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)

Current clinical gene therapy protocols for the treatment of human immunodeficiency virus type 1 (HIV-1) infection often involve the ex vivo transduction and expansion of CD4+ T cells derived from HIV-positive patients at a late stage in their disease (CD4 count <400). These protocols involve the transduction of T cells by murine leukemia virus (MLV)-based vectors encoding antiviral constructs such as the rev m10 dominant negative mutant or a ribozyme directed against the CAP site of HIV-1 RNA. We examined the efficiency and stability of transduction of CD4+ T cells derived from HIV-infected patients at different stages in the progression of their disease, from seroconversion to AIDS. CD4+ T cells from HIV-positive patients and uninfected donors were transduced with MLV-based vectors encoding beta-galactosidase and an intracellular antibody directed against gp120 (sFv 105) or Tat. (sFvtat1-Ckappa). The expression of marker genes and the effects of the antiviral constructs were monitored in vitro in unselected transduced CD4+ T cells. Efficiency and stability of transduction varied during the course of HIV infection; CD4+ T cells derived from asymptomatic patients were transducible at higher efficiencies and stabilities than CD4+ T cells from patients with acquired immunodeficiency syndrome (AIDS). Expression of the anti-tat intracellular antibody was more effective at stably inhibiting HIV-1 replication in transduced cells from HIV-infected individuals than was sFv 105. The results of this study have important implications for the development of a clinically relevant gene therapy for the treatment of HIV-1 infection.
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PMID:Inhibition of human immunodeficiency virus replication and growth advantage of CD4+ T cells from HIV-infected individuals that express intracellular antibodies against HIV-1 gp120 or Tat. 952 10

This article describes the Client Adherence Profiling-Intervention Tailoring (CAP-IT) intervention designed to enhance adherence to HIV/AIDS medications and reports the results of a pilot study aimed at assessing the feasibility of CAP-IT. Initially, CAP-IT was designed to be implemented by nurse case managers during regularly scheduled home visits; it is currently under revision for use in an outpatient, ambulatory care setting. CAP-IT is an innovative, structured nursing assessment and care-planning activity that allows a standardized assessment of client needs and tailored highly active antiretroviral therapy adherence intervention strategies. CAP-IT is significantly different from the current standard nursing case management practice. Pilot study results in a sample of 10 home care patients suggests that clients have knowledge and skill deficits related to adherence and in the management of the side effects of medications. In addition, the pilot study supported the acceptability of the protocol to clients and the feasibility of integrating CAP-IT into nurse case manager practice. The pilot study results also provided evidence for the efficacy of CAP-IT. The next steps include testing CAP-IT in a randomized clinical trial to determine its effectiveness.
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PMID:The Client Adherence Profiling-Intervention Tailoring (CAP-IT) intervention for enhancing adherence to HIV/AIDS medications: a pilot study. 1067 5

The aim of this protocol is to establish a common basis for the production of reference values and well-defined and documented reference intervals for plasma proteins, based on common standardization, using the IFCC/BCR/CAP Certified Reference Material CRM 470. The strategy is to search for racial and environmental/geographical similarities and sources of differences in order to describe the main causes for variability among smaller or larger groups in selected societies and to estimate the sizes of differences for the different proteins according to the investigated sources. For this purpose, groups of reference individuals are selected according to race and geographical/environmental location, e.g. African Americans and Caucasians from the US. The reference individuals are groups of approximately 160 healthy male blood donors, 20 to 60 years of age. Rule-out criteria are positivity for HIV, hepatitis B and C antibodies and blood hemoglobin below the lower reference limit. Exclusion in relation to different C-reactive protein (CRP) levels will be investigated. Coagulation, storage conditions, transport, and the procedure for thawing are specified. The laboratories undertaking the measurements must have adequate analytical performance, and calibration and quality of performance are defined and documented, together with recommended control materials and procedures. Statistical models for describing distributions and for comparing groups are described. It is recommended that the data be presented as reference limits with 90% confidence intervals of those limits.
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PMID:Strategy for determining racial and environmental similarities and differences for plasma proteins. 1183 31

The increased incidence of HIV/AIDS disease in women aged 15 - 49 years has identified the urgent need for a female-controlled, efficacious and safe vaginal topical microbicide. To meet this challenge, new topical microbicide candidates consisting of molecules or formulations that modify the genital environment (BufferGel, engineered Lactobacillus, over-the-counter lubricants), surfactants (C31D/Savvy, sodium dodecyl sulfate, sodium lauryl sulfate), polyanionic polymers (PRO 2000, beta-cyclodextrin, Carraguard, CAP, D2S, SPL-7013), proteins (cyanovirin-N, monoclonal antibodies, thromspondin-1 peptides, Pokeweed antiviral protein and others), reverse transcription inhibitors (PMPA [Tenofovir ]), UC-781, SJ-3366, DABO and thiourea) and other molecules (NCp7-specific virucides, chemokine receptor agonists/antagonists, WHI-05 and WHI-07) are currently being investigated for activity, safety and efficacy. This review will assess the development of these molecules in the context of cervicovaginal defences and the clinical failure of nonoxynol-9.
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PMID:Considerations and development of topical microbicides to inhibit the sexual transmission of HIV. 1215 Jul 3

