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11th International Workshop on Adverse Drug Reactions & Co-Morbidities in HIVPhiladelphia, PA, USA, 26–28 October 2009 |
Cite as: Antiviral Therapy 2009; 14(Supp. 2):x
where x is the page number
| Oral Presentations |
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| O-01 | INTERMUSCULAR ADIPOSE TISSUE IS DECREASED IN HIV INFECTION Antiviral Therapy 2009; 14(Supp. 2):A3 (abstract no. O-01 P Bacchetti1, C Grunfeld1,2, SB Heymsfield3, D Kotler4, CE Lewis5, M Punyanitya6,7, R Scherzer1, W Shen6,7 and MG Shlipak1,2 for the Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) Contrary to expectation, HIV infection is associated with decreased IMAT compared with controls, even after controlling for demographics, lifestyle, VAT, SAT and SM. Stavudine exposure is associated with decreases in both IMAT and SAT; this similarity suggests that IMAT shares cellular origins with SAT. |
| O-02 | EFFECTS OF TREATMENT AND DISCONTINUATION OF LOW DOSE PHYSIOLOGIC GROWTH HORMONE IN HIV PATIENTS WITH ABDOMINAL FAT ACCUMULATION: A RANDOMIZED, PLACEBO-CONTROLLED 36-MONTH CROSSOVER TRIAL Antiviral Therapy 2009; 14(Supp. 2):A3 (abstract no. O-02) J Lo1, S M You1, J Liebau1, J Wei1, L Hemphill2, H Lee3 and S Grinspoon1 In patients with HIV-associated visceral fat accumulation and relative GH deficiency, administration of low-dose GH for 18 months significantly reduced visceral fat and truncal obesity, triglyceride, LDL and blood pressure, but increased fasting glucose and 2 h glucose. After discontinuing GH, VAT increased back to baseline within 6 months. |
| O-03 | THE IMPACT AND CLINICAL RELEVANCE OF TESAMORELIN (TH9507), A GROWTH HORMONE-RELEASING FACTOR ANALOGUE, ON BELLY AND WEIGHT IMAGE AND HEALTHRELATED QUALITY OF LIFE (HRQOL) IN HIV-INFECTED PATIENTS WITH EXCESS ABDOMINAL FAT: A COMBINED ANALYSIS OF TWO PHASE III STUDIES Antiviral Therapy 2009; 14(Supp. 2):A4 (abstract no. O-03 RR Turner1, SL McColl2, J Falutz3, MA Testa4, D Potvin2, J-C Mamputu2, S-É Michaud2, C Marsolais2, G Soulban2, H Assaad2, M Su1 and S Grinspoon5 Treatment with 2 mg tesamorelin daily for 26 weeks results in clinically relevant improvements in belly appearance distress, patient- and physician-reported belly and weight image while maintaining HRQOL, with no increases in symptom incidence and distress. |
| O-04 | IMPACT OF CEREBROVASCULAR RISK FACTORS ON BRAIN FUNCTION AND STRUCTURE IN HIV-INFECTED INDIVIDUALS Antiviral Therapy 2009; 14(Supp. 2):A5 (abstract no. O-04) N Jahanshad1, CM Shikuma2, K Kallianpur2, B Nakamoto2, VG Valcour3 and PM Thompson1 Traditional CVD risk factors contribute to cognitive dysfunction in HIV-infected individuals. Trends suggesting an impact of these risk factors on brain microstructure were observed by DTI, suggesting the promise of this neuroimaging technique for investigating the impact of CVD on brain structure and function in larger cohorts of HIV-infected subjects. |
| O-05 | HIGH INCIDENCE AND RISK FACTORS FOR DIABETES OVER THE 9-YEAR FOLLOW-UP AFTER FIRST GENERATION PROTEASE INHIBITORS’ INITIATION IN THE ANRS CO8 APROCO-COPILOTE COHORT Antiviral Therapy 2009; 14(Supp. 2):A5 (abstract no. O-05 J-P Bastard1, V Bouteloup2, C Leport3, J Reynes4, S Herson5, G Flexor6 F Raffi7, G Chène2, J Capeau1 and the ANRS CO8 APROCO-COPILOTE study group In this cohort of patients started on first generation cART and followed over the long-term with sensitive diagnostic tests of diabetes, the incidence of diabetes was high, not different in men and women, and fourfold higher than that of a control population of similar adiposity (MONIKA/KORA Augsburg cohort). Risk factors were those traditionally associated with diabetes in the general population. In addition, incident diabetes was associated with exposure to stavudine, but not with the severity of HIV infection. Diabetes was associated with increased cardiovascular risk indicating the importance of targeted intervention. |
| O-06 | HIGHER MARKERS OF TNF-α ACTIVITY 48 WEEKS AFTER ART-INITIATION ARE ASSOCIATED WITH INCIDENT DIABETES MELLITUS IN THE ACTG/ALLRT COHORT: A NESTED CASE-CONTROL STUDY Antiviral Therapy 2009; 14(Supp. 2):A6 (abstract no. O-06) TT Brown1, K Tassiopoulos2, C Shikuma3 and GA McComsey4 Higher markers of TNF-α activity 48 weeks after ART initiation were associated with increased risk of subsequent diabetes mellitus. These findings suggest that systemic inflammation, even after ART-induced viral suppression, may contribute to diabetes pathogenesis among HIV-infected patients. |
| O-07 | INCREASED MICROALBUMINURIA IN HIV-INFECTED ADULTS WITH DIABETES IS ASSOCIATED WITH ABACAVIR AND VIRAL LOAD Antiviral Therapy 2009; 14(Supp. 2):A6 (abstract no. O-07 PS Kim1, C Woods2 L Dutcher3, P Georgoff3, A Rosenberg1, JAM Mican1, J Kopp4, MA Smith2, C Hadigan1 Individuals with HIV and diabetes have double the risk of microalbuminuria as compared with those with either disease alone. Microalbuminuria was associated with traditional risk factors such as increasing age and blood pressure, but was also independently associated with increased exposure to abacavir and HIV viral load. This might be an indication of endothelial injury in relation to abacavir use as has been seen by other investigators. Future research on the persistence, progression and management of albuminuria in this unique population is needed. |
| O-08 | BENEFICIAL EFFECT OF EXENATIDE ON GLUCOSE HOMEOSTASIS AND SURVIVAL IN RITONAVIR-TREATED MICE WITH ADVANCED DILATED CARDIOMYOPATHY Antiviral Therapy 2009; 14(Supp. 2):A7 (abstract no. O-08) AK Vyas, K-C Yang, D Woo, PY Jay and PW Hruz Exenatide improves in systemic and myocardial-specific glucose uptake and partially abrogates the detrimental effects of ritonavir on cardiac function and survival in the setting of advanced dilated cardiomyopathy. These data provide a rationale for studying the influence of impaired glucose homeostasis on cardiac function in HIV-infected patients treated with PIs and suggest that efforts to improve glucose disposal will be beneficial in preserving cardiac function. |
