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6th International Workshop on Adverse Drug Reactions
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| Oral Presentations Plenary Session Abstracts P1 through P6 |
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| P1 | NEUROENDOCRINE REGULATION OF FAT METABOLISM Antiviral Therapy 2004; 9(6):L1 E Fliers Recent experiments show that this somatotopy extends to the hypothalamus. We therefore propose that the central nervous system (CNS) plays a major role in the hitherto unexplained regulation of body fat distribution. The developments in this research area are likely to increase our insights in the pathogenesis of metabolic disorders such as type 2 diabetes mellitus and lipodystrophy syndromes. Specifically, the adipose tissue redistribution seen in HIV lipodystrophy may be mediated via the central nervous system. |
| P2 | IMPLICATIONS OF ANTIRETROVIRAL TOXICITY IN THE DEVELOPING Antiviral Therapy 2004; 9(6):L1 J Lange Abstract not available. |
| P3 | NON-HIV LIPODYSTROPHY: FOCUS ON INHERITED LIPODYSTROPHIES Antiviral Therapy 2004; 9(6):L1 R Hegele Molecular genetic characterization of FPLD2 has revealed that mechanisms related to the structure and function of the nucleoskeleton can lead to lipodystrophy. Molecular genetic characterization of FPLD3 has confirmed that human PPARγ deficiency affects adipose tissue and leads to insulin resistance, as expected from the mechanism of action of thiazolidinedione. |
| P4 | CLINICAL PHARMACOLOGY OF NRTI-TRIPHOSPHATES Antiviral Therapy 2004; 9(6):L2 CV Fletcher Recent advances in analytical methodologies have allowed the generation of new knowledge about clinical pharmacological characteristics of NRTI-triphosphates with findings of, for example, sex and disease state associations with triphosphate formation, and relationships between intracellular NRTI-triphosphate concentrations and virological response. New insights into the clinical pharmacology of NRTI-triphosphates hold promise as a tool to advance the state of HIV therapeutics. |
| P5 | TRANSCRIPTIONAL STIMULATION BY THE LIPID SENSING SREBPs Antiviral Therapy 2004; 9(6):L2 TF Osborne This model could explain why over-expression of SREBP-1a and SREBP-1c, specifically in liver, have similar phenotypes but their over-expression in adipose tissue has dramatically opposite effects. Here, 1c over-expression results in a phenotype resembling lipodystrophy including insulin resistance and diabetes. In contrast, similar over-expression of SREBP-1a resulted in massive adipocyte hypertrophy. Because the ratio of 1c to 1a varies form a high in liver (10:1) to a low in spleen (1:10), regulated expression of SREBP-1c by developmental, hormonal and nutritional signals would have pronounced different tissue specific effects on SREBP dependent gene expression. |
| P6 | THE METABOLIC SYNDROME AND CARDIOVASCULAR DISEASE: LESSONS FROM THE BRUNECK STUDY Antiviral Therapy 2004; 9(6):L3 E Bonora The 5-year follow-up of the Bruneck cohort documented that subjects with the Metabolic Syndrome had an increased incidence of carotid atherosclerosis and coronary heart disease. The risk was two- to threefold higher than in individuals without the syndrome. These results are consistent with those reported by other investigators. Therefore, a large proportion of individuals from the general population are at increased cardiovascular risk for the presence of the Metabolic Syndrome. The identification of these subjects seems to be a major goal of preventive medicine in the next future. |
| Session 1 Abstracts 1 through 4, pages L3 through L5 |
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| 1 | EFFECTS OF RECOMBINANT GROWTH HORMONE ON VISCERAL FAT ACCUMULATION: PILOT STUDY IN HIV-INFECTED ADOLESCENTS Antiviral Therapy 2004; 9(6):L3 A Viganò1, S Mora2, P Manzoni1, L Schneider1, S Beretta1, M Molinaro3 and P Brambilla1 Our data suggest that 0.028 mg/kg/daily of rhGH achieved a consistent VAT reduction, a significant increase in BMC and lean mass and decrease in total adiposity. Overall rhGH treatment was well tolerated and it was not associated with a worsening of glucose and lipid metabolism. |
| 2 | EFFECTS OF A GROWTH HORMONE RELEASING FACTOR (GRF) ANALOGUE IN HIV PATIENTS WITH ABDOMINAL FAT ACCUMULATION: A RANDOMIZED PLACEBO-CONTROLLED TRIAL Antiviral Therapy 2004; 9(6):L4 S Grinspoon1, D Kotler2, S Allas3, B Lussier3, A Chapdelaine3, JM Tellier3, MC Domec3, L Vachon3, T Abribat3 and J Falutz4 These results demonstrate that a single daily administration of TH9507 for 12 weeks safely increased lean mass, and decreased abdominal fat with a reduction in visceral fat and preservation of subcutaneous fat in patients with HIV lipodystrophy. TH9507, a GRF analogue, may be a beneficial treatment strategy for this population. |
| 3 | THE EFFECT OF RECOMBINANT HUMAN GROWTH HORMONE TREATMENT ON CIRCULATING LEPTIN AND ADIPONECTIN CONCENTRATIONS IN PATIENTS WITH HIV-ASSOCIATED FAT ACCUMULATION Antiviral Therapy 2004; 9(6):L4 JC Lo1, K Mulligan1, PJ Havel2, MA Noor3, GA Lee1, J-M Schwarz1, C Grunfeld1 and M Schambelan1 Treatment with GH is associated with an increase in adiponectin and a reduction in circulating leptin levels. The reduction in leptin is probably related to GH-induced reduction in total fat mass. The mechanism( s) underlying the increase in adiponectin and its relationship to increased HDL-C and REE are of potential clinical interest and warrant further investigation. |
| 4 | PLASMA ADIPONECTIN AND IL-6 PREDICT INSULIN SENSITIVITY IN PATIENTS WITH HIV INFECTION INDEPENDENTLY OF BODY FAT DISTRIBUTION Antiviral Therapy 2004; 9(6):L5 DN Reeds, KE Yarasheski, WT Cade, BW Patterson, WG Powderly and S Klein Plasma adiponectin and IL-6 concentrations independently predict the sensitivity of stimulation of glucose disposal and suppression of lipolysis by insulin in patients with HIV infection. Use of HAART is associated with a reduction in plasma adiponectin concentration. |
| Session II Abstracts 5 through 8, pages L8 to L9 |
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| 5 | A STRUCTURAL BASIS FOR THE EFFECTS OF HIV PROTEASE INHIBITORS ON GLUT4 ACTIVITY Antiviral Therapy 2004; 9(6):L5 P Hruz, J Hertel, H Struthers and C Baird Horj These data establish a structural basis for PI effects on GLUT4 activity and support direct binding of PIs to the transport protein as the mechanism for acute inhibition of insulin-stimulated glucose uptake. Moreover, the identification of isoform selective peptide inhibitors of GLUT4 provides novel tools for studying both normal glucose transport and the alterations in glucose homeostasis seen in patients treated with HIV protease inhibitors. |
| 6 | MECHANISMS OF INSULIN RESISTANCE IN HIV-SERONEGATIVE INDIVIDUALS ACUTELY TREATED WITH RITONAVIR BOOSTED INDINAVIR AND ATAZANAVIR REGIMENS Antiviral Therapy 2004; 9(6):L6 DA Doran1, SP Jones1,2, C Lagathu3, L Evans4, IT Cambell4, DJ Stokes1, AP Yates5, M Caron3, M Pirmohamed2, DJ Back2, SH Khoo2 and DP Maclaren1 IDV/RTV, but not ATV/RTV, acutely induces insulin resistance, an effect which is not mediated by direct inhibition of GLUT4. The effect of these drugs in vivo on the intrinsic activity of GLUT4 warrants further investigation. |
| 7 | RITONAVIR ACUTELY INDUCES INSULIN RESISTANCE IN HEALTHY NORMAL VOLUNTEERS Antiviral Therapy 2004; 9(6):L6 GA Lee1, DD Mafong2, JC Lo1, JM Schwarz1, FT Aweeka1, K Mulligan1, M Schambelan1, and C Grunfeld1 A single dose of ritonavir in HIV-negative men decreased total and non-oxidative insulin-mediated glucose disposal as assessed by the euglycaemic hyperinsulinaemic clamp. The percentage decrease in non-oxidative glucose disposal was correlated with ritonavir drug levels. These data suggest that insulin resistance will worsen further with supra-therapeutic drug levels; excess levels might be avoided with therapeutic drug monitoring. |
| 8 | ABACAVIR HYPERSENSITIVITY SYNDROME: RESULTS OF CLINICAL, IMMUNOLOGICAL AND GENETIC SCREENING Antiviral Therapy 2004; 9(6):L7 G Wong3, R Kaul2, K Shahabi2, D Nolan4, S Mallal4, S Knowles1, A Martin4, N Shear1 and E Phillips1,2 Patch testing appears to be consistently positive even remote from the original ABC HSR and showed good correlation with ABC-specific CD8+ T lymphocyte responses and presence of HLA-B*5701. This strongly suggests that ABC HSR is mediated by HLA-B*5701 restricted CD8+ T lymphocytes, and suggests that clinical, genetic and immunological tests may have complementary application in the prevention, diagnosis and management of ABC HSR. |
| Session III Abstracts 9 through 12, pages L7 to L9 |
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| 9 | HIV-LIPODYSTROPHY IS CHARACTERIZED BY INSULIN RESISTANCE FOR LEUCINE AND GLUCOSE METABOLISM: DISSIMILAR TO TYPE 2 DIABETES Antiviral Therapy 2004; 9(6):L7 KE Yarasheski, D Reeds, S Mohammed, WT Cade, X Chen, WG Powderly and S Klein These findings suggest that both whole-body glucose and amino acid (Leu) metabolism are insensitive to the anabolic actions of hyperinsulinaemia in HIV, especially in HIV lipodystrophy. Increased inflammatory cytokine (IL-6) levels may contribute to the failure of hyperinsulinaemia to suppress whole-body proteolysis in HIV-infected people. |
| 10 | ANTIRETROVIRAL THERAPY AND MARKERS OF INSULIN RESISTANCE IN THE MULTICENTER AIDS COHORT STUDY Antiviral Therapy 2004; 9(6):L8 TT Brown1, X Li2, SR Cole2, LA Kingsley3, FJ Palella4, SA Riddler3, JS Chmiel4, BR Visscher5, B Margolick2 and AS Dobs1 Fasting surrogate markers suggest increased insulin resistance in HIV-infected men which is independently related to both NRTI and PI exposure. |
