|
2nd International Workshop on Adverse Drug Reactions
|
| INTRODUCTION |
|
| MR | MEETING REPORT: 2ND INTERNATIONAL WORKSHOP ON ADVERSE DRUG REACTIONS AND LIPODYSTROPHY IN HIV Antiviral Therapy 2000; 5(Supplement 5):xv David Cooper and Morris Schambelan (Workshop Co-chairs) The 2nd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV was held over 3 days from 13-15 September 2000 in Toronto, Canada. As the incidence of treatment-associated complications increases with the prolonged use of antiretroviral drugs, this annual Workshop has become a premier forum for the exchange of basic science and clinical data on the pathophysiology and management of this diverse and multi-factorial group of conditions. |
| Oral Presentations Abstracts O1 to O33, pages 3 through 21 |
|
| O1 | THE PHYSIOLOGY OF LIPOATROPHY Antiviral Therapy 2000; 5(Supplement 5):3 (abstract no. O1) M Reitman All aspects of the A-ZIP/F-1 phenotype, including hyperphagia, hepatic steatosis, and somatomegaly, were either partially or completely reversed. The beneficial effects of transplantation were dose-dependent and required near-physiological amounts of transplanted fat. These experiments demonstrate that the lack of fat is the cause of the metabolic abnormalities of lipoatrophy. We are continuing to dissect the contributions of adipose tissue that, when absent, cause diabetes. |
| O2 | LESSON FROM LIPODYSTROPHIC MICE - A VICIOUS CYCLE IN METABOLISM Antiviral Therapy 2000; 5(Supplement 5):3 (abstract no. O2) I Shimomura Despite IRS-2 deficiency, insulin continues to stimulate production of SREBP-1c, a transcriptional factor that activates fatty acid synthesis. The combination of insulin resistance (inappropriate gluconeogenesis) and insulin sensitivity (elevated lipogenesis) establishes a vicious cycle that aggravates hyperinsulinemia and insulin resistance in lipodystrophy. |
| O3 | THE HIV-PROTEASE INHIBITOR INDINAVIR IMPAIRS ADIPOCYTE DIFFERENTIATION AND INDUCES INSULIN RESISTANCE BY PROBABLY ALTERING ADD1/SREBP-1 MATURATION Antiviral Therapy 2000; 5(Supplement 5):4 (abstract no. O3) M Caron1, M Auclair1, C Vigouroux1, M Glorian2, C Forest2 and J Capeau1 Indinavir impaired adipocyte differentiation at an early step of adipose conversion probably involving the proteolytic maturation of SREBP-1, a major transcription factor controlling adipocyte differentiation and cell response to insulin. Our findings provide a possible explanation for the mechanism of subcutaneous cellular fat loss in PI-associated lipodystrophy. |
| O4 | EFFECTS OF NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS AND HIV PROTEASE INHIBITORS ON ADIPOGENESIS AND ADIPOCYTE METABOLISM Antiviral Therapy 2000; 5(Supplement 5):4 (abstract no. O4) RA Parker, DS Meyers, BA Andrews, OP Flint and SK Durham Over 4-6 days' exposure, PIs suppressed TG accumulation and promoted lipolysis at lower concentrations than those affecting mitochondrial function. Nelfinavir, saquinavir and ritonavir were more potent inhibitors of adipogenesis than indinavir and amprenavir. In contrast, NRTIs weakly affected adipogenesis and lipolysis with minimal effects on ATP levels under these conditions. These data do not support direct NRTI-induced mitochondrial toxicity in adipocytes as a main mechanism for LD, but are consistent with a multifactorial etiology of LD in HIV-AIDS, including previous or current exposure to certain PIs. |
| O5 | PRIMARY AND SECONDARY CAUSES OF MITOCHONDRIAL DYSFUNCTION Antiviral Therapy 2000; 5(Supplement 5):5 (abstract no. O5) AHV Schapira These effects were first observed in zidovudine-treated patients who developed a myopathy with ragged red fibres and low mtDNA levels. Other drugs may have similar actions and be responsible for some of the side-effects seen with combination therapy. |
| O6 | DECREASE OF MITOCHONDRIAL DNA CONTENT IN ADIPOSE TISSUE OF HIV-1-INFECTED PATIENTS TREATED WITH NRTIs Antiviral Therapy 2000; 5(Supplement 5):5 (abstract no. O6) UA Walker1, M Bickel2, SI Lütke Volksbeck1, H Schöfer3, B Setzer1, V Rickerts2 and S Staszewski2 Treatment with NRTIs is associated with decreased mtDNA-levels in subcutaneous fat. Patients with lipoatrophy had significantly lower mtDNA content than patients without. This suggests a link between mitochondrial damage due to NRTIs and the presence of lipoatrophy in HIV infected patients. |
| O7 | SUBCUTANEOUS ADIPOSE TISSUE MITOCHONDRIAL DNA ANALYSIS FROM INDIVIDUALS WITH HAART-ASSOCIATED LIPODYSTROPHY Antiviral Therapy 2000; 5(Supplement 5):6 (abstract no. O7) C Shikuma, N Hu, C Milne and B Shiramizu Preliminary data suggest absence/ decreased amounts of mtDNA in subcutaneous adipose tissue of HIV-infected individuals with lipodystrophy, which is consistent with possible mitochondrial toxicity. Further analysis of specific mutations from the tissue-specific areas are needed to determine if deletion/insertion mutations are present in the mtDNA. |
| O8 | ANTI-OXIDANTS RESCUE NRTI-INDUCED METABOLIC CHANGES IN AKR/J MICE Antiviral Therapy 2000; 5(Supplement 5):6 (abstract no. O8) M Paulik, M Lancaster, D Croom, D Spencer, J Weiel and J Lenhard Zidovudine and stavudine had different effects on metabolism in mice, indicating these agents affect distinct metabolic pathways. Moreover, ascorbate and tocopherol reversed various effects of stavudine, indicating some metabolic changes associated with NRTIs may be due to increased oxidative stress. |
| O9 | THE EFFECTS OF A VARIETY OF PROTEASE INHIBITORS ON INSULIN BINDING, INSULIN-MEDIATED SUGAR TRANSPORT AND CELL TOXICITY IN INSULIN TARGET AND NON-TARGET CELL CULTURES Antiviral Therapy 2000; 5(Supplement 5):7 (abstract no. O9) RJ Germinario1,3, SP Colby-Germinario3, C Cammalleri2 and M Wainberg1,3 It is apparent that several metabolic effects are induced by the PIs. The effects on sugar transport and insulin binding suggest perturbations in the insulin response system. We feel that these data provide some indication of the site(s) that may be affected in vivo |
| O10 | METABOLIC EFFECTS OF INDINAVIR IN HEALTHY HIV-SERONEGATIVE SUBJECTS Antiviral Therapy 2000; 5(Supplement 5):8 (abstract no. 010) M Noor1, J Lo2, K Mulligan2, R Halvorsen2, JM Schwarz2,3, M Schambelan2 and C Grunfeld1 Treatment with indinavir in the absence of HIV infection or changes, in body composition causes insulin resistance with little effect on lipids and lipoproteins. |
| O11 | ASSESSMENT OF GROWTH HORMONE PHYSIOLOGY IN THE HIV LIPODYSTROPHY SYNDROME Antiviral Therapy 2000; 5(Supplement 5):8 (abstract no. O11) P Rietschel, C Hadigan, C Corcoran, T Stanley, J Gertner and S Grinspoon These data demonstrate that increased visceral abdominal fat strongly predicts reduced GH concentrations in patients with the HIV lipodystrophy syndrome. Further studies are necessary to determine the physiological relevance of reduced GH in patients with the HIV lipodystrophy syndrome. |
| O12 | THE EFFECTS OF RECOMBINANT HUMAN GROWTH HORMONE ON GLUCOSE METABOLISM AND BODY COMPOSITION IN HIV-POSITIVE SUBJECTS WITH FAT ACCUMULATION SYNDROMES Antiviral Therapy 2000; 5(Supplement 5):9 (abstract no. O12) JC Lo1, K Mulligan1, M Noor1, J-M Schwarz1,2, C Grunfeld1 and M Schambelan1 Short-term GH therapy at 3 mg/day reduced buffalo hump and abdominal girth in subjects with HIV-associated FA. Although insulin sensitivity and glucose tolerance initially worsened, improvement toward baseline was seen at 6 months, possibly due to reduction in body fat. Screening OGT should be obtained to exclude subjects at risk for GH-induced hyperglycemia. |
| O13 | CHANGES IN HIV-ASSOCIATED FAT MALDISTRIBUTION OVER TIME Antiviral Therapy 2000; 5(Supplement 5):9 (abstract no. O13) KA Lichtenstein1, KM Delaney2, DJ Ward3, AC Moorman2, FJ Palella4, SD Holmberg5 and K Wood5, the HOPS Investigators Although the overall increase in fat misdistribution was modest, a comparison of atrophy versus accumulation revealed marked change over the 20 months, with greater incidence of atrophy (22%) versus accumulation (8%) and contrasting rates of improvement (atrophy, 17% versus accumulation, 40%). The prevalence of fat atrophy increased substantially (17 to 33% in under 20 months) in comparison with accumulation (10 to 13%). |
| O14 | A PROSPECTIVE COHORT STUDY ON THE RISK FOR LIPODYSTROPHY IN HIV-1- INFECTED PATIENTS TREATED WITH PROTEASE INHIBITOR-CONTAINING REGIMENS Antiviral Therapy 2000; 5(Supplement 5):10 (abstract no. O14) E Martínez1, A Mocroft2, MA Garcia-Viejo1, JB Pérez-Cuevas1, JL Blanco1, J Mallolas1, L Bianchi1, I Conget1 and JM Gatell1 Risk factors for any LD, LD with SL, and LD with CO in HIV-1-infected patients receiving PI-containing HAART are multifactorial and overlapping, and cannot be exclusively ascribed to the duration of exposure to any particular antiretroviral agent. |
| O15 | PREVALENCE OF LIPODYSTROPHY IN A COHORT OF ASIAN HIV PATIENTS Antiviral Therapy 2000; 5(Supplement 5):10 (abstract no. O15) N Paton, J Aboulhab, Y-M Ng, F Karim and C-C Lee Body shape changes were reported commonly in this group of mainly Chinese HIV patients. However, the high frequency of changes in treatment-naive patients (even after excluding those with wasting and Ols) illustrates the difficulty of distinguishing treatment-related lipodystrophy from variations occurring as part of the disease course. PI treatment was significantly associated with fat accumulation or a mixed picture. |
