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4th International Workshop on Adverse Drug Reactions
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| ORAL PRESENTATIONS Session 1 |
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| 1 | INDINAVIR-INDUCED NUCLEAR LAMINA ALTERATIONS ARE CORRELATED WITH ADIPOCYTE DYSFUNCTIONS IN CULTURED ADIPOCYTES M Caron, M Auclair, M Kornprobst and J Capeau Antiviral Therapy 2002;7:L1 (abstract 1) Adipose cells have been identifyed as a major target of protease inhibitors (PIs) both in vivo and in vitro. We have previously observed that the adverse effects of indinavir on 3T3-F442A adipocyte differentiation and response to insulin could be related to the altered expression and nuclear localization of the transcription factor sterol regulatory element-binding protein-1 (SREBP-1). |
| 2 | INTRACELLULAR DISPOSITION OF ZIDOVUDINE, STAVUDINE AND PROTEASE INHIBITORS AND THEIR METABOLIC EFFECTS IN CULTURED ADIPOCYTES O Janneh, PG Hoggard, SD Sales, SP Jones, JF Tjia, SH Khoo, B Maher, DJ Back and M Pirmohamed Antiviral Therapy 2002;7:L1 (abstract 2) The development of a metabolic syndrome known as lipodystrophy characterized by dysregulated fat metabolism has offset the benefits of highly active antiretroviral therapy. Both protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs) have been implicated in the pathogenesis, but it is unclear what cellular and biochemical mechanisms are affected by the drugs. |
| 3 | ALTERED TNF-α AND IL-6 LEVELS AND THE ANTIADIPOGENIC EFFECTS OF ANTIRETROVIRALS ON CULTURED ADIPOCYTES: POSSIBLE MECHANISMS FOR THEIR ROLE IN LIPODYSTROPHY IN HIV-INFECTED PATIENTS SP Jones, O Janneh, B Maher, S Khoo, DJ Back and M Pirmohamed Antiviral Therapy 2002;7:L2 (abstract 3) The use of highly active antiretroviral therapy (HAART) has improved the morbidity and mortality of HIV-infected patients. However, it has been associated with the debilitating metabolic syndrome of lipodystrophy, characterized by fat redistribution, hyperlipidaemia and insulin resistance. |
| 4 | REDUCED LIPOPROTEIN LIPASE mRNA EXPRESSION IN THIGH ADIPOSE TISSUE FROM HIV-1-INFECTED PATIENTS WITH LIPOATROPHY J Chaparro, XP E, D Reeds, S Klein, CF Semenkovich, WG Powderly, K Yarasheski and E Li Antiviral Therapy 2002; 7:L3 (abstract 4) To determine if there is altered gene expression in adipose tissue collected from HIV-1- infected patients with subcutaneous lipoatrophy compared with HIV-1-infected patients without lipoatrophy. |
| 5 | LEPTIN REPLACEMENT THERAPY BUT NOT DIETARY POLYUNSATURATED FATTY ACID AMELIORATES HIV PROTEASE INHIBITOR-INDUCED HYPERLIPIDEMIA AND LIPODYSTROPHY IN MICE TM Riddle, NM Schildmeyer, CJ Fichtenbaum and DY Hui Antiviral Therapy 2002; 7:L3 (abstract 5) Hyperlipidemia and lipodystrophy are major complications associated with protease inhibitor (PI) therapy in patients with HIV. Previous studies have shown that ritonavir treatment results in lipid abnormalities due to constitutive induction of lipid biosynthetic pathways regulated by sterol regulatory element binding proteins (SREBPs). |
| Session 2 | |
| 6 | INDINAVIR ACUTELY INHIBITS GLUCOSE INDUCED INSULIN RELEASE FROM PANCREATIC β-CELLS THROUGH BLOCK OF GLUCOSE UPTAKE JC Koster1, M Remedi1, H Qiu2, CG Nichols1 and PW Hruz2 Antiviral Therapy 2002; 7:L4 (abstract 6) HIV protease inhibitors (PIs) acutely and reversibly inhibit the insulin responsive glucose transporter Glut 4, leading to peripheral insulin resistance and impaired glucose tolerance. Minimal modelling analysis of intravenous glucose tolerance tests on PI-treated patients has revealed an impaired insulin response when faced with decreased peripheral insulin-sensitivity, suggesting β-cell dysfunction as well. |
| 7 | INDINAVIR WITH AND WITHOUT NUCLEOSIDES ACCELERATE THE DIABETES PHENOTYPE IN MALE ZUCKER DIABETIC FATTY (ZDF FA/FA) RATS KE Yarasheski, E Zinna, S Claxton, X Chen, A Becker and S Smith Antiviral Therapy 2002; 7:L4 (abstract 7) The male Zucker diabetic fatty rat (zdf fa/fa) is a well-characterized animal model of NIDDM. It progressively develops worsening hyperglycaemia and hyperinsulinaemia from 5-10 weeks of age, and becomes insulinopenic at about 14 weeks of age. |
| 8 | INSULIN SENSITIVITY, SERUM LIPIDS AND ABDOMINAL ADIPOSE TISSUE DISTRIBUTION IN PROTEASE INHIBITOR-TREATED AND PROTEASE INHIBITOR-NAÏVE HIV-INFECTED CHILDREN A Bitnun1, E Sochett2, P Babyn3, C Arneson1, S Holowka3, J Forbes4, S Read1, and SM King1 Antiviral Therapy 2002; 7:L5 (abstract 8) The purpose of this ongoing study is to determine the extent and severity of abnormalities of glucose homeostasis, serum lipids and abdominal adipose tissue distribution in HIV-infected children, and to investigate the role of the protease inhibitors (PIs) in the development of these abnormalities. |
| 9 | STAVUDINE AND DIDANOSINE PARTLY REVERSED THE ADVERSE EFFECTS OF INDINAVIR ON CELL DIFFERENTIATION AND RESPONSE TO INSULIN BUT ENHANCED APOPTOSIS OF CULTURED ADIPOCYTES M Caron, M Auclair, M Kornprobst and J Capeau Antiviral Therapy 2002; 7:L6 (abstract 9) We previously observed that the protease inhibitor (PI) indinavir induced adverse effects on 3T3-F442A adipocyte functions. We evaluated the in vitro effects of two nucleoside reverse transcriptase inhibitors (NRTIs), stavudine and didanosine, used alone or in combination with 15 µM indinavir on adipose cell differentiation, lipid accumulation, response to insulin and survival. |
| 10 | DIFFERENTIATION OF ATAZANAVIR FROM OTHER HIV-PROTEASE INHIBITORS IN PRECLINICAL MODELS OF GLUCOSE UPTAKE, LIPOGENESIS AND PROTEASOME FUNCTION S Wang, R Mulvey, N Laing, J Leet, O Flint and RA Parker Atazanavir is an HIV-protease inhibitor (PI) in development which shows antiviral efficacy without plasma lipid disturbances seen with other PIs. |
| Session 3 | |
| 11 | HIV PROTEASE INHIBITORS PROMOTE ATHEROSCLEROTIC LESION FORMATION INDEPENDENT OF DYSLIPIDAEMIA BY INCREASING CD36-DEPENDENT CHOLESTEROL ACCUMULATION IN MACROPHAGES J Dressman, J Kincer, SV Matveev, L Guo, RN Greenberg, T Guerin, D Meade, XA Li, W Zhu, A Uittenbogaard, ME Wilson and EJ Smart Antiviral Therapy 2002; 7:L7 (abstract 11) These studies use both in vitro and in vivo models to determine if HIV protease inhibitors induce a specific increase in macrophage CD36 levels, macrophage cholesterol levels, and the formation of atherosclerotic lesions. |
| 12 | HIGHLY ACTIVE ANTIRETROVIRAL DRUGS MODULATE HUMAN AORTIC ENDOTHELIAL CELL FUNCTION: ROLE OF CELL ADHESION MOLECULES, NITRIC OXIDE AND REACTIVE OXYGEN SPECIES KC Agrawal, L Pradhan, M Ali and D Mondal Antiviral Therapy 2002; 7:L8 (abstract 12) The advent of highly active antiretroviral therapy (HAART) has significantly improved the prognosis in HIV-1 infected patients. However, long term HAART is associated with lipodystrophy and cardiovascular complications leading to a progressive deterioration in the patient’s quality of life. |
| 13 | DISRUPTED EXPRESSION OF LIPID TRANSPORT GENES IN MONOCYTES OF INDIVIDUALS WITH HIV-ASSOCIATED LIPODYSTROPHY - AN ADDITIONAL RISK FOR CARDIOVASCULAR DISEASE? PWG Mallon1,2,3, ML Munier1, K McGhie2, J Zaunders2, A Kelleher2, DA Cooper1,2,3, and A Carr2 Antiviral Therapy 2002; 7:L8 (abstract 13) Lipid accumulation within monocytes and macrophages, resulting in foam cell formation, is an important step in the development of atherosclerosis. Individuals exposed to antiretrovirals have abnormal expression of the transcription factors SREBP1 and PPARγ in adipose tissue. ABCA1, a member of the ATP-binding cassette-transporter family, regulates efflux of cholesterol from monocytes, helping to prevent intracellular lipid accumulation and foam cell formation. Its expression is regulated by these transcription factors. We hypothesised that individuals with evidence of antiretroviral induced adipose abnormalities (lipoatrophy) would also have disruption of monocyte lipid regulation. |