In this preliminary study, we evaluated the performance of the Cobas AmpliPrep/Cobas Amplicor HIV-1 Monitor Ultrasensitive Test (CAP; Roche Molecular Systems, Branchburg, NJ) for automated specimen preparation and quantitative detection of human immunodeficiency virus type 1 (HIV-1) RNA and compared it to the Cobas Amplicor HIV-1 Monitor Ultrasensitive Test (MCA; Roche), which includes a manual sample preparation protocol. A dilution panel of a patient sample was prepared. Additionally, 584 EDTA plasma samples were collected from HIV-1 infected patients. Reproducibility was estimated with six assay runs using the dilution panel. The inter-assay coefficient of variation ranged from 39.4 to 48.4% (CAP assay) and from 34.3 to 45.6% (MCA assay), whereas the intra-assay coefficient of variation ranged from 6.2 to 58.0% (CAP assay) and from 4.4 to 57.3% (MCA assay). Comparison of CAP assay results with the HIV-1 copy number of the dilution panel determined by the MCA assay resulted in a good agreement, although the CAP results were found to be slightly lower. A significant correlation between both test systems was found when clinical samples were analyzed. The mean viral load of 152 samples, which were within the linear range of both tests, was 3.70 log(10) HIV-1 copies/ml by the CAP assay compared to 3.73 by the MCA assay. In conclusion, we could demonstrate that the new Cobas AmpliPrep/Cobas Amplicor HIV Monitor Ultrasensitive Test is reproducible and sensitive. In comparison to the assay with manual extraction, no significant difference in HIV-1 RNA copy numbers was observed.
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PMID:Evaluation of the Cobas AmpliPrep/Cobas Amplicor HIV-1 Monitor Ultrasensitive Test: comparison with the Cobas Amplicor HIV-1 Monitor test (manual specimen preparation). 1246 84

A multicenter study of 638 cases of community-acquired pneumonia due to Streptococcus pneumoniae (SP-CAP) was performed to assess current levels of resistance. Of the pneumococcal strains, 35.7% had an minimum inhibitory concentration (MIC) of penicillin of > or =0.12 microg/mL (3 isolates had an MIC of 4 microg/mL), 23.8% had an MIC of erythromycin of 128 microg/mL, and 22.2% were multidrug resistant. Logistic regression determined that chronic pulmonary disease (odds ratio [OR], 1.44], human immunodeficiency virus infection (OR, 1.98), clinically suspected aspiration (OR, 2.12), and previous hospital admission (OR, 1.69) were related to decreased susceptibility to penicillin, and previous admission (OR, 1.89) and an MIC of penicillin of MIC > or =0.12 microg/mL (OR, 15.85) were related to erythromycin resistance (MIC, > or =1 microg/mL). The overall mortality rate was 14.4%. Disseminated intravascular coagulation, empyema, and bacteremia were significantly more frequent among patients with penicillin-susceptible SP-CAP. Among isolates with MICs of penicillin of > or =0.12 microg/mL, serotype 19 was predominant and was associated with a higher mortality rate. In summary, the rate of resistance to beta -lactams and macrolides among S. pneumoniae that cause CAP remains high, but such resistance does not result in increased morbidity.
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PMID:Drug-resistant pneumococcal pneumonia: clinical relevance and related factors. 1547 72

HIV-infected individuals are at risk for developing certain types of cancers. While there are data to show that non-random HIV integration may occur, our goal was to identify preferential genomic sites where HIV integration might be targeted leading to oncogenesis. Initially, a linker-primer PCR strategy was used to identify HIV integration in isolated macrophages. Inverse-PCR was then used to analyze specimens from patients diagnosed with HIV-associated malignancies. From isolated macrophages, integration near a toll-like receptor on chromosome 4 was found. Necropsy tissues from 11 cases were analyzed with 1 tumor specimen found to have HIV integrated in chromosome 22q13.2 and within 300 kb of HSCBCIP1 (CAP-binding protein complex interacting homologue). Tumor-specific primers were then used to screen uninvolved tissue from the same patient, which did not amplify the site-specific region. This report demonstrates that in both an in vitro system and human malignant tissue, specific viral integration can be identified.
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PMID:Preferential HIV-1 integration sites in macrophages and HIV-associated malignancies. 1555 24