| O16 | PREVALENCE OF LIPODYSTROPHY SYNDROME IN A COHORT OF PATIENTS EXPOSED TO ANTIRETROVIRAL DRUG THERAPY Antiviral Therapy 2000; 5(Supplement 5):11 (abstract no. O16) E Ekong1, A Uwah2 and A Akanmu3 ARV drug-induced LS is common, especially in PI-treated patients. Diabetes and other metabolic complications are also common. Truncal obesity and wasting of buttock muscles are the most common forms of lipodystrophy. |
| O17 | PREVALENCE SURVEY OF LIPODYSTROPHY IN HIV-POSITIVE PATIENTS IN JAPAN Antiviral Therapy 2000; 5(Supplement 5):12 (abstract no. O17) HE Fraser1, M Ishihara1, JE Miller2, M Law2, A Yasuoka1, Y Kikuchi1, N Tachikawa1, I Genka1, K Teruya1, M Watanabe1 and S Oka1 It appears from this survey that the prevalence of lipodystrophy in HIV-positive patients in Japan is similar to that found in studies of HIV-positive patients in Western cohorts. |
| O18 | HIV PROTEASE INHIBITORS INCREASE SECRETION OF APOLIPOPROTEIN B-LIPOPROTEINS FROM HEPATOMA CELLS BY PREVENTING PROTEASOMAL DEGRADATION Antiviral Therapy 2000; 5(Supplement 5):12 (abstract no. O18) J-S Liang1, O Distler1, DA Cooper2, SL Sturley1 and HN Ginsberg1 PI treatment can increase the assembly and secretion of apoB-lipoproteins. These results provide a potential molecular basis for PI-associated hypertriglyceridemia. |
| O19 | DIRECT EFFECTS OF PROTEASE INHIBITORS ON LIPID METABOLISM IN CULTURED MAMMALIAN CELLS Antiviral Therapy 2000; 5(Supplement 5):13 (abstract no. O19) O Distler1, JS Liang2, DA Cooper3, HN Ginsberg2, RJ Deckelbaum2 and SL Sturley2 We propose that hypertriglyceridaemia associated with ritonavir treatment may in part result from a defect in clearance of particles. The inhibition of the ACAT reaction may alter multiple aspects of lipid metabolism,. including lipoprotein assembly, lipoprotein composition and transcriptional control of cholesterol homeostasis, all of which could contribute to the complications seen with current anti-HIV therapies. |
| O20 | DIFFERENCES IN POSTPRANDIAL LIPID METABOLISM IN PATIENTS WITH PI-ASSOCIATED AND NRTI-ASSOCIATED LIPODYSTROPHY Antiviral Therapy 2000; 5(Supplement 5):13 (abstract no. O20) LJ Ware1, J Morlese2, G Burdge1, AA Jackson1, B Gazzard2 and SA Wootton1 While the PI-treated lipodystrophy group show an increased retention time of dietary lipid within the circulation as lipoprotein TAG, the NRTI-treated lipodystrophy group show an increased retention time of dietary lipid within the circulation as NEFA. These results suggest that there may be different effects of these two drug classes on lipid metabolism in vivo which may influence the development of the changes in body composition. |
| O21 | CHANGES IN REGIONAL BODY FAT AND SERUM TRIGLYCERIDES AND CHOLESTEROL IN HIV-INFECTED CHILDREN Antiviral Therapy 2000; 5(Supplement 5):14 (abstract no. O21) SM Arpadi, PA Cuff, ME Horlick, DP Kotler and J Wang Mild increases in triglyceride levels, but not cholesterol, are detectable in children with HIV-infection who experience lipoatrophy of arms and legs together with accumulation of trunk fat. Both triglyceride and abnormal regional fat changes appear to be associated with PI use. |
| O22 | INCREASED TPA ANTIGEN LEVELS IN THE HIV LIPODYSTROPHY SYNDROME ARE REDUCED IN RESPONSE TO METFORMIN Antiviral Therapy 2000; 5(Supplement 5):15 (abstract no. O22) C Hadigan, JB Meigs, J Rabe, RB D'Agostino, PWF Wilson, I Lipinska, GH Tofler and S Grinspoon. tPA antigen, a marker of impaired fibrinolysis and increased CVD risk, is increased in association with hyperinsulinemia in the HIV lipodystrophy syndrome. Metformin reduces tPA antigen concentrations in the HIV lipodystrophy syndrome and could ultimately improve associated CVD risk. |
| O23 | METABOLIC COMPLICATIONS OF HAART: NEED FOR PERSPECTIVE Antiviral Therapy 2000; 5(Supplement 5):15 (abstract no. O23) M Egger Highly active antiretroviral therapy (HAART) has led to a dramatic decrease in the morbidity and mortality of patients infected with the human immunodeficiency virus (HIV). However, metabolic adverse effects, including lipodystrophy-associated dyslipidaemia and insulin resistance, are common in patients treated with potent combination therapy. |
| O24 | USE OF HIV PROTEASE INHIBITORS IS ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION Antiviral Therapy 2000; 5(Supplement 5):16 (abstract no. O24) J Sosman, M Klein, J Bellehumeur, S Aeschlimann and J Stein Use of HIV protease inhibitors is associated with endothelial dysfunction. The metabolic changes observed with these medications may predispose to atherosclerosis and increased vascular risk. As survival of HIV-infected individuals increases, atherosclerotic vascular disease may become an important HIV-related complication. |
| O25 | INTIMA MEDIA THICKNESS AS CARDIOVASCULAR RISK MARKER IN HIV-POSITIVE PATIENTS TREATED AND UNTREATED WITH PROTEASE INHIBITORS Antiviral Therapy 2000; 5(Supplement 5):16 (abstract no. O25) A Pan1, E Seminari2, G Voltini3, R Maserati2, C Tinelli4, G Meneghetti2, G Carnevale1 and S Testa5 Carotid wall thickening is present in HAART-treated patients, and along with metabolic disturbances; these data confirm that risk factors for coronary artery disease are markedly elevated in PI exposed patients. |
| O26 | CARDIOVASCULAR DYSREGULATION IN HIV-INFECTED INDIVIDUALS TREATED WITH HAART Antiviral Therapy 2000; 5(Supplement 5):17 (abstract no. O26) T-J Weber1, F Bengel2, J-R Bogner1, A Leber3, R Haberl3, M Schwaiger2 and F-D Goebel1 Structural pathology (calcium density) is not increased after two years of severe hypercholesterolemia. Our results strongly suggest that functional myocardial defects result from HAART. Endothelial dysfunction may be discussed as an explanation. |
| O27 | LESSONS LEARNED WITH SWITCHING ANTIRETROVIRALS Antiviral Therapy 2000; 5(Supplement 5):17 (abstract no. O27) W G Powderly Reversibility of bone disease has not yet been reported. Switch studies have the potential to provide important insight into the pathogenesis of the metabolic syndromes. However, there is a need for larger, controlled studies and a more standardized approach to definition of metabolic abnormalities. |
| O28 | LIPODYSTROPHY AND METABOLIC ABNORMALITIES IN A CROSS-SECTIONAL STUDY OF PARTICIPANTS IN RANDOMIZED CONTROLLED STUDIES OF COMBINATION ANTIRETROVIRAL THERAPY Antiviral Therapy 2000; 5(Supplement 5):18 (abstract no. O28) M Law1, S Emery1, M Prench2, A Carr3, J Chuah4 and D Cooper1 While the results need careful interpretation, they suggest that stavudine plus didanosine-containing regimens result in more frequent peripheral fat changes and elevations in serum lactate. |
| O29 | SERUM AND URINE MARKERS OF BONE MINERAL METABOLISM IN HIV-INFECTED PATIENTS TAKING PROTEASE INHIBITOR-CONTAINING POTENT ANTIRETROVIRAL THERAPY Antiviral Therapy 2000; 5(Supplement 5):18 (abstract no. O29) P Tebas, KE Yarasheski, M Whyte, S Claxton, D DeMarco and WG Powderly These data suggest an increased rate of bone turnover in patients with DEXA evidence of bone demineralization while receiving PI-based ART. Whether this reflects a direct effect on bone metabolism or an indirect effect mediated through vitamin D metabolism or renal handling of calcium requires further study. |
| O30 | PROTEASE INHIBITORS INHIBIT IN VITRO CONVERSION OF 25(OH)-VITAMIN D TO 1,25(OH)2-VITAMIN D Antiviral Therapy 2000; 5(Supplement 5):19 (abstract no. O30) A Dusso, M Vidal, WG Powderly, KE Yarasheski and P Tebas In vivo, HIV-PIs inhibit cytochrome P450 enzyme activity. In vitro, HIV-PIs inhibited 1α-hydroxylase enzyme activity, which impairs bioactivation of vitamin D. Reduced formation of bioactive 1,25(OH)2-vitamin D may contribute to the bone demineralization associated with PI-containing potent antiretroviral therapy regimens in people living with HIV/AIDS. |
| O31 | LONGITUDINAL ANALYSIS OF BONE MINERAL DENSITY (BMD) IN HIV-INFECTED PATIENTS TREATED WITH HAART: CHANGES IN BMD CORRELATE WITH CHANGE IN SUBCUTANEOUS FAT; WITH AN ADDITIONAL INDEPENDENT EFFECT OF INDINAVIR THERAPY TO INCREASE BMD Antiviral Therapy 2000; 5(Supplement 5):20 (abstract no. O31) D Nolan, R Upton, I James, E McKinnon, M John and S Mallal Changes in BMD in a longitudinal analysis are positively correlated with changes in %subcutaneous fat, regardless of therapy. In addition, indinavir use is independently associated with increased BMD gain, in keeping with in vitro experimental data indicating that indinavir favours osteogenic differentiation of mesenchymal stem cells via retinoid signalling mechanisms. |
| O32 | OSTEOPENIA IN HIV-INFECTED MEN: ASSOCIATION WITH LACTIC ACIDEMIA AND LOWER WEIGHT PRE-ANTIRETROVIRAL THERAPY Antiviral Therapy 2000; 5(Supplement 5):20 (abstract no. O32) A Carr1, J Miller2 and DA Cooper1,2 |
| O33 | CASE-CONTROL STUDY OF AVASCULAR NECROSIS IN HIV-INFECTED PATIENTS Antiviral Therapy 2000; 5(Supplement 5):21 (abstract no. O33) M J Glesby and C M Vaamonde AVN was associated with prior PCP (a possible marker of corticosteroid use). Use of specific ART, including PIs, was not independently associated. Further investigation with a larger sample is needed to confirm these findings. |
| Poster Presentations Abstracts P1 to P98, pages 25 through 81 |
|