| O-09 | ANTHROPOMETRIC AND METABOLIC OUTCOMES IN A 48-WEEK RANDOMIZED, OPEN-LABEL STUDY OF THREE DIFFERENT COMBINATION ANTIRETROVIRAL REGIMENS AS INITIAL THERAPY FOR HIV INFECTION Antiviral Therapy 2009; 14(Supp. 2):A8 (abstract no. O-09 RL Puls, P Srasuebkul, K Petoumenos, S Emery and DA Cooper on behalf of the Altair study group Over 48 weeks, patients on quadruple nucleoside therapy experienced significantly greater peripheral lipoatrophy than patients receiving efavirenz, plus two nucleosides. Lipoatrophy appeared to develop more rapidly on quadruple nucleosides than previously suggested. There is some suggestion that ritonavir-boosted atazanavir resulted in less lipoatrophy than efavirenz or the quadruple nucleoside arm. |
| O-10 | CHANGES IN THE ADIPOCYTE (LIPID AND GLUCOSE METABOLISM) GENE EXPRESSION FOLLOWING 18–24 MONTHS TREATMENT WITH ZDV OR TDF-CONTAINING ART; AND ADIPOCYTE MITOCHONDRIAL GENE EXPRESSION Antiviral Therapy 2009; 14(Supp. 2):A8 (abstract no. O-10) LL Gathercole2, JW Tomlinson2, M Boothby1, KC McGee3, AL Harte3, PG McTernan3, S Das4, M Shahmanesh1 After 18–24 months treatment, there is significant down-regulation of most genes involved with lipid and cortisol metabolism compared with pre-treatment levels and controls. The shift to fatty acid beta-oxidation occurs despite an increase in peripheral and visceral fat, and is broadly similar with both AZT and TDF-containing regimens. |
| O-11 | ADIPOCYTE MITOCHONDRIAL GENE EXPRESSION FOLLOWING 18–24 MONTHS TREATMENT WITH ZIDOVIDINE OR TENOFOVIR-CONTAINING ANTIRETROVIRAL THERAPY Antiviral Therapy 2009; 14(Supp. 2):A9 (abstract no. O-11 KC McGee3, M Boothby1, JW Tomlinson2, LL Gathercole2, AL Harte3, PG McTernan3, S Das4, M Shahmanesh1 After 18–24 months treatment, there is significant down-regulation of some mitochondrial- and nuclear-encoded genes involved with the respiratory chain compared with pre-treatment levels and controls. The changes were more marked with AZT compared with TDF-containing regimens. |
| O-12 | EVALUATION OF ADIPOSE GENE EXPRESSION AND MITOCHONDRIAL DNA IN HEALTHY ADULTS OVER A 6 WEEK COURSE OF NRTI AND/OR PI TREATMENT. INDICATIONS OF DIVERGENT EFFECTS Antiviral Therapy 2009; 14(Supp. 2):A10 (abstract no. O-12) O Distler1, PW Mallon2, AD Kelleher3, A Carr4, A Calmy4 and DA Cooper3 These data suggest divergent patterns between different antiretroviral regimens on mtDNA mass and gene expression. A gradual decrease in mtDNA mass upon AZT treatment is consistent with published trends, whereas the observed increase with LPV/r was a unique finding for acute PI treatment. Effects on SREBP1c and a decoupling of PPAR? expression in addition to mtDNA transactivation may define a pathway whereby PI may blunt tNRTI effects on adipose gene expression in the short-term. |
| O-13 | COMBINED IMPACT OF C-REACTIVE PROTEIN AND STAVUDINE ON ADIPOGENESIS Antiviral Therapy 2009; 14(Supp. 2):A10 (abstract no. O-13 MV Stankov, RE Schmidt and GMN Behrens We conclude that CRP at levels circulating in patients with HIV infection might promote the antiadipogenic potential of d4T, a cooperative effect that could account for the in vivo observed variability in the development of lipoatrophy. |
| O-14 | PROGRESSION OF SUBCLINICAL ATHEROSCLEROSIS IN HIV-INFECTED PATIENTS Antiviral Therapy 2009; 14(Supp. 2):A11 (abstract no. O-14) G Guaraldi1, S Zona1, G Orlando1, F Carli1, G Ligabue2, K Luzi1, R Esposito1 and P Raggi3 CAC is common among young HIV-patients. The association between CAC progression and CD4 cell count underscores the potential vasculopathic activity of these cells known to contribute to the atherosclerotic process in experimental animal models. Finally these data confirm the cardiovascular risk inherent with VAT already shown in the general population. |
| O-15 | ARTERIAL STIFFNESS AND CARDIOVASCULAR BIOMARKERS IN HIV-INFECTED ADULTS Antiviral Therapy 2009; 14(Supp. 2):A11 (abstract no. O-15 R Richardson1, K Sinn1, DA Cooper1,2, S Pett2 and A Carr1,2 In this population, arterial stiffness was higher in patients with traditional cardiac risk factors and in patients with lower HIV viral load. The impact of cardiac biomarkers appeared less significant. |
| O-16 | SALSALATE IS POORLY TOLERATED AND FAILS TO IMPROVE ENDOTHELIAL FUNCTION AND INSULIN RESISTANCE IN VIROLOGICALLY SUPPRESSED HIV-INFECTED PATIENTS Antiviral Therapy 2009; 14(Supp. 2):A12 (abstract no. O-16) CO Hileman1, TL Carman1, BM Gripshover1, MA O’Riordan1, NJ Storer1, DE Harrill1 and GA McComsey1 Participants on ART with undetectable HIV-1 RNA did not show improvement in endothelial function after 13 weeks of salsalate. This could be because dose reduction was necessary in many participants. The toxicities we encountered, even in this stable suppressed population, are likely to limit the use of this drug as a means to decrease HIV-cardiovascular risk. |
| O-17 | DECREASED MYOCARDIAL LONGITUDINAL STRAIN IN HIV-NEGATIVE NEONATES EXPOSED TO HIV AND HAART IN UTERO Antiviral Therapy 2009; 14(Supp. 2):A13 (abstract no. O-17 WT Cade1, MR Holland1, AS Stephens1, DN Reeds1, E Laciny1, N Cilbulka2, ET Overton1 and GK Singh1,3 HIV-negative neonates exposed to HIV and HAART have subclinical LV systolic dysfunction when examined by myocardial strain imaging. LV dysfunction at birth combined with prophylactic HAART exposure during infancy may worsen cardiac function as the HIV-negative children exposed to HIV and HAART in utero worsen in pre-pubescence and adolescence, potentially predisposing these children to an increased risk for cardiac morbidity and mortality. |
