Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zidovudine or 3'-azido-2'-3'-dideoxy-thymidine (AZT) is an antiviral drug widely used to treat HIV-infected patients. Because cytotoxic T lymphocytes (CTL) are thought to contribute actively to resistance against HIV-induced disease, we studied sequentially 10 HIV-infected individuals under zidovudine treatment for a period of 6-12 months. For a given patient all lymphocyte suspensions corresponding to the complete zidovudine therapy period were tested on the same day and on the same target cells. Patients were selected for expression of HLA-A2 and/or HLA-A3 class I transplantation antigen. HLA-restricted cytotoxicity specific for env, gag and nef HIV proteins was quantified for each patient at 6 week intervals. The data clearly indicated that zidovudine has a beneficial effect on the CTL response during the first 6-12 weeks of treatment, inducing cytotoxicity levels up to 100-fold stronger than base line. This effect was usually short lived. However, patients who maintained strong levels of cytotoxicity had better clinical and survival outlook than patients who had lost all detectable cytotoxic lymphocytes. It is proposed that AZT, among other effects, delays the onset of disease in HIV-infected patients by contributing to the stimulation of the HIV-specific CTL response.
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PMID:Enhancement of HIV-specific cytotoxic T lymphocyte responses by zidovudine (AZT) treatment. 173 39

To investigate the influence of HLA specificities on the rate of progression and outcome of human immunodeficiency virus (HIV) infection, we performed (a) a case-control study in 1989-1990 of HIV-seropositive individuals stratified by both risk behavior and ethnic background, (b) a longitudinal cohort study of HIV-infected male homosexuals enrolled in 1981-1982, and (c) an analysis of individuals with a diffuse infiltrative CD8 lymphocytosis syndrome. In the case-control study, there was a significantly higher frequency of HLA-B35 among intravenous drug users, but not homosexuals, who developed illnesses meeting the case definition for AIDS compared with asymptomatic HIV-positive controls, regardless of ethnic status. In the longitudinal study, HLA-B35-positive homosexuals had a significantly increased rate of progression to AIDS and decreased survival over a 7-year period compared with those without this specificity. Finally, there was a significantly decreased frequency of HLA-B35 in individuals with the diffuse infiltrative lymphocytosis syndrome, a clinically and genetically distinctive disorder occurring in HIV infection in which a low rate of progression to opportunistic infections was found. The high rate of salivary and lacrimal gland lymphoma in this group suggests that there is dissociation between the presence of HLA-B35 and the development of particular AIDS-defining conditions. We conclude that HLA-B35 is a risk factor for more rapid progression to AIDS, particularly opportunistic infections and Kaposi's sarcoma, operating in groups with high rates of newly acquired HIV infections such as New York City male homosexuals in 1981-1982, and intravenous drug users in 1989-1990.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HLA-B35 is associated with accelerated progression to AIDS. 173 86

Tissue-typing for HLA-A, B, and DR antigens was carried out on 53 babies, 47 of them unrelated, born to mothers known to be HIV-infected from intravenous drug usage or sexual contact with drug users. These babies were followed up to assess whether HLA phenotype was associated with vertical transmission of HIV infection or disease progression. Of the 47 unrelated babies, eight became infected with HIV. The frequency of HLA-DR3 was three times higher in the HIV-positive infants compared to the HIV-negative infants (43 per cent vs 15 per cent) in our study population. Conversely, HLA-A3 was three times less common in the HIV-positive infants (12.5 per cent vs 42 per cent). A comparison of HLA antigens between our study group babies and babies born to healthy mothers unselected for HIV status revealed higher proportions of HLA-B18, B7, and DR2 in the study group. Moreover, the combination, A3, B7, DR2 was four times commoner in our study population relative to controls (RR = 3.9; p less than 0.003), but was found only in babies who were not HIV infected. The combination A1, B8, DR3, in contrast, was found less often than expected in our study group (RR = 0.39) and was disproportionately represented amongst the infected babies. We have observed an unexpectedly low (6 per cent) mother-to-infant transmission rate of HIV among prospectively studied intravenous drug users. We speculate that the unusually high ratio of the common antigen combinations (often halotypes), A3, B7, DR2 to A1, B8, DR3 in this population may be contributory.
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PMID:HLA antigen frequencies in children born to HIV-infected mothers. 174 42