| 14 | ANTIRETROVIRAL THERAPY-INDUCED CHANGES IN LIPOPROTEIN SUBCLASS PHENOTYPE: COMPARISON OF PROTEASE INHIBITOR AND NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR REGIMENS GL Simon, AP Liappis, SL Granger, AD Roberts, SZ Schuck, JR Simon, JE Clarke and DM Parenti Antiviral Therapy 2002; 7:L9 (abstract 14) To compare the lipoprotein subclass phenotypes for HIV-infected patients receiving antiretroviral therapy (ART)-utilizing regimens with and without protease inhibitors. |
| Session 4 | |
| 15 | TWELVE WEEKS OF ATAZANAVIR TREATMENT REVERSES NELFINAVIR-ASSOCIATED HYPERLIPIDAEMIA: RESULTS FROM BMS AI424-044 R Murphy1, A Thiry2, M Mancini2, V Pokrovsky3, and W Rozenbaum4 Antiviral Therapy 2002; 7:L10 (abstract 15) Atazanavir is a potent, safe and effective once-daily protease inhibitor (PI) in Phase III development. Unlike other PIs, atazanavir has not been associated with clinically relevant elevations in total cholesterol, fasting LDL or fasting triglycerides. |
| 16 | A COMPARISON OF CARDIAC OUTPUT AND ARTERIOVENOUS OXYGEN DIFFERENCE IN INDIVIDUALS WITH HIV TAKING AND NOT TAKING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY WT Cade1, LE Fantry1, SR Nabar1, DK Shaw2 and RE Keyser1 Antiviral Therapy 2002; 7:L10 (abstract 16) The aim of this study was to compare central oxygen delivery [cardiac output (Qt)] and peripheral oxygen extraction-utilization [arteriovenous oxygen difference (a-vO2)] in groups of individuals with HIV taking and not taking highly active antiretroviral therapy (HAART). |
| 17 | EVALUATION OF β-OXIDATION USING CARBON-11 ACETATE POSITRON EMISSION TOMOGRAPHY IN HIV-INFECTED PATIENTS WITH LIPODYSTROPHY SYNDROME GMN Behrens1, A-R Boerner1, K Weber1, J van den Hoff1, J Ockenga2, G Brabant1, and RE Schmidt1 Antiviral Therapy 2002; 7:L11 (abstract 17) Lipodystrophy in HIV-patients receiving highly active antiretroviral therapy (HAART) is frequently associated with abnormal lipid metabolism and increased free fatty acids (FFA). Mitochondrial toxicity induced by nucleoside-analogue reverse transcriptase inhibitors (NRTI) has been proposed to contribute to these side effects. |
| 18 | REDUCING PLASMA HIV VIRAEMIA IMPROVES MUSCLE AMINO ACID METABOLISM KE Yarasheski, M Hoffmann, S Claxton, J Schulte, E Zinna and WG Powderly Antiviral Therapy 2002; 7:L11 (abstract 18) We reported that AIDS-muscle wasting was associated with an inappropriately low rate of muscle protein synthesis and an elevated glutamine rate of appearance (Ra gln; American Journal of Physiology 1998; 275:E577–E583). We hypothesized that high plasma HIV viraemia (VL) caused dysregulation of muscle amino acid metabolism. |
| 19 | MUSCLE SPECIFIC STRENGTH, INTRAMUSCULAR ENERGY METABOLISM, AND OTHER INDICES OF MITOCHONDRIAL FUNCTION ARE NOT ALTERED IN HIV-INFECTED PATIENTS WITH MARKED PERIPHERAL LIPOATROPHY GK Sakkas1,2, K Mulligan1,2, M daSilva1,2, J Kent-Braun3, T Schleich4, and M Schambelan1,2 Antiviral Therapy 2002; 7:L12 (abstract 19) It has been suggested that lipoatrophy (LA) in patients with HIV infection may be a manifestation of mitochondrial toxicity. Although evidence of mitochondrial damage has been seen in muscle tissue taken from patients with LA, the functional consequences of possible mitochondrial alterations have not been studied. |
| Session 5 | |
| 20 | STATISTICAL POWER TO DETECT DRUG TOXICITY IN HIV CLINICAL TRIALS A Hill1, I James2, E McKinnon2, M Law3 Antiviral Therapy 2002; 7:L13 (abstract 20) Conclusions on drug safety are often made from HIV clinical trials without prior analysis of the power to detect treatment effects on various adverse events. Toxicity can be measured either from continuous data (for example, mean/median change in laboratory parameters) or categorical data (for example, Grade 3 or 4 (serious or life-threatening) events). |
| 21 | LACK OF RECURRENCE OF SYMPTOMATIC AND ASYMPTOMATIC HYPERLACTATEMIA WHEN STAVUDINE IS REPLACED BY EITHER ABACAVIR OR ZIDOVUDINE: 48-WEEK DATA T Lonergan1, G McComsey2, S Hessenthaler3, P Shalit4, T File5, V Williams3, and J Hernandez3 for the ESS40010 (TARHEEL) study team Symptomatic hyperlactatemia (≥2.2 mmol/l) is a rare complication of nucleoside reverse transcriptase inhibitor (NRTI) use. Clinical features include nausea/vomiting, anorexia/weight loss, abdominal pain/bloating, dyspnea, fatigue and tachycardia. |
| 22 | NEW TESTS FOR MEASUREMENT OF MITOCHONDRIAL DNA AND RNA RELATIVE TO NUCLEAR DNA BASED ON HIGH-THROUGHPUT REAL-TIME MONITORED DUPLEX AMPLIFICATION MP de Baar, E Timmermans, I Dobbelaer-Bosboom, B van Gemen and A de Ronde Antiviral Therapy 2002; 7:L14 (abstract 22) The emerging problems of adverse effects of highly active antiretroviral therapy (HAART) and the suspected role of mitochondrial dysfunction herein revealed the necessity of having a molecular test for the assessment of mitochondrial DNA and RNA in relation to antiviral treatment. Such an assay should measure the mitochondrial DNA and RNA copies relative to the nuclear DNA to allow a conclusion about copy numbers per cell. |
| 23 | ROLE OF PLATELET CONTAMINATION IN ASSESSING mtDNA CONTENT IN PERIPHERAL BLOOD MONONUCLEAR CELLS M Pinti1, M Nasi1, L Moretti1, C Bellodi1, L Troiano1, C Mussini2, R Esposito2 and A Cossarizza1 Antiviral Therapy 2002; 7:L15 (abstract 23) To evaluate the influence of platelet contamination in the quantification of peripheral blood mononuclear cells (PBMC) mitochondrial DNA (mtDNA) content. |
| 24 | ASSESSMENT OF MITOCHONDRIAL TOXICITY OF DIVERSE HIGHLY ACTIVE ANTIRETROVIRAL THERAPY REGIMENS BY A SIMULTANEOUS GENETIC AND BIOCHEMICAL APPROACH S López1, Ò Miró1, M García2, E Martínez2, A Milinkovic2, A Soler3, JL Blanco2, E Pedrol3, A Beato1, J Casademont1 and F Cardellach1 Antiviral Therapy 2002; 7:L15 (abstract 24) Nucleoside reverse transcriptase inhibitors are being increasingly associated with mitochondrial (mt) toxicity. We aimed to assess mt content and function in peripheral blood mononuclear cells (PBMCs) of HIV-infected patients previous to the development of clinically evident body fat changes. |
| 25 | THERAPY WITH EFAVIRENZ+RITONAVIR BOOSTED INDINAVIR, WITH OR WITHOUT STAVUDINE AFTER 24 WEEKS DOES NOT DECREASE MTDNA AND MTRNA CONTENT OF PBMC ASSESSED BY SINGLE TUBE DUPLEX REAL-TIME NASBA M Casula1, MP de Baar2, B van Gemen2, A de Ronde2, E Timmermans2, I Dobbelaer2, M Westrop2, GJ Weverling3, M van der Valk1, M Shivaprakash4, M Stek4, and P Reiss5 Antiviral Therapy 2002; 7:L16 (abstract 25) Several adverse effects of antiretroviral therapy (ART) may result from inhibition of mitochondrial DNA (mtDNA) polymerase gamma by nucleoside analogue reverse transcriptase inhibitors (NRTIs). We have previously shown that antiviral therapy with zidovudine+zalcitabine or zidovudine+didanosine may result in a decline of mtDNA in PBMCs. |
| Session 6 | |
| 26 | TUMOUR NECROSIS FACTOR ALPHA GENE - 238G/A PROMOTER POLYMORPHISM ASSOCIATED WITH MORE RAPID ONSET OF LIPODYSTROPHY D Nolan1, C Moore1, A Castley2, D Sayer2, C Mamotte2, M John1, I James1 and S Mallal1 Antiviral Therapy 2002; 7:L17 (abstract 26) In this study, carriage of the TNF-α -238G/A promoter polymorphism independently increased the risk of lipodystrophy progression in a cohort of 191 white Caucasian HAART recipients. The influence of other host and treatment-related variables on lipodystrophy progression were not altered after adjustment for the effect of TNF-α -238G/A polymorphism, indicating that effects of treatment are not contingent on the presence of this host factor. |