| P1 | ULTRASTRUCTURAL FINDINGS CONSISTENT WITH BROWN ADIPOCYTES IN BUFFALO HUMPS OF HIV-POSITIVE PATIENTS WITH FAT REDISTRIBUTION SYNDROME Antiviral Therapy 2000; 5(Supplement 5):25 (abstract no. P1) WJ Fessel, SB Follansbee and B Barker Mitochondrial damage occurs in both peripheral and central fat. Some adipocytes in buffalo humps have characteristics of brown adipocytes. These preliminary observations support the hypothesis that expanded central fat in the fat redistribution syndrome includes brown fat that has become used for storage after white fat has been more extensively damaged. This could imply that it might also occur peripherally, as we saw multilocular fat globules plus some mitochondrial characteristics of brown adipocytes in wasted fat. |
| P2 | INTERFERON-α THERAPY INCREASES PLASMA TRIGLYCERIDE CONCENTRATIONS IN HIV-1 SEROPOSITIVE PATIENTS Antiviral Therapy 2000; 5(Supplement 5):25 (abstract no. P2) JF Morlese, NA Oazi, D Asboe, BG Gazzard and MR Nelson Plasma triglyceride concentrations are increased in HIV-1-seropositive patients treated with exogenous interferon-α therapy. This evidence supports the hypothesis that increased cytokine concentrations play a role in the development of dyslipidaemia and lipodystrophy in HIV-infected patients treated with HAART. |
| P3 | INHIBITION OF ADIPOCYTE DIFFERENTIATION BY HIV-1 PROTEASE INHIBITORS: POTENTIAL MECHANISMS BASED ON CHANGES IN GENE EXPRESSION Antiviral Therapy 2000; 5(Supplement 5):26 (abstract no. P3) GJ Stevens, AC Lankford, M Chen and B Jessen The use of gene expression arrays may provide early clues to the potential mechanisms of HIV-associated body fat changes. These initial results demonstrate that PIs affect multiple pathways within adipocytes, including genes associated with lipid metabolism and adipocyte differentiation. Identifying HAART-affected pathways provides a first step in understanding their potential influence on HIV-associated body fat changes. |
| P4 | PROSPECTIVE STUDY OF THE EFFECTS OF AMPRENAVIR-BASED THERAPY ON GLUCOSE AND LIPID METABOLISM IN HIV-INFECTED PATIENTS Antiviral Therapy 2000; 5(Supplement 5):26 (abstract no. P4) MP Dubé1, D Qian2,3, H Edmondson-Melanç;on4, FR Sattler3,4, D Goodwin5, C Martinez3, V Williams5, D Johnson4 and TA Buchanan3,6 Over the first 8 weeks of this study, amprenavir-based therapy did not measurably affect glucose metabolism, but was associated with significant increases in cholesterol. In contrast, our previous study using the same measures (1st IWADRHL, 1999) showed increased fasting glucose and reduced insulin sensitivity during 8 weeks of indinavir-based therapy, without significant changes in lipids. Although they can co-exist, PI-associated glucose and lipid dysregulation may not necessarily result from the same pathogenic mechanism. |
| P5 | ASSOCIATION OF CLINICAL PROFILES AND METABOLIC ABNORMALITIES IN HIV-INFECTED MALES AND FEMALES WITH THE HIV/HAART-ASSOCIATED LIPODYSTROPHY SYNDROME Antiviral Therapy 2000; 5(Supplement 5):27 (abstract no. P5) J Falutz and G Hatzakis Despite similar clinical and treatment features in HAL negative, and mixed females and males, differences occurred in lipid and glucose metabolism profiles in HAL-negative and mixed males, but not in the female groups, suggesting gender differences in biological response to factors causing HAL-related metabolic and possibly clinical features. |
| P6 | CARDIOVASCULAR RISK IN HIV-POSITIVE PATIENTS WITH HAART-RELATED DYSLIPIDAEMIA Antiviral Therapy 2000; 5(Supplement 5):27 (abstract no. P6) T Garcia-Benayas, F Blanco, A Barrios, J de la Cruz, J Sánchez, V Soriano and J Glez-Lahoz In HIV-positive subjects under HAART with dyslipidaemia, hypercholesterolaemia is more prevalent than hypertriglyceridaemia, although both are present in more than half of patients. The association with other CV risk factors was remarkable, being most frequently a family history of CV disease and smoking, followed by physical inactivity and overweight. These findings should alert clinicians on the importance of diagnosing and controlling other CV risk factors in HIV-positive patients under HAART with dyslipidaemia, in order to prevent future CV morbidity. |
| P7 | LIPID PROFILE IN HIV-POSITIVE PATIENTS WITH HAART-RELATED HYPERLIPIDAEMIA Antiviral Therapy 2000; 5(Supplement 5):28 (abstract no. P7) T Garcia-Benayas, F Blanco, A Barrios, J de la Cruz, MJ Senchordi, J Sánchez, V Sorlano and J Glez-Lahoz In HIV-positive subjects under HAART with dyslipidaemia, hypercholesterolaemia is more prevalent than hypertriglyceridaemia, although both are present in more than half of patients. No differences between NNRTI and PI-based regimens were found. However, the NNRTI+PI combination was associated with higher cholesterol and triglyceride levels than regimens containing either NNRTI or PI. This fact may be due to a synergistic effect of these drugs on the lipid profile. |
| P8 | LIPID PROFILES IN HIV-INFECTED PATIENTS BEFORE AND AFTER PROTEASE INHIBITOR THERAPY Antiviral Therapy 2000; 5(Supplement 5):29 (abstract no. P8) C Wanke, J Gerrior, S Skinner, JR McNamara and EJ Schaefer Initiation of PI therapy does significantly and promptly alter lipid profiles in HIV-infected patients. Longitudinal studies are needed to demonstrate whether these alterations contribute to additional cardiovascular risk. |
| P9 | SELECT HIV PROTEASE INHIBITORS STIMULATE HEPATIC TRIGLYCERIDE SYNTHESIS AND PANCREATIC LIPASE ACTIVITY Antiviral Therapy 2000; 5(Supplement 5):29 (abstract no. P9) J Lenhard, D Croom, J Weiel and D Winegar We propose PI-associated hyperlipidaemia is due to increased hepatic triglyceride synthesis and suggest that meal restriction or dietary retinoids influence the effects of PIs on lipid metabolism. Additionally, select PIs may cause hyperlipidaemia by increasing pancreatic lipase activity and absorption of dietary fat. |
| P10 | EFFECTS OF EFAVIRENZ ON LIPID METABOLISM IN NAÏVE AND PROTEASE INHIBITOR-EXPERIENCED HIV-POSITIVE PATIENTS Antiviral Therapy 2000; 5(Supplement 5):30 (abstract no. P10) G Ravasi, G Meneghetti, G Barasolo, E Seminari, S Novati, R Gulminetti and R Maserati Treatment with efavirenz was not associated with metabolic abnormalities during a 6-month follow-up. In PI-experienced patients switched to efavirenz because of metabolic abnormalities a significant reduction in triglyceride levels was observed. |
| P11 | APOLIPOPROTEIN CIII AND HIGHLY ACTIVE ANTIRETROVIAL THERAPY-INDUCED HYPERTRIGLYCERIDEMIA Antiviral Therapy 2000; 5(Supplement 5):30 (abstract no. P11) AM Dupuy, S Badiou, V Baillat, J Fabre, MD Tur, JP Cristol and J Reynes HAART-induced HTG could be, in part, linked to an increase in apoCIII levels. Since fibrates decrease apoCIII expression, they appear to be an effective option to manage HAART-induced HTG. |
| P12 | LIPOPROTEIN ABNORMALITIES ASSOCIATED WITH USE OF HIV PROTEASE INHIBITORS Antiviral Therapy 2000; 5(Supplement 5):31 (abstract no. P12) J Sosman, M Klein, J Otvos, D Weibe, J Bellehumeur, S Aeschlimann and J Stein Increased levels of triglycerides and cholesterol in remnant lipoproteins and chylomicrons characterize the dyslipidemia associated with use of HIV PIs. Because this dyslipidemia may be atherogenic, screening for HIV PI-related dyslipidemia and recognizing its potential to lead to atherosclerotic vascular disease are important clinical considerations. |
| P13 | EPIDEMIOLOGICAL EVIDENCE OF INCREASING BLOOD PRESSURE IN HIV-1-INFECTED INDIVIDUALS IN THE ERA OF HAART Antiviral Therapy 2000; 5(Supplement 5):31 (abstract no. P13) D Chow1, S Souza1, S Richmond-Crum2 and C Shikuma1 While the results must be tempered by the observational nature of this study, they suggest that HAART is associated with an increase in mean SBP and DBP, independent of changes in BMI. Although the mean SBP and DBP were not in hypertensive levels, the rise in BP suggests that HAART is associated with increased autonomic function, another component of Metabolic Syndrome X, and that recent concerns are warranted regarding the cardiovascular risk in HIV-infected individuals on HAART. |
| P14 | LACTATE LEVELS IN HIV-POSITIVE PATIENTS UNDER ANTIRETROVIRAL TREATMENT Antiviral Therapy 2000; 5(Supplement 5):32 (abstract no. P14) F Blanco, F Laguna, T Garcia-Benayas, V Soriano, V Moreno, E Valencia, MJ Senchordi and J Glez-Lahoz Hyperlactataemia is quite common among HIV-positive patients under antiretroviral treatment. In the univariate analysis, male gender, homosexual behaviour, time on HAART, hyperlipaemia and morphological LD changes are all conditions associated with high lactate levels. |
| P15 | TREATMENT OF LACTIC ACIDOSIS Antiviral Therapy 2000; 5(Supplement 5):32 (abstract no. P15) K Brinkman1, SME Vrouenraets1, J vd Meer2, R Peerenboom3, R Kaufmann4, HM Weigel1 and PHJ Frissen1 Surviving lactic acidosis can be achieved with a high state of alertness, immediate interruption of NRTIs and a protocol as suggested above. |
| P16 | INCREASED ANTIRETROVIRAL THERAPY EXPERIENCE IN ZIDOVUDINE-NAÏVE SUBJECTS FAILING ON A STAVUDINE-CONTAINING REGIMEN WAS SIGNIFICANTLY ASSOCIATED WITH PERIPHERAL NEUROPATHY AND WASTING SYNDROME Antiviral Therapy 2000; 5(Supplement 5):33 (abstract no. P16) G Coodley1, P Shalit2, S Raffanti3, R Fisher4, Q Liao4, L Ross4 and J Hernandez4 Zidovudine-naïve subjects failing on a stavudine-containing regimen with CDC classification C illnesses were significantly more likely to have higher HIV-1 RNA levels. More heavily ART-experienced subjects (more than four prior ART) had significantly increased incidence of peripheral neuropathy and wasting syndrome. |
