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)

Kaposi's sarcoma (KS) is the most frequent type of cancer in patients with Acquired Immune Deficiency Syndrome (AIDS). In the western world, its incidence decreased dramatically in the era of highly active anti-retroviral therapy (HAART). In contrast, the incidence of KS has been steadily climbing in parallel with the AIDS epidemic in Africa over the past 10-15 years, being the most common cancer in adult men in countries like Uganda and Zimbabwe. AIDS-KS can be diagnosed at any stage of HIV infection, although it more commonly occurs in the setting of severe immune suppression, especially with an elevated viral load. Up to now, AIDS-KS is still an incurable disease. Its clinical course is variable, ranging from very indolent cases, requiring no or minimal therapy, to a rapidly progressive disease. Various local therapies are available to control small and asymptomatic lesions, while cytotoxic, immunological and biological therapies can be considered for more aggressive disease. The primary goal of therapy in most of the cases is to provide safe and effective palliation, in order to quality of life. Optimal anti-retroviral therapy is a key component of AIDS-KS management. There are still many questions to be answered in the management of patients with AIDS-KS, such as (1) What are the therapeutic agents that should be used in this disease, and in which sequence? and (2) What are the benefits and risks expected with each treatment option? The aim of this review is to discuss the systemic management of AIDS-KS, with special focus on the above mentioned questions.
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PMID:Systemic treatment of AIDS-related Kaposi sarcoma: current status and perspectives. 1686 Sep 39

The production of recombinant anti-HIV peptide, T-20, in Escherichia coli was optimized by statistical experimental designs (successive designs with multifactors) such as 2(4-1) fractional factorial, 2(3) full factorial, and 2(2) rotational central composite design in order. The effects of media compositions (glucose, NPK sources, MgSO4, and trace elements), induction level, induction timing (optical density at induction process), and induction duration (culture time after induction) on T-20 production were studied by using a statistical response surface method. A series of iterative experimental designs was employed to determine optimal fermentation conditions (media and process factors). Optimal ranges characterized by %T-20 (proportion of peptide to the total cell protein) were observed, narrowed down, and further investigated to determine the optimal combination of culture conditions, which was as follows: 9, 6, 10, and 1 mL of glucose, NPK sources, MgSO4, and trace elements, respectively, in a total of 100 mL of medium inducted at an OD of 0.55-0.75 with 0.7 mM isopropyl-beta-D-thiogalactopyranoside in an induction duration of 4 h. Under these conditions, up to 14% of T-20 was obtained. This statistical optimization allowed the production of T-20 to be increased more than twofold (from 6 to 14%) within a shorter induction duration (from 6 to 4 h) at the shake-flask scale.
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PMID:Sequential and simultaneous statistical optimization by dynamic design of experiment for peptide overexpression in recombinant Escherichia coli. 1705 56

HIV and tuberculosis (TB) are leading global causes of mortality and morbidity, and yet effective treatment exists for both conditions. Rifamycin-based antituberculosis therapy can cure HIV-related TB and, where available, the introduction of highly active antiretroviral therapy (HAART) has markedly reduced the incidence of AIDS and death. Optimal treatment regimens for HIV/TB co-infection are not yet clearly defined. Combinations are limited by alterations in the activity of the hepatic cytochrome P450 (CYP) enzyme system, which in particular may produce subtherapeutic plasma concentrations of antiretroviral drugs. For example, protease inhibitors often must be avoided if the potent CYP inducer rifampicin is co-administered. However, an alternative rifamycin, rifabutin, which has similar efficacy to rifampicin, can be used with appropriate dose reduction. Available clinical data suggest that, for the majority of individuals, rifampicin-based regimens can be successfully combined with the non-nucleoside reverse transcriptase inhibitors nevirapine and efavirenz. Most available HAART regimens in areas that have a high burden of TB contain one or the other of these drugs as a backbone. However, significant questions remain as to the optimal dose of either agent required to ensure therapeutic plasma concentrations, especially in relation to particular ethnic groups. The timing of HAART initiation after starting antituberculosis therapy continues to be controversial. Debate centres upon whether early initiation of HAART increases the risk of paradoxical reactions (immune reconstitution-related events) and other adverse events, or whether delay greatly elevates the risk of disease progression. Further prospective clinical data are needed to help inform practice in this area.
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PMID:Tuberculosis and HIV co-infection: a practical therapeutic approach. 1718 73