| 27 | PROSPECTIVE STUDY OF REGIONAL BODY COMPOSITION IN ANTIRETROVIRAL-NAÏVE SUBJECTS RANDOMIZED TO RECEIVE ZIDOVUDINE+LAMIVUDINE OR DIDANOSINE+STAVUDINE COMBINED WITH NELFINAVIR, EFAVIRENZ, OR BOTH: A5005s, A SUBSTUDY OF ACTG 384 MP Dubé1, R Zackin2, P Tebas3, R Roubenoff4, K Mulligan5, G Robbins6, Y Yang2, R Shafer7, S Snyder8, and SK Grinspoon6 Antiviral Therapy 2002; 7:L27 (abstract 27) Antiretroviral-naïve subjects randomized to didanosine+stavudine lost a greater proportion of limb fat than those receiving zidovudine+lamivudine at weeks 48-80. Subjects randomized to nelfinavir lost a greater proportion of limb fat at week 80 than with efavirenz. Although trunk fat increased across all groups, regimen-specific differences in trunk fat changes were not detected. Analysis of metabolic variables and self-perceived body image is needed to evaluate the clinical significance of these findings. |
| 28 | EFFECT OF STAVUDINE, ZIDOVUDINE AND HIV PROTEASE INHIBITOR THERAPY ON SUBCUTANEOUS LEG FAT WASTING IN HIV-INFECTED MALES - A LONGITUDINAL STUDY D Nolan, I James, E McKinnon and S Mallal Antiviral Therapy 2002; 7:L18 (abstract 28) In this study the use of stavudine in the first HAART regimen was associated with more rapid fat loss in the legs compared with zidovudine. The findings of this longitudinal analysis of sequential DEXA scans is in keeping with the previous study in this cohort which examined the time to onset of clinically apparent subcutaneous fat wasting. |
| 29 | QUANTIFYING LIPOATROPHY AND LIPOHYPERTROPHY USING DEXA AND MRI B Razavi, WG Powderly, P Tebas, S Claxton, M Hoffmann, D Kampwerth and KE Yarasheski Antiviral Therapy 2002; 7:L19 (abstract 29) These quantitative estimates of peripheral and central lipoatrophy and visceral lipohypertrophy may be useful in clinical trials, for example to identify subjects with adipose tissue maldistribution and to evaluate the effects of different treatment regimens. |
| POSTER PRESENTATIONS Adipocyte Biology |
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| 30 | BOTH STAVUDINE AND ZIDOVUDINE-BASED THERAPY IS ASSOCIATED WITH GLUTEAL SUBCUTANEOUS ADIPOCYTE DEPLETION J Morlese1, N Qazi1, C Orkin1, D Datta1, R Abbas1, B Gazzard1, N Francis2 and G Moyle1 Antiviral Therapy 2002; 7:L22 (abstract 30) Lipoatrophy is a stigmaitising dysmorphology observed during antiretroviral therapy (ART). The aetiology of lipoatrophy is unclear. Nucleoside analogue (NA) treatment is associated with lipoatrophy but the relative contributions of each NA to lipoatrophy has not been determined. |
| 31 | SITE-SPECIFIC DIFFERENCES IN THE ACTION OF NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR DRUGS ON ADIPOSE TISSUE INCUBATED IN VITRO WITH ACTIVATED LYMPHOID CELLS AND ITS IMPLICATIONS FOR THE LOCAL INTERACTIONS HYPOTHESIS FOR THE HIV-RELATED ADIPOSE TISSUE REDISTRIBUTION SYNDROME CM Pond, CA Mattacks, D Sadler and JD Priddle Antiviral Therapy 2002; 7:L22 (abstract 31) Existing theories of the origin of HIV-related adipose tissue redistribution syndrome cannot adequately explain simultaneous hypertrophy of certain depots and atrophy of others, or its occasional occurrence in untreated HIV-infection. Only site-specific properties of adipose tissue can account for this phenomenon. |
| 32 | DIRECT REGULATION OF ADIPONECTIN BY HIV AND ITS LINK TO LIPODYSTROPHY Q Tong1, J-L Sankalé2, CM Hadigan3, G Tan1, ES Rosenberg4, PJ Kanki2, SK Grinspoon3, GS Hotamisligil1 Antiviral Therapy 2002; 7:L23 (abstract 32) HIV-related lipodystrophy is characterized by adipose redistribution, dyslipidaemia, and insulin resistance. The underlying molecular mechanisms remain largely unknown. In this study, we have demonstrated that adipocytes express HIV receptors. Although we found no evidence of HIV entry or amplification in human adipocytes or preadipocytes, our data demonstrate that exposure to HIV virus stimulates the secretion of adiponectin from human adipocytes. We also demonstrate that T lymphocytes produce adiponectin, but adiponectin production is suppressed upon T-cell activation. |
| Insulin Resistance/Diabetes | |
| 33 | ADIPONECTIN, LEPTIN AND SOLUBLE TNF RECEPTORS CIRCULATING LEVELS ARE RELATED TO INSULIN RESISTANCE AND CARDIOVASCULAR RISK FACTORS IN HIV PATIENTS UNDER ANTIRETROVIRAL TREATMENT C Vigouroux1, M Maachi1, T-H Nguyen2, Y Salhi2, S Coussieu3, S Gharakhanian2, T Funahashi4, Y Matsuzawa4, I Shimomura4, W Rozenbaum2, J Capeau1 and J-P Bastard1 Antiviral Therapy 2002; 7:L24 (abstract 33) Altered endocrine function of the adipose tissue could be a major determinant of the lipodystophy and metabolic alterations observed in patients under antiretroviral treatment. We analysed the relations between adiponectin, leptin, IL-6, TNFα and soluble TNFα receptors circulating concentrations and the metabolic parameters in patients with different lipodystrophic phenotypes. |
| 34 | HEPATITIS B AND C CO-INFECTION AND ALANINE AMINOTRANSFERASE ARE ASSOCIATED WITH INCREASED INSULIN RESISTANCE AND DIABETES IN PATIENTS WITH FAT REDISTRIBUTION C Hadigan, R Chung, G Murray, D Purkis and S Grinspoon Antiviral Therapy 2002; 7:L24 (abstract 34) There is growing evidence of increased insulin resistance and diabetes among patients with chronic liver infection. Therefore, we evaluated hepatocellular function and insulin resistance in patients with HIV-lipodystrophy, with and without viral hepatitis. |
| 35 | GLUCOSE METABOLISM ABNORMALITIES ASSOCIATED WITH HIGHLY ACTIVE ANTIRETROVIRAL THERAPY: A COHORT STUDY T Quirino, P Bonfanti, I Faggion, E Ricci, C Martinelli, L Valsecchi, S Carradori, L Pusterla, P Fortuna, L Timillero, S Miccolis, C Magnani, S Landonio, A Gabbuti and GM Vigevani Antiviral Therapy 2002; 7:L25 (abstract 35) To assess the incidence of hyperglycaemia in HIV-positive patients receiving antiretroviral therapy including at least one protease inhibitor (PI). |
| 36 | ABSENCE OF INSULIN RESISTANCE THROUGH WEEK 24 WITH ATAZANAVIR ONCE-DAILY AND EFAVIRENZ ONCE-DAILY EACH WITH FIXED-DOSE ZIDOVUDINE PLUS LAMIVUDINE M Sension1, A Thiry2 and M Giordano2 for the AI424-034 International Study Team Antiviral Therapy 2002; 7:L26 (abstract 36) Atazanavir once-daily as part of a highly active antiretroviral regimen, like efavirenz, is not associated with the development of insulin resistance as assessed by fasting insulin, C-peptide and glucose concentrations. This is unique among PIs and consistent with atazanavir’s effect on GLUT-4 in vitro. In addition, atazanavir was not associated with increases in TC through 24 weeks. Most patients on both the atazanavir and efavirenz regimens had favorable TC/HDL-C ratios. |
| 37 | PROSPECTIVE EVALUATION OF INSULIN RESISTANCE IN HIGHLY ACTIVE ANTIRETROVIRAL THERAPY ASSOCIATED METABOLIC SYNDROME F Visnegarwala, J DarCourt, Q Hasan, P Sajja, O Ong, M Maldonado Antiviral Therapy 2002; 7:L26 (abstract 37) Increase in insulin resistance (IR) and diabetes mellitus (DM) has been associated with the use of protease inhibitors (PI) containing highly active antiretroviral therapy (HAART)-containing regimens. However prospective data in patients newly starting these regimens are limited. |
| Lipid Disorders | |
| 38 | HIV MUTATIONS ASSOCIATED WITH HYPERTRIGLYCERIDAEMIA SJ Anderson Antiviral Therapy 2002; 7:L27 (abstract 38) The lipodystrophy syndrome of HIV patients is characterized by a progressive syndrome of abnormal body fat distribution accompanied by hypertriglyceridaemia. In the course of clinical HIV genotype testing, we observed that our HIV patients with hypertriglyceridaemia had viral genotypes that were more highly mutated than those of therapy-matched control patients. |
| 39 | THE EFFECTS OF SINGLE AND COMBINATIONS OF ANTIRETROVIRAL DRUGS ON PLASMA LIPID AND GLUCOSE LEVELS IN APOE*3 LEIDEN TRANSGENIC MICE M den Boer1,2, JA Romijn2, P Reiss3, M van der Valk3, PJ Voshol1,2, LM Havekes1 Antiviral Therapy 2002; 7:L27 (abstract 39) Similar to what is seen in patients, a pronounced effect on plasma TG was observed in ritonavir-treated mice. This effect could not be explained by an increase in hepatic VLDL-TG production. Indinavir, but not ritonavir, caused impaired glucose tolerance in apoE*3 Leiden transgenic mice. |