| P17 | INSIGHTS INTO THE MOLECULAR MECHANISM OF MITOCHONDRIAL TOXICITY OF ANTIVIRAL DRUGS Antiviral Therapy 2000; 5(Supplement 5):34 (abstract no. P17) JY Feng1, AA Johnson2, KA Johnson2, RF Schinazi3, KS Anderson4 and PA Furman1 The important factors in observed activities were determined to be absolute stereochemistry, and the presence or absence of a fluorine atom in the 5-position of the cytosine ring. Among all of the cytidine analogues tested (-)emtricitabine-TP has the lowest inhibitory effect on human mitochondrial DNA polymerase. Along with the previously published studies of (-)emtricitabine-TP incorporation by HIV-1 reverse transcriptase, these data support further examination of the desirable long-term safety and efficacy of (-)emtricitabine. |
| P18 | A CONVENIENT ASSAY FOR IN VITRO EVALUATION OF MITOCHONDRIAL TOXICITY OF ANTIRETROVIRAL DRUGS Antiviral Therapy 2000; 5(Supplement 5):34 (abstract no. P18) A Foli1, F Benvenuto2, G Piccinini1, A Bareggi1, J Lisziewicz1 and F Lori1 Notably, with a didanosine twice daily regimen the Cmax of didanosine is 3.2 µM(±1.8), with a once daily regimen the Cmax of didanosine is 6.0 µM (±2.9). All patients who developed pancreatitis had been treated with hydroxyurea and a didanosine once daily regimen. In conclusion, mitochondrial toxicity can be investigated with an easy cytofluorimetric assay. This assay will be useful to assess the toxicity of in-use or potential combinations of other antiretroviral drugs. |
| P19 | EARLY DIAGNOSIS OF LACTIC ACIDOSIS IN HIV-INFECTED ADULTS RECEIVING ANTIRETROVIRALS: ANION GAP MEASUREMENT Antiviral Therapy 2000; 5(Supplement 5):35 (abstract no. P19) Y Gérard, Y Yazdanpanah, X De La Tribonnière, L Maulin, V Baclet, F Ajana, D Sissoko and Y Mouton In our cohort, incidence of elevated AG was 1.5%, more frequent under stavudine (2.7%). Routine measurement of AG seems very important in the follow-up of treated HIV-infected patients, to allow early recognition of LA. |
| P20 | HYPERLACTATAEMIA ASSOCIATED WITH CLINICAL MANIFESTATIONS IN HIV-INFECTED PATIENTS RECEIVING NUCLEOSIDE ANALOGUE COMBINATION REGIMENS Antiviral Therapy 2000; 5(Supplement 5):35 (abstract no. P20) JT Lonergan, D Havlir, E Barber and WC Mathews There is a higher IR of the hyperlactataemia syndrome in patients receiving stavudine-containing regimens compared to NRTI-containing regimens without stavudine. It appears safe to rechallenge affected patients with alternative NRTIs. |
| P21 | HYPOTHESIS: IS LONG-TERM NUCLEOSIDE ANALOGUE TOXICITY RELATED TO NUCLEAR DNA INTEGRATION Antiviral Therapy 2000; 5(Supplement 5):36 (abstract no. P21) G J Moyle New research evaluating the effects of chronic NA exposure on cell lines is required to address the possibility that nuclear genotoxicity plays a role in long-term nucleoside analogue toxicity. |
| P22 | MITOCHONDRIAL FUNCTION IN HIV-INFECTED PATIENTS WITH LIPODYSTROPHY DURING EXERCISE AND RECOVERY Antiviral Therapy 2000; 5(Supplement 5):37 (abstract no. P22) BT Røge1, J Calbet2, K Møller1, H Ullum1, HW Hendel3, J Gerstoft1, BK Pedersen1 and B Saltin2 Oxidative phosphorylation and L and Py production during exercise was normal in patients as compared to controls. The elevated levels of L and Py in patients at rest may be due to an upregulated glycolysis or impaired elimination. The similar reduction in Py and L levels during recovery do not definitely suggest that the mitochondrial function of the liver is unaffected, since L is metabolized in other tissues as well. No evidence of serious damage to skeletal muscle mitochondrial function was found. |
| P23 | MULTIPLE mtDNA DELETIONS IN HUMAN SPERMATOZOA FROM LONG-TERM HAART Antiviral Therapy 2000; 5(Supplement 5):37 (abstract no. P23) J St John1, D Mital2, S Taylor2 and DJ White2 This preliminary study indicates that multiple mtDNA deletions occur in men who have been taking HAART for more than 18 months. Analysis of mtDNA in sperm samples by Long PCR may provide a non-invasive method for monitoring and/or studying the side-effects of mitochondrial toxicity in men undergoing HAART. |
| P24 | DISREGULATION OF LIPID TURNOVER IS A KEY DEFECT IN THE HIV LIPODYSTROPHY SYNDROME Antiviral Therapy 2000; 5(Supplement 5):38 (abstract no. P24) RV Sekhar1,2, F Jahoor2, F Visnegarwala3, AC White3, M Sharma1, PJ Reeds2 and A Balaubramanyam1 ,2 These preliminary data indicate that HLS subjects have markedly accelerated FFA turnover, without a proportionate increase in fat oxidation. Thus, lower body fat is associated with increases in both intra-adipocyte re-esterification and FFA release into the plasma. The latter may be a substrate for excess VLDL-triglyceride synthesis in the liver. These whole body measurements suggest that a primary defect in lipid metabolism in adipocytes may explain many features of HLS: both increased fat wasting (in some regions) and fat storage (in others), and hypertriglyceridaemia. |
| P25 | FAT DISTRIBUTION AND METABOLIC PARAMETERS IN HIV-1 INFECTED PATIENTS, AS MEASURED BY ABDOMINAL CT-SCANS Antiviral Therapy 2000; 5(Supplement 5):38 (abstract no. P25) M Bickel1, V Rickerts1, V Jacobi2, M Jakob2, J Tews2 and S Staszewski1 ARV agents are highly associated with central obesity and an undesirable fat distribution. These findings are not limited to the use of PIs. The parameters of HIV infection seem to have no influence. Single slice CT scans (L4) are highly predictive for VAT in HIV-infected patients possibly suffering from fat redistribution. |
| P26 | MEN WITH HIV-ASSOCIATED WASTING SHOW A CENTRIPETAL PATTERN OF CHANGE IN FAT DISTRIBUTION SINCE THE INTRODUCTION OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART) Antiviral Therapy 2000; 5(Supplement 5):39 (abstract no. P26) J M Gertner and F O'Brien In HIV-positive men eligible for therapeutic trials for wasting, there was no significant difference in mean percentage body fat in the pre-HAART group versus currently treated patients. However, there were marked centripetal changes in body fat distribution, indicating that fat maldistribution is common in the current era, and is present even in patients who have suffered significant weight loss. |
| P27 | ADIPOMASTY AND LOWER LIMB WASTING IN WOMEN UNDERGOING ANTIRETROVIRAL THERAPY ARE NOT ASSOCIATED WITH AN INCREASE IN TNF-α PRODUCTION Antiviral Therapy 2000; 5(Supplement 5):39 (abstract no. P27) C Gervasoni1, A Ridolfo1, A Riva1, S Santambrogio1, M Clerici2 and M Galli1 Adipomasty and lower limb wasting seem to be related to immune reconstitution and IL-12 synthesis, and is not associated with increased TNF-α production. |
| P28 | IMPORTANCE OF CENTRALIZED ASSESSMENT OF DUAL-ENERGY X-RAY ABSORPTIOMETRY (DEXA) IN MULTICENTRED STUDIES OF HIV-ASSOCIATED LIPODYSTROPHY - THE PIILR STUDY DEXA QA PROGRAMME Antiviral Therapy 2000; 5(Supplement 5):40 (abstract no. P28) J Hudson2, J Freund1, MR Griffiths1, KA Noakes1, M Law2, A Carr3, D Smith2 and DA Cooper2,3 for the PIILR DEXA group and Investigators It is concluded that a 10-fold difference in SD was noted between central and regional interpretation of DEXA results. Careful attention to QA, preferably with a central QA site, is important in multi-centre trials using DEXA for assessment of changes in body composition. |
| P29 | INTERACTIONS AMONG SEX, HIV INFECTION AND FAT REDISTRIBUTION Antiviral Therapy 2000; 5(Supplement 5):41 (abstract no. P29) J Lopes, ES Engelson, J Wang, D Agin, SB Heymsfield and DP Kotler The interactions among sex, HIV infection, and body fat distribution are complex, as the effect of gender differs in patients with or without changes in body fat distribution. While both HIV-infected men and women may accumulate VAT, this change is accompanied by SAT depletion in men only. Decreases of SAT in women may be more indicative of malnutrition. |
| P30 | CHANGES IN BODY COMPOSITION FOLLOWING INITIATION OR SWITCH OF ANTIRETROVIRAL THERAPY Antiviral Therapy 2000; 5(Supplement 5):41 (abstract no. P30) N Paton, K Tan, Y-M Ng and J Aboulhab Switching therapy was associated with a distinct pattern of early body composition change (decreased fat, increased lean) which may reflect an underlying disturbance of fat metabolism triggered by the switch of NRTI (from zidovudine to stavudine), the introduction of a PI, or improved control of viral replication. Longitudinal DEXA measurements can detect significant treatment associated differences in fat mass in the absence of clinically apparent lipodystrophy and should therefore be incorporated in all lipodystrophy clinical trials. |
| P31 | PATHOLOGICAL FRACTURES IN PATIENTS WITH OSTEOPENIA AND OSTEOPOROSIS INDUCED BY ANTIRETROVIRAL THERAPY Antiviral Therapy 2000; 5(Supplement 5):42 (abstract no. P31) G Guaraldi1, P Ventura1, M Albuzza2, G Orlando1, A Bedini1, G Amorico1 and R Esposito1 These two case reports suggest that osteopenia and osteoporosis, induced by antiretroviral therapy, can cause pathological fractures after trivial trauma. Further investigations are needed to understand the history and evolution of accelerated bone mineral loss in HIV-infected patients receiving antiretroviral medications. |
| P32 | OSTEOPENIA IN A RANDOMIZED, MULTICENTRE STUDY OF PROTEASE INHIBITOR SUBSTITUTION IN PATIENTS WITH THE LIPODYSTROPHY SYNDROME - EXTENDED FOLLOW-UP TO 48 WEEKS Antiviral Therapy 2000; 5(Supplement 5):42 (abstract no. P32) J Hoy1, J Hudson3, M Law3 and DA Cooper2,3 for the PIILR investigators There is a high prevalence of osteopenia and osteoporosis in HIV-infected men with lipodystrophy. There was no further reduction in BMD in the PI group or improvement in BMD in the switch group over 48 weeks. Further study into the aetiology of loss of bone mineral density in this population is needed, in addition to identification of risk factors for continued reductions of BMD. |
