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anti-HIV Drugs (anti-hiv + drug)

Distribution by Scientific Domains

Chemistry	58%
Medical Sciences	33%

Selected Abstracts

A study of dietary advice and care provided to HIV positive patients referred for lipid lowering: as part of a service improvement initiative

JOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 4 2008
N.A. Billing
Background:, Combination antiretroviral therapy (ART) has dramatically reduced mortality in HIV-infected patients. As life expectancy of HIV infected patients has increased, concerns about the long-term effects of treatment grow (Sax, 2006). HIV positive patients have a greater risk of myocardial infarction (MI) and ART has been associated with a 26% increase in the rate of MI per year of exposure (DAD Study Group, 2003). The aim of this study was to evaluate provision of dietetic care to patients referred for lipid lowering advice and identify potential areas for service improvement. Methods:, Departmental activity statistics identified 117 new clients referred for lipid lowering advice in the previous 11 months. The biochemical data and dietetic record cards were screened, of the initial sample 30 were excluded as they did not have follow up biochemistry after their dietetic consultation and a further seven were excluded as they were seen primarily for other conditions. The remaining cards (n = 80) had their dietetic record cards audited to check dietary topics discussed, risk factors identified length before follow up and clinical outcomes. Results:, There were 68 men and 12 women in this sample with a mean age of 46 years and mean body mass index (BMI) of 25.4 kg m,2 (3.7 kg m,2). Of the clients referred, only 48.8% of the sample had high density lipoprotein (HDL): cholesterol ratios taken to calculate cardiovascular risk and most patients were seen an average of 30.7 days (35.3 days) after high was identified. Following their dietetic consultation, 77% of clients had a reduction in their cholesterol levels and 61% had a reduction in triglyceride levels. This sample's average percentage change in cholesterol was ,10% (16%) and triglyceride was ,6% (32%). The most popular dietary advice was reducing saturated fat intake (90%), increasing fibre intake (76%), benefits of plant stanols (40%), importance of regular meals (29%), exercise (26%) and benefits of omega three (11%). Additional risk factors identified 11% of clients seen were smokers, however most records (66%) did not have documentation on whether smoking behaviour was discussed. Only 20% of clients had a follow up appointments and not all were seen within 3 months with average time between follow up being 14.9 weeks (13.2 weeks). Discussion:, Improvement in biochemical results were comparable to a study by Henry et al., (1998) which showed that in HIV infected clients receiving ART, diet modification and increased exercise were successful in reducing cholesterol levels by 11% and triglyceride levels by 21%. The level of smoking was considerably lower than other studies (DAD Study Group, 2003) which reported 56% of HIV positive clients to be smokers. A large number of clients were lost to follow up and were not seen within 3 months. Lazzaretti et al., (2007) showed in a randomized trial that seeing patients at regular 3 month intervals for dietary intervention prevented an increase in lipid blood levels in individuals who start ART. Conclusions:, Not all clients are having their cardiovascular risk calculated before referral for dietary advice. Clients are not being seen at regular intervals by dietitians, some are lost to follow up and smoking status is not regularly documented during dietetic consultation. References, Data Collection on Adverse Events of Anti-HIV Drugs (DAD) Study Group. (2003) Combination antiretroviral therapy and the risk of myocardial infarction. N. Engl. J. Med.349, 1993,2003. Friis-Moller, N., Weber, R., Reiss, P., Thiebaut, R., Kirk, O., d'Arminio, M.A. et al. (2003) Cardiovascular disease risk factors in HIV patients' association with antiretroviral therapy. Results from the DAD study. AIDS17, 1179,1193. Henry, K., Melroe, H., Huebesch, J., Hermundson, J. & Simpson, J. (1998) Atorvastatin and gemfibrozil for protease inhibitor-related lipid abnormalities. Lancet352, 1031,1032. Sax, P.E. (2006)Strategies for management and treatment of dyslipidemia in HIV/AIDS. AIDS Care 18, 149,157. Lazzaretti, R., Pinto-Ribeiro, J., Kummer, R., Polanczyk, C. & Sprinz, E. (2007) Dietary intervention when starting HAART prevents the increase in lipids independently of drug regimen: a randomized trial. Oral abstract session: 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention: Abstract no.WEAB303. [source]