| 40 | FACTORS ASSOCIATED WITH THE DEVELOPMENT OF HIGH SERUM TRIGLYCERIDE LEVELS IN PATIENTS RECEIVING TWO NRTI COMBINATIONS M Galli, C Gervasoni, F Adorni, M Piazza, P Morelli, E Gianelli, M Vaccarezza, A d’Arminio Monforte, A Ridolfo and M Moroni Antiviral Therapy 2002; 7:L28 (abstract 40) HT is a frequent finding also in patients on ART who have never been treated with PI or triple combinations. These results confirm and extend our previous findings concerning the increased risk of HT in patients receiving stavudine (J Acquir Immune Defic Syndr 2002 Jan 1;29(1):21-31). |
| 41 | TRIGLYCERIDAEMIA, BUT NOT CHOLESTEROLAEMIA AND GLYCAEMIA, IS A PREDICTOR OF LIPODYSTROPHY: THE RESULTS OF LipoICONA LONGITUDINAL STUDY M Galli, A Cozzi-Lepri, C Gervasoni, AL Ridolfo, F Mazzotta, C de Stefano, N Piersantelli, E Pizzigallo, E Gianelli, M Piazza, M Vaccarezza, A Cappelletti, A d’Arminio Monforte and M Moroni for the LipoICONA Study Group Antiviral Therapy 2002; 7:L29 (abstract 41) The role of current triglyceride levels as a predictor of adipose tissue alterations (ATAs) development was longitudinally assessed in patients entering in their first line antiretroviral therapy (ART) enrolled in LipoICONA, a multicentre study involving 34 clinical centres nested within the Italian Cohort Naive Antiretrovirals (ICONA). |
| 42 | TREATMENT OF HIV-ASSOCIATED DYSLIPIDEMIA: A TIME TREND ANALYSIS 1998-2001 UH Iloeje1, KS Yu-Isenberg, EP Ventura2, AV Tuomari3 Antiviral Therapy 2002; 7:L29 (abstract 42) We noted a significant increase in treatment of dyslipidemia in HIV patients, the prevalence being highest in the PI-exposed with almost 1 in 5 receiving treatment in 2001. The use of a PI significantly increased the odds of receiving lipid therapy. This trend is expected to continue with continued use of PIs. The increased prescribing of lipid-lowering agents among PI patients reflects clinician concern over the risk for subsequent artherosclerosis and may place patients at risk for treatment complications. The management of dyslipidemia in this population represents a poorly described future cost driver. |
| 43 | AGE AND GENDER DIFFERENCES IN TREATMENT OF ANTIRETROVIRAL TREATMENT-ASSOCIATED DYSLIPIDEMIA AMONG HIV/AIDS PATIENTS UH Iloeje1, H Kawabata2 and Y Wu1 Antiviral Therapy 2002; 7:L30 (abstract 43) In our study, male HIV patients on PI therapy were about three times more likely to be on dyslipidemia therapy than female patients on PI therapy. Younger male patients on PI therapy are 32% more likely to be on dyslipidemia therapy than older male patients on PI therapy. These results show a bias towards treating younger male patients. These results may reflect a concern by physicians over the long-term effects of untreated dyslipidemia in these patients. |
| 44 | CHANGES IN LIPID AND LABORATORY PARAMETERS DURING TREATMENT WITH SAQUINAVIR/RITONAVIR 1000/100 MG TWICE DAILY WITH NO NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS IN HEALTHY VOLUNTEERS M Kurowski1, AM Hill2 and C Moecklinghoff3 Antiviral Therapy 2002; 7:L30 (abstract 44) Saquinavir can be boosted with low dose ritonavir (100 mg twice daily) without short-term abnormalities in lipid or other laboratory parameters. By contrast, elevated lipid levels and liver enzyme abnormalities have been observed in short-term Phase I healthy volunteer trials with higher doses of ritonavir (either with or without saquinavir). Lipid elevations have been observed with ritonavir boosted amprenavir, while atazanavir treatment has led to elevated bilirubin levels. |
| 45 | DIFFERENT IMPACT ON METABOLIC PARAMETERS OF AMPRENAVIR/RITONAVIR REGIMENS WITH TENOFOVIR VERSUS EFAVIRENZ M Thompson1, K Tashima2, R Schooley3, R Haubrich4, L Yau5, S Hessenthaler5, J Hernandez5 and K Pappa5 Antiviral Therapy 2002; 7:L31 (abstract 45) The amprenavir regimens described above in combination with low dose ritonavir were well tolerated. Lipid profiles were comparable in patients randomized to the amprenavir 600 mg and amprenavir 900 mg treatment arms. Subjects who received efavirenz with either dose of amprenavir had significant increases from baseline in their total cholesterol and fasting triglyceride levels by 24 weeks. The increase in triglycerides was greater in the efavirenz treatment groups than in the tenofovir treatment groups. |
| 46 | HIGHLY ACTIVE ANTIRETROVIRAL THERAPY WITH EFAVIRENZ: LONG-TERM METABOLIC EFFECTS B Roca, JA Ferrero, JM Marco and C Lapuebla Antiviral Therapy 2002; 7:L32 (abstract 46) HAART with efavirenz causes a mild increase in serum cholesterol, and a mild descent in uric acid, while it has no relevant effect on glucose or triglyceride. Metabolic toxicity of efavirenz seems unimportant. |
| 47 | LIPIDIC ALTERATIONS IN AIDS PATIENTS USING ANTIRETROVIRAL THERAPY REGIMEN CONTAINING LOPINAVIR/RITONAVIR JE Ribeiro1,2, JHS Pilotto1, NAS Santos1, LO Roy1, AMH Moreno1, MLE Pires2, AS Souza2, AC Varela2, CMS Machado2, EA Magalhães2 and HC Maleh2 Antiviral Therapy 2002; 7:L32 (abstract 47) We have 95% of certainty that the increase of TG related to the whole sample was, in median 12.86-326.16 mg/dl (P<0.04), after 26 weeks of using the medication. We observed that among these last 12 patients, two used efavirenz and two stavudine associated to the regimen containing lopinavir/r, but none of them were among those who showed hypertriglycerids (TG >200mg/ml). The date suggests that the late increase of TG by week 26 seems to be directly related to the use of lopinavir/r in AIDS patients. |
| 48 | SHORT-TERM METABOLIC AND ANTHROPOMETRIC EFFECTS OF A PLACEBO-CONTROLLED TRIAL OF PREDNISONE IN HIV-1-INFECTED INDIVIDUALS C Shikuma1, R Kalayjian2, J Jacobson3, RJ Bosch, E Aga4, L Fox5, R Coombs6, H Twigg7, P Bucy8, R Arakaki1 and R Wallis2 for the ACTG 349 Team Antiviral Therapy 2002; 7:L33 (abstract 48) Glucocorticoid use in non-HIV-infected populations usually results in an increase in HDL cholesterol, development of insulin resistance and an increase in total and truncal fat. Little is known about its effect when given to HIV-1-infected individuals. ACTG 349 was a phase II, randomized, multi-centre, double-blinded, placebo-controlled study of the immunological and virological effects of prednisone on HIV infection. |
| 49 | A 36-WEEK SAFETY AND TOLERABILITY STUDY OF EXTENDED-RELEASE NIACIN FOR THE TREATMENT OF HYPERTRIGLYCERIDEMIA IN SUBJECTS WITH HIV S Souza1,2,3, D Chow1,2,3, E Walsh2, D Ishimitsu2, D Ogata-Arakaki2,3 and C Shikuma2,3 Antiviral Therapy 2002; 7:L33 (abstract 49) Niacin has proven efficacious when used for hypertriglyceridemia in the general population. However, concerns regarding safety, in particular increased insulin resistance, has led to limited use in the HIV-infected population. |
| 50 | EFFECTS OF PRAVASTATIN ON LIPIDS AND LIPOPROTEIN SUB-FRACTIONS IN PATIENTS RECEIVING HIV PROTEASE INHIBITORS JH Stein, MA Merwood, JL Bellehumeur and JM Sosman Antiviral Therapy 2002; 7:L34 (abstract 50) Pravastatin is used frequently to treat HIV-infected patients with protease inhibitor (PI)- associated dyslipidemia, however its effectiveness at treating this disorder has not been established in a placebo-controlled trial. Furthermore, the effects of pravastatin on atherogenic lipoproteins and their subfractions have not been determined in patients taking PIs. |
| 51 | INCREASED LEVELS OF POST-PRANDIAL TRIGLYCERIDE-RICH LIPOPROTEINS IN PATIENTS TAKING HIV PROTEASE INHIBITORS MA Merwood, JM Sosman, JL Bellehumeur and JH Stein Antiviral Therapy 2002; 7:L35 (abstract 51) The dyslipidemia associated with use of HIV protease inhibitors (PIs) is characterized by increased levels of triglyceride-rich lipoproteins. In individuals without HIV infection, these lipoproteins are elevated in the post-prandial state. Increased postprandial lipaemia predicts progression of atherosclerosis and future coronary events. |
