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)

The majority of the immunodominant amino acid sequences of HIV-1 that have been characterized to date are coded for by hypervariable gene sequences. These variable sequences are however interspersed with sequences that are highly conserved between HIV strains. Immunogenic viral products with amino acid sequences that vary minimally between strains, and that consistently elicit both humoral and cellular immune responses, may be ideal for inclusion in a subunit vaccine. We studied HIV-seronegative and HIV-infected persons, classified as asymptomatic (AS), ARC or AIDS. Initially, we assessed the cellular immune status of each subject from results of T cell phenotype analyses, assays for serum levels of surrogate markers of disease progression, and responses to mitogens and recall antigen. In addition, we tested whether three short synthetic peptides derived from the conserved sequences of the envelope gp120 (aa 262-284) and gp41 (aa 579-601), and core p17 (aa 106-125) regions of the HTLV-IIIB isolate, could elicit B cell as well as T cell responses in HIV-infected subjects. Only the gp41-derived sequence was immunogenic at both B and T cell levels. To further characterize the gp41 epitope, we used a series of overlapping synthetic peptides derived from a conserved region of the envelope gp41 (aa 572-613). We thus identified an immunodominant 12-mer peptide sequence, gp41(8)(aa 593-604), which consistently elicited both T cell blastogenic and B cell (antibody) responses in AS HIV-seropositive individuals but not in ARC and AIDS patients. Linear regression analysis showed that in AS persons there was a strong positive correlation (P less than 0.0005) between the absolute CD8+ T cell numbers and the magnitude of blastogenic responses to the gp41(8)(aa 593-604). Furthermore, those AS subjects with T cells that proliferated in response to this gp41 analogue also had significantly greater serum levels of antibody to the same short peptide sequence than symptomatic ARC and AIDS patients. These results suggest that cellular responses to the immunodominant and highly conserved envelope sequences of HIV-1, associated with increased CD8+ T cells, may be important in the pathogenesis of HIV disease.
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PMID:Definition of an immunodominant T cell epitope contained in the envelope gp41 sequence of HIV-1. 137 Jul 73

To improve evaluation of new antiretroviral drugs in the acquired immunodeficiency syndrome (AIDS), sensitive biological markers that accurately predict response to treatment are needed. Two possible markers are endogenous interferon (E-IFN), which is a cytokine involved in the pathophysiology of AIDS, and serum triglycerides (TG), which are raised in patients with AIDS, possibly reflecting enhanced cytokine activity. E-IFN, TG, body-mass index, CD4 count, and HIV p24 were measured in 19 patients (15 with AIDS, 4 with AIDS-related complex), who were part of the phase II licensing trial of zidovudine (ZDV). 10 received ZDV and 9 received placebo. Rapid, significant, and sustained declines from initial values in E-IFN and TG concentrations were observed in ZDV patients but not in placebo patients. Baseline values of E-IFN and TG concentrations after 4 months on ZDV treatment were both important contributors to long-term survival. The findings suggest that these indicators of abnormal cytokine expression may be useful measures of not only disease severity but also efficacy of antiretroviral therapy in AIDS.
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PMID:Endogenous interferon and triglyceride concentrations to assess response to zidovudine in AIDS and advanced AIDS-related complex. 134 48

Antibodies were determined against five synthetic peptides (epitopes) of HIV-1 p17 in the sera of an immunologically and clinically well-characterized cohort (N = 292) of HIV-1 seronegative and HIV-1 seropositive high-risk homosexual men, HIV-1 seropositive i.v. drug abusers (IVDA), and AIDS patients. The synthetic peptides, representing the entire HIV-1 p17 protein sequence were: HGP-33 (aa 1-33), HGP-19 (aa 34-52), HGP-35 (aa 51-85), HGP-30 (aa 85-114), and HGP-17 ala (aa 114-131). The presence of one or more peptide-specific antibodies in the sera of all of the HIV-1 p17-positive subjects indicated that all five peptides contain B-cell epitopes. No antibodies were found in the sera of heterosexual controls, HIV-1 seronegative high-risk men, or asymptomatic HIV-1 seropositive but p17 antibody-negative study subjects. Significant differences in antibody recognition profiles to the peptide epitopes were found among the various study groups. A significantly higher proportion of HIV-1 seropositive IVDA had antibodies specific to HGP-17 ala (aa 114-131), HGP-35 (aa 51-85), and HGP-33 (aa 1-33) compared to the HIV-1 p17-positive asymptomatic homosexuals. The epitope-specific antibody responses reflected the clinical status of the HIV-1-infected study subjects, and declined to nondetectable levels as the patient progressed to ARC/AIDS. This decline preceded by several months the reduction in the antibody titer against the intact HIV-1 p17 and p24 proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Specific antibody responses to synthetic peptides of HIV-1 p17 correlate with different stages of HIV-1 infection. 137 53