Allosteric modulation of anti-HIV drug and ferric heme binding to human serum albumin

FEBS JOURNAL, Issue 24 2005
Alessio Bocedi
Human serum albumin (HSA), the most prominent protein in plasma, is best known for its exceptional capacity to bind ligands (e.g. heme and drugs). Here, binding of the anti-HIV drugs abacavir, atazanavir, didanosine, efavirenz, emtricitabine, lamivudine, nelfinavir, nevirapine, ritonavir, saquinavir, stavudine, and zidovudine to HSA and ferric heme,HSA is reported. Ferric heme binding to HSA in the absence and presence of anti-HIV drugs was also investigated. The association equilibrium constant and second-order rate constant for the binding of anti-HIV drugs to Sudlow's site I of ferric heme,HSA are lower by one order of magnitude than those for the binding of anti-HIV drugs to HSA. Accordingly, the association equilibrium constant and the second-order rate constant for heme binding to HSA are decreased by one order of magnitude in the presence of anti-HIV drugs. In contrast, the first-order rate constant for ligand dissociation from HSA is insensitive to anti-HIV drugs and ferric heme. These findings represent clear-cut evidence for the allosteric inhibition of anti-HIV drug binding to HSA by the heme. In turn, anti-HIV drugs allosterically impair heme binding to HSA. Therefore, Sudlow's site I and the heme cleft must be functionally linked. [source]

Inhibition of Hematopoietic Progenitor Cell Proliferation by Ethanol in Human Immunodeficiency Virus Type 1 Tat-Expressing Transgenic Mice

ALCOHOLISM, Issue 3 2001
Om Prakash
Background: A number of hematological abnormalities are associated with both human immunodeficiency virus type 1 (HIV-1) infection and alcohol abuse. There is little information on how alcohol abuse might further influence the survival and growth of hematopoietic progenitors in HIV-infected individuals in the presence of immune system abnormalities and anti-HIV drugs. Because there is evidence that viral transactivator Tat itself can induce hematopoietic suppression, in this study we examined the role of ethanol as a cofactor in transgenic mice that expressed HIV-1 Tat protein. Methods: Tat transgenic mice and nontransgenic littermates were given ethanol (20% v/v) and the anti-HIV drug 3,-azido-3,-deoxythymidine (AZT; 1 mg/ml) in drinking water. Immunosuppression in mice was induced by weekly intraperitoneal injections of anti-CD4 antibody. Hematopoiesis was examined by erythroid colony forming unit (CFU-E) and granulocyte/macrophage colony-forming unit (CFU-GM) assays of the bone marrow progenitor cells. Results: Administration of ethanol for 7 weeks resulted in a 50% decrease in the proliferative capacity of CFU-E- and CFU-GM-derived progenitors from transgenic mice compared with that of ethanol-treated nontransgenic controls. Similar decreases also were observed in transgenic mice treated with AZT or a combination of AZT and ethanol. Furthermore, ethanol and AZT were significantly more toxic to the granulopoietic progenitors (40,50% inhibition) than to the erythropoietic progenitors (10,20% inhibition) in Tat transgenic mice. Although a 10 day exposure of Tat transgenic and nontransgenic mice to a combination of ethanol and AZT had no suppressive effect on the erythropoietic and granulopoietic progenitor cells, there was a marked decrease (40,60%) in CFU-GM in mice made immunodeficient by CD4+ T-lymphocyte depletion. The ethanol-treated Tat transgenic mice but not the nontransgenic littermates also showed a significant decrease (25%) in CFU-GM. Conclusion: Our in vivo study strongly suggests that ethanol ingestion in HIV-1-infected individuals, particularly those on antiretroviral drugs, might increase bone marrow toxicity and contribute to HIV-1-associated hematopoietic impairment. [source]

The capsid protein of human immunodeficiency virus: intersubunit interactions during virus assembly

