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 potential for early medical intervention to slow or prevent the development of AIDS in HIV-positive individuals has led to calls for widespread testing of asymptomatic at-risk persons. Levine and Bayer discuss the ethical aspects of these proposals, distinguishing among the justifications for screening and evaluating each independently. They present current clinical evidence for early intervention and explore its potential risks and benefits. Using the ethical principles of respect for persons, the harm principle, beneficience, and justice, they analyze the justifications for and the limits of screening infants, adolescents, and adults for HIV seropositivity. Levine and Bayer conclude that while there are clinical and ethical grounds for establishing voluntary screening programs, conditions of informed consent and confidentiality must be met, and protection from discrimination and provision of follow-up services for infected individuals are essential.
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PMID:The ethics of screening for early intervention in HIV disease. 268 16

We undertook a prospective evaluation of 4 methods for the detection of Pneumocystis carinii in clinical specimens and compared an indirect immunofluorescence assay (IFA) (Diagnostics Pasteur), and a fluorescent whitening agent (FWA) (Blankophor BA 267%, Bayer, Australia) with our standard methenamine silver (MeAg) and toluidine blue O (TB) stains. Two hundred and two specimens were received from 162 patients (133 HIV infected, 19 heart or heart-lung transplant recipients, and 10 "miscellaneous"). The specimens consisted of 132 induced sputa, 56 bronchoalveolar lavage specimens, 10 fine needle aspiration lung biopsies, and 4 pleural fluid specimens. P. carinii was detected in 44 (22%) of the specimens. The sensitivities for the detection of P. carinii pneumonia were IFA: 92% (95% CI, 83-100%), FWA: 57% (95% CI, 41-73%), MeAg: 54% (95% CI, 38-70%), and TB: 49% (95% CI, 33-65%). Discordant results were greatest in specimens from patients who were receiving specific anti-P. carinii prophylaxis, or who had received treatment for several days prior to sampling. IFA was the most sensitive test and relatively easy to perform. IFA was also the most expensive test. We found the FWA method a useful screening test as it is cheap and quick to perform. However, it is less sensitive than IFA, which should be performed on the negative specimens. With the increasing use of specific anti-P. carinii prophylaxis in HIV-infected patients, methods more specific and sensitive than MeAg and TB stains are required. We have found IFA to improve significantly the rate of detection of P. carinii in this patient group.
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PMID:An evaluation of four methods for the detection of Pneumocystis carinii in clinical specimens. 752 14

We have established an expression system for full-length HIV-1 transactivator (Tat) protein in Escherichia coli. By constructing a synthetic gene for high level expression in enteric bacteria, the recombinant protein can be obtained in high yield. Fusion of the Tat sequence to an N-terminal histidine tag allows the rapid purification of the fusion protein through a single chromatographic step. After cleavage of the fusion protein with CNBr, pure Tat can be obtained through the use of a MonoS column. Reduction of the protein with Tris(2-carboxyethyl)phosphine-HCl and subsequent stepwise refolding yields biologically active Tat. Sample purity and the identity of the protein mass with the mass expected from the amino acid sequence was demonstrated by mass spectrometry. Nuclear magnetic resonance spectroscopy showed the identity of bacterially expressed and chemically synthesized Tat protein (P. Bayer et al., 1995, J. Mol. Biol. 247, 529-535). The expression of Tat in E. coli enables isotope labeling as a prerequisite for multidimensional NMR experiments toward the elucidation of the structure of the Tat-trans-activation response element complex.
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PMID:Cloning, high-yield expression in Escherichia coli, and purification of biologically active HIV-1 Tat protein. 881 37

The second generation Hoechst-Bayer non-nucleoside inhibitor, HBY 097 (S-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3, 4-dihydroqui noxalin-2(1H)-thione), is an extremely potent inhibitor of HIV-1 reverse transcriptase (RT) and of HIV-1 infection in cell culture. HBY 097 selects for unusual drug-resistance mutations in HIV-1 RT (e.g. Gly190Glu) when compared with other non-nucleoside RT inhibitors (NNRTIs), such as nevirapine, alpha-APA and TIBO. We have determined the structure of HBY 097 complexed with wild-type HIV-1 RT at 3.1 A resolution. The HIV-1 RT/HBY 097 structure reveals an overall inhibitor geometry and binding mode differing significantly from RT/NNRTI structures reported earlier, in that HBY 097 does not adopt the usual butterfly-like shape. We have determined the structure of the Tyr188Leu HIV-1 RT drug-resistant mutant in complex with HBY 097 at 3.3 A resolution. HBY 097 binds to the mutant RT in a manner similar to that seen in the wild-type RT/HBY 097 complex, although there are some repositioning and conformational alterations of the inhibitor. Conformational changes of the structural elements forming the inhibitor-binding pocket, including the orientation of some side-chains, are observed. Reduction in the size of the 188 side-chain and repositioning of the Phe227 side-chain increases the volume of the binding cavity in the Tyr188Leu HIV-1 RT/HBY 097 complex. Loss of important protein-inhibitor interactions may account for the reduced potency of HBY 097 against the Tyr188Leu HIV-1 RT mutant. The loss of binding energy may be partially offset by additional contacts resulting from conformational changes of the inhibitor and nearby amino acid residues. This would suggest that inhibitor flexibility can help to minimize drug resistance.
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PMID:Structures of Tyr188Leu mutant and wild-type HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor HBY 097: inhibitor flexibility is a useful design feature for reducing drug resistance. 981 20