| O-18 | EX VIVO INFECTION OF MESENCHYMAL STEM CELLS BY HIV-1 ALTERS DIFFERENTIATION POTENTIAL AND CELL PHENOTYPE Antiviral Therapy 2009; 14(Supp. 2):A13 (abstract no. O-18) EJ Cotter1, N Chew1, WG Powderly2 and PP Doran1 These results suggest that HIV-1 might directly interact with MSCs, resulting in alterations of their differentiation potential, findings with implications for our understanding of HIV-1-associated bone and fat toxicities. |
| O-19 | EFFECTS OF ART ON BONE TURNOVER MARKERS AND BONE DENSITY IN HIV-INFECTED PATIENTS Antiviral Therapy 2009; 14(Supp. 2):A14 (abstract no. O-19 G Moyle1, N Givens2, H Pearce2 and J Compston3 Upon initiation of ART markers of bone resorption and formation increase, indicating an acceleration of bone turnover, which tends to stabilize thereafter. Change in these markers was correlated with the accompanying reduction in hip BMD. In this study increase in bone turnover was maximal at 24 weeks. The factors responsible for bone loss have not been identified and require further study. |
| O-20 | ASSOCIATION BETWEEN INITIATION OF ANTIRETROVIRAL THERAPY WITH EFAVIRENZ AND DECREASES IN 25-HYDROXYVITAMIN D Antiviral Therapy 2009; 14(Supp. 2):A15 (abstract no. O-20) TT Brown1 and GA McComsey2 ART initiation with EFV is associated with significant decreases in 25(OH)D and an increased risk of hypovitaminosis D compared with non-EFV regimens. |
| O-21 | T-LYMPHOCYTES AND BONE LOSS IN HIV DISEASE: ROLE OF CHRONIC STIMULATION AND OXIDIZED LIPIDS Antiviral Therapy 2009; 14(Supp. 2):A15 (abstract no. O-21 RB Effros1, LS Graham1, F Parhami2 and Y Tintut2 Loss of bone mass, osteoporosis, and osteopenia are increasingly being recognized as important comorbidities of chronic HIV infection. Numerous reports have documented associations between HIV disease and diminished bone mineral density and greater incidence of fractures. With the enhanced long-term survival of HIV-infected persons, the population of elderly HIV-infected persons is progressively increasing. |
| O-22 | MITOCHONDRIAL DNA HAPLOGROUPS AND METABOLIC CHANGES DURING ANTIRETROVIRAL THERAPY (ART) IN AIDS CLINICAL TRIALS GROUP (ACTG) STUDY A5142 Antiviral Therapy 2009; 14(Supp. 2):A16 (abstract no. O-22) T Hulgan1, R Haubrich2, S Riddler3, P Tebas4, MD Ritchie1, GA McComsey5, DW Haas1 and JA Canter1 Plasma lipid and peripheral fat parameters among these non-Hispanic white HIV-infected clinical trial participants appeared to be influenced by mtDNA variation, with haplogroup I showing the greatest observed effects. Previous studies either excluded haplogroup I because of small sample sizes, or combined it with other haplogroups. Our results are limited by small haplogroup sample sizes and the lack of generalizability to other racial/ ethnic groups. These preliminary findings require replication, but suggest that mitochondrial genomics may influence metabolic ART complications. |
| O-23 | EFFECT OF SUBSTITUTING TENOFOVIR FOR ZIDOVUDINE VERSUS CONTINUING ZIDOVUDINE ON PHYSIOLOGICAL CORRELATES OF MITOCHONDRIAL FUNCTION IN HIV-INFECTED SUBJECTS ON NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR THERAPY (NRTI)-BASED HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART) – FINAL REPORT Antiviral Therapy 2009; 14(Supp. 2):A17 (abstract no. O-23 G Ionescu, R Walker, Q He, JB Albu, ES Engelson and DP Kotler Despite low baseline mitochondrial dysfunction, zidovudine-to-tenofovir switch improved adipose tissue distribution, increasing lactate metabolism, without affecting skeletal muscle, aerobic capacity and resting or peak lactate. Increased peak power and time-to-peak exercise may contribute to higher lactate AUC after switching. |
| O-24 | TENOFOVIR PUTATIVELY INDUCES FIBROSIS IN CULTURED HUMAN PROXIMAL TUBULE EPITHELIAL CELLS Antiviral Therapy 2009; 14(Supp. 2):A17 (abstract no. O-24) EJ Cotter1, WG Powderly2 and PP Doran1 Induction of fibrosis and reduced cell proliferation in the renal proximal tubular epithelium putatively contributes to the renal toxicities associated with TFV treatment. |
| O-25 | ASSOCIATION BETWEEN SYSTEMIC INFLAMMATION AND OBSTRUCTIVE SLEEP APNEA IN MEN WITH OR AT RISK FOR HIV INFECTION FROM THE MULTICENTER AIDS COHORT STUDY (MACS) Antiviral Therapy 2009; 14(Supp. 2):A18 (abstract no. O-25) TT Brown, SP Patil, LP Jacobson, JB Margolick, AM Laffan, R Godfrey, J Johnson, L Johnson, S Reynolds, AR Schwartz and PL Smith OSA is highly prevalent in treated and untreated HIV-infected men, even those with normal BMI. In HIV-infected men not receiving HAART, moderate-to-severe OSA is associated with systemic inflammation, suggesting different etiologies of OSA in the groups studied. |
| Poster Presentations Adipocyte Biology |
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| P-01 | PRE-ADIPOCYTE APOPTOSIS AND MACROPHAGES IN SUBCUTANEOUS ADIPOSE TISSUE CONTRIBUTE TO HIV-ASSOCIATED LIPOATROPHY Antiviral Therapy 2009; 14(Supp. 2):A23 (abstract no. P-01 CM Shikuma1, LE Gerschenson2, CA Kruse2, D Chow1, C Milne1, KL Ewell1, J Choi1, C Kim1, S Souza1, DE Libutti1 and M Gerschenson1 Apoptosis index in SQ adipose tissue are higher in preadipocytes than in adipocytes in both HIV-positive and HIV-seronegative subjects. Apoptosis indices are not significantly altered in lipoatrophic subjects suggesting that other forms of cell death and/or a decreased pool of adipocyte precursor cells should be considered. Lipoatrophy is associated with increased macrophage infiltration. A correlation between macrophage numbers and preadipocyte apoptosis suggests that inflammation might be contributing to cell death. |
| P-02 | mRNA EXPRESSION PROFILE OF ADIPOCYTES CELLS IN