FEBS JOURNAL, Issue 21 2009
Mauricio G. Mateu
The capsid protein (CA) of HIV-1 is composed of two domains, the N-terminal domain (NTD) and the C-terminal domain (CTD). During the assembly of the immature HIV-1 particle, both CA domains constitute a part of the Gag polyprotein, which forms a spherical capsid comprising up to 5000 radially arranged, extended subunits. Gag,Gag interactions in the immature capsid are mediated in large part by interactions between CA domains, which are involved in the formation of a lattice of connected Gag hexamers. After Gag proteolysis during virus maturation, the CA protein is released, and approximately 1000,1500 free CA subunits self-assemble into a truncated cone-shaped capsid. In the mature capsid, NTD,NTD and NTD,CTD interfaces are involved in the formation of CA hexamers, and CTD,CTD interfaces connect neighboring hexamers through homodimerization. The CA,CA interfaces involved in the assembly of the immature capsid and those forming the mature capsid are different, at least in part. CA appears to have evolved an extraordinary conformational plasticity, which allows the creation of multiple CA,CA interfaces and the occurrence of CA conformational switches. This minireview focuses on recent structure,function studies of the diverse CA,CA interactions and interfaces involved in HIV-1 assembly. Those studies are leading to a better understanding of molecular recognition events during virus morphogenesis, and are also relevant for the development of anti-HIV drugs that are able to interfere with capsid assembly or disassembly. [source]

Allosteric modulation of anti-HIV drug and ferric heme binding to human serum albumin

Structural effects of amino acid variations between B and CRF02-AG HIV-1 integrases

JOURNAL OF MEDICAL VIROLOGY, Issue 5 2008
Isabelle Malet
Abstract HIV-1 integrase is one of the three essential enzyme required for viral replication and has a great potential as a novel target for anti-HIV drugs. The sequence variability of the entire integrase (IN) was examined in HIV-1 subtype B and CRF02-AG antiretroviral naïve infected patients for the presence of naturally occurring polymorphisms IN gene sequences and protein structures from both subtypes were compared. The phylogenetic analysis showed a total concordance between the 3 pol gene sequences for patients identified as subtype B whereas 3% of patients identified as CRF02-AG showed a mixture of subtypes. The analysis of IN aa sequences showed that 13 positions (K/R14, V/I31, L/I101, T/V112, T/A124, T/A125, G/N134, I/V135, K/T136, V/I201, T/S206, L/I234, and S/G283) differed between subtypes B and CRF02-AG. As observed in the 3D model of the preintegration complex, these differences may impact the functional property of IN. The fact that most variations were grouped suggests that some of them are linked together through compensatory mechanisms. This comparison allowed us to identify several variations of amino acids in HIV-1 IN subtype CRF02-AG that could have a putative impact on anti-integrase sensitivity. In particular, the region formed by Thr125, Thr124, Val31 contains at least one residue, T125, which variation has been involved in eliciting resistance to the naphtyridine carboxamide L870,810 IN inhibitor. In conclusion, virological response to anti-integrase should be studied carefully, according to the subtype, in clinical trials. J. Med. Virol. 80:754,761, 2008. © 2008 Wiley-Liss, Inc. [source]

Lipid formulation strategies for enhancing intestinal transport and absorption of P-glycoprotein (P-gp) substrate drugs: In vitro/In vivo case studies

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2007
Panayiotis P. Constantinides
Abstract The intestinal efflux pump, P-glycoprotein (P-gp), located in the apical membranes of intestinal absorptive cells, can reduce the bioavailability of a wide range of drugs which are substrates for this membrane transporter. In addition to anticancer and anti-HIV drugs, NCEs for other disease indications are P-gp substrates and there is considerable interest in inhibiting P-gp and thus increasing the bioavailability of these molecules. In this review article, an overview of P-gp and its role in drug transport and absorption will be presented first and then formulation strategies to effectively inhibit P-gp will be discussed and compared. These strategies independently and in combination, are: (a) coadministration of another P-gp substrate/specific inhibitor, and (b) incorporation of a nonspecific lipid and/or polymer excipient in the formulation. The first approach, although very effective in inhibiting P-gp, utilizes a second active compound in the formulation and thus imposes regulatory constraints and long development timelines on such combination products. Excipient inhibitors appear to have minimal nonspecific pharmacological activity and thus potential side effects of specific active compound inhibitors can be avoided. Case studies will be presented where specific active compounds, surfactants, polymers, and formulations incorporating these molecules are shown to significantly improve the intestinal absorption of poorly soluble and absorbed drugs as a result of P-gp inhibition and enhanced drug transport in vitro. ©2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96:235,248, 2007 [source]