Fifty-eight previously treated haemophilic subjects were treated exclusively with the recombinant FVIII (rFVIII-KOGENATE) produced by Bayer Corporation (Berkeley, CA) in an international multicentre prospective study of more than 5 years duration. Fifty-four of the 58 had severe haemophilia (< 2% FVIII) and four had moderate haemophilia (2-5% FVIII); 23/58 (40%) were seropositive for HIV, while 35/58 (60%) were HIV seronegative. Patients were monitored for safety and efficacy over a median period of 4.7 years (range 0.9-5.9 years) and received 17 922 infusions totalling 25.7 million units of rFVIII. Of 7107 bleeding episodes reported in home diaries, 5831 (82%) required only one treatment with rVIII. Twenty-five invasive surgical procedures in 17 patients, including eight joint replacements, were successfully accomplished and 13 serious bleeding episodes in eight patients were successfully treated. FVIII recovery performed on 885 occasions using 39 different lots of rFVIII showed mean incremental recovery of 2.48% IU-1 kg-1 (+/- 0.64). Adverse events were associated with 42 infusions (0.2%); none caused discontinuation of therapy. Immunological parameters remained stable in HIV-seronegative subjects treated with rFVIII; a small decrease in CD4 counts was noted in HIV-seropositive individuals (mean - 37.2 cells mm-3 yr-1). No de novo formation of inhibitors to FVIII was noted; and no clinical allergic reactions occurred to murine or hamster proteins. These conclusions from the longest monitored safety study ever performed for a haemophilia treatment product (with more than 5 years of observation) confirm previous interim study reports that rFVIII is well tolerated over the long-term, has biological activity comparable to that of plasma-derived FVIII, and is safe and efficacious for the treatment of haemophilia A.
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PMID:Human recombinant DNA-derived antihaemophilic factor (factor VIII) in the treatment of haemophilia A: conclusions of a 5-year study of home therapy. The KOGENATE Study Group. 1021 42

Quantification of human immunodeficiency virus type 1 (HIV-1) RNA as a measure of viral load has greatly improved the monitoring of therapies for infected individuals. With the significant reductions in viral load now observed in individuals treated with highly active anti-retroviral therapy (HAART), viral load assays have been adapted to achieve greater sensitivity. Two commercially available ultrasensitive assays, the Bayer Quantiplex HIV-1 bDNA version 3.0 (bDNA 3.0) assay and the Roche Amplicor HIV-1 Monitor Ultrasensitive version 1.5 (Amplicor 1.5) assay, are now being used to monitor HIV-1-infected individuals. Both of these ultrasensitive assays have a reported lower limit of 50 HIV-1 RNA copies/ml and were developed from corresponding older generation assays with lower limits of 400 to 500 copies/ml. However, the comparability of viral load data generated by these ultrasensitive assays and the relative costs of labor, disposables, and biohazardous wastes were not determined in most cases. In this study, we used matched clinical plasma samples to compare the quantification of the newer bDNA 3.0 assay with that of the older bDNA 2.0 assay and to compare the quantification and costs of the bDNA 3.0 assay and the Amplicor 1.5 assay. We found that quantification by the bDNA 3.0 assay was approximately twofold higher than that by the bDNA 2.0 assay and was highly correlated to that by the Amplicor 1.5 assay. Moreover, cost analysis based on labor, disposables, and biohazardous wastes showed significant savings with the bDNA 3.0 assay as compared to the costs of the Amplicor 1.5 assay.
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PMID:Quantitative and cost comparison of ultrasensitive human immunodeficiency virus type 1 RNA viral load assays: Bayer bDNA quantiplex versions 3.0 and 2.0 and Roche PCR Amplicor monitor version 1.5. 1069 5