HIV-1-POSITIVE WITH HAART-RELATED LIPODISTROPHY Antiviral Therapy 2009; 14(Supp. 2):A23 (abstract no. P-02) S Martone1, L Milazzo1, P Cellerino2, B Menzaghi1, M Capasso1, D Misciagna1, S Genovese1, D Foschi2, M Galli1 and A Riva1 With the limitations of an investigation in a relatively small population, our study suggests a role for CEBPalpha and adiponectin in lipoatrophy. In antiretroviral-treated, HIV-infected patients, CEBPalpha deficiency might lead to defective development of adipose tissue and adiponectin might determine increased fatty acid catabolism both leading to lipoatrophy. Differential gene expression in subcutaneous adipose tissue between males and females seems to emerge and might account for the different prevalence and time to appearance of lipodystrophy between sexes. |
| P-03 | SUBCUTANEOUS ADIPOSE TISSUE ADIPOCYTE APOPTOTIC PARAMETERS IN HIV-1-INFECTED PATIENTS WITH HAART-RELATED LIPOATROPHY Antiviral Therapy 2009; 14(Supp. 2):A24 (abstract no. P-03 S Veloso1, JJ Sirvent1, M López-Dupla1, P Domingo2, C Aguilar1, J Peraire1, C Viladés1, M Gutiérrez2, M Olona1, G Mateo2, C Richart1 and F Vidal1 HIV-1-infected patients with lipodystrophy show increased SAT adipocyte apoptosis, which could be driven mainly through the death receptor pathway. |
| P-04 | STAVUDINE ALTERS EXPRESSION OF ADIPOCYTE-DERIVED ADIPOCYTOKINES AND PROMOTES INSULIN RESISTANCE IN CULTURED ADIPOCYTES Antiviral Therapy 2009; 14(Supp. 2):A25 (abstract no. P-04) R Saeedi1, V Saran1, K Johns1, M Harris2, J Montaner1,3, M Allard1 and G Bondy1 The results of this study suggest that stavudine treatment of differentiating 3T3-L1 adipocytes induces insulin resistance and increases expression of RBP-4, PAI-1, and MCP-1, and decreases expression of adiponectin. These findings provide a potential cellular mechanism that may contribute to stavudine-induced insulin resistance. |
Body Composition |
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| P-05 | BOTH ONCE-DAILY SAQUINAVIR/RITONAVIR AND ATAZANAVIR/RITONAVIR, WHEN COMBINED WITH TENOFOVIR/EMTRICITABINE CONSERVE ADIPOSE TISSUE, ONLY MODESTLY AFFECT LIPIDS AND EXHIBIT SIMILAR MILD REDUCTION IN GLOMERULAR FILTRATION OVER 48 WEEKS: THE BASIC TRIAL Antiviral Therapy 2009; 14(Supp. 2):A27 (abstract no. P-05 SME Vrouenraets1,2, E Fernandez Garcia2, A Jackson3, F Raffi4, DT Jayaweera5, C Katlama6, M Fisher7, L Slama8, D Hardy9, S Mauss10, E DeJesus11, A van Eeden12, D Prelutsky13, FWNM Wit1,2, G Moyle3 and P Reiss1,2 for the BASIC Study Group Combined with tenofovir/emtricitabine, saquinavir/r 2,000/100 mg and atazanavir/r 300/100 mg were virologically effective once-daily regimens. Each had comparable modest and potentially favourable effects on lipids, did not affect glucose metabolism, conserved adipose tissue and similarly reduced GFR. The difference in total and lean body mass changes may explain the discrepancy between GFR estimations. |
| P-06 | RISK FACTORS FOR BODY FAT REDISTRIBUTION IN A EUROPEAN COHORT OF HIV-INFECTED CHILDREN AND ADOLESCENTS Antiviral Therapy 2009; 14(Supp. 2):A27 (abstract no. P-06) NM Alam1, M Cortina-Borja1, T Goetghebuer1, A Vigano2 and C Thorne3 for the European Paediatric HIV and Lipodystrophy Study Body fat changes were prevalent in almost 50% of this cohort, which had accumulated relatively long durations of treatment. Increased risk of fat redistribution was associated with specific drugs as well as clinical and other variables. Ongoing follow-up will allow further description of the lipodystrophy phenotype and investigation of its emergence, progression and management. |
| P-07 | A STUDY ON THE RESISTIN SYSTEM IN HIV-1-INFECTED PATIENTS WITH HAART-RELATED LIPODYSTROPHY Antiviral Therapy 2009; 14(Supp. 2):A28 (abstract no. P-07 X Escoté1, S Veloso1, C Alonso-Villaverde2, P Domingo3, J Peraire1, C Viladés1, M López-Dupla1, V Alba1, I Velasco1, C Aguilar1, G Aragonès2, M Gutiérrez3, M Olona1, G Mateo3, C Richart1 and F Vidal1 Carriage of the REST-420C>G SNP is not associated with the development of lipodystrophy in HIV-1-infected patients treated with HAART, whereas a possible association exist with the vulnerability to HIV-1 infection. There is a systemic resistin overproduction in HIV-1-infected patients under HAART, which is unrelated with the presence of lipodystrophy. |
| P-08 | GENDER AND ETHNICITY DIFFERENCES IN BODY CHANGE AND DISTRESS OF HIV-POSITIVE INDIVIDUALS TAKING ANTIRETROVIRAL THERAPY IN ONTARIO Antiviral Therapy 2009; 14(Supp. 2):A29 (abstract no. P-08) M Loutfy1,2, N Andany1, M Li3, A Bayoumi4, S Rourke1,5, S Rueda5, A Rachlis6, N Mittmann6, N Risebrough6, S Walmsley1,3 W Wobeser7, RD MacArthur8, L Binder9, R Rosenes9 and JM Raboud1,3 Lipodystrophy is a common side effect of ART experienced by 58% of patients in this study. In this cohort, men and women did not differ in overall prevalence of lipodystrophy, but men were more likely to experience lipoatrophy (especially of the face, legs, and buttocks, whereas women were more likely to experience lipohypertrophy (especially of the abdomen and breasts) or mixed-fat redistribution. There were no ethnic differences in lipodystrophy in males, but Black females may be more prone to lipohypertrophy than non-Black females. |
Bone Metabolism & Toxicities |
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| P-09 | FRAX SCORE: FRACTURE RISK ASSESSMENT IN TREATED HIV PATIENTS Antiviral Therapy 2009; 14(Supp. 2):A31 (abstract no. P-09 J Falutz and L Rosenthall A minority of younger pts have a normal FN BMD. The currently low 10-year hip fracture risk in younger pts is similar to that of a significantly older population and is likely to increase as patients age. Assessment of common risk factors for bone demineralization and the role of HIV/HAART-related factors should be evaluated. |
Clinical Management of ADRs |