| 11 | OBJECTIVE EVALUATION OF HIV LIPODYSTROPHY CASE DEFINITION IN A RANDOMIZED 96 WEEK CLINICAL TRIAL Antiviral Therapy 2004; 9(6):L8 MG Law1, A Cheng2, DA Cooper1,3 and A Carr3 An adapted objective lipodystrophy case definition was more sensitive for diagnosing lipodystrophy in Gilead 903 than unprompted adverse event reports. |
| 12 | PROSPECTIVE, PARTIALLY RANDOMIZED, 24-WEEK STUDY TO COMPARE THE EFFICACY AND DURABILITY OF DIFFERENT SURGICAL TECHNIQUES AND INTERVENTIONS FOR THE TREATMENT OF HIV-RELATED FACIAL LIPOATROPHY Antiviral Therapy 2004; 9(6):L9 G Guaraldi1, G Orlando1, D De Fazio2, M Callegari2, G De Santis1, A Pedone1, A Spaggiari1, A Baccarani1, M Pinelli1, V Borghi1, G Nardini1, B Beghetto1 and R Esposito1 All three interventional techniques were highly effective in improving the aesthetic satisfaction of the patients. There were no significant differences in subjective objective variables among the three study arms. Longer follow-up is necessary to discriminate the most suitable treatment in terms of durability. |
| Session IV Abstracts 13 through 16, pages L9 to L15 |
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| 13 | ZIDOVUDINE INHIBITS THYMIDINE PHOSPHORYLATION: A NOVEL SITE OF POTENTIAL TOXICITY IN NON-MITOTIC CELLS Antiviral Therapy 2004; 9(6):L9 EE McKee1,2, MD Lynx1,2, D Susan-Resiga2, AT Bentley2, JP D'Haenens1,2, D Cullen2 and M Ferguson2 However, the phosphorylation of AZT beyond AZT-MP was not detected in either system. The production of TTP and AZT-MP in isolated liver mitochondria was an order of magnitude higher than observed in heart mitochondria. Finally, AZT inhibited thymidine phosphorylation in both systems with IC50s of 8.9 ’} 1.8 μM in liver mitochondria and 24 ’} 5 μM in the perfused heart. |
| 14 | URIDINE ABROGATES THE ADVERSE EFFECTS OF STAVUDINE AND ZALCITABINE ON ADIPOSE CELL FUNCTIONS Antiviral Therapy 2004; 9(6):L10 UA Walker1, M Auclair2, D Lebrecht1, M Kornprobst2, J Capeau2,3 and M Caron2 Uridine supplementation protects cultured adipocytes from the adverse effects of stavudine and zalcitabine on lipid accumulation, cell survival and mitochondrial functions. The beneficial effect of uridine is seen whatever the parameter tested, suggesting that the toxic effects of these NRTIs could be linked to depletion of uridine or its metabolites inside the cells. Elevating the intracellular uridine level could allow competition of uridine metabolites with NRTIs at polymerase-γ and thus prevent the decreased mtDNA synthesis. Uridine is an interesting candidate in the prevention of the NRTIinduced lipoatrophy in vivo. |
| 15 | IN VIVO NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS ALTER EXPRESSION OF BOTH MITOCHONDRIAL AND LIPID METABOLISM GENES INDEPENDENT TO HIV INFECTION Antiviral Therapy 2004; 9(6):L11 PWG Mallon1–3, P Unemori1,3, R Sedwell1,3, A Morey4, M Rafferty5, K Williams5, D Chisholm6, K Samaras6, S Emery1, A Kelleher1–3, DA Cooper1–3 and A Carr2,3 for the SAMA investigators These results characterize the central role of mitochondrial function in adipose tissue metabolism in vivo, provide evidence to support the presence of feedback mechanisms between mitochondria and the nucleus in humans, and offer an explanation for NRTI-induced lipoatrophy. |
| 16 | DIFFERENTIAL EFFECTS OF NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR (NRTI) REGIMENS ON ADIPOCYTE MITOCHONDRIAL DNA DEPLETION IN HIV-INFECTED PATIENTS Antiviral Therapy 2004; 9(6):L11 E Hammond, D Nolan, E McKinnon, I James and S Mallal These data are concordant with evidence that lipoatrophy risk is differentially and specifically associated with stavudine or zidovudine use, providing further evidence that NRTI-induced mitochondrial toxicity is central to lipoatrophy pathogenesis. Alternative NRTI regimens were not associated with adipocyte mtDNA depletion in this study, nor were demographic/disease-related factors. |
| Session V Abstracts 17 through 20, pages L15 to L20 |
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| 17 | STEATOHEPATITIS IS ASSOCIATED WITH INCREASED HEPATIC EXPRESSION OF SREBP-1 IN HIV-INFECTED LIPODYSTROPHIC PATIENTS Antiviral Therapy 2004; 9(6):L12 M Lemoine1,2, V Barbu1,2, JP Bastard2,3, D Wendum1, M Maachi2,3, F Paye1,2, R Poupon1,2, PM Girard1, C Housset2,3, J Capeau2,3 and L Serfaty1,2 In patients with ART-related lipodystrophy 1) steatohepatitis is frequent, 2) hepatic SREBP-1 mRNA is overexpressed as compared with NAFLD patients or with controls, 3) SREBP-1 overexpression is associated with steatosis and 4) expression of PPAR genes is not significantly modified. These results suggest that SREBP-1 contributes to the pathogenesis of fatty liver in these patients. |
| 18 | IN VIVO EVIDENCE FOR IMPAIRED PERIPHERAL FATTY ACID TRAPPING IN HIV-1 LIPOATROPHY Antiviral Therapy 2004; 9(6):L12 JPH van Wijk1, M Castro Cabezas1,2, EJP de Koning1,3, TJ Rabelink3 and IM Hoepelman1 The present data suggest elevated hepatic FFA flux in HIV lipoatrophy, most likely as a result of inadequate incorporation of FFA into TG in adipocytes. Impaired peripheral postprandial FFA uptake may lead to increased hepatic FFA flux, VLDL overproduction and increased concentrations of atherogenic postprandial TGrich lipoproteins in these patients. |
| 19 | RITONAVIR CAUSES HYPERTRIGLYCERIDAEMIA IN APOE*3-LEIDEN TRANSGENIC MICE BY IMPAIRING TRIGLYCERIDE CLEARANCE Antiviral Therapy 2004; 9(6):L13 M den Boer1,2, JFP Berbée1,3, PCN Rensen1,3, JA Romijn2, P Reiss4, M van der Valk4, PJ Voshol1,2 and LM Havekes1,2,5 From these data, we conclude that RTV causes hypertriglyceridaemia by impairing plasma TG clearance rather than by stimulating hepatic VLDL-TG production. |
| 20 | THE METABOLIC EFFECTS OF INTERMITTENT ANTIRETROVIRAL THERAPY WITH AND WITHOUT IL-2 (ACTG A5102) Antiviral Therapy 2004; 9(6):L13 P Tebas1, K Henry2, D Cherng3, D Katzenstein4, J Schmitz5, H Valdez6, N Jahed7, M Vargas7, L Myers8 and W Powderly9 Three cycles of IL-2 do not have significant metabolic effects on subjects receiving stable antiretroviral therapy. Treatment interruption is associated with immediate and sustained decreases in cholesterol levels (both LDL and HDL) and TG. The effects on glucose and insulin metabolism were limited in this cohort. A strategy of intermittent therapy can decrease the cardiovascular risk associated with ARV therapy and provide insight into which of the metabolic abnormalities observed in treated patients are HIV- or ARV-related. |
| Section VI Abstracts 21 through 24, pages L18 to L20 |
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| 21 | MARKED IMPAIRMENT OF ENDOTHELIAL FUNCTION WITHOUT INSULIN RESISTANCE IN HEALTHLY MEN TREATED WITH THE HIV-1 PROTEASE INHIBITOR INDINAVIR Antiviral Therapy 2004; 9(6):L14 SS Shankar1,3, MP Dubé1,2, RV Considine1,3, L Christner1,3 and HO Steinberg1,3 Four weeks of IDV markedly impairs endothelial function and insulin-mediated vasodilation, without significant impairment of whole-body glucose disposal. Thus, it appears unlikely that insulin resistance plays a major role in the induction of the endothelial dysfunction seen in this human model of IDV monotherapy. |
| 22 | RITONAVIR AND INDINAVIR PROMOTE LIPID-INDUCED ATHEROSCLEROSIS BUT INHIBIT ENDOTHELIAL DENUDATION-INDUCED NEOINTIMAL HYPERPLASIA IN MICE Antiviral Therapy 2004; 9(6):L14 NM Schildmeyer, ZWQ Moore, JT Nickel, CJ Fichtenbaum and DY Hui These results indicated that PI therapy promotes CAD mainly through its effects on metabolic parameters that lead to lipid-laden foam cell formation instead of vascular SMC activation, thus suggesting that lowering plasma lipid and glucose levels may alleviate the accelerated CAD events associated with PI therapy in HIV-infected patients. |
| 23 | PRE-ECLAMPSIA IN HIV-INFECTED PREGNANT WOMEN RECEIVING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY IS ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION AND INSULIN RESISTANCE Antiviral Therapy 2004; 9(6):L15 M Larrousse, E Martínez, A Suy, M Lonca, E de Lazzari, A Milinkovic, L Zamora, A León, M Laguno, JL Blanco, J Mallolas, S Pisa, S Hernández, V Cararach, JA Vanrell, JM Gatell and O Coll Endothelial dysfunction and insulin resistance may be potential underlying mechanisms involved in the pathogenesis of pre-eclampsia in HIV-infected pregnant women receiving HAART. |
| 24 | ENDOTHELIAL DYSFUNCTION IN HIV-INFECTED PATIENTS ON CART DOES NOT IMPROVE EVEN WHEN LIPID PROFILES IMPROVE ON PRAVASTATIN Antiviral Therapy 2004; 9(6):L15 PA Sklar1,2, JR Grubb2, JD Voell3, G Zalos4, WC Blackwelder2, JA Metcalf3, A Rupert5, MT Gladwin2, J Witek1, RT Davey3, H Masur2 and RO Cannon4 While pravastatin improves the dyslipidaemia of HIV+ individuals on CART this does not translate into improved EF. Persistently elevated CRP values suggest that there may be an ongoing stimulus towards CV risk which has yet to be elucidated. |
| Adipocyte Biology Abstracts 25 through 32, pages L23 to L27 |
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| 25 | NON-INVASIVE ASSESSMENT OF HEPATIC MITOCHONDRIAL TOXICITY IN HIV-INFECTED PATIENTS WITH NORMAL SERUM LACTATE BY 13C-METHIONINE BREATH TEST Antiviral Therapy 2004; 9(6):L19 M Banasch1, O Goetze2, I Hollborn1, B Hochdorfer3, N Brockmeyer3, WE Schmidt1 and F Schmitz1 The MBT is a simple, non-invasive method of detecting hepatic mitochondrial impairment in HIVinfected patients. The altered 13C-metabolism in patients with long-term treatment and signs of lipoatrophy was expected, reflecting the chronic mitochondrial toxicity of ART. We are the first to show that therapy-naïves also exhibit significant impairment of mitochondrial decarboxylation function. We hypothesize that mitochondrial dysfunction might rapidly improve after initiating ART. Our results provide evidence that the MBT is an invaluable diagnostic tool for both screening and follow-up monitoring of hepatic mitochondrial function. |