| 52 | NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR TREATMENT AS A RISK FACTOR FOR HYPERLIPIDAEMIA: RESULTS FROM THE FOCUS TRIAL S Walmsley, J Montaner, M Saag, A Hill, C Barylski, K Chen Antiviral Therapy 2002; 7:L35 (abstract 52) With increased use of highly active antiretroviral therapy (HAART) there is wider recognition of hyperlipidaemias and concern over their long-term impact. Hypertriglyceridaemia has been linked with increased risk of lipodystrophy; hyperlipidaemia may increase long-term risk of coronary heart disease. |
| Cardiovascular Disease | |
| 53 | ELEVATED BLOOD PRESSURE IN HIV-INFECTED INDIVIDUALS RECEIVING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY DC Chow, SC Souza, R Chen, S Richmond-Crum, A Grandinetti, B Shiramizu, K Urada, C Shikuma Antiviral Therapy 2002; 7:L36 (abstract 53) Elevated blood pressure has been associated with HIV lipodystrophy syndrome. We report on the blood pressure (BP) findings among participants of the Hawai’i Sero-Positivity and Medical Management (HSPAMM) program, a Department of Health program that provides semi-annual visits for all its participants with their own primary care physicians. |
| 54 | CORONARY HEART DISEASE IN HIV-INFECTED INDIVIDUALS: ASSOCIATIONS WITH ANTIRETROVIRAL THERAPY J Currier1, A Taylor2, F Boyd3, H Kawabata4, J Maa4, C Dezii4, B Burtcel4 and S Hodder4 Antiviral Therapy 2002; 7:L37 (abstract 54) ART was associated with an increased risk of CHD in young (18-33) but not older individuals with HIV infection adjusting for co-morbidities. Co-morbid conditions associated with CHD in the general population were important predictors of CHD in this population. |
| 55 | LACK OF SIGNIFICANT CHANGES IN BLOOD PRESSURE OF HIV+ SUBJECTS, EVEN AFTER LONG-TERM USE OF PROTEASE INHIBITOR THERAPY L Yao, MO Riordan1, MM Lederman2,3, H Valdez2,3, B Gripshover2,3, B Rodriguez2,3, R Salata2,3 and GA McComsey1,2,3 Antiviral Therapy 2002; 7:L37 (abstract 55) Hypertension (HTN) has been linked to indinavir treatment and to lipodystrophy in HIV-infected subjects. We assess here changes in blood pressure (BP) in HIV-infected patients receiving their first highly active antiretroviral therapy (HAART) regimen. |
| 56 | ASSOCIATION BETWEEN PROTEASE INHIBITORS AND INCREASED CARDIOVASCULAR RISK: A SYSTEMATIC REVIEW D Rhew1,2, M Kim2, M Bernal1, D Aguilar1, U Iloeje3 and MB Goetz2 Antiviral Therapy 2002; 7:L38 (abstract 56) To systematically review studies addressing whether protease inhibitors (PIs) increase risk for cardiovascular (CV) disease in HIV-positive patients. |
| Clinical Management of Adverse Drug Reactions | |
| 57 | LIPOATROPHY IMPROVEMENT AFTER SWITCHING STAVUDINE TO ABACAVIR T García-Benayas1, F Blanco1, J de la Cruz2, V Soriano1 and J González-Lahoz1 Antiviral Therapy 2002; 7:L39 (abstract 57) In HIV-positive patients with subcutaneous lipoatrophy, replacement of stavudine by abacavir is a safe strategy which attempts to stop and slightly improve lipoatrophy assessed by anthropometry and BIA at 12 months. However, significant loss of fat persists in patients that remain on stavudine suggesting its association with this syndrome. |
| 58 | PHYSICIANS' AND PATIENTS' PERCEPTION OF ADIPOSE TISSUE ALTERATIONS CHANGES ACCORDING TO THE MANAGEMENT STRATEGY AM Gatti1, G Guaraldi2, G Migliorino3, V Manfrin4, G Visonà1, C Savio1, R Panebianco1 and M Galli5 on behalf of GLIDER Study Team Antiviral Therapy 2002; 7:L39 (abstract 58) The interventions addressed to improve or revert adipose tissue alterations (ATA) observed in patients on antiretroviral therapy are still under investigation. The more frequently adopted strategies are drug switching (DS), administration of lipid regulating agents (LRA), diet (DT) and physical exercise (PE). The aim of this study was to assess the impact of these interventions on patients’ and physicians’ perception of ATA changes. |
| 59 | DIETARY SUPPLEMENTATION AND EXERCISE REDUCES DIARRHOEA, INCREASES MUSCULAR STRENGTH, AND IMPROVES QUALITY OF LIFE IN HIV-POSITIVE MEN RECEIVING NELFINAVIR C R Heiser1, N French2, MM Russert3, R Slotten2, T Klein2, R Martin4, T Barrett5, S Blackburn6 and J Ernst6 Antiviral Therapy 2002; 7:L40 (abstract 59) The impact of diet, suppl and exercise on nelfinavir related diarrhoea management, body composition, performance and QOL, are effective and clinically significant. The regimen was well tolerated. BIA estimates, using current equations, may be inappropriate for HIV-positive patients. |
| 60 | EFFECTIVENESS OF SUPERVISED EXERCISE PROGRAMME ON FAT ACCUMULATION AND METABOLIC LEVELS IN HIV-INFECTED AFRICAN AMERICANS AND LATINOS S Raghavan, S Iqbal, K Levine, D Tanco, R Minolfo and W El-Sadr Antiviral Therapy 2002; 7:L40 (abstract 60) To determine the effectiveness of on-site supervised bi-weekly exercise program on changes in regional body composition and metabolic levels. |
| 61 | FEASIBILITY AND COST OF IMPLEMENTING AN EXERCISE PROGRAM IN AN INNER CITY SETTING K Levine, S Raghavan, D Tanco, S Iqbal, R Minolfo and W El-Sadr Antiviral Therapy 2002; 7:L41 (abstract 61) Exercise is a potential intervention to address obesity, fat accumulation, hyperlipidemia and insulin resistance commonly reported in HIVinfected individuals. Physical exercise has been suggested as a possible means of addressing these abnormalities and as method to enhance quality of life. |
| 62 | SCIENTIFIC RATIONALE FOR THE CO-ADMINISTRATION OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY AND BICARBONATE-BUFFERED PANCRELIPASE TO TREAT HIGHLY ACTIVE ANTIRETROVIRAL THERAPY INDUCED DIARRHOEA TM Wignot1, RP Stewart2, R Nahass3 and KJ Schray2 (presented by R Holland) Antiviral Therapy 2002; 7:L42 (abstract 62) The therapeutic value of highly active antiretroviral therapy (HAART) is diminished by the side-effects of diarrhoea and steatorrhoea characterized by oily stool due to malabsorption and maldigestion of fats. Inhibition of pancreatic-lipase by HAART has been implicated as a cause of undigested fat-induced diarrhoea. |
| 63 | EFFECT OF EXOGENOUS TESTOSTERONE ON QUALITY OF LIFE AMONG HIV-INFECTED MALES ON HIGHLY ACTIVE ANTIRETROVIRAL THERAPY J Fotheringham1, W Wobeser1, P Ford1, S Tenzif2, R Ross1, and T Liu1 Antiviral Therapy 2002; 7:L42 (abstract 63) Exogenous testosterone (ET) is indicated for hypogonadism, wasting syndrome and may mitigate visceral adiposity. We studied the effect of ET on quality of life (QOL). Baseline and follow-up measures included demographics, clinical status, body composition (MRI) and QOL (MOS-HIV). Population: n=45, mean age 43.4 years, 29% IDU, 16% CD4 <200, 64% undetectable viral load (VL), 40% visceral adiposity (L4/5 visceral adipose tissue >130 cm2), 20% severe lipoatrophy (extremity subcutaneous adipose tissue <5.5kg) and 13% with both. |
| Mitochondrial Disorders | |
| 64 | LACTIC ACIDOSIS IN HIV-INFECTED PATIENTS: A SYSTEMATIC REVIEW OF PUBLISHED CASES A Arenas-Pinto1, A D Grant2, S Edwards3, and IVD Weller1 Antiviral Therapy 2002; 7:L43 (abstract 64) NRTI use and female gender appear to be risk factors for the development of LA. What other factors are involved is still not clear but might include; duration of NRTI therapy, specific drug use and genetic predisposition. A case-control study would provide more robust information on the important predisposing factors associated with the development of severe LA. |
| 65 | FIRST DIRECT PROOF OF MITOCHONDRIAL TOXICITY INDUCED CARDIOMYOPATHY IN AN HIV INFECTED PATIENT FCP Frerichs1, KP Dingemans2, PHJ Frissen1 and K Brinkman1 Antiviral Therapy 2002; 7:L43 (abstract 65) This is the first case report that clearly demonstrates mitochondriocytopathy as the cause of cardiomyopathy in an HIV-infected patient on HAART, most likely induced by the mitochondrial toxicity of NRTIs. |