The sexual transmission of human immunodeficiency virus type 1 (HIV-1) is facilitated by inflammation and related epithelial barrier perturbation. Microbicides for vaginal applications are currently being developed to reduce the risk of HIV-1 transmission. However, little is known about their interference with epithelial immune function. In recent clinical trials, nonoxynol-9 (N-9), a virucide with a long history of intravaginal use as a contraceptive, failed to protect against HIV-1 possibly due to mucosal inflammatory damage. Cellulose acetate 1,2-benzenedicarboxylate, also named CAP (for "controls AIDS pandemic"), is an anti-HIV-1 microbicide selected from pharmaceutical excipients that are regarded as safe for oral administration but have not been assessed for potential effects on inflammatory factors in the vaginal environment. Here we use a sensitive human cell culture system to evaluate proinflammatory profiles of soluble CAP in reference to N-9 and known epithelial activators such as tumor necrosis factor alpha (TNF-alpha) and bacterial lysates. Within 6 h of exposure, TNF-alpha and N-9 triggered NF-kappaB and AP-1/cFos activation and upregulated interleukins and an array of chemokines by vaginal and polarized cervical epithelial cells. The induced proinflammatory status continued after removal of stimuli and was confirmed by enhanced transepithelial neutrophil migration. While sustaining stability and anti-HIV-1 activity in the epithelial environment, CAP did not increase the production of proinflammatory mediators during or after exposure, nor did it modify the epithelial resistance to leukocyte traffic. CAP attenuated some TNF-alpha-induced responses but did not interfere with epithelial cytokine responsiveness to gonococcal determinants. The described system may be useful for predicting proinflammatory side effects of other microbicide candidates for vaginal application.
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PMID:Anti-human immunodeficiency virus type 1 microbicide cellulose acetate 1,2-benzenedicarboxylate in a human in vitro model of vaginal inflammation. 1561 12

The combination of two candidate microbicides, cellulose acetate 1,2-benzenedicarboxylate (CAP), a polymer that blocks human immunodeficiency virus type 1 (HIV-1) entry by targeting gp120 and gp41, and UC781, a tight-binding HIV-1 reverse transcriptase inhibitor (RTI), resulted in effective synergy for inhibition of MT-2 cell infection by HIV-1(IIIB), a laboratory-adapted virus strain. The 95% effective concentration values for the combination were reduced about 15- to 20-fold compared with those corresponding to the single compounds. The combination of CAP and UC781 is also synergistic in inhibiting infection of peripheral blood mononuclear cells by a primary HIV-1 isolate, 92US657. Combinations of CAP with other RTIs, such as efavirenz or zidovudine, also had significant synergistic effects on the inhibition of HIV-1 infection. In addition, CAP and UC781 had complementary effects against HIV-1 infection since (i) CAP inhibited infection by the UC781-resistant strain HIV-1(IIIB) A17 and (ii) pretreatment of MT-2 cells with UC781, but not CAP, abolished subsequent infection after removal of the compound. This suggests that the combination of CAP and UC781 represents a promising candidate microbicide for prevention of sexual transmission of HIV-1.
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PMID:Combination of candidate microbicides cellulose acetate 1,2-benzenedicarboxylate and UC781 has synergistic and complementary effects against human immunodeficiency virus type 1 infection. 1585 3

A human colorectal explant culture was developed to assess the safety and efficacy of topical microbicides proposed for use in humans. Because any product marketed for vaginal application will likely be used for anal intercourse, it is important to evaluate these products in colorectal explant tissue. Microbicides tested included cellulose acetate 1,2-benzenedicarboxylate (CAP), PRO 2000, SPL7013, Vena Gel, and UC781, along with their accompanying placebos. Colorectal tissues were exposed to microbicides overnight and either fixed in formalin to evaluate toxicity by histological analysis or placed in 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) to quantitatively determine tissue viability. Histological analysis showed minimal toxicity for CAP, UC781, and Vena Gel. Shedding of epithelium with intact lamina propria occurred for the PRO 2000 and SPL7013 products, and shedding of epithelium and necrosis of the lamina propria occurred in explants cultured with nonoxynol-9. The MTT assay confirmed these results for PRO 2000 (4% and 0.5%), SPL7013 (and placebo), and nonoxynol-9 but also demonstrated reduced viability for CAP. However, viability of tissues treated with all products was not significantly different from that of the medium control. Efficacy of the microbicides was evaluated by measuring human immunodeficiency virus type 1 (HIV-1) infection of explants in the absence or presence of products. All microbicide formulations tested were highly effective in preventing HIV infection. However, explants treated with some of the placebo formulations also exhibited a lower level of infection. Most of the products developed for vaginal application showed minimal toxicity and were effective in reducing HIV-1 infection in colorectal tissues. These results suggest that this model is useful for evaluating the safety and efficacy of topical microbicides when used rectally.
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PMID:A human colorectal explant culture to evaluate topical microbicides for the prevention of HIV infection. 1620 69


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