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7th International Workshop on Adverse Drug Reactions
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| Plenary Session | |
| P1 | OBJECTIVE MEASUREMENTS OF BODY COMPOSITION IN VIVO USING MAGNETIC RESONANCE IMAGING Antiviral Therapy 2005; Supplement 3:L1 D Gallagher The use of MRI continues to provide insights into the relationship between adipose tissue distribution, ectopic lipids and the pathophysiology of different disease states that may have a positive impact on patient treatment and clinical care. Recognized limitations of MRI include access to available scanners and high cost of image acquisition and image/compartment analyses. However, no other currently available, radiation free, body composition technique can quantify soft-tissue depots in vivo. |
| P2 | DRUG SAFETY IN THE BALANCE: PAST, PRESENT AND FUTURE Antiviral Therapy 2005; Supplement 3:L1 SJW Evans There is a need for improvements to the whole process and some suggestions for better use of existing data and new methods to obtain data will be given. |
| P3 | A REVIEW OF THE DISCOVERY AND EXPLORATORY DEVELOPMENT OF MARAVIROC (UK-427,857): A NOVEL CCR5 ANTAGONIST FOR THE TREATMENT OF HIV Antiviral Therapy 2005; Supplement 3:L2 CA Hitchcock Maraviroc has potency, pharmacokinetic and toleration profiles that merit its further evaluation as a new therapy for patients with HIV/AIDS. |
| P4 | HEPATIC STEATOSIS: THE COMMON DENOMINATOR FOR INSULIN RESISTANCE IN OBESE AND LIPOATROPHIC SUBJECTS Antiviral Therapy 2005; Supplement 3:L2 H Yki-Järvinen Treatment of both lipodystrophic and type 2 diabetic patients with PPARγ agonists but not metformin decreases liver fat content and increases serum adiponectin levels. The fatty liver may help to explain why some, but not all, obese individuals are insulin resistant and why even lean individuals lacking subcutaneous fat are insulin resistant, and thereby at risk of developing type 2 diabetes and cardiovascular disease. |
| P5 | HIV AND THE KIDNEY Antiviral Therapy 2005; Supplement 3:L3 P Klotman Current HAART regimens include several antivirals excreted by the kidneys, which may be associated with nephrotoxicity. Recognizing those complications that are due to drugs versus those that represent other renal complications is a challenging but not insurmountable task that we all face in managing the HIV epidemic effectively. |
| P6 | PREVENTION OF CARDIOVASCULAR DISEASE Antiviral Therapy 2005; Supplement 3:L3 S MacMahon Abstract withdrawn at author's request. |
| Session I | |
| 1 | HIV-INFECTED MONOCYTES AND MACROPHAGES IN ADIPOSE TISSUE CONTRIBUTE TO THE DEVELOPMENT OF LIPOATROPHY Antiviral Therapy 2005; Supplement 3:L4 CM Shikuma Abstract withdrawn. |
| 2 | ASSESSING THE CONTRIBUTION OF ART, HIV AND HOST FACTORS TO ADIPOSE TISSUE CHANGES OCCURRING IN HIV-INFECTED INDIVIDUALS: RISK PROFILE FOR LIPOATROPHY Antiviral Therapy 2005; Supplement 3:L4 E Hammond1, D Nolan1, E McKinnon1, C Pace1, C Metcalf2 and S Mallal1 Profiling of adipose tissue morphology, cytokine protein expression and mtDNA depletion identified ART [d4T>AZT>ABC (without d4t/AZT)= naïve], but not viral or host variables, as risk factors for lipoatrophy. |
| 3 | INCREASE IN LIMB FAT AFTER NUCLEOSIDE ANALOGUE CESSATION IS NOT ASSOCIATED WITH DECREASED VISCERAL FAT AND HAS DIFFERENT RISK FACTORS Antiviral Therapy 2005; Supplement 3:L5 H Wand1, MG Law1, S Emery1, DA Cooper1,2 and A Carr2 for the MITOX and ROSEY Study Groups An increase in limb fat in men recovering from lipoatrophy is not associated with a reduction in VAT, but rather an increase. Changes in limb fat and VAT also have differing risk factors. Both findings suggest that lipoatrophy and visceral obesity are at least partially independent processes. Lipoatrophy improved in 50% of patients after 18 months and was less likely in those with lower BMI. |
| 4 | BASELINE AND EARLY ON-TREATMENT PREDICTORS OF LIPOATROPHY AT 64 WEEKS IN A RANDOMIZED TRIAL OF INITIAL ANTIRETROVIRAL THERAPY: A SECONDARY ANALYSIS OF A5005S, A SUBSTUDY OF ACTG 384 Antiviral Therapy 2005; Supplement 3:L5 RA Parker1,2, L Komarow1,2, SK Grinspoon2, K Mulligan3, GK Robbins2, P Tebas4 and MP Dubé5 Nucleoside assignment, greater baseline CD4 and BMI, but not age, sex or white race were associated with lipoatrophy in univariate analyses. Baseline TGs and cholesterol (and their early changes), but not measures of glucose metabolism, were associated with lipoatrophy. In multivariate models, increases in TGs and ddI+d4T treatment were associated with lipoatrophy. We did not find evidence of an association between lower nadir CD4+ cell counts and white race with lipoatrophy. |
| Session II | |
| 5 | INAPPROPRIATE GLYCATED HAEMOGLOBIN VALUES AND HAEMOLYSIS IN HIV-INFECTED PATIENTS Antiviral Therapy 2005; Supplement 3:L6 M-E Diop1, J-P Bastard1, N Meunier1, S Thévenet2, M Maachi1, J Capeau1, G Pialoux2 and C Vigouroux1 HbA1c should be interpreted with caution in HIV-infected patients. Its under-evaluation of mean fasting glycaemia could be due to haemolysis, associated with lamivudine treatment. Further study is needed to specifically explore this hypothesis. |
| 6 | CREATINE SUPPLEMENTATION FAILS TO AUGMENT THE BENEFITS DERIVED FROM RESISTANCE EXERCISE TRAINING IN PATIENTS WITH HIV INFECTION Antiviral Therapy 2005; Supplement 3:L6 GK Sakkas1,2, K Mulligan1, ML DeSilva1, J Doyle1, H Khatami1, J Kent-Braun3 and M Schambelan1 Resistance exercise training improved muscle size and strength in HIV-infected men. Although creatine supplementation increased LBM, it failed to augment the increase in strength derived from resistance exercise training. |
| 7 | URIDINE SUPPLEMENTATION INCREASES SUBCUTANEOUS FAT IN PATIENTS WITH HAART-ASSOCIATED LIPODYSTROPHY: A RANDOMIZED, PLACEBO-CONTROLLED TRIAL Antiviral Therapy 2005; Supplement 3:L7 J Sutinen1, UA Walker2, K Sevastianova1, AM Hakkinen1, M Ristola1 and H Yki-Jarvinen1 NucleomaxX® increased predominantly the amount of subcutaneous fat, but did not change liver fat content in lipoatrophic patients with unchanged HAART. |
| 8 | IMPROVEMENTS IN FACIAL LIPOATROPHY AT 48 WEEKS FOLLOWING SUBSTITUTION OF A THYMIDINE ANALOGUE WITH TENOFOVIR (TDF) OR ABACAVIR (ABC): A RANDOMIZED, OPEN-LABEL STUDY IN PEOPLE WITH LIPOATROPHY AND VIROLOGICAL SUPPRESSION ON HAART Antiviral Therapy 2005; Supplement 3:L7 P Benn1, V Sauret2, J Cartledge1, C Ruff2, CA Sabin3, G Moyle4, R Richards2, G Reilly5 and SG Edwards1 In lipoatrophic HIV-infected adults, switching from a thymidine analogue to abacavir or tenofovir DF for 48 weeks leads to similar significant improvements in both limb fat and facial lipoatrophy. Changes in total facial cheek volume significantly correlate with increases in limb fat shown by DEXA imaging. |
| Session III | |
| 9 | ADIPOCYTE ATP LEVELS CONTRIBUTE TO THE AETIOLOGY OF HIV LIPOATROPHY Antiviral Therapy 2005; Supplement 3:L8 M Gerschenson, S Steele, DE LiButti and CM Shikuma HIV lipoatrophic adipocyte ATP levels were 0.047 ±0.048 pM/cell and decreased significantly compared to HIV non-lipoatrophic at 0.160 ±0.009 (P=0.011) and HIV seronegative at 0.115 ±0.161 (P=0.013). The preadipocyte fraction ATP amounts were similar among the three cohorts. There was mtDNA depletion in the HIV lipoatrophic SC fat: 165 ±78 mtDNA copies/cell compared with the seronegative at 715 ±615 (P<0.001) but not compared with the non-lipoatrophic. This data demonstrates that HIV lipoatrophy is associated with ATP depletion in adipocytes but not in the preadipocyte fraction. |
| 10 | PRESERVED CYTOCHROME C OXIDASE ACTIVITY DESPITE MITOCHONDRIAL DNA DEPLETION IN ADIPOSE TISSUE OF HIV-INFECTED PATIENTS WITH LIPODYSTROPHY Antiviral Therapy 2005; Supplement 3:L8 MJ Kim1,2, C Jardel1, C Barthélémy1, V Jan2,3, J-P Bastard2,3, S Chapin1, S Houry4, P Levan5, J Capeau2,3 and A Lombès1 Despite severe mtDNA depletion, mitochondrial function and proteins depending on the mtDNA are preserved in the patients’ adipose tissue. This is associated with mitochondrial proliferation, the mechanism of which remains to be clarified as it was not explained by upregulation of transcription factors usually involved in mitochondrial biogenesis. Alteration of transcriptional regulation of mitochondrial biogenesis was related to that of adipogenesis and to metabolic parameters supporting a complex role for mitochondria dysfunction in lipodystrophy. |