| 66 | MITOCHONDRIAL DNA CONTENT IN CD4 AND CD8 PERIPHERAL BLOOD LYMPHOCYTES OF HIV+ PATIENTS WITH LIPODYSTROPHY A Cossarizza1, A Riva2, M Pinti1, S Ammannato2, P Fedeli2, C Mussini3, R Esposito3, and M Galli2 Antiviral Therapy 2002; 7:L44 (abstract 66) To evaluate mitochondrial DNA (mtDNA) content in CD4 and CD8 peripheral blood lymphocytes (PBL) from patients with different types of adipose tissue alterations on antiretroviral therapy (ART). |
| 67 | LACTATE ENDOGENOUS PRODUCTION IS A GOOD TOOL TO EVALUATE MITOCHONDRIAL DYSFUNCTION P Leclercq, M Derradji, B Colombe and XM Leverve Antiviral Therapy 2002; 7:L44 (abstract 67) Increase in lactate production is a better marker of mitochondrial impairment than basal lactatemia and is well correlated with clinical outcome. In HIV patients, hyperlactatemia is associated with increase in lactate production and not with an impaired clearance. |
| 68 | This abstract was withdrawn before the Workshop. |
| 69 | REVERSIBLE MITOCHONDRIAL DNA DEPLETION AND MITOCHONDRIAL RESPIRATORY CHAIN DYSFUNCTION IN SYMPTOMATIC HYPERLACTATAEMIA S López1, Ò Miró1, M García2, E Martínez2, A Milinkovic2, JL Blanco2, B Rodríguez3, A Beato1, J Casademont1 and F Cardellach1 Antiviral Therapy 2002; 7:L46 (abstract 69) Depletion in mtDNA occurs during HAART leading to a primary general MRC dysfunction and, consequently to hyperlactataemia as a final phenotypic expression. Our data seem to confirm that mitochondrial dysfunction lies at the basis of developed hyperlactataemia during HAART. |
| 70 | MATCHED CASE CONTROL STUDY TO EVALUATE RISK FACTORS FOR HYPERLACTATAEMIA IN HIV PATIENTS ON ANTIRETROVIRAL THERAPY GJ Moyle, D Datta, S Mandalia, J Morelese and BG Gazzard Antiviral Therapy 2002; 7:L46 (abstract 70) This case control study indicates that when controlling for didanosine use and other metabolic factors, stavudine use is an additional risk for persistent hyperlactataemia. The combination of didanosine and stavudine should be used with care and consideration given to routine monitoring of lactate in these patients. |
| 71 | MITOCHONDRIAL DNA AND SPERM QUALITY IN PATIENTS UNDER ANTIRETROVIRAL THERAPY S Diehl1, P Vernazza2, A Trein3, E Schnaitmann3, B Grimbacher1, B Setzer1 and UA Walker1 Antiviral Therapy 2002; 7:L47 (abstract 71) Some nucleoside reverse transcriptase inhibitors (NRTIs) have been identified in high concentrations in seminal plasma where they may interfere with spermatogenesis and sperm motility by inhibiting the replication of mitochondrial DNA (mtDNA). |
| Body Composition | |
| 72 | REPRODUCIBILITY OF DEXA ESTIMATIONS OF BODY FAT IN HIV LIPODYSTROPHY: IMPLICATIONS FOR RESEARCH RB Cavalcanti, A Cheung, J Raboud and S Walmsley Antiviral Therapy 2002; 7:L48 (abstract 72) DEXA measurements of regional body-fat mass in subjects with HIV lipodystrophy show similar reproducibility to that found in other populations studied. Minimal detectable differences were smaller than changes observed in published cohort data for all measurements except trunk-fat mass. DEXA is a sensitive tool for detecting long-term changes in peripheral fat among patients with HIV lipodystrophy. |
| 73 | THE IMPACT OF LIPODYSTROPHY ON HEALTH RELATED QUALITY OF LIFE, BODY IMAGE, MOOD, SELF-ESTEEM AND MEDICATION COMPLIANCE EJ Collins1, RW Burgoyne1, CA Wagner2, MH Halman1 and SL Walmsley3 Antiviral Therapy 2002; 7:L48 (abstract 73) LD is negatively associated with some self-report measures of QOL. Despite significant impairment in BI there is no apparent effect on mood, self-esteem or medication compliance as measured in this sample. The impact on QOL was greater in younger subjects suggesting that age may mediate the negative impact of LD. |
| 74 | ANTHROPOMETRIC MEASURES ARE POOR SURROGATE MARKERS FOR MONITORING CHANGE IN ABDOMINAL ADIPOSITY IN HIV PATIENTS TREATED WITH GROWTH HORMONE DP Kotler1, M Thompson2,P Chang3, J Gertner3, N Muurahainen3, and the STARS Trial Investigator Group4 Antiviral Therapy 2002; 7:L49 (abstract 74) Waist circumference and waist/hip ratio appear to be poor surrogate markers to track changes in DXA trunk fat or VAT on abdominal CT scan in this setting. Although the linear regressions had statistically significant P values, the strength of correlation was low. |
| 75 | VISCERAL ADIPOSITY IN A GROUP OF MEN ON ANTIRETROVIRAL THERAPY IS ASSOCIATED WITH LOW SERUM TESTOSTERONE T Liu1, W Wobeser1, P Ford1, S Tenzif2, R Ross1 and J Fotheringham1 Antiviral Therapy 2002; 7:L49 (abstract 75) Exogenous testosterone is indicated for HIV-associated wasting syndrome. However, the effect of exogenous testosterone on body habitus changes in HIV is not known. Visceral adiposity is a marker of increased metabolic risk for cardiovascular events, which is a common finding among persons on antiretroviral therapy. |
| 76 | LIFESTYLE CORRELATES OF HIV-RELATED LIPODYSTROPHY DE Lyon1, J Salyer2, J Settle3 Antiviral Therapy 2002; 7:L50 (abstract 76) Both the short-term and long-term health risks of antiretroviral are becoming a primary concern of persons living with HIV disease. In addition, cosmetic changes related to this syndrome are very distressing for those affected. As such, researchers and clinicians need to develop better measures of HIV-lipodystrophy syndrome and to develop interventions to ameliorate the health risks of this metabolic complication. Since life-style modifications have improved morbidity and mortality in other chronic disease populations, it is important to further explore the relationship of potentially modifiable risk factors (dietary habits and functional capacity) and their relationship to physical and metabolic alterations observed in HIV-lipodystrophy syndrome. |
| 77 | RAPID DEVELOPMENT OF CENTRAL ADIPOSITY AFTER ANTIRETROVIRAL EXPOSURE - A PROOF OF PRINCIPLE? S Mauss, F Berger, H Carls and G Schmutz Antiviral Therapy 2002; 7:L51 (abstract 77) This is the first case report of the development of central lipohypertrophy in an HIV-seronegative patient after exposure to antiretroviral combination therapy. Although the patient did not develop metabolic abnormalities nor lipoatrophy, this case report may be a limited proof of principle that the changes in adipose tissue are caused by antiretroviral treatment rather than HIV-infection itself. |
| 78 | PRETREATMENT LEPTIN LEVELS MAY PREDICT RISK OF LIPOATROPHY WHILE CD4 CELL COUNTS, TUMOUR NECROSIS FACTOR AND ON-TREATMENT CHANGES IN THESE INDICES DO NOT G McComsey1,2, J Maa3, B Gripshover2, H Valdez2, R Kalayjian2, R Salata2 and MM Lederman2 Antiviral Therapy 2002; 7:L51 (abstract 78) Host factors may play a role in development of LA after antiretroviral therapy. Longer duration of therapy, older age, and lower pretherapy leptin levels correlated with increased risk of future LA. Pretherapy body fat, weight, CD4, plasma TNF and TNF rII levels were similar in the patients who later developed LA and those who did not. On-treatment changes in these indices did not predict risk of LA. |
| 79 | COMPARATIVE ASSESSMENT OF BODY COMPOSITION IN ANTIRETROVIRAL-NAÏVE HIV-INFECTED ADULTS WITH DIFFERENT OBJECTIVE METHODS A Milinkovic, E Martinez, S Vidal, L Bianchi, C Ayuso, JL Blanco, F Pons and JM Gatell Antiviral Therapy 2002; 7:L52 (abstract 79) In antiretroviral-naïve asymptomatic HIV-infected adults without clinical evidence of body fat abnormalities, fat measurements are highly dispersed. This dispersion may be due in part to BMI but not to sex. DEXA, abdominal CT scan and sonography may be indistinctly used to measure regional fat in HIV-infected adults. |