| P33 | OSTEOPENIA: A CONSEQUENCE OF HIV NOT HAART? Antiviral Therapy 2000; 5(Supplement 5):43 (abstract no. P33) GJ Moyle, C Newey, C Baldwin, C Torti, S Mandalia and BG Gazzard Osteopenia in persons with HIV infection may be a consequence of HIV infection per se rather than antiretroviral therapies. Virological control with therapy may diminish the risk of osteopenia. |
| P34 | OSTEONECROSIS ON ANTIRETROVIRAL THERAPY Antiviral Therapy 2000; 5(Supplement 5):43 (abstract no. P34) L Roudière and JP Viard In our cohort, ON involved around 2% of treated patients and 10% of patients with clinical lipodystrophy. We propose that ON should be carefully monitored since HAART provokes hypertriglyceridaemia, a risk factor for ON. We suggest that studies trying to establish a case definition for lipodystrophy consider ON as a candidate diagnostic criterion. |
| P35 | RELATIONSHIPS AMONG ADRENAL HORMONES AND SERUM LIPIDS DIFFER IN CAUCASIAN AND AFRICAN-AMERICAN HIV-POSITIVE WOMEN TREATED WITH COMBINATION ANTIRETROVIRAL THERAPY Antiviral Therapy 2000; 5(Supplement 5):44 (abstract no. P35) LL Bausserman, DS Maceroni and MG DiSpigno Adrenal hormones are correlated with serum lipids but not glucose, insulin or anthropometric measures in HIV-positive women treated with HAART. However, the relationships are different in white and black women. Cortisol is related to measures of LDL and aldosterone with triglycerides in white women; and cortisol, DHEA and aldosterone with measures of HDL in black women. |
| P36 | PSYCHOSOCIAL IMPACT OF BODY CHANGES IN LIPODYSTROPHY Antiviral Therapy 2000; 5(Supplement 5):44 (abstract no. P36) E Collins, C Wagner and S Walmsley There are a number of negative psychosocial effects associated with the body changes of lipodystrophy and appear to significantly impact individual's self-reported quality of life. A larger quantitative study is underway to study this, analyse the effects of gender, age and severity of illness, assess coping strategies, and compare differences between HIV-infected individuals with and without lipodystrophy. |
| P37 | MENTAL DISORDERS RELATED TO LIPODYSTROPHY BODY-SHAPE CHANGES IN HIV-POSITIVE PATIENTS WITH HOMOSEXUAL RISK BEHAVIOUR Antiviral Therapy 2000; 5(Supplement 5):45 (abstract no. P37) L Gallego, F Blanco, V Gordillo, J de la Cruz, T García-Benayas, E Castillo, P López and J Glez-Lahoz The frequency of mental disorders in homosexual HIV-positive men with antiretroviral treatment-related lipodystrophy tends to be higher than in those subjects without body-shape changes. The most prevalent are affective disturbances. A multi-disciplinary approach with mental health providers is warranted in these patients. |
| P38 | SUPERIOR MESENTERIC VEIN THROMOBOSIS - A POTENTIAL COMPLICATION FOR HIV/HCV-CO-INFECTED PATIENTS RECEIVING PROTEASE INHIBITOR-CONTAINING ANTIRETROVIRAL THERAPY Antiviral Therapy 2000; 5(Supplement 5):46 (abstract no. P38) CB Hsiao, ES Piotrowski and S Yoon Superior mesenteric vein thrombosis (SMVT) is a rare disorder that can develop rapidly with intestinal infarction or subacutely with abdominal pain due to intestinal ischaemia. The syndrome is rare and the clinical presentation is usually vague or confusing and is similar to that of antiretroviral-related lactic acidosis. |
| P39 | THE IMPACT OF GENDER AND HEPATITIS C VIRUS CO-INFECTION ON LIPID PROFILES IN HIV-INFECTED PATIENTS ON NELFINAVIR AND NNRTI (NEVIRAPINE OR EFAVIRENZ)-CONTAINING ANTIRETROVIRAL THERAPY Antiviral Therapy 2000; 5(Supplement 5):46 (abstract no. P39) CB Hsiao1, PW Chen2, MJ Shelton1 and RG Hewitt1. (i) Gender, HCV serology and choice of ART appear to be important factors affecting lipid profiles in patients infected with HIV; (ii) with a similar backbone of NUC, more women had higher HDL if they received NEV or EFV than if they received NEF. |
| P40 | HAART-ASSOCIATED OSTEOPENIA IS CAUSED BY OXIDIZED LIPOPROTEINS: A HYPOTHESIS Antiviral Therapy 2000; 5(Supplement 5):47 (abstract no. P40) J Morlese, G Moyle and B Gazzard Osteopenia has recently been described in HIV-1-seropositive patients treated with protease inhibitor-containing HAART. Although the long-term sequelae of these patients is unknown, it may result in increased bone fractures in later life. |
| P41 | ASSOCIATION BETWEEN BASELINE PSYCHIATRIC ILLNESS AND DEVELOPMENT OF PSYCHIATRIC SYMPTOMS IN PATIENTS RECEIVING EFAVIRENZ-CONTAINING REGIMENS Antiviral Therapy 2000; 5(Supplement 5):47 (abstract no. P41) L Park-Wyllie and E Boyle In an inner city health setting, patients with previous psychiatric history were nearly three times more likely to develop psychiatric symptoms. However, this finding was not statistically significant. |
| P42 | MALE BREAST ENLARGEMENT FOLLOWING SUCCESSFUL HAART, A POSSIBLE IMMUNE RESTORATION PHENOMENON? Antiviral Therapy 2000; 5(Supplement 5):48 (abstract no. P42) NA Qazi, JF Morlese, DM King, BG Gazzard and MR Nelson Our study is the first to show that gynaecomastia can occur with all classes of antiretrovirals and that it is indeed due to glandular proliferation and not subcutaneous fat deposition. All the patients developed symptoms of breast enlargement rapidly and all were on a successful regimen. Of the patients originally identified more than 75% (12/15) have had complete resolution of their symptoms without any intervention 6 months after diagnosis. In the absence of any other obvious mechanism we postulate that gynaecomastia may be a result of increased cytokine activity. Cytokines may be involved in up-regulation of cell oestrogen receptors, or may directly stimulate the oestrogen receptor. Immune restoration, as a unifying mechanism in our patients, may also explain why gynaecomastia occurs with all classes of antiretrovirals and why it resolves in the majority of cases without intervention. |
| P43 | EFFECT OF SWITCHING FROM PROTEASE INHIBITORS TO ABACAVIR ON INSULIN SENSITIVITY AND FASTING LIPIDS: 12-MONTH FOLLOW-UP Antiviral Therapy 2000; 5(Supplement 5):48 (abstract no. P43) R Walli, K Huster, JR Bogner and FD Goebel Switching from PI to abacavir is associated with an improvement of insulin sensitivity and a decrease in both total cholesterol and triglycerides in the majority of patients with PI-associated metabolic disturbances. This effect is seen as early as 3 months after switching, and is sustained over 12 months. |
| P44 | PREDICTORS OF NEVIRAPINE-ASSOCIATED ADVERSE EVENTS: FEMALE GENDER AND STEROID PROPHYLAXIS INCREASE THE RISK OF CUTANEOUS HYPERSENSITIVITY REACTIONS Antiviral Therapy 2000; 5(Supplement 5):49 (abstract no. P44) A De Luca1, A Baracchini2, F Baldini1, M Zaccarelli2, A Cingolani1, P De Longis2, S Di Giambenedetto1, V Tozzi2, MG Rizzo1, R Murri1, G Ippolito2, A Ammassari2 and A Antinori2 Female HIV-positive patients, those taking steroid prophylaxis and those with higher CD4 counts have increased risk of developing NVP-associated CHR, while NVP induction reduces the risk of CHR. |
| P45 | L-ACETYL-CARNITINE THERAPY IN HIV-ASSOCIATED PERIPHERAL NEUROPATHY: A QUANTITATIVE IMMUNOHISTOCHEMICAL STUDY OF CUTANEOUS INNERVATION Antiviral Therapy 2000; 5(Supplement 5):50 (abstract no. P45) AM Hart1, G Terenghi1, M Johnson2 and M Youle2 Oral LAC therapy improved symptoms, and caused cutaneous peripheral nerve regeneration. LAC is proposed as a pathogenesis-based therapy for drug-related HIV neuropathy. |
| P46 | INCIDENCE AND RISK FACTORS OF STATIN- OR FIBRATE-INDUCED HEPATITIS AND MYOSITIS IN HIV-INFECTED PATIENTS Antiviral Therapy 2000; 5(Supplement 5):50 (abstract no. P46) D Lee, WC Mathews and E Barber Incidence of H or M in HIV-infected patients receiving S or F is higher than in non-HIV patients. Concurrent PI therapy may increase the risk of developing S- or F-induced H and M. No other predictors of developing H or M were found. |
| P47 | TOENAIL PARONYCHIA IN HIV-POSITIVE PATIENTS ON ANTIRETROVIRAL TREATMENT Antiviral Therapy 2000; 5(Supplement 5):51 (abstract no. P47) G Barasolo, G Ravasi, D Zanaboni, L Rizzi, G Meneghetti and R Maserati We confirmed that paronychia is almost always linked to an indinavir- and lamivudine-containing ART (9/10). In one case it occurred during a dual zidovudine plus lamivudine ART. Although treated with avulsion or antimicotic agents, paronychia recurred in half of the patients. |
| P48 | HAART TOLERABILITY: POST-EXPOSURE PROPHYLAXIS IN HEALTH CARE WORKERS VERSUS TREATMENT IN HIV-INFECTED PATIENTS Antiviral Therapy 2000; 5(Supplement 5):51 (abstract no. P48) P Bonfanti1, F Niero2, E Ricci1, E Lemoli1, L Valsecchi1, L Timillero1, 5 Landonio1, I Faggion1, F Alessi1, R Cinelli2, F Parazzini1 and T Ouirino1 Our study shows that treatment interruption is eightfold in HIV-negative subjects compared to HIV-seropositive patients, and that the incidence of adverse events is approximately six times higher, though such events are for the most part light. |
| P49 | ADVERSE EVENTS IN PATIENTS TREATED WITH PROTEASE INHIBITORS: A COHORT STUDY Antiviral Therapy 2000; 5(Supplement 5):52 (abstract no. P49) P Bonfanti1, E Ricci2, S Landonio2, I Faggion2, L Valsecchi2, S Carradori2, L Pusterla2, P Fortuna2, L Timillero2, F Alessi2, G Ghiselfi2, A Gabbuti2, C Martinelli1, F Parazzini2 and T Quirino2 i) We confirm the high frequency of adverse reactions in HAART still being the primary cause of treatment discontinuation; and (ii) either ritonavir alone or associated with saquinavir HCG is the PI that most frequently generates adverse events in HAART-treated patients; nelfinavir presents the lower IR for severe adverse events. |