| 11 | RITONAVIR IMPAIRS LIPOPROTEIN LIPASE-MEDIATED LIPOLYSIS AND DECREASES UPTAKE OF FATTY ACIDS IN ADIPOSE TISSUE Antiviral Therapy 2005; Supplement 3:L9 MAM den Boer1,2, JFP Berbée2,3, P Reiss4, M van der Valk4, PJ Voshol1,2, F Kuipers5, LM Havekes2,3,6, PCN Rensen2,3 and JA Romijn1 We conclude that RTV causes hypertriglyceridaemia via decreased LPL-mediated clearance of VLDL-TG. In addition, RTV specifically impairs the uptake of FA in adipose tissue, which may contribute to the lipodystrophy that is frequently observed in HIV-infected subjects on antiretroviral therapy. |
| 12 | SAFETY AND EFFICACY OF EXTENDED-RELEASE NIACIN FOR THE TREATMENT OF DYSLIPIDAEMIA IN PATIENTS WITH HIV INFECTION: A PROSPECTIVE, MULTICENTRE STUDY (ACTG 5148) Antiviral Therapy 2005; Supplement 3:L9 MP Dubé1, JW Wu2, JA Aberg3, MA Deeg1, ME McGovern4, BL Alston5, SL Shriver6, ML Greenwald1, D Lee7 and JH Stein8 ERN at doses up to 2000mg/day is a safe, well-tolerated and effective agent for treating dyslipidaemia in HIV-infected individuals receiving ART. |
| Session IV | |
| 13 | USE OF ORAL GLUCOSE TOLERANCE TESTING TO ESTIMATE INSULIN SENSITIVITY IN PATIENTS WITH HIV INFECTION Antiviral Therapy 2005; Supplement 3:L10 K Mulligan, JC Lo, H Khatami and M Schambelan Although the OGTT is not primarily intended to measure insulin sensitivity, our results suggest that measurements of glucose and insulin during a 2- or 3-h OGTT can be used to provide an estimation of insulin sensitivity in patients with HIV infection that is highly correlated to results obtained by the glucose clamp technique and is superior to estimates of insulin sensitivity or resistance based on fasting measurements alone. |
| 14 | DEPOT SPECIFIC REGULATION OF GLUCOSE INTAKE AND INSULIN SENSITIVITY IN HIV LIPODYSTROPHY Antiviral Therapy 2005; Supplement 3:L10 D Kamin1, C Hadigan1, J Liebau1, S Mazza1, S Barrow2, M Torriani3, R Rubin4, S Weiss2, A Fischman2 and S Grinspoon1 This is the first study to directly demonstrate increased glucose uptake in subcutaneous fat of lipoatrophic patients, which may partially compensate for loss of subcutaneous adipose tissue. Furthermore, we demonstrate a clear relationship between VAT and glucose metabolism in multiple fat and muscle depots, suggesting the crucial importance of this depot in the regulation of glucose and highlighting the significant potential role of adiponectin in this process. |
| 15 | A SINGLE DOSE OF AMPRENAVIR DOES NOT INDUCE INSULIN RESISTANCE IN HEALTHY NORMAL VOLUNTEERS Antiviral Therapy 2005; Supplement 3:L11 GA Lee, MN Rao, JM Schwarz, FT Aweeka and C Grunfeld A single dose of amprenavir in HIV-negative men did not decrease insulin-mediated glucose disposal as assessed by the euglycaemic hyperinsulinaemic clamp. Relatively lower therapeutic levels of amprenavir may explain why amprenavir inhibits GLUT4 in vitro, but does not inhibit insulin-mediated glucose disposal. |
| 16 | EVALUATION OF INSULIN SENSITIVITY IN HEALTHY VOLUNTEERS TREATED WITH LOW-DOSE RITONAVIR COMBINED WITH ATAZANAVIR (ATV/RTV) OR LOPINAVIR (LPV/RTV): A PROSPECTIVE, RANDOMIZED STUDY USING HYPERINSULINAEMIC, EUGLYCAEMIC CLAMP AND ORAL GLUCOSE TOLERANCE TESTING Antiviral Therapy 2005; Supplement 3:L11 MA Noor1, OP Flint1, RA Parker1, J Maa1, J Witek1 and SL Hodder2 Treatment with RTV in combination with ATV for 10 days did not significantly affect insulin sensitivity by clamp. A small increase from BL in insulin AUC during OGTT was perhaps due to an increase in triglycerides. In contrast administration of LPV/RTV induced insulin resistance by clamp and OGTT with greater increases in triglycerides. Further data should assess clinical significance for diabetes outcome. |
| Session V | |
| 17 | MITOCHONDRIAL NEPHROTOXICITY, A POTENTIAL MECHANISM OF KIDNEY DYSFUNCTION IN HIV-INFECTED PATIENTS ON HAART Antiviral Therapy 2005; Supplement 3:L12 HCF Coté1,3, AB Magil2,3, M Harris1, BJ Scarth1, I Gadawski1, NY Wang1, E Yu4, B Yip1, N Zalunardo2, R Werb2, RS Hogg1, PR Harrigan1 and JS Montaner1 Renal dysfunction in patients receiving TDF can be mediated through mitochondrial nephrotoxicity, influenced by both HIV infection and concurrent TDF/ddI therapy, two drugs that are cleared renally. The current clinical relevance of these findings needs to be further evaluated given the recommendation for lower doses of ddI when used with TDF. |
| 18 | ANTIRETROVIRALS USED TO TREAT HIV INFECTION INDUCE PREMATURE SENESCENCE IN HUMAN FIBROBLASTS Antiviral Therapy 2005; Supplement 3:L13 M Caron1, M Auclair1, C Vigouroux1,2 and J Capeau1,2 PIs and NRTIs known to induce adipocyte dysfunctions in vitro also induced premature cellular senescence in fibroblasts. Whether mitochondrial dysfunction and ROS hyperproduction are the origin or the consequence of senescence remains to be investigated. Premature cell ageing might participate to the lipodystrophy syndrome and the metabolic alterations induced by the antiretrovirals in HIV-infected patients. |
| 19 | EXOGENOUS HIV-1 PROTEINS INDUCE ALTERATIONS IN DIFFERENTIATION AND MODULATION OF HIV-1 RECEPTORS IN PRIMARY HUMAN MESENCHYMAL STEM CELLS Antiviral Therapy 2005; Supplement 3:L13 A Patricelli, PP Doran and WG Powderly Herein we have demonstrated the capacity of exogenous HIV p55 and REV to modulate the differentiation of primary hMSCs to osteoblasts, suggesting that these proteins may contribute to decreased osteoblast cell number with consequent osteopaenia, in vivo. In addition we have demonstrated an increase in HIV-1 receptors CD4, CCR5 and CXCR4 expression in hMSCs in response to the structural proteins p55 and gp120, while a decreased expression after regulator proteins REV, TAT treatment, suggesting a selective role of the HIV-1 proteins during the replicative phase. These data present exciting new avenues for exploration in our efforts to determine the molecular mechanism of HIV associated osteopaenia. |
| Session VI | |
| 20 | MUSCLE MITOCHONDRIAL DNA AND RNA COPY NUMBER/CELL ARE REDUCED IN TREATMENT-NAÏVE HIV-INFECTED PEOPLE, REGARDLESS OF GLUCOSE IN/TOLERANCE Antiviral Therapy 2005; Supplement 3:L14 D Reeds1, WT Cade1, A Becker1, S Mohammed1, WG Powderly1, MP de Baar2, E de Rooij2 and KE Yarasheski1 Lower mtDNA and mtRNA levels predict a reduced capacity of muscle mt to synthesize proteins, regardless of glucose in/tolerance status. Although not definitive in this cross-sectional study, the mediator(s) of muscle mtDNA and mtRNA depletion appear more related to HIV-associated factors and less related to metabolic syndromes or HAART components. |
| 21 | HIV-1 INFECTION DIVERTS REVERSE CHOLESTEROL TRANSPORT TOWARD ATHEROGENIC PATHWAY Antiviral Therapy 2005; Supplement 3:L14 H Rose1, J Hoy2, I Woolley2, A Dart1 and D Sviridov1 Reverse cholesterol transport in HIV patients is diverted toward transferring cholesterol from anti-atherogenic HDL toward atherogenic apolipoprotein- B-containing lipoproteins. This would reduce the efficiency of RCT and consequently increase the risk of development of atherosclerosis. Our findings also suggest that CETP inhibitors may be effective for correcting the effect of HIV on RCT. Furthermore, our findings suggest that HIV infection itself, rather than treatment is likely to be the major contributor to the impairment of RCT in HIV patients. |
| 22 | DIASTOLIC FUNCTION IS ASSOCIATED WITH WHOLE-BODY PALMITATE OXIDATION AND SERUM HIGH DENSITY LIPOPROTEIN IN HIV+ SUBJECTS TAKING ART Antiviral Therapy 2005; Supplement 3:L15 WT Cade1, DN Reeds1, V Davila-Roman1, A Waggoner1, S Klein1, WG Powderly2 and KE Yarasheski1 HIV infection, regardless of PI use, was associated with increased whole-body FFA oxidation rates during rest and exercise. Increased FFA oxidation and lower serum HDL levels were predictive of depressed cardiac, specifically diastolic, function. |