The use of highly active antiretroviral therapy (HAART) has resulted in sustained reductions in mortality from HIV infection. In recent years, HAART has also been associated with metabolic complications that may increase patients' cardiovascular disease risk. Recent studies have begun to support a more complex interaction between HAART, HIV infection itself, and other traditional social and immunologic factors that may predispose patients to premature cardiovascular disease. Substantial progress has been made in the development of newer antiretroviral therapies that have a better metabolic profile with respect to dyslipidemia, hyperglycemia, and lipodystrophy. Optimal selection of metabolically neutral antiretroviral therapies, together with aggressive management of other modifiable coronary risk factors, may improve cardiovascular disease risk in the long term.
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PMID:Cardiovascular risks of antiretroviral therapies. 1721 29

Optimal HIV vaccines should elicit CD8+ T cells specific for HIV proteins presented on MHC class I products, because these T cells contribute to host resistance to viruses. We had previously found that the targeting of antigen to dendritic cells (DCs) in mice efficiently induces CD8+ T cell responses. To extend this finding to humans, we introduced the HIV p24 gag protein into a mAb that targets DEC-205/CD205, an endocytic receptor of DCs. We then assessed cross-presentation, which is the processing of nonreplicating internalized antigen onto MHC class I for recognition by CD8+ T cells. Low doses of alphaDEC-gag, but not control Ig-gag, stimulated proliferation and IFN-gamma production by CD8+ T cells isolated from the blood of HIV-infected donors. alphaCD205 fusion mAb was more effective for cross-presentation than alphaCD209/DC-SIGN, another abundant DC uptake receptor. Presentation was diverse, because we identified eight different gag peptides that were recognized via DEC-205 in 11 individuals studied consecutively. Our results, based on humans with highly polymorphic MHC products, reveal that DCs and DEC-205 can cross-present several different peptides from a single protein. Because of the consistency in eliciting CD8+ T cell responses, these data support the testing of alphaDEC-205 fusion mAb as a protein-based vaccine.
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PMID:DEC-205 receptor on dendritic cells mediates presentation of HIV gag protein to CD8+ T cells in a spectrum of human MHC I haplotypes. 1722 38

Over the past 10 years, the management of HIV infection has been transformed by an increased number of effective antiretrovirals (ARVs), with more convenient dosing and improved tolerability. Optimal management of HIV infection includes at least three effective ARVs; from at least two different drug classes. Current strategies and drugs can effectively control HIV and significantly reduce morbidity and mortality. However, no cure is yet possible. Appropriate use of ARVs leads to suppression of virological replication (to below the limit of detection using commercial assays to measure HIV in plasma) and an increase in CD4(+) T cells with few adverse effects. Greater than 95% adherence to drug therapy is required for effective viral suppression and immunological improvement. Monotherapy, two-drug combinations, sequential ARVs, drug "cycling", and treatment interruptions are ineffective management strategies and lead to earlier disease progression and emergence of drug resistance. Drug-drug interactions are common and caution is required when prescribing ARVs that inhibit or induce the cytochrome P450 pathway.
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PMID:Ten years of highly active antiretroviral therapy for HIV infection. 1730 5

The cellular chemistry of metallopeptide complexes designed to target and inactivate an HIV Rev response element (RRE) RNA sequence in vivo has been evaluated by use of an efficient cellular fluorescence assay. Transcribed messenger RNA encoding the green fluorescent protein (GFP) that includes a target RNA sequence is sensitive to cleavage chemistry mediated by metal derivatives of GGH(G)(x)TRQARRNRR RRWRERQR (x = 0, 1, 2, 4, 6). This results in a significant decrease in expression of GFP that can be quantified by fluorimetry. Optimal inactivation of the target RRE RNA was achieved with linkers where x = 0 or 1. Neither the Rev control peptide (lacking metal-binding or linker sequences) nor the metal-binding motif alone had any significant effect. Consequently, both the cleavage motif and the RNA targeting motif are essential to promote cellular cleavage of the target RRE RNA. However, target inactivation was also observed in experiments with metal-free peptide, consistent with recruitment of intracellular metal ion by the peptide following cellular uptake, with subsequent cleavage of the RRE target RNA. The RRE RNA cleavage activities of metallopeptide complexes were further confirmed by in vitro experiments and mammalian cell assays.
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PMID:Cellular activity of Rev response element RNA targeting metallopeptides. 1735 72