| P50 | NEUROPATHY AND ARTHRALGIA IN PEOPLE TAKING ANTIRETROVIRAL THERAPY Antiviral Therapy 2000; 5(Supplement 5):52 (abstract no. P50) R Colebunders, W Schrooten, E Florence, A De Roo, E Bottieau and C Dreezen, on behalf of the Eurosupport II group Signs of neuropathy and arthralgia were frequently reported by patients taking ARV treatment, particularly by those taking PI-containing regimens. |
| P51 | IMMUNOHISTOLOGICAL CHARACTERIZATION OF SKIN RASH OBSERVED IN PATIENTS ON ABACAVIR WHO EXPERIENCE A HYPERSENSITIVITY REACTION Antiviral Therapy 2000; 5(Supplement 5):53 (abstract no. P51) LM Thurmond1, D Thorborn2, J Ravitch1, C Bazin3, E Bouvet4, B Hoen5, A Lafeuillade6, F Raff7, S Matheron4 and S Hetherington1 These preliminary data suggest that the immune response in the skin does not involve antibody responses and type 2 cytokines directly, but may be primarily a type 1 cytokine response. The absence of CD4 cells in the epidermis distinguishes this rash from more severe cutaneous adverse events such as Stevens Johnson syndrome. The ongoing evaluation of rash will focus on antigen-presenting cells in uninvolved skin, and will eventually include comparisons with systemic lymphocyte cytokine profiles and functional markers. These studies will clarify the histological response in the skin of patients with hypersensitivity while on abacavir, and will enhance our understanding of the immunological components of hypersensitivity. |
| P52 | SERUM-LACTATE IN NUCLEOSIDE ANALOGUE-TREATED HIV PATIENTS CORRELATES WITH SERUM-LIPIDS Antiviral Therapy 2000; 5(Supplement 5):54 (abstract no. P52) D Meyer1, G Behrens1, A Schneider2, MP Manns2, M Stoll1 and RE Schmidt1 These data support the hypothesis that antiretroviral treatment with NRTI therapy increases serum lactate as an indicator for mitochondrial toxicity. Increased serum lipids correlate with higher serum lactate supporting the notion of occurrence of lipodystrophy and metabolic abnormalities observed under NRTI treatment. |
| P53 | FAT REDISTRIBUTION SYNDROME/ LIPODYSTROPHY IN WOMEN: SUBANALYSIS OF A MULTICENTRE US STUDY Antiviral Therapy 2000; 5(Supplement 5):54 (abstract no. P53) D Berger1, G McComsey2, L Shaker-Irwin2, S Follansbee2, R Clark2, A LaMarca2, L Cardona2, R Anderson2, N Bellos2, R Dretler2, S Segal-Maurer2 and F Ottery2 A broad-based multicentre US study demonstrates differences in components of COLM between genders and questions the appropriate T:E ratio for FRS in women. Metabolic abnormalities were more pronounced in women. |
| P54 | NO DIFFERENCE IN LIPODYSTROPHY INCIDENCE IN STAVUDINE VERSUS ZIDOVUDINE NUCLEOSIDE BACKBONE: BLINDED EVALUATION IN A COHORT ON FIRST LINE HAART Antiviral Therapy 2000; 5(Supplement 5):55 (abstract no. P54) JR Bogner, G Michl, W Neuhofer, V Vielhauer, R Walli and FD Goebel Both stavudine and zidovudine-containing nucleoside backbones result in relatively high frequencies of lipoatrophy and lipohypertrophy. |
| P55 | LIPODYSTROPHY AND METABOLIC DISORDERS IN HIV-INFECTED PATIENTS TREATED BY PROTEASE INHIBITORS: IS THERE AN ASSOCIATION? Antiviral Therapy 2000; 5(Supplement 5):55 (abstract no. P55) J Capeau1, F Raffi2, M Savèse3, W Rozenbaum4, C Perronne5, A Basdevant6, R Laurent7, C Leport8, G Chêne3 and APROCO (ANRS EP11) Study Group There is a higher frequency of glucose/lipidic abnormalities in patients with lipodystrophy, although metabolic disorders are not infrequent in patients without clinical signs of lipodystrophy. Early detection and specific management of metabolic disorders should be implemented, even in the absence of clinical signs of lipodystrophy. |
| P56 | EFFECT OF NRTI INTENSIFICATION ON PREVALENCE OF BODY COMPOSITION ABNORMALITIES AT WEEK 144 OF RITONAVIR PLUS SAQUINAVIR THERAPY IN AN HIV-INFECTED COHORT Antiviral Therapy 2000; 5(Supplement 5):56 (abstract no. P56) C Cohen1, W Cameron2, Y Xu3, R Rode3, J Mellors4, C Farthing5, D Poretz6, D Markowitz7, D Ho7, D McMahon4, D DrennanB, K Selness3, J Ryan3, E Sun3 and AJ Japour3 In this study, treatment intensification with NRTIs, higher baseline HIV RNA and older age were associated with an increased risk of body composition abnormalities. Signs of lipoatrophy (buttock wasting and cheek thinning) were more common among NRTI-intensified subjects. The potential for fewer BCAs using nucleoside-sparing regimens should be further evaluated. |
| P57 | LIPODYSTROPHY IN WOMEN TAKING ANTIRETROVIRAL TREATMENT Antiviral Therapy 2000; 5(Supplement 5):57 (abstract no. P57) R Colebunders, C Dreezen, A De Roo, E Florence, I de Mey and W Schrooten, on behalf of the Eurosupport II group Signs of lipodystrophy were frequently reported by women taking antiretroviral treatments, particularly with PI-containing regimens. |
| P58 | PROPOSAL FOR A CLINIC CLASSIFICATION OF MORPHOLOGICAL AND METABOLIC ALTERATIONS UNDER ART Antiviral Therapy 2000; 5(Supplement 5):57 (abstract no. P58) M Galli, R Polo, T Saint-Marc and R Walli for the ART-associated Lipodystrophy European Collaborative Study (ALECS) group As recently assessed in several case files, the Marrakech classification may be a good tool in describing MAA, both for study purposes and in current clinical practice. |
| P59 | RISK OF DEVELOPING METABOLIC AND MORPHOLOGICAL ALTERATIONS UNDER ANTIRETROVIRAL THERAPY ACCORDING TO THE DRUG COMBINATIONS Antiviral Therapy 2000; 5(Supplement 5):58 (abstract no. P59) M Galli, F Veglia, G Angarano, A Cargnel, F Gritti, F Mazzotta and A Lazzarin for the Lipodystrophy Italian Multicenter Study (LIMS) Distinct MMA, observed in patients with different therapeutic history, suggest the existence of multifactorial mechanisms inducing adipose tissue alterations in ART-receiving patients. |
| P60 | RISK OF DEVELOPING ADIPOSE TISSUE ALTERATIONS AFTER STARTING ANTIRETROVIRAL THERAPY IN NAÏVE PATIENTS Antiviral Therapy 2000; 5(Supplement 5):59 (abstract no. P60) M Galli, A Cozzi-Lepri, AL Ridolfo, C Gervasoni, L Ravasio, L Corsico, E Gianelli, V Vullo, A Cargnel, L Minoli, F Gritti, G Scalise, A Antinori, G Antinucci, A d'Arminio Monforte and M Moroni for the LipoICONA Study In NP MoA grouped according to the Marrakech classification present different correlates of increased risk, suggesting the existence of distinct pathogenetic pathways. |
| P61 | RISK FACTORS ASSOCIATED WITH TYPES OF METABOLIC AND MORPHOLOGICAL ALTERATIONS ACCORDING TO THE MARRAKECH CLASSIFICATION Antiviral Therapy 2000; 5(Supplement 5):59 (abstract no. P61) M Galli, F Veglia, G Angarano, A Cargnel, F Gritti, F Mazzotta and A Lazzarin for the Lipodystrophy Italian Multicenter Study (LIMS) Different types of MMA recognize different risk factors. What is grouped today as MMA may contain different pathologies. This is important in order to understand the pathogenesis and to look for a therapy of these disorders. |
| P62 | EVOLUTION OF CLINICAL AND LABORATORY FEATURES IN PATIENTS WITH HIV-ASSOCIATED LIPODYSTROPHY SYNDROME TREATED WITH HAART REGIMENS INCLUDING AMPRENAVIR Antiviral Therapy 2000; 5(Supplement 5):60 (abstract no. P62) N Adda1, Y Salhi1, S Gharakhanian2 and W Rozenbaum1 Evaluating LD is a difficult task in the absence of the natural history of this new multifactorial syndrome. However, clinicians need data for the choice of HAART. This pilot study shows the clinical evolution/stable laboratory markers in regimens including amprenavir over 6 months. Amprenavir needs a prospective, controlled evaluation for LD. |
| P63 | EARLY OCCURRENCE OF LIPODYSTROPHY IN HIV-1-INFECTED PATIENTS TREATED DURING PRIMARY INFECTION Antiviral Therapy 2000; 5(Supplement 5):61 (abstract no. P63) C Gouiard1, F Boufassa2, C Deveau2, D Laskri2, JF Delfraissy2 and L Meyer2 for the PRIMO group Lipodystrophy can occur early after HAART initiation even after primary infection. This finding militates against the sole role of the duration of HIV-l infection in the pathogenesis of lipodystrophy. In our cohort, good responders to HAART were more likely to present with lipodystrophy. |
| P64 | CLINICAL FACTORS ASSOCIATED WITH INCIDENCE AND PREVALENCE OF FAT ATROPHY AND ACCUMULATION Antiviral Therapy 2000; 5(Supplement 5):61 (abstract no. P64) KA Lichtenstein1, KM Delaney2, DJ Ward3 and FJ Palella4 Over time, factors associated with the incidence and prevalence of fat atrophy and accumulation differ. Accumulation is most likely to manifest between 3 and 5 years of ART. |
| P65 | CHANGES IN BODY HABITUS AND SERUM LIPID ABNORMALITIES IN HIV-POSITIVE WOMEN ON HAART: A 3.5-YEAR FOLLOW-UP STUDY Antiviral Therapy 2000; 5(Supplement 5):62 (abstract no. P65) A Mahajan, MM Flynn, LL Bausserman, MGDi Spigno and KT Tashima Body habitus changes, which developed in women within 1 year of HAART, appear to be essentially stable during 2.5 more years of HAART. Only modest and inconsistent improvement was observed with alterations in therapy. A minority of women on HAART appear to develop body habitus change well beyond 1 year of HAART. |
| P66 | NEVIRAPINE-INDUCED LIVER TOXICITY: A PROSPECTIVE COHORT STUDY Antiviral Therapy 2000; 5(Supplement 5):66 (abstract no. P66) E Martínez1, JA Arnaiz2, A Cruceta1, JB Pérez-Cuevas1, A Mocroft3, X Carné2 and JM Gatell1 Nevirapine was generally well tolerated. Clinical hepatitis seldom appeared and other underlying factors might be related. Abnormalities in ALAT or ASAT increased steadily along first year of therapy, but they were mainly asymptomatic. LFT monitoring during first 1-2 months of therapy does not seem to be justified. |