| 23 | CHANGES IN BODY COMPOSITION AND CARDIOVASCULAR MEASURES IN HYPERCHOLESTEROLAEMIC HIV-INFECTED MEN TREATED WITH PRAVASTATIN: A RANDOMIZED, PLACEBO-CONTROLLED STUDY Antiviral Therapy 2005; Supplement 3:L15 PWG Mallon1,2, J Miller2, J Kovacic3, J Kent- Hughes2, R Norris2, K Samaras4, M Feneley3, DA Cooper1,2 and A Carr2 Despite limited effects on cholesterol, use of pravastatin 40mg daily for 12 weeks in this population resulted in significant increases in limb fat. |
| POSTER PRESENTATIONS | |
| 24 | HIV-1 INFECTION ALTERS MITOCHONDRIAL, METABOLIC AND ADIPOCYTOKINE GENE EXPRESSION IN SUBCUTANEOUS ADIPOSE TISSUE Antiviral Therapy 2005; Supplement 3:L19 JP Guallar1, P Domingo2, ML Rodriguez de la Concepcion1, M Alegre2, JC Domingo1, F Villarroya1 and M Giralt1 Major disturbances in adipose tissue gene expression are already present in untreated HIV-1-infected patients, thus indicating a major role of HIV-1 infection itself in eliciting adipose tissue alterations that produce HALS. |
| 25 | ROLE OF DISTURBANCES OF BROWN WITH RESPECT TO WHITE ADIPOCYTE BIOLOGY IN HAART-ASSOCIATED LIPODYSTROPHY AND LIPOMATOSIS: STUDIES IN VITRO AND IN VIVO Antiviral Therapy 2005; Supplement 3:L19 ML Rodriguez de la Concepcion1, JP Guallar1, P Yubero1, JC Domingo1, M Alegre2, R Iglesias1, P Domingo2, M Giralt1 and F Villarroya1 Lipomas and ScAT of patients under HAART show a distorted pattern of adipocyte gene expression. In lipomas, several features of brown adipocytes appear but not the acquisition of a full-blown brown fat phenotype. Only minor signs of this phenomenon occur in ScAT. Studies in vitro indicate that antiretroviral drugs had differential effects on brown adipocyte differentiation and gene expression, from activation (nevirapine, d4T) to repression (efavirenz, nelfinavir, saquinavir). |
| 26 | ZIDOVUDINE INHIBITS ADIPOGENIC DIFFERENTIATION OF 3T3–L1 CELLS THROUGH INHIBITION OF CLONAL EXPANSION Antiviral Therapy 2005; Supplement 3:L20 M Stankov1, RE Schmidt1 and GMN Behrens1 Zidovudine impairs the proliferative activity in preadipocytes. Inhibition of clonal expansion during conversion from the 3T3-L1 preadipocyte into fully differentiated adipocytes appears to be the critical step of the zidovudine anti-adipogenic effect. |
| 27 | FOUR WEEKS OF INDINAVIR DOES NOT ALTER ADIPOGENIC TRANSCRIPTION FACTORS IN HEALTHY HIV-NEGATIVE SUBJECTS Antiviral Therapy 2005; Supplement 3:L20 SS Shankar, LN Bell, HO Steinberg and RV Considine Four weeks of the protease inhibitor indinavir does not alter adipogenic transcription factors in healthy HIV-negative subjects. Our findings indicate that indinavir does not appear to have a direct role in the development of lipodystrophy, suggesting that the lipodystrophy is likely either due to an interaction between drug and disease, or attributable to antiretroviral agents other than indinavir. |
| 28 | PIS AND NRTIS INCREASE OXIDATIVE STRESS AND PRO-INFLAMMATORY CYTOKINE AND CHEMOKINE PRODUCTION IN HUMAN AND MURINE ADIPOCYTES AND MACROPHAGES Antiviral Therapy 2005; Supplement 3:L21 C Lagathu1, B Eustace3, D Frantz3, Y Gu3, J-P Bastard2, M Maachi2, M Briggs3, M Caron1 and J Capeau1,2 These results suggest that some PIs and NRTIs can act on adipocytes and macrophages to alter chemokine and/or cytokine production through ROS production. The altered chemokine production could be involved in macrophage recruitment to adipose tissue. The altered IL-6 production could be involved in cell loss. These results suggest a link between antiretroviral molecules and lipodystrophy through ROS, chemokine and cytokine production. |
| 29 | EFFECT OF ATAZANAVIR AND RITONAVIR ON THE DIFFERENTIATION AND ADIPOKINE SECRETION OF HUMAN SUBCUTANEOUS AND OMENTAL PREADIPOCYTES Antiviral Therapy 2005; Supplement 3:L21 SP Jones, C Waitt, DJ Back and M Pirmohamed1 In conclusion, our data indicate that RTV, but not ATV, can inhibit differentiation of Sc and Om adipocytes to a similar extent. Region-specific differences, however, were apparent for adiponectin and leptin secretion. The role of region-specific alterations in adipokine secretion and apoptosis in the pathogenesis of HIV-lipodystrophy requires further attention. |
| 30 | BODY FAT CHANGES AND LIPODYSTROPHY IN HIV-INFECTED CHILDREN: IMPACT OF HAART Antiviral Therapy 2005; Supplement 3:L22 A Dzwonek, V Novelli and M Lawson HIV-infection in childhood treated with HAART is associated with body fat redistribution changes that are most pronounced in children exposed to PI therapy. Longitudinal studies are required to differentiate the relative impact of different HAART regimens and to assess the potential for prevention. |
| 31 | VISCERAL FAT-MASS IN 175 HAART-TREATED HIV-INFECTED PATIENTS Antiviral Therapy 2005; Supplement 3:L22 I Poizot–Martin1, C Marimoutou1, D Di Stephano2, M-P Drogoul-Vey1, K Djemli1,3, P Vague3 and J-A Gastaut1 These HAART-treated patients presented a CT-measured high VAT significantly associated to the insulin resistance profile. VAT was correlated with the waist-to-hip ratio. These elements highlight the cardiovascular risk for HAART-treated patients with lipodystrophy, arguing for a rapid specific cardio-vascular management of such patients. |
| 32 | CARDIOVASCULAR RISK FACTORS IN PATIENTS WITH HIV-ASSOCIATED ADIPOSE REDISTRIBUTION SYNDROME (HARS) Antiviral Therapy 2005; Supplement 3:L23 C Grunfeld1, S Brown2, G Richmond3, N Muurahainen4 and DP Kotler5 on behalf of Study 24380 Investigators Despite exclusion criteria of diabetes, severe hypertriglyceridaemia, uncontrolled hypertension and impaired glucose tolerance, many patients with HARS who entered this trial had, in addition to increased WC and WHR, significant other additional cardiovascular risk factors: male gender, age over 40, dyslipidaemia, hypertension, high BMI, current or recent smoking history and family history of premature CAD. Increased attention should be paid to modifiable cardiovascular risk factors in this population. |
| 33 | METABOLIC SYNDROME AND HIV: COMPARISON WITH THE PREVALENCE IN THE GENERAL POPULATION (SIMONE VS PAMELA) Antiviral Therapy 2005; Supplement 3:L23 P Bonfanti1, R Facchetti2, S Melzi3, M Bombelli2, L Cordier1, M Franzetti4, H Polo Friz2, C Sfara5, T Quirino3 and R Sega2 MS was more frequent among HIV+ subjects than in the general population. This probably reflects the metabolic changes related to the HIV infection and its treatment. |
| 34 | PSYCHOSOCIAL ADJUSTMENT TO FACIAL LIPOATROPHY IN PEOPLE WITH HIV Antiviral Therapy 2005; Supplement 3:L24 CA O'Donovan, M Hourihan, J Petrak and M Murphy Patients attending a lipoatrophy clinic have high levels of anxiety and depression and quality of life and self esteem is lower than in other reports of chronic illnesses. There is a high level of concern about enforced disclosure of HIV status due to the visible nature of facial lipoatrophy and stigma related to HIV. |
| 35 | OFFICE-BASED ASSESSMENT OF BODY COMPOSITION ABNORMALITIES IN PATIENTS UNDER HAART Antiviral Therapy 2005; Supplement 3:L24 WH Belloso1, ML Sanchez1, MR Ajzenszlos1, GD Lopardo2, AM Galich1, P Fainstein Day1, D Torres1, IM Otegui1, LD Stern1 and LO Clara1 Some but not all relevant parameters of body composition can be accurately assessed by office-based inexpensive methods in HIV-positive patients. Subcutaneous fat values are more precisely predicted in men. |
| 36 | FAT MASS RATIO: AN OBJECTIVE TOOL OF HIV LIPODYSTROPHY SYNDROME DIAGNOSIS? Antiviral Therapy 2005; Supplement 3:L25 P Freitas1, D Carvalho1, AJ Madureira2, R Serrao3, J Pereira4, M Tavares3, R Marques3, I Ramos2, A Mota-Miranda3 and JL Medina1 Therefore we concluded that the FMR seems to be an objective tool to more accurately diagnose the HIV lipodystrophy syndrome and simultaneously highly correlated with body composition evaluated by CT. |
| 37 | CHANGES IN FACIAL FAT OVER TIME MEASURED BY MRI AND 3-DIMENSIONAL LASER SCANNING Antiviral Therapy 2005; Supplement 3:L25 N Paton1, Y Yang2, YY Sitoh3 and NO Tha2 Abstract not presented. |