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| P-10 | INCIDENCE OF GASTROINTESTINAL ADVERSE EVENTS BY BASELINE CD4+ T-CELL COUNT IN ANTIRETROVIRAL-NAÏVE SUBJECTS AFTER STARTING LOPINAVIR/RITONAVIR (LPV/R)-BASED THERAPY IN STUDY M05-730 Antiviral Therapy 2009; 14(Supp. 2):A33 (abstract no. P-10) DE Cohen, BA da Silva, S Gibbs, J Hairrell, T Marsh, C Naylor, L Fredrick, B Bernstein In antiretroviral-naïve subjects starting a LPV/r-based regimen, low BL CD4+ T-cell count was not associated with an increased risk of moderate/ severe-related GI AEs or with an increased risk of premature discontinuation because of GI AEs. |
| P-11 | COMPLEMENTARY THERAPY USE IN HIV-POSITIVE PEOPLE: AN ONLINE COMMUNITY SURVEY Antiviral Therapy 2009; 14(Supp. 2):A34 (abstract no. P-11 NR Vergel The majority of this sample of HIV-positive people used CTs and derived perceived benefits. Unfortunately, there are little to no efficacycontrolled data available for most CTs. Also lacking are interaction studies between most nutritional/herbal supplements and HIV antiretrovirals (ARVs). As CT use seems to be common and pervasive in the self-management of adverse events and quality of life, the HIV-positive community would benefit from more controlled studies on popular CTs and supplement interaction data with ARVs. |
| P-12 | IMPLEMENTATION OF A METABOLIC CLINIC WITHIN A LARGE HIV CLINICAL CARE SETTING: FINDINGS FROM THE FIRST YEAR Antiviral Therapy 2009; 14(Supp. 2):A34 (abstract no. P-12) HM Crane, B Atkinson, JE Lee, BW Kosel, AJ Bartels, T Stone, S Dhanireddy and RD Harrington We have demonstrated the feasibility and value of incorporating a metabolic clinic into a large HIV clinic with minimal resource investment. After 2–12 months of follow-up, patients seen in the new clinic have experienced significant improvements in metabolic parameters. Next steps to improving metabolic parameters in the entire clinic population include letters to providers inquiring if they would like individual patients with poorly controlled diabetes, dyslipidemia or hypertension to be evaluated in metabolic clinic. |
| P-13 | PATTERNS OF HLA-B*5701 ALLELE TESTING FOR ABACAVIR HYPERSENSITIVITY REACTION AND THE INFLUENCE OF TEST RESULTS ON ABACAVIR PRESCRIBING Antiviral Therapy 2009; 14(Supp. 2):A35 (abstract no. P-13 KJ Lepik1,2, R Barrios1,2, PR Harrigan1, D Milan1, M Harris2, K Chan1, B Yip1, l Akagi1,2, J Toy2, RS Hogg1 and JSG Montaner1,2 Since HLA-B*5701 testing became available, most abacavir-naïve patients are tested before starting abacavir; however, many abacavir-experienced patients remain untested and may continue or restart abacavir even if HLA-B*5701-positive. Delayed onset abacavir HSR may occur; therefore, testing all abacavir-treated patients is advisable. |
Cardiovascular disease |
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| P-14 | ABSTRACT WITHDRAWN Antiviral Therapy 2009; 14(Supp. 2):A37 (abstract no. P-14) |
| P-15 | OMEGA-3 FATTY ACIDS SUPPLEMENTATION IMPROVE INFLAMMATION AND ENDOTHELIAL ACTIVATION IN HIV-INFECTED ADULTS ON STABLE ANTIRETROVIRAL THERAPY Antiviral Therapy 2009; 14(Supp. 2):A37 (abstract no. P-15 CO Hileman, M O’Riordan and GA McComsey The most significant limitation of this study is that it is an uncontrolled observational study in which the dose, components and adherence to fish oil could not be confirmed and examined in relation to the magnitude of the outcome. Despite this, hs-CRP, sVCAM-1 and sICAM-1 decreased without alternate explanation, results not expected in a population on stable ART with good virological control. However, the same positive effect was not seen for TNF-α or adiponectin. It is possible that despite our careful selection of study participants and samples, there were factors not controlled for that may have contributed to the increase in TNF-α and decrease in adiponectin. |
Insulin resistance |
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| P-16 | RELATIONSHIP OF SYSTEMIC INFLAMMATION WITH ADIPOKINES AND INSULIN SENSITIVITY IN HIV-INFECTED PATIENTS Antiviral Therapy 2009; 14(Supp. 2):A39 (abstract no. P-16) B Antuna-Puente1, E Lanoy2, L Slama3, M Maachi1, C Vigouroux1, W Rozenbaum4, D Costagliola2, J-P Bastard1, J Capeau1 and the LIPIOT ANRS 113 study group In two independent groups, CRP levels were strongly associated with overall inflammatory markers but not adipokines, even in lipoatrophic patients. By contrast, pioglitazone-induced variations of adiponectin and CRP were inversely related further supporting the anti-inflammatory effect of pioglitazone. These data suggest that adipokines are not related to low-grade systemic inflammation present in well-controlled HIV-infected patients. |
| P-17 | THE PROTEASE INHIBITOR COMBINATION LOPINAVIR/RITONAVIR DOES NOT DECREASE INSULIN SECRETION IN HEALTHY, HIV-SERONEGATIVE VOLUNTEERS Antiviral Therapy 2009; 14(Supp. 2):A39 (abstract no. P-17 VY Pao1,2, GA Lee1,2, S Taylor1,2, FT Aweeka3, J-M Schwarz1,4,5, K Mulligan1,4, M Schambelan1,4 and C Grunfeld1,2 While administration of lopinavir/ritonavir for 4 weeks to healthy, HIV-seronegative volunteers resulted in increased triglyceride and decreased HDL cholesterol levels, there was no change in first-phase insulin secretion during the hyperglycaemic clamp. The reported effects of PI on insulin secretion in HIV-infected individuals may be due to changes in HIV-related factors and not a direct drug effect. |
| P-18 | THE IMPACT OF MARAVIROC ON INSULIN SENSITIVITY, LIPIDS AND ADIPOKINES AFTER 2 WEEKS IN HIV-NEGATIVE MALE VOLUNTEERS Antiviral Therapy 2009; 14(Supp. 2):A40 (abstract no. P-18) P Randell, A Jackson, J Taylor and G Moyle Two weeks of dosing with maraviroc 300 mg twice-daily does not have a significant impact on insulin sensitivity, adipokines (adiponectin and leptin) or lipid parameters in HIV-negative male subjects. |