Early views on the relationship between adherence and resistance postulated a bell-shaped relationship that balanced selective drug pressure and improved viral suppression along a continuum of adherence. Although this conceptual relationship remains valid, recent data suggest that each regimen class may have different adherence-resistance relationships. These regimen-specific relationships are a function of the capacities of resistant virus to replicate at different levels of drug exposure, which are largely, but not entirely, determined by the impact of mutations on susceptibility of the virus and the impact of the mutations on the inherent ability of the virus to replicate efficiently. Specific patterns of adherence, such as treatment discontinuations, may influence adherence-resistance relationship to combination regimens comprised of medications with differing half-lives. Host genomics that alters antiretroviral drug distribution and metabolism may also impact adherence-resistance relationships. Optimal antiretroviral regimens should be constructed such that there is little overlap in the window of adherence that selects for antiretroviral drug resistance.
Curr HIV/AIDS Rep 2007 May
PMID:Adherence-resistance relationships to combination HIV antiretroviral therapy. 1754 27

Theileria parva is the causative agent of East Coast fever (ECF), an important cattle disease in East and Central Africa. One of the methods for control of ECF is 'infection and treatment', a procedure in which an animal is infected with the live parasite and at the same time treated with a long-acting oxytetracycline formulation, restraining the infection and allowing a protective cellular immune response to develop. Optimal immunizing doses were estimated using models of trichotomous response: dysimmunization (death or severe reaction during immunization), immunization failure (death or severe reaction during lethal challenge) and successful immunization (neither dysimmunization nor immunization failure). In this paper we present methods of interpreting immunization trials and apply these methods to previously unpublished data from two such trials: one with a mixture of three T. parva stocks and one with a single T. parva stock. We explain why titration trials conducted with a cocktail of antigens could predict a suboptimal immunization dose. Indeed it is possible for a combination of three individually efficient stocks to result in a mixture with which optimal immunization response might be difficult to achieve, because of averaging effects. The corresponding interpretation provides insights into why standard immunization trials for T. parva have not yielded the results that might be expected of them. The results of this work may also have implications for the use of antigen cocktails in cancer, HIV and malaria vaccine trials.
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PMID:Titrating Theileria parva: single stocks against combination of stocks. 1815 95

Optimal adherence to antiretroviral medications is critical to the effective long-term management of HIV infection. Although prospective memory (ProM; i.e., "remembering to remember") has long been theorized to play an important role in medication adherence, no prior studies have evaluated whether HIV-associated ProM impairment possesses unique predictive value in this regard. Results from this study demonstrate a robust association between ProM impairment and self-reported medication management in 87 HIV-infected persons currently prescribed antiretroviral medications. Specifically, more frequent ProM complaints and performance deficits on both laboratory and semi-naturalistic ProM tasks were all independently related to poorer self-reported medication management. A series of hierarchical regression analyses revealed that HIV-associated ProM impairment accounted for a significant amount of variance in self-reported medication management beyond that which was explained by other factors known to predict nonadherence, including mood disorders, psychosocial variables, environmental structure, and deficits on a traditional battery of neuropsychological tests. Overall, these findings support the hypothesis that ProM captures a unique and largely untapped aspect of cognition that is germane to optimal medication adherence. The potential benefits of individualized remediation strategies that are informed by conceptual models of ProM and specifically target medication adherence warrant further exploration.
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PMID:Prospective memory in HIV infection: is "remembering to remember" a unique predictor of self-reported medication management? 1824 45


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