| 38 | DISAGREEMENT BETWEEN CLINICIANS' AND PATIENTS' REPORTED OUTCOMES IN LIPODYSTROPHY Antiviral Therapy 2005; Supplement 3:L25 M Duracinsky1,3, A Wu2 and O Chassany3 PROs are weakly correlated with biological markers, and although overlapping, each of the PROs measures a distinct concept. Clinicians cannot infer the QoL of their patients neither from a viral load nor from a clinical exam. The patient’s perspective is essential in medical decision making and so it is with lipodystrophy: that is the psychological and social distress related to the body changes must be measured in clinical trials, to make sure that life is not lengthened at the expense of its quality. |
| 39 | IMPROVEMENT IN LIPOATROPHY FOLLOWING SWITCHING FROM STAVUDINE TO DIDANOSINE: 48 WEEK FOLLOW-UP Antiviral Therapy 2005; Supplement 3:L26 C Bowonwatanuwong1, P Seur2 and J Waiwaravut1 Switching from d4T to ddI resulted in marked improvement in the symptoms of lipoatrophy after 1-year follow-up and correlated with the satisfactory immunological and virological responses. Further studies with a larger number of patients and objective measurement of mitochondrial study, for example peripheral fat content by DEXA scan and subcutaneous adipose mitochondrial DNA content, will be warranted. |
| 40 | BODY COMPOSITION CHANGES IN HIV-INFECTED PATIENTS WITH LIPOATROPHY ONE AND 2 YEARS AFTER SWITCHING FROM STAVUDINE TO TENOFOVIR DISOPROXIL FUMARATE Antiviral Therapy 2005; Supplement 3:L26 G Tsekes1, M Chini1, N Tsogas1, N Mangafas1, A Lioni1, I Salpigktis1, N Delikanakis2 and MC Lazanas1 In a group of HIV-infected individuals with lipoatrophy, replacing stavudine with tenofovir resulted in a modest but significant improvement in lipoatrophy after 48 weeks of treatment. The beneficial effect of switching on fat mass was maintained during the second year of treatment, but no further improvement was noticed. |
| 41 | Surgical treatment of the buttocks and hip atrophy in feminine lipodystrophic patient Antiviral Therapy 2005; Supplement 3:L27 J Fontdevila1, J Benito1, E Martínez2, JM Serra-Renom1 and J Gatell2 At present, the increase of buttock volume by means of silicone prostheses is a much more sure and effective option long term that the infiltration of synthetic materials. A wider casuistic it is necessary to study the results of the treatment with objective parameters. |
| 42 | A PRACTICAL CLASSIFICATION FOR THE SURGICAL FILLING OF FACIAL LIPOATROPHY Antiviral Therapy 2005; Supplement 3:L28 J Fontdevila1, E Martínez2, JM Rubio-Murillo1, A Milinkovic2, JM Serra-Renom1 and J Gatell2 The proposed anatomical-based classification for facial lipoatrophy is easily applicable, shows good reproductibility among different investigators and its categories are significantly correlated with the amount of fat needed. |
| 43 | EFFICACY AND SAFETY OF MEDICAL AND SURGICAL INTERVENTIONS FOR TREATING 43 HIV-RELATED LIPODYSTROPHY IN WOMEN Antiviral Therapy 2005; Supplement 3:L28 G Orlando1, G Guaraldi1, S Cavuto1, V Borghi1, G Nardini1, B Beghetto1, C Cappi1 and R Esposito1 Italian women with LD differ with previous reports of other ethnic groups. Interventions proposed in this multidisciplinary system are efficacious and safe to improve biochemical parameters, facial lipoatrophy and psycho-social aspects connected with LD. |
| 44 | EFFECTIVENESS AND DURABILITY OF POLYACRYLAMIDE HYDROGEL INJECTIONS FOR TREATING HIV-RELATED FACIAL LIPOATROPHY Antiviral Therapy 2005; Supplement 3:L29 G Orlando1, G Guaraldi1, A Pedone1, A Spaggiari1, A Baccarani1, V Borghi1, G Nardini1, B Beghetto1, C Cappi1 and G De Santis1 Physical and psychological benefits of PHI were sustained over at least 12 months. There were no serious immediate or delayed adverse events. |
| 45 | PSYCHOMETRIC EVALUATION IN PATIENTS UNDERGOING FILLERS INJECTIONS FOR THE TREATMENT OF HIV-RELATED FACIAL LIPOATROPHY: POLYLACTIC ACID VERSUS POLYACRYLAMIDE Antiviral Therapy 2005; Supplement 3:L29 G Guaraldi1, G Orlando1, M Vandelli2, M De Paola2, D Comelli2, G De Santis1, A Pedone1, A Spaggiari1, A Baccarani1, M Pinelli1, D De Fazio3, M Blini3, V Borghi1, G Nardini1, B Beghetto1 and R Esposito1 Psychometric tools can be sensitive indicators to assess the psychological distress of people with HIV-related face lipoatrophy and to monitor the efficacy of surgical procedures. QoL evaluation needs new instruments to analyse the role of lipodystrophy and of face lipoatrophy in a new era of HIV infection. |
| 46 | AUTOLOGOUS FAT TRANSFER FOR THE TREATMENT OF HIV-RELATED FACE LIPOATROPHY: 1-YEAR FOLLOW-UP Antiviral Therapy 2005; Supplement 3:L30 G Guaraldi1, G Orlando1, D De Fazio2, A Rottino2, A Grisotti2, M Blini2, V Borghi1, G Nardini1 and R Esposito1 Our results showed that autologous fat transplant is effective and durable over time for correction of facial lipoatrophy in HIV-infected people, even if a considerable number of patients needed a retouch with filler implants to optimize the aesthetic results. The presence of mixed forms of fat redistribution could explain the lack of a significant improvement in ABCD PSD scores. |
| 47 | HEPATIC STEATOSIS AND INSULIN RESISTANCE IN HIV INFECTION Antiviral Therapy 2005; Supplement 3:L30 J Liebau1, R Andersen1, S Grinspoon1, N Holalkere2, D Sahani2 and C Hadigan1 We identify a high prevalence of steatosis among HIV-infected subjects. Subjects with steatosis had significantly greater insulin resistance and increased visceral adipose tissue, and these variables were tightly correlated with the degree of hepatic steatosis. Further studies are needed to determine the prevalence and extent of steatosis in the general population of HIV-infected patients. Our data suggest that hepatic steatosis is a common finding and we show strong correlations between steatosis and risk factors known to be associated with fatty liver in the general population. |
| 48 | ALANINE AMINOTRANSFERASE LEVELS GIVES A PREDICTION OF INSULIN RESISTANCE IN HIV LIPODYSTROPHY Antiviral Therapy 2005; Supplement 3:L31 W Bengnwi1, M Brandy2, R Lefeh3 and S Owell4 Abstract not presented. |
| 49 | ARE DISORDERS OF GLUCOSE METABOLISM IN HIV INFECTION RELATED TO PROTEASE INHIBITORS TREATMENTS OR TO HIV INFECTION ITSELF? Antiviral Therapy 2005; Supplement 3:L31 E Álvarez García1, C Miralles Álvarez2, A Repáraz Andrade1, D Rodríguez Pérez1, G Mariño Valiño1, F Barreiro Pérez3, A López Domínguez2, J De la Fuente Aguado2, RV García-Mayor3 and MA Andrade Olivié1 HOMA-IR was significantly higher in the patients groups compared with the control group. We do not find statistical differences among the four groups of patients nor among viral load groups. Our data suggest that neither PIs nor viral load levels are unlikely to play a major role in the insulin resistance of the HAARTinduced metabolic syndrome. These data probably show the multifactorial origin of the syndrome and other factors such fatty redistribution may have an important role. |
| 50 | COMPARATIVE EFFECTS OF ATAZANAVIR VERSUS OTHER HIV PROTEASE INHIBITORS ON GLUCOSE AND AMINO ACID STIMULATED INSULIN SECRETION Antiviral Therapy 2005; Supplement 3:L32 OP Flint, J Lubinski, RA Parker and MA Noor Inhibition of both glucose- and amino acidstimulated insulin release varied among the PIs tested, but was not dependent on glucose uptake suggesting a mechanism other than b-cell glucose sensing. Atazanavir differed from the other PIs in exhibiting little or no inhibition, possibly due to differences in its molecular structure. The data are consistent with the hypothesis that differential b-cell inhibition by PIs contributes to differential impairment of glucose and insulin homeostasis and may help to explain the neutral glucose metabolic profile of atazanavir in the clinic. |
| 51 | SUPPRESSION OF LIPOLYSIS DECREASES SKELETAL MUSCLE INSULIN RESISTANCE IN HIV-INFECTED PATIENTS WITH LIPODYSTROPHY Antiviral Therapy 2005; Supplement 3:L32 B Lindegaard1,2, AM Petersen1,2, P Plomgaard1,2, B Mittendorfer3 and BK Pedersen1,2 Suppresion of lipolysis in subjects with HIV LD increases the sensitivity of muscle glucose uptake but not hepatic glucose production to insulin. |