| P-19 | IMPACT OF NON-THYMIDINE ANALOGUES ON INSULIN RESISTANCE: ARE THEY ALIKE? Antiviral Therapy 2009; 14(Supp. 2):A40 (abstract no. P-19 A Rodríguez1, E Álvarez2, C Miralles1, A Lavandeira2, A Ocampo1, M Las Heras3, M Andrade2 and C Martinez-Vazquez1 HOMA-IR was significantly higher in the patients groups compared with the control group. We did not find statistical differences among the nonthymidine analogues in the non-nucleoside reverse trancriptase inhibitors groups. The HOMA index was higher in both IPs groups. Ours results seem to indicate the similar and benign profile of both non-thymidine analogues and reflect our clinical experience. |
Other toxicities |
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| P-20 | CHANGES IN CREATINE KINASE (CK) LEVELS ASSOCIATED WITH RALTEGRAVIR THERAPY IN CLINICAL PRACTICE Antiviral Therapy 2009; 14(Supp. 2):A43 (abstract no. P-20) T Antoniou1,2,3, J Raboud1,4, D Su4, C Kovacs1,5, J Brunetta3, G Smith3, D Fletcher5, F Crouzat5 and M Loutfy1,3 Slight increases in CK levels were observed among patients receiving treatment with raltegravir during follow-up. Potentially significant grade 2 or higher changes in CK were associated with increased levels of this variable at baseline. |
| P-21 | NEUROPSYCHIATRIC ADVERSE EVENTS IN THE MONET TRIAL: DARUNAVIR/RITONAVIR WITH AND WITHOUT NUCLEOSIDE ANALOGUES FOR PATIENTS WITH HIV RNA <50 COPIES/ML AT SCREENING Antiviral Therapy 2009; 14(Supp. 2):A43 (abstract no. P-21 G di Perri1, G Fätkenheuer2, A Hill3, Y van Delft4 and C Moecklinghoff5 In this study for patients with HIV RNA<50 copies/ml at screening, drug-related neuropsychiatric adverse events were infrequent for DRV/r, either with or without nucleoside analogues: most reported adverse events were grade 1 (mild) and not drug-related. Patients reported no loss in concentration or memory over 48 weeks. |
| P-22 | FORTY-EIGHT WEEK CHANGES IN QUALITY OF LIFE AND ADHERENCE IN THE MONET TRIAL: DARUNAVIR/RITONAVIR (DRV/R) WITH AND WITHOUT NUCLEOSIDE ANALOGUES (NRTIS) FOR PATIENTS WITH HIV RNA<50 COPIES/ML AT SCREENING Antiviral Therapy 2009; 14(Supp. 2):A44 (abstract no. P-22) C Stephan1, J Arribas2, A Carosi3, A Hill4, A Anceau5 and C Moecklinghoff6 In this study for patients with HIV RNA<50 copies/ml at screening, switching to DRV/r monotherapy showed maintained or improved quality of life. Patient-reported adherence levels were high, and did not correlate with transient or sustained episodes of viraemia. |
| P-23 | CORRELATION BETWEEN LABORATORY PARAMETERS AND USE OR DISCONTINUATION OF NUCLEOSIDE ANALOGUES IN THE MONET TRIAL Antiviral Therapy 2009; 14(Supp. 2):A44 (abstract no. P-23 A Hill1 Y van Delft2 and C Moecklinghoff3 In the MONET study, changes in laboratory parameters were correlated with use or discontinuation of NRTIs; rises in liver enzymes were correlated with chronic or acute infection with hepatitis A or C. |
Renal toxicities |
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| P-24 | ASSESSING THE DYNAMICS OF RENAL FUNCTION IN PATIENTS WITH HIV, HBV OR HIV–HBV COINFECTION Antiviral Therapy 2009; 14(Supp. 2):A47 (abstract no. P-24) S Mauss1, F Berger1, N Filmann2, J Henke1, C Athmann1, P Hegener1, G Schmutz1 and E Herrmann2 Untreated HBV infection has an adverse effect on renal function as does untreated HIV infection with high viral load. Therapy of HBV infection even with potentially nephrotoxic drugs, such as tenofovir or adefovir, has a beneficial effect on renal function. By contrast, a marked positive effect of antiretroviral therapy on eGFR in HIV patients could not be observed in this Caucasian population with a low prevalence of HIV-associated nephropathy. |
| P-25 | MICROALBUMINURIA IN A LONGITUDINAL COHORT OF ADOLESCENTS AND YOUNG ADULTS WITH HIV INFECTION ACQUIRED IN INFANCY OR CHILDHOOD Antiviral Therapy 2009; 14(Supp. 2):A47 (abstract no. P-25 D Dimock1, S Vakkalanka2, J Kopp3, J Purdy4, R Hazra2,5 and C Hadigan1 The prevalence of microalbuminuria in this HIV cohort was greater than seen in studies of children receiving ART and equivalent to data from adults receiving ART. The inverse correlation with CD4% suggests possible effects of HIV or immune function on microalbuminuria. In addition, traditional risk factors such as AA race and blood pressure may also play a role. Further studies are necessary to determine the mechanisms of HIV-associated microalbuminuria and its consequences in this population. |
| P-26 | ESTIMATING RENAL IMPAIRMENT AND EVALUATING ANTIRETROVIRAL (ARV) DOSE ADJUSTMENTS AMONG HIV-POSITIVE PATIENTS IN HIGH CASE LOAD GP CLINICS IN MELBOURNE Antiviral Therapy 2009; 14(Supp. 2):A48 (abstract no. P-26) K Mackie1, N Roth2,3, J Howard3, J Hoy3, C Fairley4, J Willcox5, R Moore3,5, T Lee1 and A Duncan1 The prevalence of renal impairment in HIV patients seen at these high case load GP clinics is low. However, a number of patients require dosage adjustment. This study has identified the need for a system that identifies patients requiring renal monitoring and subsequent dosage adjustment. |
| P-27 | THE PITFALLS OF THE ESTIMATED GLOMERULAR FILTRATION RATE – ‘HITTING THE GYM AND CREATINE SUPPLEMENTATION’ Antiviral Therapy 2009; 14(Supp. 2):A49 (abstract no. P-27 M Rayment1 J Willis2, N Nwokolo1, J Levy2, R Jones1 and G Moyle3 Alternatively, high rates of creatine ingestion may reflect the body conscious nature of the cohort. Normal blood pressure, normal urinalysis, and the prompt normalization of serum creatinine/eGFR following discontinuation of supplements should reassure the physician that the diagnosis was correct. |
| P-28 | EFFICACY AND TOLERABILITY OF TENOFOVIR-CONTAINING REGIMENS IN COMBINATION WITH EITHER LOPINAVIR/RITONAVIR OR ATAZANAVIR/RITONAVIR IN A VETERAN POPULATION Antiviral Therapy 2009; 14(Supp. 2):A50 (abstract no. P-28) L Lee1, HB Fung1 and JC Bandres1,2 Despite the reported pharmacokinetic interactions between TDF and ATV, we did not find any clinical differences in this retrospective study with respect to CD4 increase or percentage of patients achieving undetectable viral loads. Also, main indices of toxicity, like change in GFR, lipid abnormalities and liver toxicity, were not different between these two groups of patients. |