We studied 684 sera obtained from 20 hemophilia patients with AIDS/AIDS-related complex (ARC), 89 asymptomatic HIV+, 76 HIV- hemophilia patients and 151 healthy controls for antibodies against recombinant CD4 (rCD4). Twenty-two percent of AIDS/ARC patients, 10% of asymptomatic HIV+ patients, 17% of HIV-patients, and 1% of healthy controls had anti-rCD4 antibodies. Purified anti-rCD4 antibodies did not react with human CD4+ lymphocytes. This may explain why formation of anti-rCD4 antibodies correlated neither with the occurrence of autoantibodies against CD4+ lymphocytes nor with a decrease in CD4+ cell counts. Antibodies that were eluted from CD4+ lymphocytes after sequential adsorption and elution with separated CD8+ and CD4+ cells reacted with CD4+ lymphocytes of only some healthy individuals, suggesting diversity of CD4 expression.
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PMID:Autoantibodies in HIV-infected hemophilia patients against different epitopes on CD4+ lymphocytes and recombinant CD4. 137 80

Didanosine is a dideoxynucleoside analogue which undergoes intracellular conversion to the putative active triphosphate metabolite. The active metabolite appears to inhibit viral reverse transcriptase and terminate the proviral DNA, and produces virustatic inhibition of actively replicating human immunodeficiency virus (HIV) at clinically relevant concentrations. In phase I studies didanosine had beneficial effects on various surrogate markers of clinical efficacy and also improved clinical manifestations of HIV infection, with a 21-month survival rate of 80% in patients with acquired immune deficiency syndrome (AIDS) and 93% in patients with AIDS-related complex (ARC) in 1 study. Didanosine also improved CD4+ cell counts in a phase II/III trial in patients previously treated with zidovudine, whereas cell counts declined in patients continuing zidovudine therapy. However, the effects of didanosine on clinical end-points (disease progression, survival, HIV encephalopathy) remain to be established. Peripheral neuropathy and pancreatitis are the predominant dose-limiting adverse events and didanosine therapy should be withdrawn in patients developing signs or symptoms of pancreatitis and during acute treatment of Pneumocystis carinii pneumonia. However, at currently recommended clinical dosages didanosine is generally well tolerated with minimal haematological toxicity. Thus, in a therapeutic area with few treatment options, didanosine offers a welcome alternative for patients intolerant of, or resistant to, zidovudine. There are a number of clinical trials in progress evaluating didanosine alone or in combination with other antiviral agents, and these results are awaited with considerable interest.
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PMID:Didanosine. A review of its antiviral activity, pharmacokinetic properties and therapeutic potential in human immunodeficiency virus infection. 137 14

The development of AIDS-related lymphomas (ARL) has been on the rise in recent years. During an analysis of ARL from AIDS patients, one individual developed atypical syncytial variants of high-grade Burkitt's-type B-cell lymphomas, which prompted further study. However, the search for a HIV-1 retrovirus, which we hypothesized was infecting these cells, led to the subsequent discovery of a type D retrovirus in two early-passage lymphoma cell lines derived from this patient. Nucleotide and amino acid sequence analysis, as well as immunologic reactivity, indicated that the virus was closely related to Mason-Pfizer monkey virus (MPMV) or simian retrovirus type 1 (SRV-1). MPMV and SRV-1 are immunosuppressive type D retroviruses that cause an AIDS-like syndrome in rhesus macaques. Amplification of DNA from the patient's diagnostic bone marrow biopsy specimen by the polymerase chain reaction generated MPMV-specific fragments indicative of infection by a retrovirus similar to MPMV. Additionally, the patient's serum contained antibodies that recognized type D retroviral env proteins (gp20 and gp70) and gag proteins (p27 and p14) as assayed by immunoblot and radioimmunoprecipitation techniques. Although there have been reports of human cell lines infected with type D retroviruses and of type D reactive human sera, this is the first report of a type D retrovirus infection in a human confirmed by virus isolation, serum immunoreactivity, and viral DNA identification in tumor tissue.
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PMID:Studies on a type D retrovirus isolated from an AIDS patient lymphoma. 138 Dec 7

Patients with ARC and AIDS develop a variety of symptoms that significantly affect their nutritional status. Podiatrists, although not directly involved with the intricacies of the nutritional management of people with AIDS, should be aware of the effect of the virus on the human body. Investigators are predicting that almost 100% of the estimated 12 million HIV-positive persons in the world will develop AIDS. By giving people with AIDS nutritional education, not only may there be a beneficial response in respect to treatment but it may enhance an individual's quality of life and positive self-image.
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PMID:Nutrition for the patient with acquired immunodeficiency syndrome. 139