| 26 | ADDITION OF TENOFOVIR TO A DIDANOSINE-BASED HAART DOES NOT INCREASE MITOCHONDRIAL DNA DEPLETION BUT DECREASES CYTOCHROME C OXIDASE FUNCTION AND MITOCHONDRIAL MASS Antiviral Therapy 2004; 9(6):L19 G Garrabou1, S López1, AB Infante1, E Negredo2, J Puig2, L Ruiz2, E Sanjurjo1, J Casademont1, F Cardellach1, B Clotet2 and Ò Miro1 A decrease in mitochondrial mass, mtDNA content and COX activity is detected after 12 months of the addition of TDF to HAART schedules containing ddI. This diffuse deterioration of mitochondrial parameters could be due to the effects of TDF itself, the increase of ddI concentrations caused by TDF or both. The relevance of these biochemical findings in clinical practice remains to be determined. |
| 27 | MITOCHONDRIAL STUDIES IN ADIPOSE TISSUE OF HIV-INFECTED PATIENTS WITHOUT FAT REDISTRIBUTION Antiviral Therapy 2004; 9(6):L20 S López1, G Garrabou1, E Martínez2, P Domingo3, J Fontdevila4, JM Gatell2, AB Infante1, X Gallart5, A Milinkovic2, F Cardellach1, J Casademont1 and Ò Miró1 Decreased mtDNA content in AT of HIV-infected patients is closely associated with decreased COX activity, irrespective of the presence of HAART, before LD appears. The exact role that HIV itself and HAART play in adipocyte changes remains to be determined. |
| 28 | MITOCHONDRIAL DNA DEPLETION IN ASYMPTOMATIC HIV-INFECTED PATIENTS RECEIVING DIDANOSINE PLUS STAVUDINE-BASED HAART REGIMEN SEEMS TO BE COMPENSATED BY UP-REGULATORY MECHANISMS Antiviral Therapy 2004; 9(6):L24 S López1, G Garrabou1, MR de la Concepción3, E Martínez2, E Pedrol4, AB Infeante1 M Giralt3, F Cardellach1, JM Gatell2, F Vilarroya3, J Casademont1 and Ò Miró1 Decreased mitochondrial mass and mtDNA content are associated with ddI+d4T treatment, but the expression of COX-II and COX activity remains unaltered. These data suggest that, at least during the initial phases of treatment, up-regulatory transcriptional or post-transcriptional mechanisms compensate mtDNA depletion caused by ddI+d4T. |
| 29 | HIV INFECTION IS ASSOCIATED WITH INCREASED SKELETAL APOPTOSIS ASSESSED BY TUNEL Antiviral Therapy 2004; 9(6):L21 S López1, G Garrabou1, J Fernández-Solà1, E Pedrol3, E Badia1, AB Infante1, E Martínez2, F Cardellach1, JM Gatell2, J Casademont1 and Ò Miró1 Skeletal muscle of HIV-infected patients exhibits increased apoptosis compared with healthy uninfected individuals. Further studies are necessary to elucidate the mechanisms by which HIV infection leads to increased apoptosis. |
| 30 | URIDINE PHARMACOKINETICS OF MITOCNOL, A SUGAR CANE EXTRACT Antiviral Therapy 2004; 9(6):L21 N Venhoff1, M Zilly2, D Lebrecht1, D Schirmer2, H Klinker2, J Thoden1, P Langmann2 and UA Walker1 Mitocnol effectively increases uridine serum levels in humans. |
| 31 | ZIDOVUDINE INHIBITS THYMIDINE PHOSPHORYLATION: A NOVEL SITE OF POTENTIAL TOXICITY IN NON-MYTOTIC CELLS Antiviral Therapy 2004; 9(6):L22 MD Lynx1,2, JP D'Haenens1,2, AT Bentley2, D Susan- Resiga2 and EE McKee1,2 The results obtained showed that AZT is phosphorylated only to AZT-MP and that AZT inhibited the production of TTP, with an IC50 of 8.9 ±1.8 µM AZT. This is comparable with the results seen in isolated rat heart mitochondria. The kinetics of thymidine phosphorylation to TMP differs between heart and liver. The maximal velocity (Vmax) and affinity constant (Km) are an order of magnitude higher in liver than in heart. Liver also displays either strong negative cooperativity or the presence of two enzymes, one with a Vmax and Km similar to TK2 in rat heart mitochondria and one with much higher Vmax and Km. This second enzyme may represent several possibilities including contaminating thymidine kinase 1, a different isoform of TK2, or another yet uncharacterized kinase. |
| 32 | THYMIDINE AND ZIDOVUDINE METABOLISM IN ISOLATED RAT HEART: ZIDOVUDINE INHIBITION OF THYMIDINE PHOPSPHORYLATION Antiviral Therapy 2004; 9(6):L22 D Susan-Resiga1, AT Bentley1, J D'Haenens1,2, D Cullen2, MD Lynx1,2 and E McKee1,2 These data taken together extend the observations made in isolated heart mitochondria and suggest that mitochondrial toxicity in the heart may be caused by a limiting cellular pool of TTP lowering the rates of mitochondrial DNA replication. |
| Cardiovascular Diseases Abstracts 33 through 40, pages L28 to L32 |
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| 33 | THE IMPACT OF NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR (NRTI) TREATMENT DURATION AND INSULIN RESISTANCE ON FASTING ARTERIALIZED LACTATE LEVELS IN PATIENTS WITH HIV INFECTION Antiviral Therapy 2004; 9(6):L23 JC Lo, M Kazemi, PY Hsue, JN Martin, SG Deeks, M Schambelan and K Mulligan Increasing duration of NRTI use is associated with higher lactate levels that may be mediated, in part, through increasing insulin resistance. Acknowledgements: SCOPE study, NIH (AI052745, DK45833, DK54615, RR-00083), UCSF Academic Senate, Doris Duke Foundation. |
| 34 | THE DEVELOPMENTAL STAGE DETERMINES THE EFFECT OF NRTIS ON ADIPOCYTE MTDNA DEPLETION AND ADIPONECTIN PRODUCTION Antiviral Therapy 2004; 9(6):L23 M Stankov, RE Schmidt and G Behrens Different NRTIs affect mtDNA content of adipose tissue and its function through different mechanisms depending on the developmental stage. We provide evidence at the cellular level that d4T-induces mitochondrial DNA depletion and that this depletion is associated with decrease in adiponectin production. |
| 35 | MITOCHONDRIAL DYSFUNCTION OF HAART-RELATED HYPERLACTATAEMIA IS DEMONSTRABLE BY NON-INVASIVE STUDIES Antiviral Therapy 2004; 9(6):L24 G Garrabou1, S López1, E Sanjurjo1, A Infante1, J Riba2, J Casademont1, F Cardellach1 and Ò Miró1 Mitochondrial functionality analysis and the FAET match clinical manifestations in an HIV patient undergoing symptomatic HAART-related hyperlactataemia and after clinical recovery. The FAET could be a non-invasive useful tool for the screening of mitochondrial abnormal function and reduced oxygen consumption. |
| 36 | PLATELET CONTAMINATION AFFECTS MITOCHONDRIAL DNA (mtDNA) LEVELS SIGNIFICANTLY IN PERIPHERAL BLOOD MONONUCLEAR CELLS FROM HIV PATIENTS Antiviral Therapy 2004; 9(6):L24 M Gerschenson, J Lloyd, DE LiButti, D Tran, B Shiramizu, L Day, M Marcelo and CM Shikuma MtDNA quantification from PBMCs isolated using Ficoll separation may be affected by platelet contamination and this can be as much as 20%. Platelet removal by magnetic chromatographic separation can minimize the variability caused by contamination. This research was supported by National Institutes of Health, USA (RR16467 and MD000173). |
| 37 | DO STATINS ENHANCE HIV THERAPY-INDUCED MITOCHONDRIAL TOXICITY? Antiviral Therapy 2004; 9(6):L25 MP de Baar1, KGM Smolders1, M Buitelaar1, JT Dekker1 and AH Klerkx2 Furthermore, cells were cultured in the presence of nucleoside RT inhibitors (ddC, ddI, d4T), simvastatin, ciprofibrate and combinations thereof. We observed higher toxicity on cells that were exposed to nucleoside analogues in combination with statins relative to any of the other cultures. Since treatment with nucleoside RT inhibitors can result in mitochondrial toxicity-related adverse events, our second hypothesis is that this mitochondrial toxicity might be worsened by the treatment with statins due to a combined toxic effect on the mitochondria. |
| 38 | EFFECTS OF ANTIRETROVIRAL THERAPY (ART) ON LIVER ENZYMES OF BRAZILIAN CHILDREN WITH AIDS Antiviral Therapy 2004; 9(6):L25 AC Montes-Gil1, R Lorenzetti1, G Bergsten-Mendes1 and MMS Vilela2 Our results suggest that ambulatory HIV positive children receiving ART can display elevations of hepatic enzymes without associated evidence of the clinical diagnosis of hepatotoxicity.We observed mild to moderate, grade 1, usually no more than four times the upper limit of normal, asymptomatic elevations of hepatic enzymes in our patients. Our findings point to a relationship between hepatic enzyme elevations and stage C3 of HIV disease, and use of antiretroviral regimens containing four drugs and co-administration of antituberculosis drugs. |
| 39 | ASSESSMENT OF THE LIVER FUNCTION IN HIV-INFECTED PATIENTS TREATED WITH ANTIRETROVIRAL DRUGS IN CAMEROON Antiviral Therapy 2004; 9(6):L26 O Lowe and G Lando HIV infection significantly increase liver markers; this appear to be higher in treated patients. One of the parameters (GOT) appear to be a marker of survival. The combinations used, in particular tritherapy, are hepatotoxic. Close monitoring of HIV-infected Cameroonian patients treated with antiretroviral drugs is required to improve their survival. |
| 40 | ADIPOCYTE VIABILITY AND FUNCTION BUT NOT INHIBITION OF PREADIPOCYTE DIFFERENTIATION IS COMPROMISED BY INDINAVIR Antiviral Therapy 2004; 9(6):L26 M Stankov, RE Schmidt and G Behrens Molecular or cellular changes that occur during acquisition of the adipocyte phenotype promote susceptibility to IDV-induced cell death. We provide evidence for a direct inhibition of adiponectin production by IDV. These results suggest that IDV may promote adipose tissue atrophy by directly compromising adipocyte function and not by inhibition of preadipocyte differentiation. |
| Insulin Resistance/Diabetes Abstracts 41 through 47, pages L32 to L36 |
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| 41 | NEVIRAPINE DID NOT ALTER CELL DIFFERENTIATION, LIPID METABOLISM, INSULIN RESPONSE AND SURVIVAL IN CULTURED ADIPOCYTES Antiviral Therapy 2004; 9(6):L27 M Caron1, M Auclair1, M Kornprobst1, C Lagathu1 and J Capeau1,2 Thus, in the therapeutic range (4–10 µM), NVP had no effect on the main adipose cell functions measured in vitro. These data are of interest since NVPcontaining regimens are often used as a switching option in patients treated with PI-containing regimens. |