Ambidirectional studies are useful when information about disease status is available on a cohort but a risk factor has still to be recorded. An example is the study of the influence of HLA phenotypes on the progression of HIV carriers towards AIDS. An ambidirectional design is proposed in which the cases and controls are defined by the survival duration of the subjects; it includes as special cases some other ambidirectional designs. Its efficiency is compared with that of a random selection cohort design both analytically and by computer simulation. It is shown that when the size of the cohort is large, appreciable gains in power can be achieved by this type of design even when there is no censoring.
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PMID:Comparative efficiency of a survival-based case-control design and a random selection cohort design. 179 69

We have previously reported the identification of highly conserved homologous regions located in the carboxy terminus of the HIV 1 gp41 (aa 837-844), and the amino-terminal of the beta chain of all human HLA class II antigens (aa 19-25). Murine monoclonal antibodies raised against synthetic peptides from these homologous regions bound not only to the isolated peptides, but also to "native" HLA class II molecules on cells. Screening of sera from HIV 1 infected individuals revealed high frequency of sera (35%) containing anti-class II crossreactive antibodies (CRAb), not only in AIDS patients, but also in early, asymptomatic patients. The CRAb containing sera caused potent inhibition of normal CD4-bearing cells' proliferative responses to tetanus toxoid in vitro. They could also kill class II bearing cells by ADCC. The possible contribution of these antibodies to the establishment of immunodeficiency state in HIV 1 infected individuals and/or to disease progression, was examined in two clinical studies: I. Asymptomatic patients were tested in parallel for their PBL responses to flu/tetanus, HLA alloantigens, and PHA (proliferation and IL2 production), and for the presence of anti-class II CRAb. About 50% of these patients showed a selective loss of their in vitro responses to recall antigens (flu/tetanus), which depend on CD4+ cells, while still responding to PHA and ALLO. Interestingly, positive correlation was found (P less than 0.001) between patients' lack of responsiveness to flu/tetanus and the presence in their sera of anti-class II CRAb. II. Retrospective study of HIV 1-infected hemophiliacs, suggest that patients with high titers of CRAb early in the disease progressed faster to full blown disease.
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PMID:Common sequence in HIV 1 GP41 and HLA class II beta chains can generate crossreactive autoantibodies with immunosuppressive potential early in the course of HIV 1 infection. 180 76

A survey was conducted to determine the frequency and semiological characteristics of spondylarthropathies seen during hospital consultation in Lome, Togo. Spondylarthropathy was diagnosed in 13 of 1498 consulting patients. All were male and ranged in age from 18 to 44 at the onset of the disease. 6 patients suffering from ankylosing spondylitis had bilateral sacroiliitis--5 were HIV positive and had no signs of sacroiliitis on pelvic x-rays and the remaining 2 were HIV negative and had no sacroiliitis. HLA typing was not carried out in any patient. The symptoms of ankylosing spondylitis in these patients were comparable to those of European patients. The symptoms of HIV-positive patients were reminiscent of those describing reactive arthritis in such patients. The results of this study contradict the reputed scarcity of ankylosing spondylitis and other spondylarthropathies in black Africa. HIV infection may increase the incidence of reactive arthritis and, as a consequence, that of spondylarthropathies in this region. (author's)
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PMID:[Spondylo-arthritis in Togolese patients]. 180 78

Four synthetic peptides corresponding to the IIIB sequence of gp160 of HIV were recently reported to stimulate Th cell function by PBL from HIV-infected, asymptomatic patients. In the present report, we used these same peptides to demonstrate CTL activity in a similar patient population. EBV-transformed B-cell lines from asymptomatic, HIV seropositive and seronegative control donors were pre-incubated with the peptides. Fresh PBL from 19 (76%) of 25 HIV seropositive donors lysed autologous targets pulsed with at least one of the four peptides. Autologous targets pulsed with two non-immunogenic peptides were not lysed. PBL from none of the eight HIV seronegative controls lysed peptide-preincubated autologous targets. The CTL activity was mediated by T cells, was predominantly MHC class I restricted, and was increased by in vitro restimulation of PBL with the peptides. HLA A-2 was identified as a restricting element for all four peptides in different patients, and for three of the peptides in the same donor. HLA-A1 or -B8 may also present some of the peptides. Thus, the same peptides can be recognized by human Th cells and class I MHC-restricted CTL.
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PMID:Detection of cytotoxic T lymphocytes specific for synthetic peptides of gp160 in HIV-seropositive individuals. 182 20