| 80 | THE EFFECT OF CENTRALIZED BODY COMPOSITION DATA ANALYSIS ON AN OBJECTIVE CASE DEFINITION OF HIV LIPODYSTROPHY RL Puls1, M Law1, J Freund2, D Gallagher3, M Punyanitya3, S Kalnins2 and A Carr2 for the HIV Lipodystrophy Case Definition Study Group Antiviral Therapy 2002; 7:L53 (abstract 80) Centralized DEXA and CT soft tissue data did not differ significantly from data derived from local analysis, but were up to 9% less variable. Central analysis did not substantially simplify the original LD CD model, nor significantly alter its sensitivity or specificity. |
| 81 | HYPOTHALAMIC PITUITARY GONADAL AXIS NORMALIZATION PROTOCOL AFTER ANDROGEN TREATMENT N Vergel1, AL Hodge2, MC Scally3 Antiviral Therapy 2002; 7:L53 (abstract 81) The use of androgens has been reported to improve lean body mass, strength, sexual function, and mood, accompanied by side-effects caused by continuous uninterrupted use of these compounds (polycythemia, testicular atrophy, hypertension, liver dysfunction [oral androgens] and alopecia). Androgeninduced HPGA suppression causes a severe hypogonadal state in most patients that often require an extensive period of considerable duration for normalization. This prevents most if not all individuals from cycling off these medications due to the adverse impact of this state on their previously gained LBM and quality of life. The protocol of hCG-clomiphene-tamoxifen was successful in restoring the HPGA within 45 days after androgen cessation. Further controlled studies are needed to determine if these results can be duplicated in HIV-positive subjects. |
| 82 | A PROSPECTIVE STUDY OF BODY FAT REDISTRIBUTION AND METABOLIC ABNORMALITIES IN PATIENTS INITIATING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY S Walmsley, A Foster, J Raboud, R Saskin, A Cheung, G Fantas, R Clarke and K Logue Antiviral Therapy 2002; 7:L54 (abstract 82) Mild changes in body fat redistribution primarily in the trunk and waist occur within the first 2 years of initiation of PI-based antiretrovirals. Increases in cholesterol and triglyceride are observed, although usually remain within the normal range. Although insulin resistance is noted, frank diabetes is uncommon. |
| Bone Disease | |
| 83 | IMPAIRMENT IN BONE REMODELLING IN HIV-INFECTED MEN BEFORE THE ONSET OF ANTIRETROVIRALS C Amiel1, L Slama1, T Nguyen1, A Ostertag2, E Lajeunie3, MC de Vernejoul2 and W Rozenbaum1 Antiviral Therapy 2002; 7:L55 (abstract 83) Bone formation is decreased and bone resorption is increased in patients compared with controls. Among the HIV-positive, bone formation is decreased in untreated patients compared with patients treated with PI. In conclusion, treating patients for HIV infection could reduce the defect in bone formation. |
| 84 | RELATION BETWEEN REGIONAL BODY COMPOSITION AND BONE MINERAL DENSITY: EFFECT OF THE HIV/HAART-ASSOCIATED LIPODYSTROPHY SYNDROME J Falutz and L Rosenthal Antiviral Therapy 2002; 7:L55 (abstract 84) Increased trunk/peripheral FM ratio in HAL-positive patients may be due more to peripheral lipoatrophy than to truncal fat accumulation. Compared with HIV-negative patients, there is preferential BMC loss in HAL-positive patients at the femoral neck relative to the lumbar spine, possibly due to increased peripheral FM loss. |
| 85 | BONE MINERAL DENSITY IS DECREASED IN HIV-INFECTED MEN BEFORE THE ONSET OF ANTIRETROVIRALS C Amiel1, L Slama1, T Nguyen1, A Ostertag2, E Lajeunie3, MC de Vernejoul,2, W Rozenbaum1 Antiviral Therapy 2002; 7:L56 (abstract 85) Osteoporosis has been reported in HIV-infected patients and has been suggested to be related to antiretrovirals (ARVs). In order to assess this risk, and to investigate its putative link with ARVs, we compared the BMD of HIV-positive men treated with protease inhibitors (PI+), treated without PI (PI–) using three nucleoside reverse transcriptase inhibitors (NRTIs) or using two NRTIs + one non-nucleoside reverse transcriptase inhibitor (NNRTI), and untreated patients (UT). |
| Hepatoxicity | |
| 86 | DRUG INDUCED HEPATITIS IN HIV-POSITIVE PATIENTS B Dalal1, P Dalal2, P Garg1, J Shah1, H Shah1, H Desai2, K Nanavati1, I Dalal3, K Goplani1, T Madan1, K Lakhani1 and S Agarwal1 Antiviral Therapy 2002; 7:L56 (abstract 86) In developing countries AKT induced hepatitis is still common cause of hepatic involvement in HIV-positive patients. Nevirapine induced hepatic dysfunction is not frequently encountered compared with the other studies. Probable reason behind this is low dose of nevirapine (200 mg once a day) during the first two weeks, which was then increased to 200 mg twice a day. Because of the lower number of symptomatic patients problems of liver dysfunction are ignored in HIV-positive patients, but proper considerations will definitely improve the outcome. |
| 87 | THE VIRAMUNE® (NEVIRAPINE) HEPATIC SAFETY PROJECT: ANALYSIS OF SYMPTOMATIC HEPATIC EVENTS SM Imperiale, SF Lanes, JO Stern, JT Love, PA Robinson, DL Mayers. Antiviral Therapy 2002; 7:L57 (abstract 87) A number of cohort studies and prospective analyses have demonstrated that the incidence of asymptomatic elevations of ALT and AST is similar for all antiretrovirals and is associated with viral hepatitis co-infection and elevated baseline values. Nevirapine, however, has been associated with an increased risk of symptomatic hepatic events. The objective of this analysis was to characterize as fully as possible the hepatic safety of nevirapine. |
| 88 | TARGET: INCIDENCE OF ELEVATED ALT/AST WITH HIGHLY ACTIVE ANTIRETROVIRAL THERAPY IN A LARGE OBSERVATIONAL COHORT SM Imperiale, SF Lanes, JO Stern, JT Love, PA Robinson and DL Mayers Antiviral Therapy 2002; 7:L58 (abstract 88) Abnormal liver function tests (LFTs) are common in HIV patients receiving highly active antiretroviral therapy (HAART). However, a perception exists that these events are more frequent with nevirapine- based regimens than with other HAART regimens. In order to investigate the role of nevirapine and other possible risk factors, we have studied a large observational cohort. |
| 89 | LOW INCIDENCE OF HEPATIC EVENTS IN PATIENTS SWITCHING FROM PROTEASE INHIBITOR TO NEVIRAPINE SM Imperiale, S Storfer, JO Stern and DL Mayers Antiviral Therapy 2002; 7:L58 (abstract 89) Analysis of controlled studies of nevirapine have shown that the risk of rash-associated hepatic events is increased in women with CD4 cell counts >250 cells/mm3 and in men with counts >400 cells/mm3. While these previous analyses were conducted in treatment-naïve patients or patients who were failing nucleoside analogue therapy, many subjects now initiate nevirapine after developing protease inhibitor (PI)-associated lipodystrophy. This retrospective analysis therefore investigated the incidence of hepatic events in patients who switched from a PI to nevirapine after undergoing immune reconstitution. |
| 90 | MECHANISMS UNDERLYING MITOCHONDRIAL TOXICITY IN HIGHLY ACTIVE ANTIRETROVIRAL THERAPY-ASSOCIATED LACTIC ACIDOSIS AND HEPATOTOXICITY PV Nerurkar1, L Pearson1, JE Frank2, R Yanagihara1 and VR Nerurkar1 Antiviral Therapy 2002; 7:L59 (abstract 90) Mitochondrial uncoupling proteins are known to alter membrane potential and oxygen consumption, and are proposed to play a major role in energy expenditure. Our results indicate that ARTassociated uncoupling of oxidative phosphorylation is probably involved in HAART-associated lactic acidosis and hepatotoxicity. These results indicate that not only NRTIs, but also PIs and NNRTIs can contribute towards HAART-associated mitochondrial toxicity. Understanding the mechanisms underlying hepatotoxicity will provide safer drug design as well as assist clinicians in determining the best combination therapy with fewer adverse side effects. |