| 42 | PIs AND NRTIs WITH ADVERSE EFFECTS ON ADIPOCYTE LIPID METABOLISM AND SURVIVAL ALTER THE PRODUCTION OF PRO-INFLAMMATORY CYTOKINES AND ADIPONECTIN IN ADIPOCYTES Antiviral Therapy 2004; 9(6):L27 C Lagathu1, JP Bastard1,2, M Auclair1, M Maachi1,2, M Kornprobst1, J Capeau1,2 and M Caron1 These results suggest that increased cytokine and decreased adiponectin secretion and expression induced by some PIs and NRTIs may contribute to the adipose tissue loss (via apoptosis and lipid leakage) and the insulin resistance associated with the lipodystrophy syndrome. |
| 43 | COMPARATIVE EFFECTS OF ATAZANAVIR ALONE AND IN COMBINATION WITH LOW CONCENTRATION OF RITONAVIR ON TRIGLYCERIDE AND CHOLESTEROL SYNTHESIS IN VITRO Antiviral Therapy 2004; 9(6):L28 MA Noor1,2, R Mulvey1, C Elosua1, F Wang1, RA Parker1 and OP Flint1 Atazanavir as a single drug at 10 μM or combined with ritonavir up to 2 μM has very little effect on lipogenesis, whereas lopinavir as a single drug at 10 μM or combined with ritonavir up to 2 μM affects lipogenesis. The data are consistent with the current hypothesis that ritonavir-boosted atazanavir used clinically will maintain the favourable lipid profile of unboosted atazanavir. Confirmatory clinical data are needed. |
| 44 | EFFECTS OF HAART ON RESISTIN AND PERILIPIN mRNA EXPRESSION IN MOUSE 3T3-L1 AND PRIMARY HUMAN ADIPOCYTES Antiviral Therapy 2004; 9(6):L28 PV Nerurkar1, L Pearson1, JK Cope1, K Adeli2, J Frank1 and VR Nerurkar1 Based on our in vitro data, it would therefore appear that PPARγ agonists may not be suitable for treating HIV-infected patients on HAART regimens that specifically increase adipocyte differentiation. Understanding the underlying pathophysiological mechanisms can assist in identifying new therapeutic molecular targets to treat HAART-associated metabolic disorders and/or newer drug design. Supported by NCRR, NIH (G12RR003061 and P20RR011091) and the Hawaii Community Foundation (20012061) grants. |
| 45 | INTERACTIONS BETWEEN T LYMPHOCYTES AND PREADIPOCYTES INCREASE HIV PRODUCTION AND APOPTOSIS OF LYMPHOCYTES AND BLOCK ADIPOCYTE DIFFERENTIATION Antiviral Therapy 2004; 9(6):L29 DE Lewis1, D Ng-Tang1, H Mersmann2 and A Balasubramanyam3 Significant interactions between preadipocytes and HIV-infected lymphocytes increase HIV-1 production, G2/M arrest of the cell cycle, as well as apoptosis in lymphocytes, and cause a marked differentiation block in pre-adipocytes. The interactions are mediated by soluble factors – potentially cytokines, adipokines or HIV-1 Vpr. Identifying these factors and specifying mechanisms of action are important for understanding the pathophysiology of HIV lipodystrophy. |
| 46 | BODY COMPOSITION CHANGES IN TREATMENT-EXPERIENCED HIV-INFECTED PATIENTS INITIATING A TENOFOVIR-CONTAINING ANTIRETROVIRAL REGIMEN Antiviral Therapy 2004; 9(6):L29 G Tsekes1, N Mangafas1, N Tsogas1, C Psathas1, I Vlachadami1, N Batakis2 and MC Lazanas1 In a group of treatment-experienced HIV-infected individuals, switching to tenofovir-containing antiretroviral regimens resulted in some improvement in lipodystrophy and hypercholesterolaemia, without loss of virological control after 48 weeks of treatment. |
| 47 | REVERSIBILITY OF LIPOATROPHY ASSOCIATED WITH HIGHLY ACTIVE ANTIRETROVIRAL THERAPY 1 YEAR AFTER SWITCHING FROM STAVUDINE TO TENOFOVIR DISOPROXIL FUMARATE Antiviral Therapy 2004; 9(6):L30 G Tsekes1, N Tsogas1, N Mangafas1, D Koukios1, C Michalakeas1, A Feretis2 and MC Lazanas1 In a small group of HIV-infected individuals with lipoatrophy, switching from stavudine to tenofovir resulted in significant improvement of lipoatrophy without loss of virological control after 52 weeks of treatment. |
| Mitochondrial Disorders Abstracts 48 through 61, Pages L37 to L45 |
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| 48 | BODY COMPOSITION CHANGES IN TREATMENT-EXPERIENCED HIV-INFECTED PATIENTS: 10 YEARS OF FOLLOW-UP Antiviral Therapy 2004; 9(6):L31 G Tsekes1, N Mangafas1, N Tsogas1, I Salpigktis1, N Batakis2, V Georgiou3 and MC Lazanas1 In a group of HIV-infected individuals receiving HAART after the initial double NRTI regimen, a considerable amount of limb fat was found to be lost in a 10-year follow-up. Trunk fat and lean body mass did not change significantly. The aforementioned morphologic changes were accompanied by metabolic abnormalities (dyslipidaemia). |
| 49 | SOFT TISSUE AUGMENTATION WITH POLYMETHYMETHACRYLATE (PMMA) FOR CORRECTION OF LIPODYSTROPHY RELATED BODY FAT ATROPHY Antiviral Therapy 2004; 9(6):L31 MS Serra1 and LK Oyafuso2 Use of PMMA solution for treatment of body contours in lipodystrophy is shown to be safe and effective with good cosmetic results, helping patients to become more self confident and improving their quality of life. |
| 50 | THE PROPORTION OF PATIENTS REPORTING BODY FAT REDISTRIBUTION WAS UNCHANGED BETWEEN WEEK 48 AND WEEK 120 IN SUBJECTS RECEIVING FOSAMPRENAVIR/RITONAVIR IN STUDY APV30005 Antiviral Therapy 2004; 9(6):L32 S Walmsley1, S Staszewski2, J Yeo3, D Thorpe3 and N Givens3 Over 120 wks, the majority of BCCs were fat accumulation combined with an increase in body weight but no change in waist/hip ratio. Of note, the proportion of subjects reporting fat wasting, fat accumulation or any fat redistribution change did not increase between wk 48 and wk 120. |
| 51 | OXYMETHOLONE AS THERAPY TO MAINTAIN BODY COMPOSITION IN HIV-POSITIVE MEN Antiviral Therapy 2004; 9(6):L32 A Urbina, M Miller and I Hance Oxymetholone 50 mg can be considered effective in maintaining lean body mass in HIV-positive patients, without an adverse impact on CD4 count, liver function or vital signs. |
| 52 | INTRATHORACIC FAT IN HIV-INFECTED PATIENTS Antiviral Therapy 2004; 9(6):L33 A León, A Biglia, E Martínez, JL Blanco, M Sánchez, E de Lazzari, A Milinkovic, M Larrousse, M Laguno, M Lonca, J Mallolas and JM Gatell In HIV-infected adults without clinical evidence of lipodystrophy, intrathoracic fat content was higher than in healthy persons and positively correlated with intra-abdominal fat. |
| 53 | ESTIMATED PREVALENCE OF HIV-ASSOCIATED ADIPOSE REDISTRIBUTION SYNDROME (HARS) – ABNORMAL ABDOMINAL FAT ACCUMULATION – IN HIV-INFECTED PATIENTS Antiviral Therapy 2004; 9(6):L53 K Lichtenstein1, C Wanke2, K Henry3, M Thompson4, N Muurahainen5 and DP Kotler6 The prevalence of HARS, with or without peripheral lipoatrophy, averaged 32% of HIV-infected patients surveyed. This might be an overestimation because most surveys relied on patient self-report or physician diagnoses rather than objective quantification of body composition including measurement of VAT. Studies using objective criteria to quantify VAT accumulation in HIV patients with increased girth versus controls would provide a more accurate estimate of the true prevalence of HARS. |
| 54 | MEASUREMENT OF FAT MASS IN HIV PATIENTS: COMPARISON BETWEEN ANTHROPOMETRY AND BIOELECTRIC IMPEDANCE Antiviral Therapy 2004; 9(6):L34 C Miralles1, E Álvarez-García2, M Las-Heras3, F Barreiro4 and MJ Márquez4 Both bioelectric impedance and anthropometry are sensitive and simple methods to calculate fat mass of HIV and AIDS patients. The strong correlation between the measurements indicates that both methods are equally reliable. |
| 55 | ABDOMINAL SUBCUTANEOUS ADIPOSE TISSUE (SAT) AND VISCERAL ADIPOSE TISSUE (VAT) MEASUREMENTS IN HIV+ ADULTS: INFLUENCES OF MEASUREMENT SITE Antiviral Therapy 2004; 9(6):L34 KJ Ellis1, B Grund2, F Visnegarwala1, C Mullin2, CG Miller3, CE Chesson4, W El-Sadr5 and A Carr6 for the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) and the Body Composition Substudy of Strategies for Management of Anti-Retroviral Therapy (SMARTCPCRA 065C) The magnitude of the differences in abdominal VAT and SAT values between the three intervertebral sites precludes their interchangeability for the assessment of abdominal SAT and VAT. Using the VAT/SAT ratio does not overcome this limitation. Furthermore, the substantial differences in SAT and VAT values between the three slices at an intervertebral site indicate that precise re-positioning of the scans is needed for longitudinal studies. In summary, our findings suggest that nine-slice abdominal CT at three intervertebral levels provides a more complete assessment of abdominal fat distribution than does single-slice CT. |
| 56 | EVALUATION OF HIV-ASSOCIATED LIPODYSTROPHY USING STANDARDIZED PHOTOS: A REPRODUCIBILITY STUDY Antiviral Therapy 2004; 9(6):L35 RB Cavalcanti, M Christian, K Logue, R Kaul and S Walmsley With the use of standardized photos in HIVLD, reproducibility of ratings of body shape changes by physicians is at best moderate. Inter-rater agreement was similar to ratings of HIV-LD after clinical examination. Standardized descriptors for levels of severity may improve reliability of questionnaires aimed at identifying presence and severity of HIV-LD changes. |
| 57 | LOSS OF WEIGHT IN THE ERA OF HAART IS ASSOCIATED WITH ELEVATED PBMC PROVIRAL DNA LEVELS Antiviral Therapy 2004; 9(6):L35 CM Shikuma, V Valcour, S Ratto-Kim, AE Williams, S Souza, M Gerschenson, JH Kim and B Shiramizu Weight loss in the era of HAART may be driven by residual HIV infection in cells of the monocyte/macrophage lineage. |
| 58 | USEFULNESS OF ANTHROPOMETRY IN DETECTING PAEDIATRIC LIPODYSTROPHY Antiviral Therapy 2004; 9(6):L36 P Brambilla1, S Mora2, C Figini1, L Cafarelli1, V Giacomet1, P Manzoni1 and A Viganò1 The use of anthropometry may have an important role in detecting LA and LH. W can be used to screen subjects with increased trunk fat, even if a normal W does not exclude an increased IAT, especially when metabolic abnormalities are present. Arm anthropometry does not give satisfactory results for SN; the high SP of arm circumference, however, allows us to identify patients with LA. The better results obtained with arm circumference with respect to triceps could be due the better reproducibility of the first. |