Statistical analysis of a limiting dilution assay (LDA) showed that the occurrence of infectious human immunodeficiency virus type 1 (HIV-1)-harboring cells in serially diluted samples of peripheral blood mononuclear cells (PBMCs) of HIV-1-seropositive patients fits the model describing a single-hit Poisson distribution. This observation led to the discovery that there is a direct correlation (r = 0.957) between the number of HIV-1-positive cells and the time when viral culture produces 1 ng of the HIV-1 p24 gag protein per ml. Frequency estimates based on this relationship were highly accurate (P less than 0.01) within the first 15 days of viral culture, which consisted of coculture of 10(6) normal PBMCs with the equivalent number of test PBMCs. This approach was less cumbersome than LDA and was sensitive enough to detect a single infectious HIV-1-harboring cell among as many as 320,000 cells. The values obtained for 57 patients agreed well with the data in the literature and showed that the frequencies of infectious cells in PBMCs reflect the advancement in the clinical stage, being 1/38,000, 1/11,000, and 1/7,000 for asymptomatic patients (Centers for Disease Control [CDC] group II/III), patients with AIDS-related complex (CDC group IVa), and patients with AIDS (CDC group IVb/c), respectively. A nearly 10-fold disparity in mean frequencies was observed when these values were correlated with the numbers of CD4-positive cells (1/9,000, 1/1,500, and 1/300, respectively, for asymptomatic patients, patients with AIDS-related complex, and patients with AIDS). The described method provides a simple means of determining infectious HIV-1-positive cells in blood samples.
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PMID:Relationship between frequency of infectious human immunodeficiency virus type 1-harboring cells and kinetics of viral replication: a simple procedure for quantitation of infectious virus-carrying cells in blood samples. 140 Sep 50

Thailand had its first case of AIDS in 1984, but HIV transmission remained rather low during 1984-86 (0-10 HIV positive cases, 1 AIDS case for 1984 and 1985 and 0 in 1986, and 0-8 cases of AIDS-related complex [ARC]). Beginning in 1987, however, the number of HIV positive, ARC and AIDS cases grew very rapidly (from 194 to an estimated 5384 [1987-end of 1989]). At the end of June 1989, 7978 people (91% male and 9% female) were either HIV positive or had AIDS or ARC. These infections were most prevalent in 20-29 year olds (3797 cases) followed by 30-39 year olds (2946 cases). 19 children (0.2%) were infected. HIV had infected people in all 73 provinces by June 1989. Drug use was by far the leading risk factor of HIV infections in Thailand (91.3% or 6889 cases) followed by heterosexual intercourse (502 cases, 406 of whom were women). HIV prevalence rose considerably among iv drug users. Between 1985 and 1987, it was less than 1%, but by 1988, it rose to 9.5% to 42%, based on a study of 14 provinces. The government has been increasing funds for HIV prevention and control activities. If the epidemiologic trend were to continue, Thailand would have 100,000 HIV-infected cases and 1400 AIDS cases in 1996. 5 Working Committees address prevention, treatment, and rehabilitation; health worker training; public education; coordination; and knowledge of HIV infection. Strategies they have developed to reduce HIV transmission are creation of a central group to monitor, control, and evaluate future projects; coordination of projects between public and private sectors; establishment of an information center; creation of clinics specializing in treatment of patients infected with HIV; health personnel training; and research.
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PMID:HIV infection control in Thailand. 140

In this study we investigated the performance of fourteen different assays capable of simultaneously detecting antibodies to HIV-1 and HIV-2, referred to as combined screening assays (CSAs), on a panel of 371 sera, with a prevalence of 51.5% and 1.3% for HIV-1 and HIV-2 antibodies respectively. The geographic distribution of the sera was as follows; Europe (121), Africa (203) and Latin America (47). These sera were collected from different clinical groups of patients; Asymptomatic (36), AIDS-Related Complex/AIDS patients (18), infected individuals with generalised lymphadenopathy (12), blood donors (149), and subjects with unknown clinical status (156). The Dupont Western blot (WB) kit for detection of HTLV-III antibodies and the Pasteur new Lav-Blot II kit were used for the confirmation of HIV-1 and HIV-2 infection respectively. Of the 14 tests studied, 9 were enzyme linked immunosorbent assays (ELISAs), and 5 were non-Elisa tests requiring visual reading. An alternative approach for HIV antibody testing was studied restrospectively, whereby sera positive in an initial CSA (A) were retested on a second CSA (B), that was different from the first. The use of WB was limited to sera that gave discrepant (A+B-) results in the two CSAs. A positive result in both CSAs was reported as anti-HIV positive. A negative result in the first CSA was reported anti-HIV negative. Sensitivity, specificity, cost, and the delta (delta) values (delta values of the ELISA assays) were taken into consideration when selecting suitable pairs of assays. All the ELISAs scored 100% sensitivity, but for the non-ELISAs, the sensitivity ranged from 96.0% to 100%. The specificity for the ELISAs and non-ELISAs varied from 87.4% to 100% and from 51.4% to 100% respectively. Delta (delta) values for the ELISAs ranged from 3.82 to 136.68 and from -1.15 to -3.08 for the anti-HIV positive and anti-HIV negative populations respectively. Of the 121 test combinations studied, 9 (7.4%) pairs yielded 100% sensitivity and specificity and 61 (50.4%) pairs of CSAs required further testing on WB. This implies 100% positive predictive value, at a cost that was on average 6 times less, and a testing time that was 5 times faster than the conventional algorithm. We conclude that there are several combinations of pairs of CSAs that can be used in the alternative algorithm that can provide accurate results at a much lower cost than the conventional algorithm requiring confirmation by WB of all initially reactive CSA results.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:HIV screening and confirmation: a simplified and less expensive testing algorithm. 141 60


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