| 52 | ADIPONECTIN IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED YOUTHS: RELATIONSHIP TO BODY COMPOSITION AND INSULIN RESISTANCE Antiviral Therapy 2005; Supplement 3:L33 M Stefano1, P Brambilla2, V Giacomet2, L Cafarelli2, P Erba2, M Merlo2 and A Viganò2 These data suggest a strong relationship between adiponectin and central fat accumulation in HIVinfected youths. Low adiponectin levels may contribute significantly to the alterations in insulin response. Acknowledgements: The research in this article was supported by Grant No 30F.54 from Istituto Superiore di Sanità. |
| 53 | DOES LEPTIN DEFICIENCY OR LEPTIN RESISTANCE CONTRIBUTE TO ABNORMAL LIPID METABOLISM IN HIV LIPODYSTROPHY? Antiviral Therapy 2005; Supplement 3:L33 RV Sekhar1, AB Khan1, D Iyer1, F Jahoor2, S Patel1, AM DePaoli3 and A Balasubramanyam1 These data appear to suggest that leptin deficiency (as commonly defined) is unrelated to abnormal lipid metabolism in patients with HIV lipodystrophy. However, a plausible alternative explanation is that HLS is characterized by severe leptin resistance that is not compensated by a range of apparently normal circulating levels of leptin. Hence leptin resistance combined with relative leptin insufficiency may contribute to abnormal lipid metabolism and lipotoxicity in HLS. |
| 54 | GEOGRAPHIC REGION, ETHNIC ORIGIN, GENDER AND BASELINE LIPID LEVELS WERE SIGNIFICANT FACTORS FOR LIPID CHANGES DURING THE SOLO STUDY: A MULTIVARIATE ANALYSIS. Antiviral Therapy 2005; Supplement 3:L34 S Mauss1, S Walmsley2, J Flamm3, N Givens4 and T Stark4 Geographic region, ethnic origin and BL lipid levels had the strongest effect on OT lipid levels. Gender, age, and HIV-parameters had a smaller effect. No differences in levels of cholesterol and its subclasses were observed between FPV/r and NFV. This modelling suggests that BL demographics of a certain patient population may affect the extent and composition of lipids levels observed in antiretroviral studies. Conducting antiretroviral studies in countries outside EU and NA may result in substantially different findings concerning dyslipidaemia. |
| 55 | ASSESSMENT OF THE RISK OF CLINICAL RELEVANT DYSLIPIDAEMIA ASSOCIATED WITH SPECIFIC ANTIRETROVIRALS IN ANTIRETROVIRAL COMBINATION THERAPIES Antiviral Therapy 2005; Supplement 3:L34 S Mauss1, G Faetkenheuer2, E Wolf3, S Holm4, N Schmeisser2, G Schmutz1, B Kuhlmann4, F Berger1 and WO Richter5 In this large cohort analysis with a variety of antiretroviral combinations only few antiretrovirals showed distinct effects on lipids. Using clinical thresholds instead of average lipid changes no major differences between most NRTIs, except tenofovir, and between boosted protease inhibitors, with the exception of high triglycerides for lopinavir/r, occurred. |
| 56 | LIMITATIONS OF DIFFERENT CARDIOVASCULAR DISEASE (CVD) RISK CLASSIFICATION SCHEMES IN THE IDENTIFICATION OF HIV PATIENTS WITH CVD RISKS Antiviral Therapy 2005; Supplement 3:L35 J Falutz and L Rosenthall The prevalence of high-risk CVD patients in this cohort was significant. MS occurs as commonly in this population as in the general population. Increased trunk fat does not occur more often in patients stratified by any particular risk schema. There is poor agreement between different risk schemes in identifying high-risk patients. Consensus on identifying these high-risk CVD patients is urgently needed. |
| 57 | ENDOTHELIAL FUNCTION IS IMPAIRED IN NON-ALCOHOLIC STEATOHEPATITIS Antiviral Therapy 2005; Supplement 3:L36 SS Shankar, N Chalasani and HO Steinberg Endothelial function is impaired in subjects with NASH. This impairment is over and above that associated with the obesity of NASH. Whether the endothelial dysfunction is attributable to the elevated LDL-cholesterol levels, or the differences in insulin sensitivity, or to the intrinsic process of NASH itself, requires further investigation. |
| 58 | HEART POSITIVE 1: RESTING ENERGY EXPENDITURE IS RELATED TO HIV INFECTION, NOT LIPODYSTROPHY, IN PATIENTS WITH HIV/HAART-ASSOCIATED DYSLIPIDAEMIA Antiviral Therapy 2005; Supplement 3:L36 ET Chang1, RV Sekhar1, LW Scott2, G Cardwell3, A Garza1, T Rodriguez3, N Salazar3, H Subramanian1, A Balasubramanyam1 1. REE, which has been reported in several studies to be increased in HIV patients with and without lipodystrophy, correlates positively with markers of active HIV infection, but not with altered body composition or fat redistribution. 2. Altered body composition and fat redistribution in patients with HIV/HAART-associated dyslipidaemia are associated with decreased cardiovascular fitness and muscular strength. 3. There is a trend towards an association between increased energy expenditure/ metabolic rate and dyslipidaemia (higher LDL-C, lower HDL-C). |
| 59 | IMPACT OF LOPINAVIR PLASMA LEVELS IN LIPID PROFILE AND BODY FAT AFTER 24 WEEKS 59 OF A LOPINAVIR/RITONAVIR-CONTAINING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY Antiviral Therapy 2005; Supplement 3:L37 A León1, E Martinez1, M Sarasa2, Y López2, J Mallolas1, E De Lazzari3, M Laguno1, A Milincovic1, JL Blanco1, M Larrousse1, M Lonca1 and JM Gatell1 These results suggest a homogeneous gain in body fat and a lack of correlation between LPV plasma level and the changes in the lipid profile or in the body fat during the first 24 weeks of a highly active antiretroviral regimen including LPV/r. |
| 60 | TRIGLYCERIDES AND LDL PARTICLE SIZE IMPROVE IN PATIENTS WHO SWITCHED FROM A PROTEASE INHIBITOR TO AN EFAVIRENZ-BASED REGIMEN: RESULTS FROM THE VEST-QD METABOLIC SUB-STUDY Antiviral Therapy 2005; Supplement 3:L37 E DeJesus1, B Rodwick2, R Khanna3, K Porter3, J Maa3, G Thal3 and D Seekins3 In virologically suppressed patients on an initial PI-based regimen, a switch to an efavirenz-based regimen demonstrated expected beneficial effects on HDL concentration, the total to HDL cholesterol ratio and triglycerides. Change in LDL particle number was not significant. A significant increase in LDL particle size was observed over 12 weeks in patients with very small LDL or baseline triglycerides >200mg/dl. Clinical implications warrant further study. |
| 61 | EFFECTIVENESS OF SWITCHING HAART TO A RITONAVIR-BOOSTED ATAZANAVIR-BASED REGIMEN FOR DYSLIPIDAEMIA IN HIV-1 INFECTED AMBULATORY CLINIC PATIENTS Antiviral Therapy 2005; Supplement 3:L38 D Lee1, P Patel1, C Ballard1 and RE Barber1,2 Switching from a HAART regimen to a ritonavir-boosted ATV-based regimen was found to be useful in the management of dyslipidaemia, while maintaining virological suppression in HIV-1-infected patients in a real-world clinic setting. Further prospective studies are needed to fully evaluate the effectiveness of this strategy in this patient population. |
| 62 | IMPROVED METABOLIC PROFILE WITH REPLACEMENT OF STAVUDINE BY TENOFOVIR DF AFTER 6 YEARS OF A LOPINAVIR/RITONAVIR-BASED REGIMEN Antiviral Therapy 2005; Supplement 3:L38 B da Silva1, M Albrecht2, C Benson3, J Eron4, R Gulick5, M Glesby5, C Hicks6, H Kessler7, R Murphy8, M Thompson9, AC White10, P Wolfe11, F McMillan1, K Niemi1, M King1 and G Hanna1 In this subgroup of patients receiving lopinavir/ritonavir+stavudine+lamivudine for 6 years, virological suppression was maintained after a switch to tenofovir from stavudine. Replacement of stavudine with tenofovir resulted in significantly improved TC and TG levels, suggesting some of the lipid increases observed were attributable to stavudine use. Significant decreases in fasting insulin and increases in adiponectin were observed, suggesting a favourable impact on insulin sensitivity. Significant improvements in leptin were also observed. |
| 63 | IMPROVEMENTS IN DYSLIPIDAEMIA AT 48 WEEKS FOLLOWING SUBSTITUTION OF STAVUDINE (D4T) WITH TENOFOVIR DF (TDF) Antiviral Therapy 2005; Supplement 3:L39 JM Llibre1, P Domingo2, MJ Perez3, C Miralles4, R Palacios5, MI Ruiz6, J Santos5, ML Alvarez7, S Moreno3 and Recover Study Group Even though the dyslipidaemia improved significantly in the first 12 weeks after switching from d4T to TDF, this improvement continued beyond week 12 and at least up to 48 weeks. |