| P67 | LIPODYSTROPHY PATTERNS SECONDARY TO ANTIRETROVIRAL THERAPIES Antiviral Therapy 2000; 5(Supplement 5):63 (abstract no. P67) E Seminari1, P Sacchi2, G Meneghetti1, C Zocchetti2, R Bruno2 and R Maserati1 This study documents that different patterns of lipodystrophy are featured by different metabolic profiles. Type I was associated with mild metabolic toxicity, while types II and III were associated with more severe abnormalities. |
| P68 | RISK FACTORS FOR HIV-ASSOCIATED LIPODYSTROPHY SYNDROME IN PATIENTS WITH UNIFORM DURATION OF ANTIRETROVIRAL TREATMENT (LIPART) Antiviral Therapy 2000; 5(Supplement 5):63 (abstract no. P68) S Mauss1, M Corzillius2, E Wolf3, A Schwenk4, H Jaeger3,H Knechten5, J Goelz6 and A Goetzenich7 for the LipART Network These findings suggest roles for nucleoside analogues and immunosuppression in the pathogenesis of HIV-associated lipodystrophy syndrome. Although protease inhibitors had no significant risk, protease inhibitor-sparing regimens appeared to be associated with a reduced risk of lipodystrophy. The lipodystrophic changes seem to affect the quality of life in the majority of patients. |
| P69 | FAT REDISTRIBUTION SYNDROME/LIPODYSTROPHY AND ANABOLIC AGENTS: RESULTS OF A LARGE MULTICENTRE US STUDY Antiviral Therapy 2000; 5(Supplement 5):64 (abstract no. P69) G McComsey1, L Shaker-Irwin2, S Follansbee2, R Clark2, A LaMarca2, D Berger2, L Cardona2, R Anderson2, N Bellos2, R Dretler2, S Segal-Maurer2 and F Ottery2 A broad-based multicentre study confirms use of T:E >2.46 in men for BC change in FRS, with clear differences in COLM between genders. A comparable incidence of FRS was seen across AA groups. |
| P70 | THE AUSTRALIAN LIPODYSTROPHY PREVALENCE SURVEY Antiviral Therapy 2000; 5(Supplement 5):65 (abstract no. P70) JE Miller, S Emery, M French, D Baker, DA Cooper and the Australian Lipodystrophy Syndrome Research Group This survey confirms and expands upon earlier reports of LD in terms of prevalence and clinical features. The prevalence and severity of LD reflects both length and type of treatment with ARV therapy. |
| P71 | DIFFERENT FACTORS ARE ASSOCIATED WITH ABNORMAL FAT ACCUMULATION AND FAT DEPLETION IN MEN AND WOMEN WITH HIV Antiviral Therapy 2000; 5(Supplement 5):65 (abstract no. P71) N Muurahainen1, M Glesby2, J Falutz3, J Balser1, M Kleintop1, R Pettit1, DP Kotler4 and the SALSA Investigators Group Although it has been reported that different variables are associated with lipohypertrophy (FA) and lipoatrophy (FD) in HIV patients with fat maldistribution - raising the consideration that more than one type of HIV-associated lipodystrophy syndrome may exist - these findings indicate that there may also be gender and/or demographic differences regarding variables associated with FA and FD. To further evaluate this possibility, larger cohorts of women and longitudinal analyses are recommended. |
| P72 | PREVALENCE OF LIPODYSTROPHY (LIPOATROPHY, HYPERTROPHY AND MIXED SYNDROME) AND METABOLIC COMPLICATIONS IN HIV-INFECTED PATIENTS: A CROSS-SECTIONAL STUDY Antiviral Therapy 2000; 5(Supplement 5):66 (abstract no. P72) R Polo1, A Muñoz2, M Colmenero3, P Segarra4, J Sanz5, MJ Galindo6, F Pulido7, V Estrada8, P Lainez9, A Frances10, JL Gomez-Sirvent11, M Gonzalez-Muñoz1, J Verdejo1 and The GEAM Study Group Lipodystrophy is frequently observed in HIV-treated patients. The frequency is higher in NRTIs plus PIs than NRTIs plus NNRTIs regimens (58.8 versus 37.5%; P<0.001). The three clinical manifestations of lipodystrophy were more frequent in PI containing regimens; the differences were greater in hypertrophic and mixed syndromes (7.7 versus 20.6% and 24.1 versus 58.7%) than in lipoatrophic syndrome (39.1 versus 44.2%). |
| P73 | LIPO-ACCUMULATION AMONG HIV-POSITIVE, PROTEASE INHIBITOR-NAÏVE PATIENTS RECEIVING ANTIRETROVIRAL THERAPY Antiviral Therapy 2000; 5(Supplement 5):67 (abstract no. P73) C Rice1, AD Luber1,2, A Pavlatos3, P Morrow4 and G Cohan1 Body habitus changes among HIV-infected, PI-naïve patients are infrequently reported in the PI era. Whereas previous data suggest that the nucleoside analogues may be responsible for lipoatrophy and PIs may be responsible for lipoaccumulation, these data show that even among PI-naïve patients, lipo-accumulation disorders can be seen. |
| P74 | INCIDENCE AND FACTORS ASSOCIATED WITH BODY SHAPE CHANGES IN HIV-INFECTED PATIENTS Antiviral Therapy 2000; 5(Supplement 5):67 (abstract no. P74) V Rickerts, M Bickel, S Klauke, T Leder, A Carlebach, A Muller and S Staszewski Body shape changes are frequent. Gender, use of alcohol and stavudine may influence the phenotype of body shape changes. Cumulative time on ARV was strongly associated with of fat loss, but not of fat accumulation. |
| P75 | INCIDENCE OF LIPODYSTROPHY AND METABOLIC ALTERATIONS AMONG PATIENTS RECEIVING ANTIRETROVIRAL THERAPY SINCE PRIMARY HIV INFECTION Antiviral Therapy 2000; 5(Supplement 5):68 (abstract no. P75) AL Ridolfo, A Gori, C Gervasoni, F Franzetti and M Galli The incidence of LD in our PHI patients receiving zidovudine-containing triple combination therapy seems to be lower than the incidence reported by others in patients receiving stavudine-based regimens. Nevertheless metabolic alterations were a frequent finding and diabetes developed within 18 months of treatment in all of the patients older than 50 at enrolment in the study. |
| P76 | RISK FACTORS FOR LIPODYSTROPHY AND IMPACT ON THE QUALITY OF LIFE AFTER TREATMENT WITH METACRYLATE Antiviral Therapy 2000; 5(Supplement 5):68 (abstract no. P76) M Serra Although some patients developed lipodystrophy just using stavudine plus lamivudine, and these drugs are included in 80% of the regimens, and are related with mitochondrial toxicity, what was really surprising was the long time of HIV infection. 93% of patients had at least 5 years of SD, and that most of them were at that time diagnosed with AIDS, they probably have a longer time of HIV infection, showing that HIV infection plays itself a important role in developing lipodystrophy. Facial implants had wonderful results, helping patients recover self-esteem, keep adherence to ART and improve quality of life. |
| P77 | EFFECTS OF TREATMENT REGIMEN ON SUBCUTANEOUS FAT DISTRIBUTION: A LONGITUDINAL ANALYSIS Antiviral Therapy 2000; 5(Supplement 5):69 (abstract no. P77) AH Shevitz, TA Knox, C McCormack, J Hamel and SL Gorbach Persons with HIV lose peripheral and trunk subcutaneous fat; the rate of loss may be slowed by PIs and increased by NNRTIs. Anthropometry provides important information on fat distribution not available from DXA. |
| P78 | INCREASED RISK OF LIPODYSTROPHY WHEN INCLUDING NRTIs IN THE TREATMENT OF HIV-1 INFECTION WITH PROTEASE INHIBITORS: RESULTS FROM A RANDOMIZED CONTROLLED TRIAL Antiviral Therapy 2000; 5(Supplement 5):70 (abstract no. P78) M van der Valk1, E Gisolf1, P Reiss1, F Wit1, A Japour2, G Weverling1 and S Danner1 on behalf of the Prometheus study group This randomized clinical trial strongly supports a contributory role of NRTIs in the development of ART-associated lipodystrophy. Furthermore, the low incidence of lipodystrophy in patients with no or limited NRTI exposure, at least over a period of 2 years, warrants the further evaluation of NRTI-sparing regimens as potentially less toxic alternatives to current standard ART. |
| P79 | THE EVALUATION OF METABOLIC FUNCTION AND FAT REDISTRIBUTION IN CLINICAL TRIALS Antiviral Therapy 2000; 5(Supplement 5):70 (abstract no. P79) S Walker on behalf of the Steering Committee for the Evaluation of Metabolic Complications of HAART Changes in lipid and carbohydrate metabolism and in body composition associated with the most potent and effective therapies available are being reported with increasing frequency. These changes could potentially lead to increased risks of cardiovascular disease. Clinical trials set up to investigate new antiretroviral therapies need to explore their impact on these potentially serious adverse outcomes, at least in a subset of patients. |
| P80 | LIPID ELEVATIONS IN A SURVEY OF LIPODYSTROPHY IN HIV-INFECTED AMBULATORY PATIENTS Antiviral Therapy 2000; 5(Supplement 5):71 (abstract no. P80) DJ Ward1, KM Delaney2, KA Lichtenstien3, AC Moorman2 and SD Holmberg2 Elevated cholesterol and triglyceride values in HIV treatment are not necessarily linked to each other and appear to have different correlations to both medicines used and lipodystrophic clinical factors. |
| P81 | PREVALENCE OF AN OBESE PRESENTATION AMONG ASYMPTOMATIC HIV PATIENTS AT AN URBAN CLINIC Antiviral Therapy 2000; 5(Supplement 5):71 (abstract no. P81) P Wasserman, S Segal-Maurer and D Rubin No historical data on obesity in AIDS is available, as it had not been considered problematic until its association with protease inhibitor usage. Our obese patients BCM% (body weight obesity adjusted) were consistent with prolonged survival in Kaplan-Meier analyses of patients with normotypic BMI, thus no occult wasting was noted. Higher nadir and test CD4 number and percentage among women were not protective for lipodystrophy. Our obese cohort is characterized by significant improvement in the absolute number CD4, long duration of HAART (average 33.6 months) and long-term survival since diagnosis. |