| 91 | CHARACTERISTICS OF PATIENTS WHO DIE IN THE HIGHLY ACTIVE ANTIRETROVIRAL THERAPY ERA B Roca and JM Marco Antiviral Therapy 2002; 7:L59 (abstract 91) The availability of highly active antiretroviral therapy (HAART) has had a dramatic impact in the HIV epidemic, with a clear decline in morbidity and mortality. Nevertheless, even in developed countries with the widespread use of effective treatment, HIV-related deaths are still occurring. We describe the characteristics of the HIV-infected patients of our cohort who have died in the HAART era. |
| Other toxicities | |
| 92 | HAEMATOLOGICAL CHANGES IN PATIENTS RANDOMIZED TO HAART REGIMENS CONTAINING EITHER ZIDOVUDINE OR STAVUDINE J Amin1, A Carr2, A Hill3, S Emery1, M Law1, and DA Cooper1,2 Antiviral Therapy 2002; 7:L60 (abstract 92) To compare differences in change from baseline to week 52 in haematological parameters between HIV-infected patients randomized to HAART regimens containing zidovudine or stavudine. |
| 93 | HIGH RATE OF GASTROINTESTINAL SIDE EFFECTS IN PATIENTS TREATED WITH AMPRENAVIR, LOPINAVIR AND RITONAVIR (200 MG TWICE DAILY) S Mauss1, S Scholten2, E Wolf3, F Berger1, G Schmutz1, E Postel3, and JK Rockstroh2 Antiviral Therapy 2002; 7:L61 (abstract 93) Diarrhoea and nausea are frequent side effects in a pilot study with amprenavir 600 mg twice daily, lopinavir 400 mg twice daily boostered by ritonavir 200 mg twice daily leading to treatment discontinuation in the majority of patients. Tolerance seems to be substantially lower compared to historical controls on ritonavir 100 mg twice daily without substantial increases in amprenavir or lopinavir drug levels. In addition the discontinuation rate is in excess of study data reported from lopinavir or amprenavir as a single ritonavir boostered protease inhibitor. |
| 94 | A META-ANALYSIS OF CHANGES IN HAEMOGLOBIN, CD4 AND VIRAL LOAD OVER 24 AND 48 WEEKS ACROSS SIX RANDOMISED TRIALS OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY REGIMENS COMPARING STAVUDINE AND ZIDOVUDINE IN TREATMENT-NAÏVE INDIVIDUALS GJ Moyle1, M Law2, AW Sawyer and A Hill3 Antiviral Therapy 2002; 7:L61 (abstract 94) Haematological abnormalities may increase risk of morbidity and mortality HIVinfected individuals. In both antiretroviral treated and untreated individuals anaemia is independently associated with increased risk of disease progression and death. A fall in haemoglobin (Hb) of 1 g/dl was associated with an increased relative risk of death of 1.4 in two studies and recovery from anaemia has been associated with improved prognosis. Anaemia also impacts a range of dimensions of quality of life most commonly due to its association with fatigue. |
| 95 | THYROID ABNORMALITIES IN PATIENTS RECEIVING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY T Quirino, P Bonfanti, E Chebat, I Faggion, C Martinelli, R Giuntini, L Valsecchi, S Carradori, S Landonio, A Gabbuti, C Gulisano and GM Vigevani Antiviral Therapy 2002; 7:L62 (abstract 95) This study was designed to assess the frequency of thyroid hormone abnormalities in HIV-positive patients treated with a highly active antiretroviral therapy (HAART) regimen. |
| 96 | HIGH RATE OF THYROID DYSFUNCTION IN HIV-INFECTED CHILDREN RECEIVING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY A Viganò1, S Riboni1, R Bianchi1, S Beccio1, T Vago2, B di Natale1 Antiviral Therapy 2002; 7:L62 (abstract 96) Thyroid abnormalities occur frequently in HAART-treated children with long-lasting immune recovery and control of viral replication. Three distinctive features were identified: isolated low FT4 syndrome, sub-clinical hypothyroidism and autoimmune thyroiditis. These findings indicate the need for regular monitoring of thyroid function in HAART-treated children. |
| Cohort Studies | |
| 97 | VISIBLE VEINS - THE MOST SPECIFIC CLINICAL SIGN IN LIPOATROPHY. RESULTS FROM THE OSLO HIV-COHORT STUDY 2000 BM Bergersen1, L Sandvik2, O Dunlop1 and JN Bruun1 Antiviral Therapy 2002; 7:L63 (abstract 97) In our study 49% of white, non-injecting men who had been on ART ≥2 years had visible veins. However, visible veins were very unusual in ART-naïve patients and thus the most specific clinical sign in ART-induced lipoatrophy. Visible veins did not become apparent until 2 years on ART. We propose that the appearance of visible veins is a late, but specific clinical sign in ART-induced lipoatrophy. These findings may be a helpful tool in differentiating between ‘classical’ wasting and ART-induced lipoatrophy and should be taken into account in future studies of ART-induced body changes. |
| 98 | THE SCOLTA PROJECT: AN ON-LINE ITALIAN POST-MARKETING SURVEILLANCE METHOD FOR REPORTING ADVERSE REACTIONS TO ANTIRETROVIRAL DRUGS P Bonfanti, T Quirino, S Landonio, I Faggion, F Parazzini and GM Vigevani for the CISAI group Antiviral Therapy 2002; 7:L64 (abstract 98) The highly active antiretroviral therapy (HAART) regimen has radically changed the course of HIV infection, reducing mortality and lowering the incidence of opportunistic infections. However, adverse events (AE) related to therapy are on the rise. Some are completely unforeseeable, appearing either in the short term or after considerable intervals. |
| 99 | PHYSICIAN-PATIENT CONCORDANCE ON LIPODYSTROPHY SEVERITY AM Gatti1, G Guaraldi2, G Migliorino3, V Manfrin4, G Visonà1, C Savio1, R Panebianco1, M Galli5 on behalf of GLIDER Study Team Antiviral Therapy 2002; 7:L64 (abstract 99) Measurement and classification criteria for lipodystrophy during antiretroviral therapy (ART) are still under discussion. Several studies are based on clinical observation, including or not including patients reports or complaints. Studies on adherence showed frequent patient–physician discordance: the same could occur in lipodystrophy evaluation considering that patient selfperception has a relevant impact on psychological status. |
| 100 | THE TEMPORAL RELATIONSHIP BETWEEN LIPOATROPHY AND LIPOHYPERTROPHY IN HIV-ASSOCIATED LIPODYSTROPHY WF Pewen, BC Calhoun, SA Riddler and LA Kingsley Antiviral Therapy 2002; 7:L65 (abstract 100) HIV-infected men of the Pittsburgh Multicenter AIDS Cohort Study (MACS) were studied for 3 years at 6 month intervals to assess the development of lipodystrophy (HIV-LS). Isolated lipoatrophy (LA) was determined when examiner-assessed moderate or severe lipoatrophy of two or more sites (face, arms, legs and buttocks) was present (n=27). Mixed lipodystrophy (ML) added moderate or greater lipohypertrophy of the abdomen or breast (n=12). After 3 years, the prevalence of LA increased from 7.7% to 28.1%, whereas ML prevalence increased from 1.0% to 12.5%. |
| 101 | BASELINE LINE RESULTS OF THE INCIDENCE AND INTENSITY OF ADVERSE EVENTS ACCORDING TO DIFFERENT HAART REGIMENS OF A 3 YEAR PROSPECTIVE COHORT (THEMIS) OF 725 HIV-POSITIVE PATIENTS AND THEIR 108 PHYSICIANS E Trenado, D Smadja and H Gaigi (Médiscan) Antiviral Therapy 2002; 7:L65 (abstract 101) To evaluate the incidence of adverse events in HIV-positive patients, according to the type of highly active antiretroviral therapy (HAART) prescribed through self-administrated questionnaires. |
| 102 | SIGNIFICANT PREVALENCE OF WASTING AMONG WOMEN ON HAART 1997-2002 DOCUMENTED BY BIOELECTRICAL IMPEDANCE ANALYSIS P Wasserman, S Segal-Maurer and David Rubin Antiviral Therapy 2002; 7:L66 (102) Over half of the cohort was either obese or wasted at one point during observation. Change occurred primarily in FM. FM remains more labile than BCM in wasting and obesity in the setting of HIV infection. Repletion after wasting and weight gain, involved increases in BCM and FM. Risk of weight loss or gain appears equal. Incidence of wasting is close to three times that of obesity. Obesity appears more host-than treatment-related, as incidence is much lower than prevalence. Our data suggests that repletion of BCM as well as FM, in patients with HIV wasting on HAART, occurs despite recent reports to the contrary. |
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