| 64 | IMPROVEMENT IN LIPOATROPHY AND LIPID ABNORMALITIES FOLLOWING SWITCH FROM STAVUDINE (D4T) TO TENOFOVIR DF (TDF) IN COMBINATION WITH LAMIVUDINE (3TC) AND EFAVIRENZ (EFV) IN HIV-INFECTED PATIENTS: A 48-WEEK FOLLOW-UP FROM STUDY 903E Antiviral Therapy 2005; Supplement 3:L40 L Zhong1, G Cotton1, J Enejosa1 and AK Cheng1, for the 903E Study Team In virologically suppressed patients, switching d4T to TDF in a once-daily regimen containing 3TC and EFV maintains virological suppression through week 48. Changes in spine BMD were not seen. Decreases in fasting lipids, particularly triglycerides, cholesterol and LDL-C, as well as improvement in limb fat, were observed 48 weeks after switch. |
| 65 | HOW TO BEST REVERSE PI-ART-INDUCED METABOLIC SIDE EFFECTS: CHANGE TO NON-PI-ART OR LONG-TERM TREATMENT INTERRUPTION? Antiviral Therapy 2005; Supplement 3:L40 K Koppel, G Bratt, and E Sandstrom In 3T3-L1 adipocytes, exposure to d4T or 3TC results in different effects on mtDNA quantity and quality depending on the stage of cellular differentiation. Both d4T and 3TC have greater effects on differentiating cells. This might reflect different mtDNA replicating activity, with differentiated cells having lower activity, leaving them less susceptible to NRTI-effect. Greater decrease in distal region may reflect chain termination induced by DNA pol-g inhibition. |
| 66 | HIV- AND HAART-RELATED HYPERTRIGLYCERIDAEMIA. POLYUNSATURATED FATTY ACIDS (PUFA) VERSUS FIBRATES, IN ITS PHARMACOLOGICAL CONTROL Antiviral Therapy 2005; Supplement 3:L41 R Manfredi, L Calza and F Chiodo Abstract not presented. |
| 67 | NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR EFFECTS ON ADIPOCYTE MITOCHONDRIAL DNA QUANTITY AND QUALITY IN VITRO Antiviral Therapy 2005; Supplement 3:L41 HGW Lim1,2, R Sedwell1,2, N Duarte2, DA Cooper1,2,3, A Kelleher1,2,3, A Carr2,3 and PWG Mallon1,2,3 In 3T3-L1 adipocytes, exposure to d4T or 3TC results in different effects on mtDNA quantity and quality depending on the stage of cellular differentiation. Both d4T and 3TC have greater effects on differentiating cells. This might reflect different mtDNA replicating activity, with differentiated cells having lower activity, leaving them less susceptible to NRTI-effect. Greater decrease in distal region may reflect chain termination induced by DNA pol-γ inhibition. |
| 68 | PROTEASE INHIBITORS AND APOPTOSIS: STUDIES ON PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMCS) Antiviral Therapy 2005; Supplement 3:L42 S López1, G Garrabou1, J Villaroya2, AB Infante1, M Rodríguez de la Concepción2, R Escayola3, M Giralt2, JM Gatell4, F Cardellach1, J Casademont1, F Villaroya2 and O Miró1 HAART regimens containing the PI nelfinavir seem to have some beneficial effects to counteract the increased apoptosis present in HIV+ untreated patients. |
| 69 | USE OF STAVUDINE IS ASSOCIATED WITH A HIGH RISK OF SEVERE HYPERLACTATAEMIA IN BLACK WOMEN Antiviral Therapy 2005; Supplement 3:L42 Y Gérard, Y Yazdanpanah, F Ajana, H Melliez, N Viget, I Alcaraz, V Baclet, X de la Tribonnière, M Valette, P Choisy and Y Mouton This study revealed a high frequency of severe hyperlactataemia in females from sub-Saharan Africa. The risk of hyperlactataemia in sub-Saharan Africa needs to be measured urgently, particularly in those patients receiving stavudine-containing regimens. |
| 70 | Mitochondrial function in HAART-related hyperlactataemia Antiviral Therapy 2005; Supplement 3:L43 G Garrabou1, S López1, E Sanjurjo1, AB Infante1, M Larrousse2, A Milinkovic2, E Martinez2, J Riba3, J Casademont1, F Cardellach1, JM Gatell2 and O Miró1 HAART-related hyperlactataemia is associated with decreases in mtDNA content (although not statistically significant) and enzymatic activities of mtDNA-encoded MRC complexes III and IV. |
| 71 | PERIPHERAL BLOOD MONONUCLEAR CELLS OF HIV-1-INFECTED PATIENTS LONG-TERM NON-PROGRESSORS SHOW MILD MITOCHONDRIAL IMPAIRMENT AND LOW MITOCHONDRIALLY-DRIVEN APOPTOSIS Antiviral Therapy 2005; Supplement 3:L43 G Garrabou1, S López1, F Vidal2, Ò Miró1, P Domingo3, E Pedrol4, F Villarroya5, M Saumoy2, AB Infante1, E Martínez1, Miguel López Dupla2, MA Sambeat3, E Deig4, J Villarroya5, MR Chacón2, À Fontanet3, C Richart2, M Giralt5 and JM Gatell1 HIV-1-infected patients LTNP show lower PBMC mitochondrially-driven apoptosis and have better preserved mitochondria than UP. |
| 72 | EFFECTS OF AZT TREATMENT ON LIPOGENIC CAPACITY OF SUBCUTANEOUS AND VISCERAL ADIPOSE TISSUES OF LEAN AND OBESE RATS Antiviral Therapy 2005; Supplement 3:L44 C Deveaud, B Beauvoit, A Reynaud and J Bonnet Our study confirms and extends the previous observation that AZT treatment induces a decrease in the mitochondrial oxidative capacity of subcutaneous adipose tissue. In this regards, it is worth noting that obese rats appeared to be more sensitive than lean rats. In parallel, lipogenic capacity of subcutaneous adipose tissue was also decreased by AZT treatment. Our working hypothesis is that subcutaneous lipogenic and oxidative capacity decreases are linked. The mechanisms by which these alterations would be linked are now under investigation. |
| 73 | IMPAIRED MITOCHONDRIAL FUNCTION INDUCED BY NRTIS IS ONLY DETECTABLE IN THE MONOCYTE (CD14+) SUBSET OF HUMAN PBMC Antiviral Therapy 2005; Supplement 3:L44 R Sedwell1, PWG Mallon1,2, N Duarte3, J Zaunders3, A Kelleher1,2,3, DA Cooper1,2 and A Carr2 DiIC(5) is a simple, robust assay in which to study NRTI-induced functional changes in mitochondria in peripheral blood. The CD14+ subset of PBMCs shows higher mtMP, suggesting that CD14+ cells exhibit more mitochondrial energy production. A significant decrease in mtMP was seen only in the CD14+ monocyte population and not the PBMC+ or PBMC– population. This suggests that CD14+ monocytes are a better peripheral blood surrogate to study NRTI-induced mitochondrial toxicity. |
| 74 | PRAVASTATIN DOES NOT ENHANCE IN VITRO CHANGES IN MITOCHONDRIAL DNA AND RNA CAUSED BY NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS Antiviral Therapy 2005; Supplement 3:L45 M van Schilfgaarde, KGM Smolders, M Buitelaar and MP de Baar We conclude that there is no effect on mtDNA and mtRNA levels from pravastatin at the tested concentrations, and that there is no synergistic effect of pravastatin on the changes in mtDNA and mtRNA levels caused by various NRTIs. This in vitro study is the first indication that pravastatin can be safely used with the tested NRTIs without any effects on mtDNA or mtRNA, but this will need to be confirmed with in vivo studies. |
| 75 | EFFECTS OF DIFFERENT DOSES OF DIDANOSINE COMBINED WITH TENOFOVIR ON PERIPHERAL BLOOD MONONUCLEAR CELL MITOCHONDRIAL PARAMETERS Antiviral Therapy 2005; Supplement 3:L46 S López1, G Garrabou1, E Negredo2, AB Infante1, J Puig2, E Grau2, JM Gatell3, J Casademont1, F Cardellach1, B Clotet2 and O Miró1 A dose reduction of ddI from 400mg to 250mg when it is combined with TDF (300mg) produced a significant amelioration of the mtDNA content, but some toxic mitochondrial effects remain. |
| 76 | AZT COMPETITIVELY INHIBITS THYMIDINE PHOSPHORYLATION IN ISOLATED RAT HEART AND LIVER MITOCHONDRIA Antiviral Therapy 2005; Supplement 3:L46 MD Lynx1,2, AT Bentley2, M Hatch1, J Gingerich2, D Susan–Resiga2 and EE McKee1,2 Further investigation in isolated rat heart and liver mitochondria revealed that AZT appears to be a competitive inhibitor of thymidine phosphorylation, with an inhibitory constant (Ki) of 12.4 ±1.9 µM AZT for heart mitochondria and of 16.0 ±1.4 µM AZT for liver mitochondria. This work suggests a different method of AZT toxicity wherein AZT’s inhibition of thymidine phosphorylation leads to a depletion of mitochondrial stores of TTP, which may limit mitochondrial DNA replication. |
| 77 | FACTORS ASSOCIATED WITH INCREASED OXIDANT STRESS DURING HIV THERAPY WITH THYMIDINE ANALOGUE NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS Antiviral Therapy 2005; Supplement 3:L47 T Hulgan1,2, C Mwenya1, L Dageford1, N Emeagwali3, M Markovic1, I Oboho1, R Misra1, S Sanchez1, H Erdem1, J Morrow1 and DW Haas1,2 Plasma F2-IsoP levels, a reliable index of oxidant stress, were independently associated with nonfasting TC, smoking, and BMI. These factors may contribute to oxidant injury during chronic ART exposure. Plasma F2-IsoP levels were not independently associated with stavudine- or zidovudine-containing regimens, with lipoatrophy, or with peripheral neuropathy. Longitudinal studies to further elucidate relationships between oxidant stress and ART toxicity are ongoing. |