| P82 | RAISED LACTATE LEVELS ARE COMMON AND MAY BE PREDICTIVE OF SUBCUTANEOUS FAT WASTING Antiviral Therapy 2000; 5(Supplement 5):72 (abstract no. P82) AJ White1, M John2, C Moore2, IR James2, D Nolan2 and SA Malla2 Although decompensated lactic acidosis is rare, compensated elevations in plasma lactate are common and may help predict patients at risk for the development of subcutaneous fat wasting. |
| P83 | METABOLIC OUTCOME (LIPID PROFILE AND LIPODYSTROPHY BODY SHAPE CHANGES) IN HIV-POSITIVE PATIENTS AFTER SWITCHING PI TO NNRTI Antiviral Therapy 2000; 5(Supplement 5):72 (abstract no. P83) F Blanco, C Casimiro, F Gómez, J de la Cruz, P Barreiro, T García-Benayas, V Soriano and J Glez-Lahoz SP strategies (PI to NNRTI) improve LD morphological alterations in a significant proportion of patients previously treated with PI, and seem to be virologically and immunologically safe. However, a benefit in the lipid profile is not achieved and other lipid-lowering interventions must be considered. |
| P84 | A RANDOMIZED, MULTICENTRE STUDY OF PROTEASE INHIBITOR SUBSTITUTION IN AVIRAEMIC PATIENTS WITH LIPODYSTROPHY (LD): 48-WEEK DATA Antiviral Therapy 2000; 5(Supplement 5):73 (abstract no. P84) A Carr1, J Hudson, M Law and DA Cooper1,2 (*for the PIILR investigators) PI(s) cessation and substitution with abacavir and nevirapine (with or without adefovir/hydroxyurea) in heavily antiretroviral-pretreated patients with LD maintained HIV RNA suppression. Central fat accumulation and lipids improved, but peripheral lipoatrophy and insulin resistance did not. |
| P85 | IMPROVEMENT IN FACIAL LIPOATROPHY AFTER SUBSTITUTION OF STAVUDINE Antiviral Therapy 2000; 5(Supplement 5):73 (abstract no. P85) A Clark Substituting stavudine resulted in an improvement in the FW of almost all the patients, suggesting stavudine as a potential cause. Where patients have alternative options, a simple change in the regimen may improve or reverse FW without compromising viral suppression. However, many heavily treated patients have no alternative substitutes, and may instead choose to interrupt their ART in favour of resolving FW. Further studies are imperative to elucidate the pathogenesis of FW and to examine these findings in a larger study. Prescribing potentially disfiguring drugs is unacceptable if little is attempted to address the problem, and will promote lack of adherence. |
| P86 | CHANGES IN LIPIDS, INSULIN AND BODY COMPOSITION DURING STRUCTURED TREATMENT INTERRUPTION Antiviral Therapy 2000; 5(Supplement 5):74 (abstract no. P86) RA Hoh1, J Troiano2, M Christiansen3, SG Deeks1 and MK Hellerstein3 Interrupting antiretroviral therapy for 12 weeks led to significant improvements in lipid profile and lean body mass; however, fasting insulin and body anthropometric measurements remained stable. |
| P87 | EFFECTS ON CHOLESTEROL AND TRIGLYCERIDE LEVELS AFTER SWITCHING FROM NON-AMPRENAVIR PROTEASE INHIBITOR ANTIRETROVIRAL REGIMENS TO AMPRENAVIR ANTIRETROVIRAL REGIMENS Antiviral Therapy 2000; 5(Supplement 5):75 (abstract no. P87) AD Luber, L Shaker-Invin, J Burdick, PR Wolfe and G Cohan Overall, changes in cholesterol and triglycerides after switching to amprenavir-based ART regimens were minimal. However, some patients did experience substantial declines from baseline following the switch. These data suggest that amprenavir may provide some benefit for high-risk patients with elevated cholesterol and/or triglyceride levels. while receiving ART. Further prospective clinical trials are recommended based upon these results. |
| P88 | REDUCTION IN LIPID ABNORMALITIES DURING TREATMENT WITH AMPRENAVIR IN SUBJECTS EXPERIENCING HYPERLIPIDAEMIA ON A PROTEASE INHIBITOR-CONTAINING REGIMEN Antiviral Therapy 2000; 5(Supplement 5):75 (abstract no. P88) L Pedneault1, C Garris1, S Castillo1, M Rogers1, N Graham1, L Garrett2, B Akil3 and T Scott1 The data from this cohort of subjects suggest that amprenavir combination therapy had a beneficial clinical effect in subjects experiencing hyperlipidemia on a PI-containing regimen. |
| P89 | METABOLIC AND CLINICAL EVALUATION OF LIPODYSTROPHY 48 WEEKS AFTER SWITCHING FROM TWO NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS/PROTEASE INHIBITOR TO TWO NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS/ABACAVIR (FRENCH SUBSTUDY, CNA30017) Antiviral Therapy 2000; 5(Supplement 5):76 (abstract no. P89) W Rozenbaum1,2, JF Delfraissy2, M Bentata2, P DeTruchis2 and Z Antoun3 Switching from a PI to abacavir gives a trend of improved cholesterol and insulin tolerance test at 48 weeks. These study results should be confirmed in larger comparative trials. |
| P90 | EVOLUTION OF FASTING METABOLIC PARAMETERS AND FAT DISTRIBUTION AFTER SWITCHING PROTEASE INHIBITOR IN THE PROTRA STUDY Antiviral Therapy 2000; 5(Supplement 5):77 (abstract no. P90) M Bickel1, V Rickerts1, V Jacobi2, S Klauke1, J Tews2, V Miller1 and S Staszewski1 Replacement of PI with abacavir plus efavirenz demonstrated an improvement in fasting lipid parameters, which was not sustained up to 48 weeks. The glycaemic parameters tend to improve. The CT-scans show a progress of the fat redistribution, despite patients' self-report of improvement of lipodystrophy. |
| P91 | SIGNIFICANTLY IMPROVED CARDIOVASCULAR RISK PROFILE IN WOMEN WHO SWITCH FROM A PROTEASE INHIBITOR TO EFAVIRENZ Antiviral Therapy 2000; 5(Supplement 5):77 (abstract no. P91) KT Tashima, MM Flynn, L Bausserman, MG Di Spigno and CCJ Carpenter After change from a PI- to an efavirenz-based HAART regimen, no significant change in HIV-RNA was observed and a modest increase in CD4 cell count occurred. Changes that are generally associated with decreased risk of coronary heart disease occurred in plasma lipids, with increases in HDL-c and HDL2-c, and decreases in total cholesterol, LDL cholesterol, triglycerides and apolipoprotein B. The observed changes in plasma lipids were not accompanied by significant changes in body habitus. |
| P92 | SWITCHING FROM PROTEASE INHIBITOR- TO NEVIRAPINE-BASED POTENT ANTIRETROVIRAL THERAPY INCREASES LEAN BODY MASS Antiviral Therapy 2000; 5(Supplement 5):78 (abstract no. P92) KE Yarasheski, P Tebas, S Claxton, B Stanerson, D Marin, K Bae and WG Powderly Switching to nevirapine-based ART increased whole-body and appendicular lean mass in the thighs, but this did not appear to be muscle tissue. Removing PIs and introducing nevirapine may improve non-muscle protein balance and augment LBM. Increased DEXA-derived LBM may result from increased tissue hydration, increased connective tissue mass in the arms and legs, or altered dietary protein absorption/utilization. Future studies should monitor changes in regional lean and muscle mass during potent ART. |
| P93 | HIV-PROTEASE INHIBITOR SWITCH TO NEVIRAPINE IMPROVES INSULIN TOLERANCE BUT DOES NOT CORRECT ADIPOSE TISSUE MALDISTRIBUTION Antiviral Therapy 2000; 5(Supplement 5):78 (abstract no. P93) KE Yarasheski, P Tebas, S Claxton, B Stanerson, D Marin, D DeMarco, K Bae and WG Powderly The switch to nevirapine improved fasting insulin tolerance, glucose and lipid blood chemistries, and reduced thigh but not visceral adiposity. Switching from PI- to nevirapine ART may not protect against peripheral lipoatrophy or central adipose tissue deposition. DEXA and MRI quantitation of regional adipose tissue mass/area agreed well. |
| P94 | THE EFFECTS OF POLYLACTIC ACID AS THERAPY FOR LIPOATROPHY OF THE FACE Antiviral Therapy 2000; 5(Supplement 5):79 (abstract no. P94) P Amard1, T Saint-Marc2 and P Katz1 Our data confirm the positive effects of intradermal injections of PLA on facial lipoatrophy while maintaining antiretroviral therapy. |
| P95 | EFFECTS OF LOW-DOSE GROWTH HORMONE THERAPY FOR HIV-ASSOCIATED VISCERAL ADIPOSITY Antiviral Therapy 2000; 5(Supplement 5):80 (abstract no. P95) ES Engelson1, M Glesby2, D Mendez2, Q He1 and DP Kotler1 Over 24 weeks, low-dose GH resulted in a 20% loss of VAT, without any significant effect on SAT. Even at the low dose, GH showed an anabolic effect. Adverse effects appeared to be less troublesome overall. Low-dose GH may be an effective alternative or follow-up to the standard 6 mg/day dose. |
| P96 | FAT EXPANSIONS, IN PATIENTS ON HAART WITH FAT REDISTRIBUTION SYNDROME, SHRINK AFTER NIACIN-INDUCED INCREASE IN PLASMA HDL Antiviral Therapy 2000; 5(Supplement 5):80 (abstract no. P96) WJ Fessel, SE Follansbee, TT Luu, B Anderson, TP Young and J Rego Intra-abdominal fat expansion diminished after raising plasma HDL. Diminution was related to duration of niacin therapy. |
| P97 | SHORT-TERM EXERCISE TRAINING ATTENUATES BODY COMPOSITIONAL AND HYPERLIPIDAEMIA CHANGES ASSOCIATED WITH LIPODYSTROPHY Antiviral Therapy 2000; 5(Supplement 5):81 (abstract no. P97) SP Jones, D Doran, B Maher and M Pirmohamed Our study suggests that exercise training may improve selected lipid profiles and body fat redistribution abnormalities associated with lipodystrophy, and is associated with an improvement in overall physical fitness. The potential use of exercise in reducing the cardiovascular risk profiles of affected individuals as an adjunct to traditional therapy warrants further study. |
| P98 | LACK OF EFFECT OF L-CARNITINE ON HIV-ASSOCIATED LIPODYSTROPHY Antiviral Therapy 2000; 5(Supplement 5):81 (abstract no. P98) S Mauss and G Schmutz The results do not support the use of L-carnitine for reversal of HIV-associated lipodystrophy. However, a cholesterol lowering effect of L-carnitine was observed. |
This information is designed to support, not replace, the relationship that exists between you and your doctor.