| 59 | SAFETY AND EFFICACY OF INTRADERMAL POLY-L-LACTIC ACID (SCULPTRA™) INJECTIONS IN PATIENTS WITH HIV-ASSOCIATED FACIAL LIPOATROPHY Antiviral Therapy 2004; 9(6):L36 DR Mest and G Humble Poly-L-lactic acid demonstrated safety and efficacy in treatment of HIV-associated lipoatrophy up to the last study time point of 12 months. Further studies are required to determine efficacy beyond 12 months. The novel mechanism of action of this compound as a volume enhancer (rather than filler) is well suited to treat the effects of all grades of lipoatrophy. |
| 60 | BIO-ALCAMID™, A HIGH-VOLUME INJECTABLE PROSTHESIS FOR FACIAL RECONSTRUCTION IN HIV-RELATED LIPOATROPHY: REPORT ON 100 PATIENTS Antiviral Therapy 2004; 9(6):L37 LC Casavantes1 and M Gottlieb2 This study demonstrates that Bio-Alcamid™ is a safe and effective treatment option for HIV-related lipoatrophy. The procedures were performed in an outpatient setting and, regardless of the severity level, excellent permanent restoration results were achieved to the satisfaction of both patient and investigator. |
| 61 | FOSAMPRENAVIR/RITONAVIR AND NELFINAVIR HAVE COMPARABLE EFFECTS ON BODY FAT CHANGES IN ANTIRETROVIRAL-NAÏVE PATIENTS: 48-WEEK RESULTS FROM THE SOLO STUDY Antiviral Therapy 2004; 9(6):L37 S Walmsley1, A Horban2, R Jain3, C Garris3 and T Stark3 Over 48 wks, a comparable proportion of subjects reported BCC in the FPV/RTV and NFV groups combined with a similar weight gain but no change in waist/hip ratio. The majority of changes were fat accumulation. Of note, in both groups a low rate of fat wasting was observed which may relate to abacavir/lamivudine. |
| Lipid Disorders Abstracts 62 through 74, Pages L45 to L52 |
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| 62 | LONGITUDINAL CHANGES IN BODY SHAPE AND METABOLIC PARAMETERS IN HIV-INFECTED, TREATMENT-NAÏVE PATIENTS INITIATING NNRTI REGIMENS IN SOUTH INDIA Antiviral Therapy 2004; 9(6):L38 S Saghayam1, N Kumarasamy1, S Solomon1, N Aliabadi2, AJ Cecelia1, P Balakrishnan1, G Shivaji3, T Flanigan4, K Mayer4 and C Wanke2 Six months of NNRTI–HAART improved virological and nutritional parameters in South India. All body shape changes were symmetrical on nevirapine; there was a trend to increased fat on efavirenz. Glucose tolerance did not change. Lipid parameters increased on efavirenz but not nevirapine. Most striking was the increase in HDL on efavirenz. |
| 63 | ANTIRETROVIRAL PROTEASE INHIBITORS PREVENT L6 MUSCLE CELL FUSION BY REDUCING CALPAIN ACTIVITY Antiviral Therapy 2004; 9(6):L38 SP Colby-Germinario1, LE Chalifour1,3, A Antoneccchia2 and RJ Germinario1–4 Thus, whereas muscle differentiation was unaffected by protease inhibitors, calpain activity was reduced and myotube formation prevented. We conclude that RTV and IDV reduced myotube formation by reducing calpain activity. The data suggest that protease inhibitors included in HAART might be involved in muscle wasting by reducing muscle remodeling. |
| 64 | THE EFFECT OF DIFFERENT COMBINATION THERAPIES ON OXIDATIVE STRESS MARKERS IN HIV INFECTED PATIENTS IN CAMEROON Antiviral Therapy 2004; 9(6):L39 JL Ngondi and J Oben HIV infection therefore increases the oxidative stress process, while antiretroviral combination therapy increased protein oxidation. |
| 65 | USE OF EMTRICITABINE (FTC) AS PART OF HAART IN AN INNER-CITY CLINIC SETTING RESULTS IN NO APPEARANCE OF PIGMENTATION CHANGES IN HIV-POSITIVE PATIENTS OF COLOUR Antiviral Therapy 2004; 9(6):L39 W Jordan1, B Guyer2 and R Jefferson1 In our experience, the use of FTC in HIV-positive patients of colour has resulted in no appearance of pigmentations changes, regardless of whether these are HAART-naïve patients or HAART-experienced patients. |
| 66 | IMPACT OF RACE ON NERVOUS SYSTEM SIDE-EFFECTS OF SUBJECTS TAKING EFAVIRENZ Antiviral Therapy 2004; 9(6):L40 DW Seekins, LJ Lupo, JF Maa, LJ Bessen and SL Hodder Despite concerns regarding different rates of EFV clearance among some racial populations, this study found no evidence to suggest an increased risk of NSS among blacks and Hispanics compared with whites. |
| 67 | ADVERSE REACTION OF NEVIRAPINE (NVP) IN ANTIRETROVIRAL-NAÏVE HIV-SEROPOSITIVE SUBJECTS Antiviral Therapy 2004; 9(6):L40 SK Dey1 and NK Pal2 The high rate of hypersensitivity to NVP in Asian populations is a stumbling block towards increasing access for all to HAART, as other groups of antiretroviral drugs are very costly. Newer approaches such as structured interrupted therapy requiring fewer drugs need to be devised in resource-constrained settings like India, home to 5.1 million HIV-positive individuals. Alternatively, boosted protease inhibitors using indinavir 800 mg plus ritonavir 100 mg twice daily instead of NVP may be used. |
| 68 | A PRACTICAL PRECLINICAL MODEL FOR ASSESSING THE POTENTIAL FOR UNCONJUGATED HYPERBILIRUBINAEMIA PRODUCED BY HIV PROTEASE INHIBITORS Antiviral Therapy 2004; 9(6):L40 DJ Kempf, K Marsh, JF Waring, DC Morfitt, P Werner, B Ebert, M Mitten, B Nguyen, JT Randolph, DA DeGoey & LL Klein This practical preclinical model, which recapitulates the hyperbilirubinaemia produced by HIV protease inhibitors in humans, may be useful for the identification of new protease inhibitors that are devoid of effects on serum bilirubin. |
| 69 | CONCURRENT STATIN THERAPY BLUNTS CD4+ CELL GAIN IN COMBINATION ANTIRETROVIRAL THERAPY (CART) TREATED HIV-INFECTED PATIENTS Antiviral Therapy 2004; 9(6):L41 UH Iloeje1, Y Yuan2, AC Moorman3, KC Wood4 and SD Holmberg3 These data suggest that statin therapy is associated with a blunting of CD4+ cell response in patients on CART. The clinical significance of this finding remains to be determined. |
| 70 | TENOFOVIR AND HOW TO ASSESS RENAL FUNCTION IN PATIENTS ON ANTIRETROVIRAL THERAPY Antiviral Therapy 2004; 9(6):L41 S Mauss, F Berger and G Schmutz Treatment with tenofovir is associated with mild renal dysfunction in a higher proportion of patients. GFR assessed by creatinine clearance or, alternatively, by serum cystatin C seem to be the appropriate methods. Calculation of GFR by MDRD-formula on the basis of serum creatinine seems to be relatively insensitive. For convenience, determination of cystatin C in serum may be a useful screening marker for impaired renal function. Determination of 24-h proteinuria adds further information on tubular and glomerular dysfunction. |
| 71 | FUNCTIONAL IMPAIRMENT OF NRTI-RELATED MITOCHONDRIAL DNA-DEPLETION IN PRIMARY HUMAN T LYMPHOCYTES Antiviral Therapy 2004; 9(6):L42 B Setzer, M Schlesier and UA Walker MtDNA measurements in HIV patients are not necessarily a marker for the mitochondrial toxicity of antiretrovirals, although didanosine (and possibly also other NRTIs) do induce a time-dependent mtDNAdepletion in cultivated T lymphocytes, which is of potential clinical relevance. In vitro, this mitochondrial toxicity leads to a functional impairment of the lymphocytes with a 'lazy' phenotype initially, followed by increased cell death with prolonged exposure. |
| 72 | INCIDENCE AND RISK FACTORS FOR NUCLEOSIDE ANALOGUE TRANSCRIPTASE INHIBITORS TOXICITY IN TREATED HIV-HCV CO-INFECTED PATIENTS Antiviral Therapy 2004; 9(6):L43 M Laguno, A Milinkovic, E de Lazzari, J Murillas, E Martinez, JL Blanco, M Lonca, A Biglia, A Leon, M Larrousse, F Garcia, JM Miro, JM Gatell and J Mallolas Our study confirms that concomitant use of ribavirin plus didanosine should be avoided, and that routine monitoring of lactate and pancreatic enzymes may be cost effective. |
| 73 | NEUROCOGNITIVE/FINE MOTOR FUNCTION IS SLOWED IN ASYMPTOMATIC HIV-INFECTED PERSONS RECEIVING ANTIRETROVIRAL THERAPY Antiviral Therapy 2004; 9(6):L43 T Hulgan1, C Mwenya1, M Markovic1, I Oboho1, N Emeagwali2 and DW Haas1 Poorer performance on an integrated test of neurocognitive/motor functioning associated with ART, even in subjects without apparent PN, suggests that exposure to at least some ART agents might be toxic to the brain. Longitudinal analyses with more comprehensive neurocognitive assessments and with relevant covariates are needed to address this question. |
| 74 | WHY DO PATIENTS WITH HIV STOP ANTIRETROVIRALS USED AS PART OF AN INITIAL HIGHLY ACTIVE ANTIRETROVIRAL REGIMEN? Antiviral Therapy 2004; 9(6):L44 A Mocroft1, AN Phillips1, V Soriano2, J Rockstroh3, A Blaxhult4, C Katlama5, A Boron-Kaczmarska6, L Viksna7, O Kirk8, JD Lundgren8 for the EuroSIDA study group Patients with HCV were more likely to discontinue all or part of their HAART regimens due to toxicity or patient/physician choice. Managing adverse events must remain a key intervention in maintaining HAART. There is a need for further studies to describe the relationship between HCV, specific antiretrovirals and different treatment strategies. |
| Body Composition Abstracts 75 through 103, Pages L53 to L70 |
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| 75 | THE SCOLTA PROJECT: AN ITALIAN APPROACH TO MONITORING THE SAFETY OF NEW ANTIRETROVIRAL DRUGS Antiviral Therapy 2004; 9(6):L44 P Bonfanti, E Ricci, G Penco, D Migliorini, G Madeddu, S Melzi, C Magnani, D Zeme and T Quirino for the CISAI Group The online recording system for adverse events helps to optimize the postmarketing pharmacosurveillance and this data collection method gives timely 'real-life' information to assess the impact of short- and long-term toxicity of new antiretroviral drugs. In the LPN/r cohort, the incidence of adverse events is lower in naïve patients compared with experienced patients. |