| 78 | EFFECT OF TENOFOVIR IN COMBINATION WITH OTHER ANTI-HIV NRTIS ON INTRACELLULAR NUCLEOTIDE POOLS Antiviral Therapy 2005; Supplement 3:L47 JE Vela, MD Miller, GR Rhodes and AS Ray These data illustrate that tenofovir, either alone or in combination with other NRTIs, does not alter intracellular nucleotide levels and that changes in nucleotide levels are unlikely to explain the poor response observed for some triple NRTI-only regimens. |
| 79 | COST OF THE NRTI-RELATED TOXICITIES IN HIV-1-INFECTED HEAVILY EXPERIENCED PATIENTS Antiviral Therapy 2005; Supplement 3:L48 S Moreno1, MA Casado2, P Domingo3, JM Llibre4, E Martínez5, C Miralles6, J Santos7, MJ Pérez Elías1 and R Sánchez de la Rosa8 In the routine clinical practice NRTIs normally have lower drug acquisition costs than other antiretroviral agents. However, the management of the NRTI-related toxicities (produced by outpatient visits, diagnostic and laboratory tests, hospitalization stays, surgeries, additional medication and productivity losses) are significantly higher than the initial drug costs with the final outcome of a significant increase in the cost of HIV medical care for the final payer. |
| 80 | EFFECTS ON MITOCHONDRIA AND THYMUS OF THE SWITCH FROM STAVUDINE TO TENOFOVIR IN HIV-INFECTED CHILDREN Antiviral Therapy 2005; Supplement 3:L48 R Rosso1, M Nasi2, M Pinti2, E Nemes2, E Roat2, A Di Biagio1, E Repetto1, M Bassetti1, A Cossarizza2 and D Bassetti1 In the routine clinical practice NRTIs normally have lower drug acquisition costs than other antiretroviral agents. However, the management of the NRTI-related toxicities (produced by outpatient visits, diagnostic and laboratory tests, hospitalization stays, surgeries, additional medication and productivity losses) are significantly higher than the initial drug costs with the final outcome of a significant increase in the cost of HIV medical care for the final payer. |
| 81 | METABOLIC AND MITOCHONDRIAL CHANGES AFTER 6 MONTHS OF SWITCHING OF ANTIRETROVIRAL-EXPERIENCED PATIENTS TO ENFUVIRTIDE, TENOFOVIR AND SAQUINAVIR/RITONAVIR Antiviral Therapy 2005; Supplement 3:L49 O Miró1, G Garrabou1, S López1, E Deig2, I Vidal2, AB Infante1, F Cardellach1, J Casademont1 and E Pedrol2 The switching of antiretroviral-experienced patients to a HAART regimen consisting of T20+TDF+SQV/rtv has a favourable profile with respect to recovery of mitochondrial toxicity. In addition to other advantages linked to the switching, improvement of mitochondrial functionality should be considered. |
| 82 | EFFECT OF NUCLEOMAXX® ON FAT AND BLOOD MITOCHONDRIAL DNA IN D4T-TREATED SUBJECTS WITH CLINICAL LIPOATROPHY Antiviral Therapy 2005; Supplement 3:49 GA McComsey1,2, M O’Riordan1, B Setzer3, D Lebrecht3, E Baron2 and UA Walker3 NucleomaxX® is safe and well-tolerated in HIV-infected subjects with lipoatrophy. Despite an improvement in patient- and physician-generated clinical lipoatrophy score, no significant changes in fat or PBMC mtDNA levels were seen after 16 weeks of NucleomaxX®. Our results suggest that pyrimidine-depletion could be one of the factors contributing to fat atrophy. |
| 83 | ORAL URIDINE SUPPLEMENTATION IMPROVES DISTINCTLY HEPATIC MITOCHONDRIAL FUNCTION IN THYMIDINE ANALOGUE TREATED HIV-INFECTED PATIENTS Antiviral Therapy 2005; Supplement 3:L50 M Banasch1, O Goetze2, K Knyhala1, S Kollar1, A Potthoff3, R Schlottmann1, WE Schmidt1 and NH Brockmeyer3 Mitocnol supplementation confers a specific and reproducible improvement of hepatic mitochondrial decarboxylation function in thymidine analogue treated HIV-infected patients. Repeated administration in shorter treatment intervals may maintain this effect. These preliminary data may suggest Mitocnol as a promising agent for treatment and probably prevention of HIV/NRTI-related (hepatic) mitochondrial dysfunction. |
| 84 | PROTECTIVE EFFECT OF ACETYL-L-CARNITINE ON OXIDATIVE DAMAGE INDUCED BY ANTIRETROVIRAL DRUGS Antiviral Therapy 2005; Supplement 3:L50 R Ferraresi1, L Troiano1, E Roat1, E Nemes1, M Iannuccelli2, M Calvani2 and A Cossarizza1 ALCAR was able to protect, at least in part, two different cell lines from the production of ROS induced by stavudine and zidovudine. This observation suggests a rationale for the use of this molecule as a support during therapies with drugs such as NRTI that can cause an increase in intracellular ROS. |
| 85 | PROTEASE INHIBITORS SELECTIVELY INDUCE CHEMOKINE EXPRESSION IN HUMAN OSTEOBLASTS Antiviral Therapy 2005; Supplement 3:L51 A Patricelli, PP Doran and WG Powderly Herein we have demonstrated that osteoblasts, key cellular players in active bone formation, release the pro-inflammatory cytokines MCP1 and IL-8 following exposure to pharmacological concentration of NFV. This enhanced protein expression was due to de novo gene expression induction as demonstrated by real-time PCR. These data suggest that induction of local inflammatory cascades may contribute to the development of decreased bone mineral density in HAART-treated HIV patients. |
| 86 | INCIDENCE AND NATURAL HISTORY OF OSTEONECROSIS IN HIV-INFECTED ADULTS Antiviral Therapy 2005; Supplement 3:L52 CG Morse1, JM Mican2, EC Jones2, GO Joe1, E Formentini2 and JA Kovacs1 Results from this prospectively studied cohort provide further evidence that HIV-infected patients are at increased risk for developing osteonecrosis. Longitudinal observations suggest that slower disease progression may occur in asymptomatic compared to symptomatic patients. Follow-up studies are needed to further evaluate risk factors and to assess preventive and treatment strategies. |
| 87 | ANTIRETROVIRAL THERAPY AND THE PREVALENCE OF OSTEOPAENIA AND OSTEOPOROSIS: A META-ANALYSIS Antiviral Therapy 2005; Supplement 3:L52 TT Brown1 and RB Qaqish2 The prevalence of osteoporosis in HIV-infected subjects is more than three times greater compared to HIV-seronegative controls. ART-exposed and PI-exposed subjects have a higher prevalence of reduced BMD and osteoporosis compared to their respective controls. The influence of other disease and treatment variables on these estimates could not be determined. |
| 88 | FOUR WEEKS OF INDINAVIR DOES NOT AFFECT BONE TURNOVER IN HEALTHY HIV-NEGATIVE SUBJECTS Antiviral Therapy 2005; Supplement 3:L53 SS Shankar and HO Steinberg Indinavir does not alter markers of bone turnover in healthy HIV-negative subjects. This indicates that the HIV-1 protease inhibitor indinavir does not appear to have a direct effect on bone resorption. |
| 89 | CHANGES IN ALKALINE PHOSPHATASE IN HIV+ PATIENTS UNDER TENOFOVIR-CONTAINING REGIMENS Antiviral Therapy 2005; Supplement 3:L53 T García-Benayas1, C Velásquez1, F Blanco1, J Gonzázlez-Lahoz1 and V Soriano1 Abstract not presented. |
| 90 | BONE MASS CHANGES IN HIV-INFECTED INDIVIDUALS AFTER A 48-WEEK TREATMENT WITH TENOFOVIR DISOPROXIL FUMARATE Antiviral Therapy 2005; Supplement 3:L53 G Tsekes1, N Tsogas1, M Chini1, A Lioni1, N Mangafas1, V Grammelis1, I Papagiannakopoulos2 and MC Lazanas1 Unlike the control group, patients receiving TDF for 48 weeks preserved their whole body BMC. Lumbar spine and total femur BMD did not change but both groups exhibited a significant decrease in the femur neck BMD. Our data indicate that, in HIV-infected individuals, a 48-week treatment with tenofovir is associated with impairment of bone mass no more than a TDF-sparing antiretroviral regimen. |
| 91 | EFFLUX OF TENOFOVIR BY THE MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 4 (MRP4) IS NOT AFFECTED BY HIV PROTEASE INHIBITORS Antiviral Therapy 2005; Supplement 3:L54 AS Ray, JE Vela, KL Robinson, T Cihlar and GR Rhodes These findings indicate that MRP4 contributes to the active tubular secretion of TFV. PIs were found not to inhibit this transport mechanism when tested at supra-pharmacological concentrations. This observation does not support the hypothesis that PIs can increase the accumulation of TFV in proximal tubule cells. |