Efficacy of antiretroviral treatment is evaluated usually according to reduction of serious events (e.g. opportunistic infections while on therapy) and improvement of survival time. In stages of asymptomatic disease treatment trials have to cover very long time periods to fulfil these requirements. In asymptomatic stages, when viremia is commonly absent, monitoring the host's immune response is an indirect means of measuring antiviral efficacy. CD4+ lymphocyte counts are generally accepted as surrogate in all major trials. The subsets of the CD8+ compartment reflect early and late activation and cytotoxic immune response. CD38+, CD57, CD8+ HLA/DR+ subsets reflect the host's vigorous cellular immune response even in early stages. These subsets are candidate surrogate markers in early and late stages of HIV infection. On the other hand, CD3+ CD4- CD8-, CD19/20 (B lymphocytes) and CD16+ (natural killer cells) do not exhibit any properties of candidate surrogate markers. Established and experimental cellular surrogate markers are discussed including own data and a review of the literature.
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PMID:Lymphocyte subsets as surrogate markers in antiretroviral therapy. 182 74

High levels of the soluble form of the CD8 molecule (sCD8) are detectable in the serum of HIV-1-infected patients. To investigate the mechanisms accountable for the release of this molecule we evaluated the presence of sCD8 in the supernatants obtained from in vitro cultures of highly purified CD8 cells isolated from 20 HIV-1-infected patients. At resting conditions cultured CD8 cells from HIV-1-infected patients released low amounts of sCD8; no statistically significant differences were observed between unstimulated cultures from HIV-1-seropositive patients and from HIV-1-seronegative subjects at risk for HIV-1 infection or normal healthy controls. Following in vitro activation of highly purified CD8 cells with a series of stimulatory agents, including phorbol myristate acetate, phytohemagglutinin (PHA) and recombinant interleukin-2, CD8 cells of HIV-1-infected patients significantly increased the shedding of sCD8. By expressing the results of activation-related release index (ARRI = sCD8 levels detected in the cultures with stimulatory agent/sCD8 levels detected in the unstimulated cultures), significantly higher values were observed upon PHA stimulation in HIV-1-infected patients than in control subjects. In order to identify the cell subset responsible for the enhanced release of sCD8 by PHA-stimulated cultures, we correlated the amounts of sCD8 detected in the supernatants with the phenotypic profile of CD8+ cells recovered from the cultures. A significant relationship was demonstrated between the percentage of CD8+/HLA-DR+ lymphocytes and sCD8 levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Shedding of the soluble form of the CD8 complex by CD8+/HLA-DR+ cells in HIV-1-infected patients. 183 45

To evaluate whether host genotype influences disease progression among persons infected with human immunodeficiency virus type 1 (HIV-1), molecular techniques were used to determine genotypes at immune response loci for 114 HIV-1-infected homosexual/bisexual white men in the San Francisco Men's Health Study. Candidate genes evaluated were HLA-DQA1 and -DRB1, complement C4A and C4B, alpha- and beta-interferons, and the heavy chain of immunoglobulin gamma 1. Of the 114 men, 29 were asymptomatic, 21 were symptomatic men and AIDS patients (p = 0.02). Specifically, the HLA haplotype DRB1*0702-DQA1*0201 was associated with absence of symptoms (p = 0.003). Conversely, the frequency of the complement C4B-L allele was higher among patients with symptoms or with AIDS than among asymptomatic subjects (p = 0.02). These results suggest that genes in or near the major histocompatibility complex may influence the rate of disease progression among HIV-1-infected men.
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PMID:Influence of host genotype on progression to AIDS among HIV-infected men. 185 93


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