| 76 | INCREASED FREQUENCY OF PRESCRIPTIONS AND ASSOCIATED COSTS OF DRUGS FOR THE TREATMENT OF ANTIRETROVIRAL (ARV)-INDUCED METABOLIC DISORDERS Antiviral Therapy 2004; 9(6):L45 L Normén1, B Yip2, JSG Montaner1–3, M Harris1,2, J Frohlich3, G Bondy3 and RS Hogg2,3 In this specialized clinic of mostly PI-treated patients, the number of prescriptions of concomitant drugs to treat metabolic disorders increased over time, but associated costs did not differ between PI-treated versus non-PI treated HIV+ patients. |
| 77 | EFFECTIVENESS OF A DEDICATED LIPODYSTROPHY CLINIC IN REDUCING HYPERLIPIDAEMIA IN HIV-INFECTED INDIVIDUALS Antiviral Therapy 2004; 9(6):L45 V Carter3, I Woolley1, K Costello1, A Dart2, K Lim3 and A Mijch1 The most recent levels of all patients seen are equal or reduced for all patients but one, who has a small rise in triglycerides. Mean declines are 106.2 for cholesterol (range of reduction 0–706.6) and 266.4 for triglycerides (range of reduction –92.7 to 2316.7) to give current mean levels of 216.2 for cholesterol (SD=61.8) and 169.9 for triglycerides (SD=162.2), P values for significance by t-test <0.001 for both cholesterol and triglycerides. A dedicated multidisciplinary clinic is effective at reducing lipid levels significantly. |
| 78 | ROSIGLITAZONE FOR HIV LIPOATROPHY: 84 WEEKS FOLLOW-UP Antiviral Therapy 2004; 9(6):L46 D Carey1, C Workman2, G Rogers3, D Baker4, A Martin1, H Wand1, S Emery1, DA Cooper1,5 and A Carr5, ROSEY study group Rosiglitazone 4 mg twice daily for 84 weeks did not improve lipoatrophy in HIV-infected adults receiving antiretroviral therapy. |
| 79 | ASSOCIATION OF RISK OF TOXICITY WITH DRUG LEVELS OF SAQUINAVIR WHEN BOOSTED WITH RITONAVIR IN THE MAXCMIN1&2 TRIALS Antiviral Therapy 2004; 9(6):L46 JD Lundgren1, Z Fox2, US Justesen3, S Warmsley4, M Youle5, P Vernazza6, J Gerstoft7, M Losso8 and UB Dragsted1 on behalf of the MaxCmin trial groups An apparent association between higher saquinavir concentrations at W4 with grade 3/4 GI toxicity and increases in cholesterol was identified in this analysis. Most patients had saquinavir drug levels that far exceed those required to inhibit wild-type HIV. This post hoc analysis did not have sufficient power to exclude associations with other toxicities. Conversely, the data suggest that, as saquinavir troughs above 2 µg/ml far exceed the concentration required to suppress wild-type HIV replication, doses could be reduced without loss of efficacy as long as the subjects have not acquired HIV with diminished susceptibility to saquinavir. |
| 80 | IMPACT OF SWITCHING PI-CONTAINING ANTIRETROVIRAL THERAPY ON LIPODYSTROPHY AND METABOLIC COMPLICATIONS, APROCO COHORT STUDY (ANRS EP11) Antiviral Therapy 2004; 9(6):L47 G Chene1, R Lassalle2, F Raffi3, C Michelet4, W Rozembaum5, C Perronne6, C Roussillon7, F Alkaïed8, J-M Bard9, J Capeau10 and C Leport and the Aproco-Copilote (ANRS EP11) Study Group11 In an observational setting, patients who switched were those who succeeded in therapy or had LD symptoms frequently. Switching to a PI-sparing regimen was not associated with clear improvements in metabolic abnormalities after 1 year. Lower prevalence of peripheral lipoatrophy at M2 may be explained by the use of other nucleosides than stavudine. Additional strategies to limit metabolic complications are warranted in this context. |
| 81 | IMPACT OF STRUCTURED THERAPY INTERRUPTIONS ON PLASMA LIPIDS AND BODY FAT IN PATIENTS WITH PRIMARY HIV-1 INFECTION Antiviral Therapy 2004; 9(6):L47 A Milinkovic, E Martínez, S Vidal, E de Lazzari, X Claramonte, O Sued, JL Blanco, JB Pérez-Cuevas, C Tortajada, J Mallolas, JM Gatell and JM Miro Structured therapy interruptions showed a short-term positive impact on plasma lipids and body fat that persisted 1 year after definitive discontinuation of antiretroviral therapy. |
| 82 | IMPROVEMENT IN LIPID PROFILE IN HIV-INFECTED VIROLOGICALLY CONTROLLED PATIENTS SWITCHED TO A SIMPLE QD REGIMEN: PRELIMINARY RESULTS OF THE COOL TRIAL EVALUATING EFV/TDF VS EFV/TDF/3TC Antiviral Therapy 2004; 9(6):L48 P Mercié1, A Trylesinski2, A Cabié3, C Michelet4, R Verdon5, C Katlama6, L Weiss7, JL Pellegrin8, D Sereni9, M Bentata10, J Durant11, A Simon6, L Morand-Joubert12, G Chêne13 and PM Girard12 Despite low lipid levels at baseline, switching to a tenofovir based combination can mildly decrease total and LDL-cholesterol and significantly reduce triglycerides. In patients with virologically controlled HIV infection, switching to a simplified maintenance regimen results in an improved lipid profile. The 48-weeks evaluation will assess lipid evolution and correlation between lipid disturbances and morphological changes. |
| 83 | EFFECTIVENESS OF EZETIMIBE ON HYPERLIPIDAEMIA IN HIV-1-INFECTED PATIENTS Antiviral Therapy 2004; 9(6):L48 FC von Lintig1, D Lee1, P Patel1, J Epp1, RE Barber1,2 and WC Mathews1 Ezetimibe appears to be useful in the treatment of hyperlipidaemia in HIV-1-infected patients already on LLD. Further prospective studies are needed to evaluate the safety, efficacy and potential drug interactions of ezetimibe in this patient population. |
| 84 | REEXPOSURE TO NUCLEOSIDE ANALOGUES AFTER LACTIC ACIDOSIS/HYPERLACTATAEMIA SYNDROME Antiviral Therapy 2004; 9(6):L49 C Galera, C Redondo, G Poza, M Bermejo, P Aroca and A Sánchez Lactic acidosis syndrome is a potentially fatal complication of NRTIs. Re-exposure to other NRTIs, with a theoretically lower mitochondrial toxicity, is likely to be safe and efficient. Symptoms and lactate levels should be closely monitored. |
| 85 | PERSISTENT TUBERCULOUS ADENITIS DUE TO AN UNSUSPECTED DRUG INTERACTION WITH EFAVIRENZ AND RIFABUTIN Antiviral Therapy 2004; 9(6):L49 H Edelstein and Y Cuadros Rifabutin levels may be markedly decreased when used with efavirenz, and recommended dose increases of rifabutin may not overcome this drug interaction. |
| 86 | ARE PATIENTS GIVEN ADEQUATE DIETARY INFORMATION WHEN STARTING ON A LOPINAVIR/RITONAVIR-CONTAINING HAART REGIMEN? Antiviral Therapy 2004; 9(6):L50 MN Phillpot, E Kabaroff and TL Visser For those patients who said they were given guidance on how to take Kaletra, a greater percentage took it with the correct amount of food. However, patient error must be considered when carrying out retrospective questionnaires and dietary recall. |
| 87 | AUTOLOGOUS FAT TRANSFER FOR THE TREATMENT OF HIV-RELATED FACE LIPOATROPHY: A LONG FOLLOW-UP EXPERIENCE Antiviral Therapy 2004; 9(6):L50 G Guaraldi1, G Orlando1, D De Fazi2, M Vigo2, I De Lorenzi2, A Rottino2, A Grisotti2, V Borghi1, G Nardini1 and R Esposito1 Our results showed that autologous fat transplant is effective and durable over time for correction of lipoatrophy in HIV-infected people. |
| 88 | RELAPSE OF HIV-RELATED BUFFALO HUMP AFTER LIPOSUCTION Antiviral Therapy 2004; 9(6):L51 G Orlando1, G Guaraldi1, D De Fazio2, A Grisotti2, V Borghi1, G Nardini1, B Beghetto1 and R Esposito1 Objective evaluation with ultrasound did not reveal a statistically significant variation of subcutaneous and dermal fat thickness 1 year after surgery. 10% of patients needed a re-intervention. Patients expressed improved satisfaction with body image after surgery, nevertheless surgery did not relieve the psychosocial distress linked to buffalo hump as shown by the ABCD questionnaire. |
| 89 | PSYCHOMETRIC EVALUATION OF PATIENTS UNDERGOING SURGICAL TREATMENT OF HIV-RELATED FACIAL LIPOATROPHY Antiviral Therapy 2004; 9(6):L561 G Orlando1, G Guaraldi1, M Vandelli2, M De Palma2, D Comelli2, G De Santis1, A Pedoni1, A Spaggiari1, A Baccarani1, M Pinelli1, D De Fazio3, V Borghi1, G Nardini1, B Beghetto1 and R Esposito1 AFT, PLA and PAC treatment resulted in an improvement of body image satisfaction. MOS-HIV questionnaires showed improvement in QoL domains just in the PLA and PAC groups. Beck scale revealed an amelioration of the depression score in PLA and PAC groups. |
| 90 | LONG-TERM FOLLOW-UP OF GRAFT HYPERTROPHY AFTER AUTOLOGOUS FAT TRANSFER FOR HIV-RELATED FACE LIPOATROPHY (HAMSTER SYNDROME 1 YEAR LATER) Antiviral Therapy 2004; 9(6):L52 G Guaraldi1, G Orlando1, D De Fazio2, A Grisotti2, V Borghi1, G Nardini1, B Beghetto1 and R Esposito1 A clinical implication is that when autologous fat transplantation is chosen for facial atrophy treatment, the subcutaneous adipose graft site should not be the buffalo hump area. Liposuction from the face after fat graft transplant may be complicated by the development of a fibrotic tissue and may have only limited aesthetic success. |
| 91 | HOMA-IR IN THE ASSESSMENT OF INSULIN RESISTANCE IN HIV PATIENTS Antiviral Therapy 2004; 9(6):L53 E Álvarez García1, C Miralles Álvarez2, A RepÁraz Andrade1, D Rodríguez Pérez1 and A López Domínguez2 HOMA-IR was significantly higher in the HIV-positive groups compared with the control group. These data suggest that the tendency towards insulin resistance may be more related to the HIV infectious process or to factors associated with immunological dysfunction rather than the HAART. A deeper study including CD4 cell counts and considering IP treatments should be done in order to confirm these results. |
| 92 | ABDOMINAL OBESITY PREDICTS INSULIN RESISTANCE BUT NOT TO FASTING TRIGLYCERIDE CONCENTRATION IN MALES TREATED WITH PI-CONTAINING HAART Antiviral Therapy 2004; 9(6):L53 RB Cavalcanti and S Walmsley Similar to what is found other populations, AO is correlated with insulin resistance in this group of males treated with PI-containing HAART. However, fasting triglyceride levels were not correlated with AO, suggesting that mechanisms accounting for hypertriglyceridaemia in patients receiving PI differ from those observed in the metabolic syndrome. |