| 92 | LONG-TERM RENAL SAFETY OF TENOFOVIR IN ANTIRETROVIRAL-EXPERIENCED Antiviral Therapy 2005; Supplement 3:L55 A Viganò1, V Giacomet1, M Merlo1, P Erba1, S Beretta1, P Luraschi2, G Rombolà3, and S Mora4 Through 96 weeks, TDF administered in combination with EFV and lamivudine is not associated with renal dysfunction in HIV-infected children with normal renal function at baseline. TDF use is associated with a significant decrease of lactate levels and it might suggest a low degree of mithochondrial toxicity. |
| 93 | SIMILAR RENAL SAFETY PROFILE BETWEEN TENOFOVIR DF (TDF) AND STAVUDINE (D4T) USING MODIFICATION OF DIET IN RENAL DISEASE AND COCKCROFT–GAULT ESTIMATION OF GLOMERULAR FILTRATION RATE IN ANTIRETROVIRAL-NAÏVE PATIENTS THROUGH 144 WEEKS Antiviral Therapy 2005; Supplement 3:L55 S Staszewski1, AL Pozniak2, B Lu3, G Cotton3, J Enejosa3 and AK Cheng3 for the 903 Study Team Through 144 weeks on the TDF arm, there were no significant changes from baseline in GFR estimated by MDRD or CG. There were no differences in the incidence of NKF chronic kidney disease stages between TDF and d4T through 144 weeks. |
| 94 | REGIMENS CONTAINING EFAVIRENZ WITH COMBINATIONS OF ABACAVIR, LAMIVUDINE, AND/OR ZIDOVUDINE DO NOT AFFECT GFR DURING LONG–TERM TREATMENT OF HIV-NAIVE SUBJECTS Antiviral Therapy 2005; Supplement 3:L56 J Hernandez These results illustrate that regimens containing abacavir, lamivudine, zidovudine and efavirenz in various combinations to treat HIV naïve subjects do not appear to adversely affect GFR. |
| 95 | A PROSPECTIVE COMPARISON OF HEPATOTOXICITY OF THE TWO CURRENTLY AVAILABLE NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR IN A HOMOGENEOUS CASE-MIX OF HIV-INFECTED PATIENTS TREATED FOR THE FIRST TIME WITH EFAVIRENZ OR NEVIRAPINE, ACCORDING TO THEIR DIFFERENT BASELINE CONDITIONS Antiviral Therapy 2005; Supplement 3:L56 R Manfredi, L Calza and F Chiodo Abstract not presented. |
| 96 | TESTOSTERONE GEL SWITCH STRATEGY: PERCEPTIONS OF NON-RESPONSE SPECIFIC TO SEXUAL FUNCTION/SATISFACTION AND DOSE TITRATION ISSUES OF HIV-POSITIVE MEN Antiviral Therapy 2005; Supplement 3:L57 S Schrader1, A Mills2, M Scheperle3 and JE Block4 Proof of concept was achieved: Although the limitations of this study precluded the investigators from reliably determining if Testim 1% gel therapy should be considered in HIV+ males who inadequately responded (re: sexual functioning/libido) to prior AndroGel therapy, the 'real life' clinical model of this trial revealed clinical issues that require further, rigorous, scientific investigation to improve the effectiveness of testosterone replacement therapy in HIV+ hypogonadal men. |
| 97 | SEXUAL DYSFUNCTION IN HIV-INFECTED MEN: PREVALENCE AND ASSOCIATED FACTORS Antiviral Therapy 2005; Supplement 3:L58 D Malmusi1, G Guaraldi2, E Martínez3, E de Lazzari3, K Luzi2, A Granata2, JL Blanco3, G Orlando2, R Murri4 and JM Gatell3 Sexual dysfunctions, and particularly ED, were common in sexually active HIV-infected southern European men. High prevalence of SD suggests a routine evaluation of sexual function in the clinical evaluation of HIV disease. In our population, HAART and hypogonadism were not associated with SD or ED. Questionnaires to assess SD need to be validated in this particular population. |
| 98 | TOLERABILITY OF EFAVIRENZ AFTER NEVIRAPINE-RELATED RASH Antiviral Therapy 2005; Supplement 3:L58 JA Collins, JL Claros and C Rojas Abstract not presented. |
| 99 | LOW INCIDENCE OF HYPERPIGMENTATION SKIN DISORDERS IN HIV-INFECTED SUBJECTS TREATED WITH AND WITHOUT ZIDOVUDINE IN 54 CLINICAL TRIALS Antiviral Therapy 2005; Supplement 3:L59 J Hernandez1, A Cutrell1, M Edwards1, D Gordon2, A Murray2 and C Brothers1 The overall incidence of hyperpigmentation skin disorders in this cohort was very low (<1%). Black subjects treated with HAART, with and without zidovudine, had a higher incidence compared to Whites. Although the incidence of hyperpigmentation was higher in Black subjects treated with zidovudine, this incidence was low and appeared to be lower when fixed combination tablets were used. |
| 100 | NO INCREASE IN DIARRHOEA WHEN SWITCHING TREATMENT OF HIV-RNA SUPPRESSED PATIENTS FROM THE NELFINAVIR 250 MG TABLET TO THE NELFINAVIR 625 MG TABLET Antiviral Therapy 2005; Supplement 3:L59 AK Petersen1, E Daniels2 and M Saag3 Steady state pharmacokinetics of nelfinavir 625mg tablet showed bioequivalence with the 250mg tablet and comparable safety and efficacy profiles in nelfinavir-treatment-experienced HIV patients. |
| 101 | PREVALENCE, CHARACTERISTICS AND MANAGEMENT OF ABACAVIR HYPERSENSITIVITY SYNDROME IN THE CLINICAL PRACTICE Antiviral Therapy 2005; Supplement 3:L60 C Galera1, C Redondo1, G Poza1, MJ Bovaira2, L Lorente2 and D Perez3 Prevalence of AHS was 8.6% in our cohort, outside of clinical trials. Fever and constitutional symptoms were more common than rash and others. In all the definitive diagnosed cases, symptoms appeared after the 10th day. Apart from AHS, tolerability and durability of ABV regimens were very good. |
| 102 | DETERMINANTS OF AND HEALTHCARE UTILIZATION ASSOCIATED WITH EARLY DISCONTINUATION OF ABACAVIR: A CASE FOR GENETIC SCREENING Antiviral Therapy 2005; Supplement 3:L60 EJ Phillips1, B Yip1, RS Hogg1 and JSG Montaner1 EDABC is common, associated with higher and more costly healthcare utilization and its incidence appears to have increased with heightened awareness of ABC HSR. Since ABC HSR is the major reason for permanent EDABC this supports the case for genetic screening programs. |
| 103 | Association of HLA-B*5701 and hypersensitivity to abacavir in a sample of Thai patients Antiviral Therapy 2005; Supplement 3:L61 C Bowonwatanuwong1, L Warren2, M Mosteller2, S Haneline2, A Handley2, P Champreeda3, C Brothers2, W Spreen2, A Hughes2 and J Hernandez2 The sensitivity of HLA–B*5701 in the Thai sample set is comparable to that previously observed by GSK in Caucasians. These results should be viewed as preliminary; independent confirmation of this association would be valuable. As HLA–B*5701 is not fully predictive and because of a risk of more serious abacavir HSR upon re-challenge, HLA–B*5701 screening must never be used as a diagnostic test when symptoms suggest HSR. A patient‘s HLA status must not alter the clinical management of a suspected abacavir HSR. The utility of prospective HLA–B*5701 screening to identify patients who may benefit from abacavir treatment warrants further investigation. |
| 104 | IMPACT OF ANAEMIA ON ANTIRETROVIRAL DISCONTINUATIONS Antiviral Therapy 2005; Supplement 3:L61 M Emons1, J Richardson2, B Young3 and RK Baker2 ZDV is associated with the overwhelming majority of ART discontinuations attributed to anaemia. Among ZDV discontinuations due to toxicity, anaemia was a frequent toxicity cited. Further research is needed to investigate how these regimen changes impact clinical outcomes in patients with HIV/AIDS. |
| 105 | SERUM RETINOIC ACID AND RETINOL LEVELS ARE ALTERED DURING HAART AND DURING HIV THERAPEUTIC VACCINATION AND HAART INTERRUPTION Antiviral Therapy 2005; Supplement 3:L62 M Loignon1, H Brodeur1, S Deschenes1, PV Bhat1 and E Toma1 Synthesis and/or metabolism of retinoic acid and intestinal absorbtion and/or utilisation of retinol is altered by protease inhibitors containing HAART. Elevated RAs levels in different tissues but not in plasma might be responsible for retinoid-like or other adverse metabolic effects. |
| 106 | ANTIVIRAL THERAPY WITH RIBAVIRIN AND PEGYLATED INTERFERON HAS NO MAJOR EFFECT ON METABOLIC PARAMETERS IN PATIENTS WITH CHRONIC HEPATITIS C Antiviral Therapy 2005; Supplement 3:L62 S Mauss1, F Berger1, K Mulligan2 and G Schmutz1 Treatment with ribavirin and peginterferon in HCV-infected patients was associated with minor changes in lipids which may not be clinically relevant. Glucose metabolism and lactate were not affected. |
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