Accurate and sensitive quantification of human immunodeficiency virus type 1 (HIV-1) RNA has been invaluable as a marker for disease prognosis and for clinical monitoring of HIV-1 disease. The first generation of commercially available HIV-1 RNA tests were optimized to detect the predominant HIV-1 subtype found in North America and Europe, subtype B. However, these tests are frequently suboptimal in detecting HIV-1 genetic forms or subtypes found in other parts of the world. The goal of the present study was to evaluate the performance of a new viral load assay with non-subtype B viruses. A transcription-mediated amplification method for detection and quantitation of diverse HIV-1 subtypes, called the Gen-Probe HIV-1 viral load assay, is under development. In this study we examined the performance of the Gen-Probe HIV-1 viral load assay relative to that of the commonly used commercial HIV-1 RNA assays using a panel of primary isolates from Kenya. For comparison, we included several subtype B cloned viruses, and we quantified each virus using an in-house quantitative-competitive reverse transcriptase PCR (QC-RT-PCR) method and gag(p24) antigen capture. The Gen-Probe HIV-1 viral load assay and a version of the Roche AMPLICOR HIV-1 MONITOR test (version 1.5) that was designed to detect a broader range of subtypes were both sensitive for the quantification of Kenyan primary isolates, which represented subtype A, C, and D viruses. The Gen-Probe HIV-1 viral load assay was more sensitive for the majority of viruses than the Roche AMPLICOR HIV-1 MONITOR test version 1.0, the Bayer Quantiplex HIV RNA 3.0 assay, or a QC-RT-PCR method in use in our laboratory, suggesting that it provides a useful method for quantifying HIV-1 RNAs from diverse parts of the world, including Africa.
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PMID:Evaluation of performance of the Gen-Probe human immunodeficiency virus type 1 viral load assay using primary subtype A, C, and D isolates from Kenya. 1087 65

HIV RNA was quantified in blood plasma from 209 patients and in control specimen comparing the NucliSens HIV-1 QT test (Organon Teknika), which is based on the nucleic acid sequence amplification procedure, and the Quantiplex 3.0 test (Bayer), which uses hybridization signal enhancement by branched DNA (bDNA) probes. A highly significant correlation (P=0.01) was found between the two methods with 88% of the samples showing similar results. In cases of discrepant findings, higher virus load was observed with either test (14xNASBA>bDNA; 12xbNDA>NASBA). Differences could neither be related to clinical features nor to divergent virus subtypes. Standard preparations containing 35000 and 222000 copies were quantified with intra-assay coefficients of variation of <20% using both methods. A preparation of 192 copies was measured with lower precision by both tests, yet was detected more reliably by the bDNA method.
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PMID:Comparison between a nucleic acid sequence-based amplification and branched DNA test for quantifying HIV RNA load in blood plasma. 1099 51

We developed a rapid and highly reproducible assay based on real-time PCR (TaqMan, Applied Biosystems, Foster City, CA) to quantitate simian immunodeficiency virus (SIV) RNA in plasma samples. This assay was compared with the current branched-chain DNA assay (Bayer, Emeryville, CA). Results obtained with the real-time TaqMan PCR assay were comparable to those obtained with the branched-chain DNA assay in overlapping ranges of sensitivities (r = 0.9429, p < 0.05). However, the real-time TaqMan PCR assay was capable of detecting as few as 50 copies of RNA/ml, whereas branched-chain DNA was only sensitive to 1,500 copies of RNA/ml. Therefore, several animals that tested negative by branched-chain DNA were positive by realtime TaqMan PCR. Two false positive tests were also recorded for the branched-chain DNA test. False negative and positive tests were confirmed by cell culture isolation and conventional nested RT-PCR. The SIV TaqMan assay detected a wide range of wild-type, cloned, and recombinant SIV strains with similar amplification efficiency, including SIVmac251, SIVmac239, SIVmac239 containing the 184V mutation in RT, SIV1A11, SIVmac239 delta3, SIVmac-M4, and chimeras (SHIVs) containing specific HIV-1 genes, such as reverse transcriptase (RT-SHIV) or Env (SHIV-E). In conclusion, the high sensitivity, increased specificity, wide dynamic range, simplicity, and reproducibility of the real-time SIV RNA quantitation allow the screening of large numbers of samples and make this method especially suitable for measuring both viral DNA and RNA levels during vaccine and therapy studies.
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PMID:Real-time TaqMan PCR as a specific and more sensitive alternative to the branched-chain DNA assay for quantitation of simian immunodeficiency virus RNA. 1117 7

Four pharmaceutical companies have presented a $640 million offer to settle legal claims filed by Americans with hemophilia who contracted HIV through blood-clotting products. Corey Dubin, chief negotiator for infected hemophiliacs and head of the Committee of Ten Thousand, acknowledges that while the offer is substantial, he still plans to pursue litigation. The offer provides roughly $120,000 to each infected hemophiliac in the United States. The four paying companies are Bayer Corporation, Rhone-Poulenc Rorer, Alpha Therapeutic, and Baxter Healthcare. About half of the nation's 20,000 hemophiliacs contracted HIV through contaminated blood-clotting products in the late 1970s and early 1980s. On April 16, 1996, the House of Representatives sponsored a bill that would set up a $1 billion fund for HIV-positive hemophiliacs.
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PMID:Drug companies propose $640 million claims settlement. 1136 58


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