| 93 | MYO-INOSITOL/D-CHIRO-INOSITOL METABOLISM IN HIV LIPODYSTROPHY SYNDROME Antiviral Therapy 2004; 9(6):L54 J Placek, M Palmer, J Currier and G Vasquez The results demonstrate that there is probably not a difference in myo-inositol/D-chiro-inositol when patients with HIVLS are compared with those on PIs but without HIVLS, and to those with HIV but not on a PI. However, the ratios are quite high for all three groups compared with those seen in normal healthy controls in the published literature. Perhaps insulin resistance is involved with HIV pathophysiology. |
| 94 | RESISTIN DECREASES AFTER 3 MONTHS OF ROSIGLITAZONE IN HIV-INFECTED PATIENTS WITH LIPODYSTROPHY Antiviral Therapy 2004; 9(6):L54 DS Kamin1, C Hadigan1, M Lehrke2, MA Lazar2 and S Grinspoon1 Among HIV-infected patients with insulin resistance and lipodystrophy, PPAR-γ agonists administration results in decreased resistin levels, a putative adipocytokine which may regulate insulin sensitivity. Further investigation into the mechanistic role of resistin in insulin resistance among HIV-infected patients with lipodystrophy is warranted. |
| 95 | NO EVIDENCE FOR REDUCED INSULIN-MEDIATED GLUCOSE UPTAKE IN SKELETAL MUSCLE WITH 4 WEEKS OF INDINAVIR IN HEALTHY MEN Antiviral Therapy 2004; 9(6):L55 In healthy subjects, 4 weeks of IDV did not impair glucose extraction at the level of skeletal muscle, suggesting no impairment of GLUT4 transport activity in vivo, in spite of a marked impairment in endotheliumdependent vasodilation. This could imply that the decrease in large vessel endothelial function primarily affected non-nutritive perfusion, while nutritive perfusion was preserved. Alternatively, skeletal muscle glucose uptake may be independent of large vessel endothelial function, or IDV-related increases in adiponectin may protect against insulin resistance. |
| 96 | HAART MODULATES LIVER LIPID METABOLISM THROUGH DIRECT EFFECT ON HEPATOCYTES Antiviral Therapy 2004; 9(6):L55 M Stankov, RE Schmidt and G Behrens IDV, RTV and AZT activate important effector genes of the SREBP-1 pathway. This is consistent with major HAART-related adverse effects like hyperlipidaemia and hepatic lipid accumulation. The short-term effect of AZT on lipogenic gene expression attributes additional mechanisms to this drug other than mitochondrial toxicity. |
| 97 | CHANGES IN NUCLEAR GENE EXPRESSION RESULTING FROM NRTI-INDUCED INHIBITION OF MITOCHONDRIAL TRANSCRIPTION REVEAL LINKS BETWEEN MITOCHONDRIAL DYSFUNCTION AND LIPID METABOLISM Antiviral Therapy 2004; 9(6):L56 PWG Mallon1–3, R Sedwell1,3, P Unemori1,3, M Rafferty4, K Williams4, D Chisholm5, K Samaras5, S Emery1, A Kelleher1–3, DA Cooper1–3 and A Carr2 These results suggest significant compensatory changes in nuclear gene expression of genes important for lipid metabolism in response to NRTI-induced inhibition of mtRNA expression in vivo. Decreases in PPARγ expression, previously described with protease inhibitor exposure now seen with NRTI exposure, help explain how NRTIinduced mitochondrial dysfunction may lead to lipoatrophy and offer a molecular explanation for the increased severity of lipodystrophy, observed clinically when NRTIs and PIs are used in combination. |
| 98 | NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTI) DECREASE ADIPOCYTE AND MONOCYTE MITOCHONDRIAL (MT) MESSENGER RNA TRANSCRIPTION IN THE ABSENCE OF CHANGES IN MTDNA OR CELL MORPHOLOGY Antiviral Therapy 2004; 9(6):L56 PWG Mallon1–3, R Sedwell1,3, P Unemori1,3, K Merlin3, C McGinley3, P Ammaranond1,3, M Peperias3, M Rafferty4, K Williams4, K Samaras6, AL Morey5, D Chisholm6, A Kelleher1–3, DA Cooper1–3 and A Carr2 These data suggest that NRTIs inhibit mtRNA transcription by a means other than through mtDNA depletion mediated through DNA pol-γ inhibition, and that monocyte mtRNA expression may be a useful peripheral blood surrogate to monitor NRTI-induced mitochondrial toxicity. |
| 99 | FAVOURABLE INCREASES IN HIGH-DENSITY LIPOPROTEIN CHOLESTEROL (HDL-C) IN HIV-INFECTED THERAPY NAÏVE SUBJECTS RECEIVING FOSAMPRENAVIR/RITONAVIR IN THE SOLO/APV30005 STUDY – 120 WEEK ANALYSIS Antiviral Therapy 2004; 9(6):L57 J Flamm1, M Lorber2, D Thomas3, N Givens3 and T Stark3 In chronically HIV-infected ART-naïve patients with overall low BL HDL-C, substantial increases in HDLC combined with minimal changes in the TC/HDL-C ratio were observed following long-term treatment with FPV/r once daily over 120 weeks. |
| 100 | LONG-TERM EFFICACY OF NELFINAVIR, ADVERSE EVENTS AND LIPODYSTROPHY Antiviral Therapy 2004; 9(6):L57 E Daniels1, B Clotet2, P Clax1, C Artega1 and M Nelson3 Extended nelfinavir-based HAART was safe and resulted in sustained suppression of HIV and sustained CD4+ cell count >500 for 2–8 years (median=4.9 years). |
| 101 | SIMPLIFIED PROTEASE INHIBITOR TRIAL (SPRINT): METABOLIC EFFECTS OF ONCE DAILY SAQUINAVIR SGC PLUS RITONAVIR (SQV/R) VS TWICE-DAILY INDINAVIR PLUS RITONAVIR (IDV/R) Antiviral Therapy 2004; 9(6):L58 M Harris1, N Press1, A Thorne1, C Zala2, P Cahn2, C Ochoa2, S Schneider3, B Hanna4, J Singer1, J Montaner1 and the CTN 161 (SPRINT) study team A once-daily regimen of SQV/r with two RTIs and a twice-daily regimen of IDV/r with two RTIs have similar effects on fasting lipids and glucose after 24 and 48 weeks of treatment. |
| 102 | IMPROVEMENT IN DYSLIPIDAEMIAS AMONG PATIENTS RECEIVING HAART AFTER SUBSTITUTION OF TENOFOVIR DF (TDF) FOR STAVUDINE (D4T) WITH OR WITHOUT USE OF A CONCOMITTANT LIPID LOWERING AGENT (LLA) Antiviral Therapy 2004; 9(6):L69 J Gilmore1, B Guyer2 and C Barbour1 For patients switched from d4T to TDF, the need for an LLA should be individualized and may not be required for every patient. Switching to TDF represents another treatment option for patients who experience HAART-associated dyslipidaemias. |
| 103 | INHIBITION OF REVERSE CHOLESTEROL TRANSPORT IN RITONAVIR-TREATED HAMSTERS Antiviral Therapy 2004; 9(6):L59 PV Nerurkar, YK Lee, J Frank and VR Nerurkar Based on our data, it is highly possible that decreased hepatic ABCA1 expression may contribute to RTV-associated increases in liver and plasma cholesterol and reduced apoA1 in HIVinfected patients on PI-containing regimens. Both CYP7A1 and ABCA1 are negatively regulated by the nuclear orphan receptor farensoid X-receptor (FXR). In our studies, RTV significantly increased hepatic FXR mRNA expression (P<0.05). Overall, our data suggest that inhibition of reverse cholesterol transport may contribute towards RTV-associated dyslipidaemia. |
| Clinical Management of ADRs Abstracts 104 through 117, Pages L70 to L78 |
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| 104 | NRTI SPARING TRIAL: METABOLIC EFFECTS OF NEVIRAPINE (NVP) + LOPINAVIR/RITONAVIR (LPV/R) VS ZIDOVUDINE/LAMIVUDINE (AZT/3TC) + NVP VS AZT/3TC + LPV/R Antiviral Therapy 2004; 9(6):L59 M Harris1, C Ochoa2, C Allavena3, E Negredo4, A Thorne1, P Cahn2, C Zala2, F Raffi3, B Clotet4, J Singer1, J Montaner1 and the CTN 177 study team After 24 weeks of treatment in antiretroviral-naïve patients, NVP/LPV/r and AZT/3TC/LPV/r had similar effects on lipid profiles, increasing both TC and TG. TC and TG were lowest in patients receiving AZT/3TC/NVP. The three arms did not differ with respect to impact on LDL, HDL, TC/HDL, glucose, lactate, BMI or WHR. |
| 105 | STUDY OF LIPODYSTROPHY IN TREATED HIV PATIENTS AND EVALUATION OF THEIR PSYCHOLOGICAL PROBLEMS Antiviral Therapy 2004; 9(6):L60 F Jalali and NP Moghadam LD is a major health problem in HIV-infected patients who are treated with highly active antiretroviral therapy (HAART). LD is often accompanied by cardiovascular risk factors like insulin resistance, diabetes mellitus, hyperlipidaemia and a disturbed endothelial function. Severe LD causes depressive symptoms and anxiety. |
| 106 | ASSOCIATION OF LIPID PROFILES IN HIV-SEROPOSITIVE PATIENTS WITH ANTIRETROVIRAL THERAPY IN A REAL WORLD SCENARIO Antiviral Therapy 2004; 9(6):L60 S Mauss1, F Berger1, G Schmutz1, S Holm2, B Kuhlmann2, E Wolf3 and WO Richter4 After adjustment for a variety of patient characteristics, different antiretroviral drugs in a variety of antiretroviral combinations are characterized by distinct lipid profiles, which may have implications for the cardiovascular risk management in HIV-positive patients. |
| 107 | METABOLIC COMPLICATION AND FAT CHANGES IN THAI HIV-INFECTED PATIENTS Antiviral Therapy 2004; 9(6):L61 M Homsanit1, J Cofrancesco Jr2 and KE Nelson3 Fat changes and metabolic abnormalities are common in Thai HIV-infected patients, similar to western populations. Antiretroviral therapy, especially PI-based regimens, are significantly associated with these derangements. |
| 108 | DIETARY EVALUATION AND METABOLIC ALTERATIONS IN HIV-RELATED LIPODYSTROPHY Antiviral Therapy 2004; 9(6):L61 G Orlando1, G Guaraldi1, F Giuricin1, G Grisendi1, F Carubbi1, S Galetti2, I Zini1, V Borghi1 and R Esposito1 A direct relationship between metabolic alterations and dietary habits has been observed in plurimetabolic syndrome. This study, however, was unable to detect a direct influence of diet on metabolic alteration in HIV-related lipodystrophy, supporting a multifactorial hypothesis. A follow-up study will allow investigation of the role of nutritional counselling in the management of metabolic alterations in these patients. |
| 109 | INCREASED CD36 EXPRESSION ON CIRCULATING MONOCYTES DURING HIV INFECTION Antiviral Therapy 2004; 9(6):L62 L Meroni1, A Riva1, P Morelli1, M Galazzi1, D Mologni1, F Adorni2 and M Galli1 HIV-1 infection is associated with an increased expression of CD36 on circulating monocytes and antiretroviral drugs play only a minor role in its complex homeostasis. Being related to HIV infection itself, CD36 over-regulation is a permanent condition in infected patients, resulting in the potential for continued lipid accumulation and foam cell formation. Thus, CD36 overexpression might act in accordance with other wellknown proatherogenic conditions associated with HIV infection, such as pro-inflammatory effects on endothelium, insulin resistance and dyslipidaemia. |