Lipid Metabolism |
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| P-29 | COMPARISON OF LIPID PROFILE WITH NEVIRAPINE VERSUS ATAZANAVIR/RITONAVIR, BOTH COMBINED WITH TENOFOVIR DF AND EMTRICITABINE (TDF/FTC), IN TREATMENT-NAÏVE HIV-1-INFECTED PATIENTS: ARTEN STUDY WEEK 48 RESULTS Antiviral Therapy 2009; 14(Supp. 2):A51 (abstract no. P-29 D Podzamczer1, V Soriano2, J Andrade-Villanueva3, B Clotet4, S Taylor5, J Rockstroh6, P Domingo7, P Reiss8, HJ Gellermann9, V Cairns9 and L de Rossi9 Compared with atazanavir/ritonavir, nevirapine-containing regimens were associated with markedly greater increases in HDL-C and ApoA1 concentrations, no increase in TG concentrations and reduction in TC:HDL-C ratio over 48 weeks. Overall, data suggest a more favourable lipid profile for nevirapine than atazanavir/ritonavir, when combined with tenofovir DF and emtricitabine. |
| P-30 | APOLIPOPROTEIN B GENE POLYMORPHISMS ARE ASSOCIATED WITH HIGHER CHOLESTEROL LEVELS IN HIV-INFECTED INDIVIDUALS ON HAART Antiviral Therapy 2009; 14(Supp. 2):A52 (abstract no. P-30) VS Mattevi1, AS Gasparotto1, RK Lazzaretti2, MH Hutz3, R Kuhmmer2, JP Ribeiro2 and E Sprinz2 These data suggest that APOB gene polymorphisms are associated with total cholesterol and LDL levels among HAART users, irrespective of antiretroviral regimen. Therefore, carriers of the del-T haplotype may be at higher risk to the development of hypercholesterolemia when exposed to HAART. |
| P-31 | HIV-1 INFECTED PATIENTS WITH SUPPRESSED PLASMA VIRAEMIA ON TREATMENT HAVE PRO-INFLAMMATORY HDL Antiviral Therapy 2009; 14(Supp. 2):A52 (abstract no. P-31 T Kelesidis, OO Yang, JS Currier, AM Fogelman and M Navab HIV patients on ART with suppressed plasma viraemia have proinflammatory HDL. Treatment in vitro of their plasma with L-4F significantly reversed the inflammatory properties of their HDL. |
| P-32 | GRACE (GENDER, RACE AND CLINICAL EXPERIENCE): EFFECTS OF DARUNAVIR/RITONAVIR-BASED THERAPY ON METABOLIC AND ANTHROPOMETRIC PARAMETERS IN WOMEN AND MEN OVER 48 WEEKS Antiviral Therapy 2009; 14(Supp. 2):A53 (abstract no. P-32) JS Currier1, C Martorell2, O Osiyemi3, M Yin4, R Ryan5, G De La Rosa6 and J Mrus6 In GRACE, triglyceride elevations were more common in men; women generally experienced larger increases in weight and other anthropometric measurements. Darunavir/ritonavir-based therapy was associated with small-to-moderate changes in metabolic parameters, with few between-sex differences. |
| P-33 | FRAMINGHAM RISK AND LIPOPROTEIN CHANGES AFTER 24 WEEKS OF TREATMENT WITH ABACAVIR/LAMIVUDINE (ABC/3TC) AND RALTEGRAVIR (RAL) IN ANTIRETROVIRAL (ARV)-NAÏVE HIV-1-INFECTED SUBJECTS Antiviral Therapy 2009; 14(Supp. 2):A54 (abstract no. P-33 B Young1, T Vanig2, E DeJesus3, T Hawkins4, L Yau5, B Ha5 and SHIELD study team In this pilot study, ABC/3TC+RAL was associated with rapid virological suppression, with most subjects maintaining BL CV risk status through W24. While TC/HDL ratios were largely unchanged, NMR lipoprofile analysis based on the limited sample size suggest that lipid changes may be mediated through increases in LDL particle numbers. These data support the generally favourable lipid profile of ABC/3TC+RAL, but reinforce the need to address modifiable CV risk factors along with virological suppression. |
| P-34 | EFAVIRENZ ALTERS THE EXPRESSION OF GENES INVOLVED IN LIPID METABOLISM Antiviral Therapy 2009; 14(Supp. 2):A54 (abstract no. P-34) D Ballesteros1,2, A Blas-García1,2, C Gomis-Coloma2, M Gómez-Soler1,3, LJ Gómez-Sucerquia1, N Apostolova1,3 and JV Esplugues1,2,3 Both doses of EFV significantly increased the expression of CD36 and enhanced that of FATP after 4 h of treatment, whereas gene expression of transcription factors was modified at 24 h, leading to an increase in PPARγ (only with 25 µM) and LxR, and a decrease in SREBP-1c. This pattern of gene expression is associated with an enhanced capture of extracellular lipids by Hep3B cells, which could lead to an increase in intracellular lipid content and the development of hepatic steatosis. |
| P-35 | EFFECTS OF ONCE-DAILY DARUNAVIR/RITONAVIR VERSUS LOPINAVIR/RITONAVIR ON LIPID PARAMETERS AND ANTHROPOMETRICS IN TREATMENT-NAÏVE HIV-1-INFECTED ARTEMIS PATIENTS AT WEEK 96 Antiviral Therapy 2009; 14(Supp. 2):A55 (abstract no. P-35 E Baraldi1, J Morales-Ramírez2, S Schneider3, A Stoehr4, A Orani5, T Van De Casteele6, L Lavreys6 and A Hill6 Once-daily darunavir/ritonavir 800/100 mg was less frequently associated with elevations in triglycerides and total cholesterol than lopinavir/ritonavir 800/200 mg total daily dose. Darunavir/ritonavir patients had significantly greater increases in weight and BMI versus lopinavir/ritonavir. The favourable lipid profile seen with darunavir/ritonavir at week 48 was also demonstrated at week 96. |
| P-36 | PRE-TREATMENT ALTERATIONS IN LIPOPROTEIN METABOLISM PREDICT CHANGES IN BLOOD LIPIDS AFTER ANTIRETROVIRAL THERAPY Antiviral Therapy 2009; 14(Supp. 2):A56 (abstract no. P-36) M Shahmanesh1, S Das2 and M Umpleby3 Pre-treatment apoB-100-containing lipoprotein metabolism in HIV-infected patients are important in determining changes in blood cholesterol and HDL cholesterol in the first 2 years after treatment. |
| P-37 | METABOLIC EVALUATION OF STUDY M06-802 THROUGH WEEK 48: PHASE III, RANDOMIZED, OPEN-LABEL, STUDY OF LOPINAVIR/RITONAVIR (LPV/R) TABLETS ONCE DAILY (QD) VERSUS TWICE DAILY (BID), IN ANTIRETROVIRAL (ARV)-EXPERIENCED HIV-1 INFECTED SUBJECTS Antiviral Therapy 2009; 14(Supp. 2):A56 (abstract no. P-37 A Lawal, T Podsadecki, l Fredrick and B Bernstein ARV-experienced subjects treated with LPV/r QD and BID-based regimens through 48 weeks showed similar mean increases in TG with small increases in TC, LDL and HDL consistent with known effects of LPV/r. Based on lipid ratios and Framingham, these changes are not expected to result in increased CV risk for most subjects. No significant mean increases in HOMA values were observed over time. |
