin, and CD4 cell counts were determined at entry and 3-5 months before AIDS diagnosis in 20 untreated, asymptomatic human immunodeficiency virus type 1 (HIV-1)-seropositive subjects, who progressed to AIDS within 5.5 years of study entry, and in an equal number of HIV-seronegative and untreated seropositive controls, who remained asymptomatic. At entry, concentrations of sTNF alpha R type II and beta 2-microglobulin were elevated and increased further in progressors. The odds ratio (OR) for sTNF alpha R type II concentrations > or = 6.5 ng/mL was 18.4 and for beta 2-microglobulin concentrations > or = 3 mg/L was 6.6; CD4 cell counts were not predictive. Five months before diagnosis, the OR was 102.0 for sTNF alpha R type II concentrations > or = 7.5 ng/mL, 13.5 for beta 2-microglobulin concentrations > or = 4 mg/L, and 6.9 for CD4 cell counts < 250/mm3 (counts < 500/mm3 were not predictive). Of the three variables, sTNF alpha R type II was proved by bivariate analysis to be the strongest and earliest predictor of disease progression.
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PMID:Soluble receptors for tumor necrosis factor as predictors of progression to AIDS in asymptomatic human immunodeficiency virus type 1 infection. 790 41

Identification of cell-derived molecules on infectious human immunodeficiency virus type 1 (HIV-1) particles may be helpful in investigating mechanisms of HIV infection and in vaccine studies. Some of these molecules were detected on HIV-1 virions in previous studies, but rather elaborate methods were used. The method presented here allows an extensive characterization of the cell surface molecules associated with HIV-1 by capturing virus particles on monoclonal antibodies to cell membrane antigens bound to plastic wells. Binding of infectious virus was assessed by adding permissive target cells (C8166) and determining viral replication. With this procedure, beta 2-microglobulin, HLA-DR, intercellular adhesion molecule-1, and leukocyte function antigen-1 were found on HIV-1 particles from laboratory strains and primary clinical isolates. In contrast, CD19, CD4, and CD8 molecules were not detected.
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PMID:A simple and reliable method to detect cell membrane proteins on infectious human immunodeficiency virus type 1 particles. 790 44


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