| 110 | THE REDUCTION IN SERUM ADIPONECTIN LEVELS IN HIV PATIENTS CORRELATES WITH APOLIPOPROTEIN-B CLEARANCE Antiviral Therapy 2004; 9(6):L62 M Shahmanesh1, S Das1, F Shojaee-Moradie2, M Stolinski2, W Jefferson2, N Jackson2, G Gilleran2, NJ Crabtree1, P Nightingale1, R Cramb1 and M Umpleby2 Adiponectin levels are significantly lower in HIV-infected patients including those who are treatment naïve. The strong correlation with VLDL and IDL, and LDL apoB FCR and plasma lipid levels suggests an effect on lipoprotein and hepatic lipase activity that may be independent of insulin. |
| 111 | LIPOPROTEIN (A) AS CARDIOVASCULAR RISK FACTOR IN HIV-INFECTED PATIENTS Antiviral Therapy 2004; 9(6):L63 WO Richter1, E Issler2, A Schaffert2, E Schnaitmann2 and A Trein2 About one-fifth of HIV-infected patients, whether on antiviral treatment or not, had a strongly increased risk for cardiovascular disease due to elevated lipoprotein (a). |
| 112 | INVESTIGATION OF CYTOKINE PROMOTER POLYMORPHISMS IN THE TUMOUR NECROSIS FACTOR (TNF)-α, AND INTERLEUKIN (IL)-10 GENES IN HIV-INFECTED PATIENTS WITH LIPODYSTROPHY Antiviral Therapy 2004; 9(6):L63 A Farajallah1, D Chew1, E Albanese1, W Chen1, J Rodrigues1, J Greytok2 and H Fernandes1 The results demonstrate an increase of the low and intermediate IL-10 phenotype in HIV-infected individuals compared with HIV-negative controls, suggesting a link between IL-10 polymorphisms and HIV infection. The phenotypic variation between the HIV patients with and without lipodystrophy points to a possible difference between the two groups. The IL-10 promoter haplotype should be further investigated as a possible risk factor in HIV patients with lipodystrophy. |
| Cardiovascular Disease Abstracts 113 through 124, Pages L64 to L70 |
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| 113 | EVALUATION OF BLOOD LIPID DISORDERS AND ATHEROSCLEROSIS MEASURED BY THE INTIMA MEDIA THICKNESS IN A COHORT OF HIV-POSITIVE PATIENTS Antiviral Therapy 2004; 9(6):L64 F David-Ouaknine1, D Lagasse1, S Marque2 and J Rivargoda1 In our cohort, the cardiovascular risk factors usually described in HIV-seropositive patients (heavy smoking, low HDL cholesterol and hypertension) were only found in a small percentage of patients. A link was found between classical cardiovascular risk factors and the intima media thickness, but there was no significant increase in the intima media thickness in the treated patients compared with the untreated ones. The start of antiretroviral treatment is a good time to screen for and to correct cardiovascular risk factors. |
| 114 | IMPAIRED ACTIVITY OF PRAVASTATIN ON CAROTID INTIMA-MEDIA THICKNESS IN HIV-INFECTED PATIENTS Antiviral Therapy 2004; 9(6):L64 F Boccara1, T Simon2, P Boutouyrie1, PM Girard3, P Jaillon2, B Laloux1, E Bozec1 and S Laurent1 The use of pravastatin was not associated with a significantly lower carotid IMT in HIV+. The role of lipodystrophic syndrome and associated metabolic disorders in accelerated atherosclerosis need to be further investigated. |
| 115 | CORONARY ARTERY BYPASS GRAFT IN HIV-INFECTED PATIENTS. A MULTICENTER CASE CONTROL STUDY Antiviral Therapy 2004; 9(6):L65 F Boccara1, A Cohen1, G Odi1, E Di Angelantonio1, E Teiger2, G Barbarini3 and G Barbaro4; on behalf the French Italian Study on Coronary Artery Disease in AIDS Patients (FRISCA-2) CABG is a feasible and safe revascularization procedure in HIV-infected patients. Immediate postoperative outcome demonstrate no difference between HIV+ and HIV– patients. At long-term follow-up, the rate of MACE was significantly higher in HIV+ patients compared with HIV– due to an increased rate of repeat revascularization procedure (reCABG and PCI). |
| 116 | EVALUATION OF CORONARY ARTERY CALCIFICATION BY ELECTRON BEAM COMPUTED TOMOGRAPHY (EBCT) IN HIV-INFECTED MEN RECEIVING PROLONGED PROTEASE INHIBITOR (PI) THERAPY Antiviral Therapy 2004; 9(6):L65 DM Parenti, A Klouj, MM Rice, AD Roberts, AP Liappis, N Bisby, SZ Schuck, J Ehrlich, AG Wasserman and GL Simon There appears to be no difference in CAC scores when PI-treated patients are compared with age-range matched published norms for asymptomatic men, but there appears to be an association between boosted PI use and coronary artery calcification. These findings suggest that further studies be done examining the effects of boosted PI regimens on accelerated atherosclerosis. |
| 117 | ENDOTHELIAL DYSFUNCTION, ADIPONECTIN PLASMA LEVELS AND LIPODYSTROPHY IN PATIENTS ON ANTIRETROVIRAL THERAPY Antiviral Therapy 2004; 9(6):L66 V Estrada, JL Zamorano, T Sainz, S Serrano, L de Isla, MT Martinez-Larrad, JL Gonzalez and M Serrano Rios Endothelial dysfunction is observed in 18% of patients on ART, in a similar proportion to naïve patients. Its presence is independent of fat redistribution abnormalities, plasma adipokines, lipoproteins, immune status or use of PI or NNRTI. |
| 118 | COMPARISON OF FRAMINGHAM AND PROCAM SCORES FOR RISK ASSESSMENT OF CARDIOVASCULAR DISEASE IN HIV-POSITIVE ADULTS WITH METABOLIC COMPLICATIONS Antiviral Therapy 2004; 9(6):L66 L Normén1, B Yip2, JSG Montaner1–3, M Harris1,2, J Frohlich3, G Bondy3 and RS Hogg2,3 The average CHD risk in the studied HIV-positive adults with metabolic complications was moderate using both Framingham and PROCAM scores. A substantial number had a very high, predicted 10-year risk of developing CHD. Both risk scores gave similar results in this particular population, whether on PIs or not. However, the predictive value of both methods on actual CHD development still needs to be established in the general HIV-positive population. |
| 119 | CARDIOVASCULAR RISK ASSESSMENT WITH CAROTID ULTRASOUND AND CORONARY CALCIUM SCORE IN A COHORT OF HIV-INFECTED SUBJECTS Antiviral Therapy 2004; 9(6):L67 A Mangili1,2, J Gerrior1, A Tang1, DH O’Leary3, JF Polak3, EJ Schaefer1, SL Gorbach1,2 and CA Wanke1,2 Of participants , 8–22% had abnormal surrogate markers of CVD, but those were not associated with HAART or PI use. There were more significant correlations with IMT than with CCS, but CCS might measure more advanced CVD. At the current time, the correlations were primarily with traditional CVD risk factors. Some HIV-specific (not treatment-specific) factors were observed; they may become more evident with prolonged HIV infection and treatment. |
| 120 | HS-CRP IS ELEVATED IN HIV-POSITIVE PATIENTS WITH A TREND TO INCREASED LEVELS IN PATIENTS PRIOR TO CORONARY EVENTS Antiviral Therapy 2004; 9(6):L67 I Woolley1, H Schneider2, A Dunne3, T Middleton4, V Sundararajan5, V Carter6, A Dart7 and A Mijch1 As a substudy of this study we examined the highly sensitive C reactive protein (HS-CRP) levels in our cases and controls prior to censoring from stored viral load samples usually taken at routine outpatient visits. The CRP level has been shown to be one of the stronger predictors of a cardiac event in an HIV-negative population and postulated to be a direct player in the pathogenesis of coronary disease. Whereas the normal levels in an HIVnegative population are less than 5, the levels in our study were a mean of 6.70 (n=49, SD=10.41) for controls and 10.92 (n=23, SD=18.92) for cases. The difference between cases and controls did not reach statistical significance by univariate analysis. |
| 121 | PERCUTANEOUS CORONARY INTERVENTION IN HIV-INFECTED PATIENTS: IMMEDIATE RESULTS AND LONG-TERM PROGNOSIS Antiviral Therapy 2004; 9(6):L68 F Boccara1, E Teiger2, A Cohen1, G Odi1, E Di Angelantonio1, G Barbarini3 and G Barbaro4; on behalf the French Italian Study on Coronary artery disease in AIDS patients (FRISCA-1) PCI is feasible and safe in HIV+ patients. At 1-year follow-up after PCI, no differences in MACE and restenosis rates were observed in either HIV+ or HIV– patients. |
| 122 | ANTIRETROVIRAL EXPOSURE AND CAROTID INTIMAL MEDIAL THICKNESS IN A MULTICENTRE CANADIAN HIV COHORT Antiviral Therapy 2004; 9(6):L68 M Smieja1, E Lonn1, FM Smaill1, L Kelleher1, S Schmidt1, S Smith1, S Holmes1, W Cai1, K Gough2, S Trottier3, J Gill4 and M Harris5 for the Canadian HIV Vascular Study Investigators Age, gender, smoking, cholesterol, glucose and systolic blood pressure, but not antiretroviral exposure, were the main determinants of atherosclerosis in HIV subjects. Longer term follow-up is needed to determine more precisely whether antiretrovirals accelerate atherosclerosis. |
| 123 | HIV VIRAL PROTEIN R CAUSES ATRIAL CARDIOMYOCYTE MITOSIS, MESENCHYMAL TUMOUR, DYSRHYTHMIA, AND HEART FAILURE Antiviral Therapy 2004; 9(6):L69 W Lewis, YK Miller, CP Haase, T Ludaway, J McNaught, R Russ, J Steltzer, A Folpe, R Long and J Oshinski These results indicate that Vpr targeted to cardiomyocytes caused defective contractility and development of proliferative atrial tumours. Despite the absence of such cardiac tumours in humans with AIDS, Vpr cardiomyocytic effects resemble some of those found in terminally differentiated immunocytes. Findings with this TG model of Vpr-induced cell dysfunction may mechanistically link AIDS CM to other cellular defects in AIDS through shared cellular events. |
| 124 | BLOOD PRESSURE ELEVATION AND HYPERTENSION IN PAEDIATRIC PATIENTS WITH OR WITHOUT HUMAN IMMUNODEFICIENCY VIRUS-ASSOCIATED LIPODYSTROPHY Antiviral Therapy 2004; 9(6):L70 S Benavides1, KI Koranyi2 and MC Nahata3 EBP and HTN are prevalent in paediatric patients with HIV with and without lipodystrophy. Clinical significance of this finding, particularly in the presence of other metabolic abnormalities and their management, need to be prospectively studied. |
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