Inhibition of Hematopoietic Progenitor Cell Proliferation by Ethanol in Human Immunodeficiency Virus Type 1 Tat-Expressing Transgenic Mice

Fungal infections associated with HIV infection

ORAL DISEASES, Issue 2002
LP Samaranayake
Oral candidiasis is perhaps the commonest infection seen in HIV disease. The aim of this workshop was to provide a sketch of the multifarious aspects of the disease from a global perspective. To this end the panellists addressed issues such as the virulence of Candida, emergence of antifungal resistance, management of candidiasis and other exotic, oral mycotic diseases. An all-pervasive theme was the dramatic differences in the management of fungal infections consequential to the availability (or the lack) of anti-HIV drugs in the developed and the developing world. Further, the social stigmata associated with the HIV disease in many developing regions in Africa and Asia appears to modify the therapeutic strategies. Additionally, the lesser-known regional variations in the disease manifestations and therapeutic approaches were stark. Further work is direly needed to address these issues. [source]

Erratum: Sensitive analysis of anti-HIV drugs, efavirenz, lopinavir and ritonavir, in human hair by liquid chromatography coupled with tandem mass spectrometry

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 7 2010
Yong Huang
No abstract is available for this article. [source]

Determination of lamivudine/stavudine/efavirenz in human serum using liquid chromatography/electrospray tandem mass spectrometry with ionization polarity switch

BIOMEDICAL CHROMATOGRAPHY, Issue 6 2002
Bin Fan
A high-performance liquid chromatography/tandem mass spectrometry (LC-MS-MS) method with ionization polarity switch was developed and validated in human serum for the determination of a lamivudine (3TC)/stavudine (d4T)/efavirenz combination HIV therapy. Solid phase extraction (SPE) was used to extract these anti-HIV drugs and internal standard aprobarbital. A gradient mobile phase consisting of acetonitrile and 20,mM ammonium acetate buffer with pH adjusted to 4.5 using glacial acetic acid was utilized to separate these drugs on a hexylsilane column (150,×,2.0,mm i.d.). The total run time between injections was 18,min. The precursor and major product ions of these drugs were monitored on a triple quadrupole mass spectrometer in the multiple reactions monitoring (MRM) mode. Ionization polarity was switched in the middle of the LC run allowing these anti-HIV drugs with different physicochemical properties to be detected simultaneously. The effect of ion suppression from human serum was studied and no interference with the analysis was noted. The method was validated over the range of 1.1,540,ng/mL for 3TC, 12.5,6228,ng/mL for d4T and 1.0,519,ng/mL for efavirenz. The method was shown to be accurate, with intra-day and inter-day accuracy less than 14.0% and precise, with intra-day and inter-day precision less than 13.1%. The extraction recoveries of all analytes were higher than 90%. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Study on the inhibitory mechanism and binding mode of the hydroxycoumarin compound NSC158393 to HIV-1 integrase by molecular modeling

BIOPOLYMERS, Issue 9 2009
Ming Liu
Abstract Human immunodeficiency virus type 1 integrase (IN) is an essential enzyme in the life cycle of this virus and also an important target for the study of anti-HIV drugs. In this work, the binding modes of the wild type IN core domain and the two mutants, that is, W132G and C130S, with the 4-hydroxycoumarin compound NSC158393 were evaluated by using the "relaxed complex" molecular docking approach combined with molecular dynamics (MD) simulations. Based on the monomer MD simulations, both of the two substitutions affect not only the stability of the 128,136 peptides, but also the flexibility of the functional 140s loop. In principle, NSC158393 binds the 128,136 peptides of IN; however, the specific binding modes for the three systems are various. According to the binding mode of NSC158393 with WT, NSC158393 can effectively interfere with the stability of the IN dimer by causing a steric hindrance around the monomer interface. Additionally, through the comparative analysis of the MD trajectories of the wild type IN and the IN-NSC158393 complex, we found that NSC15893 may also exert its inhibitory function by diminishing the mobility of the function loop of IN. Three key binding residues, that is, W131, K136, and G134, were discovered by energy decomposition calculated with the Molecular Mechanics Generalized Born Surface Area method. Characterized by the largest binding affinity, W131 is likely to be indispensable for the ligand binding. All the above results are consistent with experiment data, providing us some helpful information for understanding the mechanism of the coumarin-based inhibitors. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 700,709, 2009. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source]