| P-38 | LIPID PROFILES IN HIV-INFECTED ADULTS RECEIVING ATAZANAVIR AND ATAZANAVIR/RITONAVIR IN RANDOMIZED TRIALS: SYSTEMATIC REVIEW AND META-ANALYSIS Antiviral Therapy 2009; 14(Supp. 2):A58 (abstract no. P-38) D Carey, J Amin and S Emery In HIV-infected adults, fasting lipid parameters were significantly lower with ATV/RTV compared with other boosted protease inhibitor regimens after 48 weeks. RTV boosting resulted in higher fasting total and non-HDL cholesterol levels compared with ATV alone. |
Liver disease and hepatotoxicity |
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| P-39 | LIVER FIBROSIS BY TRANSIENT ELASTOGRAPHY IN HIV PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) Antiviral Therapy 2009; 14(Supp. 2):A59 (abstract no. P-39 M Schiavini, P Meraviglia, D Minisci, M Ortu, L Carenzi, D Pocaterra, E Ricci and P Bonfanti Liver fibrosis prevalence in the population enrolled is 18.9%. Patients with liver fibrosis showed an association with a pattern of insulin resistance. Another biochemical marker like IGF-1 could be useful to identify patients at risk. Early fibrosis detection by Fibroscan can contribute to a better management of HIV-patients with NAFLD. |
| P-40 | POSSIBLE INFLUENCE OF CART AND GBV-C/HGV COINFECTION ON TRANSAMINASE ELEVATION IN HIV-POSITIVE PERSONS FROM AIDS-CENTER PRAGUE Antiviral Therapy 2009; 14(Supp. 2):A59 (abstract no. P-40) V Aster1, J König2, L Machala3, H Rozsypal4 and M Stankova5 Both HGV coinfection and antiretroviral therapy might contribute to transaminase level elevation in HIV-infected patients. No HGV viraemia supression in patients on cART was observed. |
Mitochondrial disorders |
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| P-41 | EFV-INDUCED REDUCTION OF MITOCHONDRIAL RESPIRATION IS DUE TO THE INHIBITION OF COMPLEX I Antiviral Therapy 2009; 14(Supp. 2):A61 (abstract no. P-41 A Blas-García1,2, VM Víctor2, M Gómez-Soler1,3, LJ Gómez-Sucerquia1, N Apostolova1,3 and JV Esplugues1,2,3 Previous reports have demonstrated that clinical concentrations of efavirenz (EFV) induce bioenergetic stress in hepatic cells by inhibiting mitochondrial respiration. We have evaluated the molecular mechanisms underlying this inhibition and have investigated, by analysing the effects of nevirapine (NVP), whether this effect is general to all NNRTI. |
| P-42 | EXERCISE CAPACITY AND MARKERS OF MITOCHONDRIAL FUNCTION IN HIV-INFECTED PATIENTS ON NRTI THERAPY Antiviral Therapy 2009; 14(Supp. 2):A61 (abstract no. P-42) E Glover1,2, J Martin1,2, NJ Mocellin1,2, D Elston3, F Smaill2,3 and MA Tarnopolsky1,2,3 Use of the NRTIs ddI/d4T/AZT appears to be associated with diminished aerobic exercise capacity at the whole body level and lower full-length mtDNA and oxidative enzyme activity at the muscle level. The deleterious effects may persist in muscle after cessation of use, as previous users were also shown to exhibit lower mtDNA levels and impaired exercise responses. Aerobic exercise testing may have utility in detecting NRTI-induced mitochondrial dysfunction in users of ddI/d4T/AZT, even among patients who do not display lipodystrophy or overt myopathy. |
| P-43 | EFFECTS OF HIV AND ANTI-RETROVIRAL THERAPY ON MITOCHONDRIAL DNA LEVELS IN MUSCLE, ADIPOSE TISSUE, AND PBMCS Antiviral Therapy 2009; 14(Supp. 2):A62 (abstract no. P-43 C Morse1, J Voss2, G Rakocevic3, C Huber4, C Vinton4, M Mclaughlin1, M Dalakas5 and J Kovacs4 These results suggest that HIV infection affects fat metabolism, leading to increased mtDNA content in adipose tissue of patients not on ART. In individuals tolerant of NNRTI-based ART for 1 year or greater, ART does not affect mitochondrial function in muscle or PBMCs, or compensatory mechanisms are in place to mitigate the mitochondrial toxic effects; decreased mtDNA in adipose tissue, however, suggests mitochondrial toxicity or, alternatively, a reversal of HIV-mediated effects. Because mtDNA levels in PBMCs do not correlate with mtDNA levels in other tissues, this might not be a good surrogate for mitochondrial toxicity. |
| P-44 | EFFECT OF MICRONUTRIENT SUPPLEMENTATION ON LACTATE METABOLISM AND MITOCHONDRIAL RESPIRATORY CHAIN PROTEIN EXPRESSION IN PERSONS TREATED FOR HIV Antiviral Therapy 2009; 14(Supp. 2):A63 (abstract no. P-44) E Morgan1, W Wobeser1, V Gambhir2, M Iourtchenko2 and P Zhang2 These data confirm previous findings of resting hyperlactataemia in patients receiving antiretroviral therapy. In addition, increased lactate production during the lactate challenge suggests that this excess lactate is a result of increased endogenous production of lactic acid, rather than decreased lactate clearance. Although previous studies have suggested a beneficial effect of metabolic cofactor supplementation in HIV-related lactic acidosis, we did not find any significant change in resting lactate levels or lactate clearance after supplementation; however, increased expression of mitochondrial chain proteins was detected in peripheral blood cells. |
| P-45 | MITOCHONDRIAL TOXICITY DEPLETES PREDOMINANTLY SLOW MUSCLE FIBRES IN ZIDOVUDINE-INDUCED MYOPATHY Antiviral Therapy 2009; 14(Supp. 2):A63 (abstract no. P-45 D Lebrecht1, AC Venhoff1, J Kirschner2, N Venhoff1,3 and UA Walker1,4 Zidovudine induces a mitochondrial myopathy with thinned and degenerated muscle fibres, in which mtDNA is predominantly depleted in slow fibres. All these effects are antagonized by Mitocnol. |
| P-46 | HIV AND ANTIRETROVIRAL-MEDIATED MITOCHONDRIAL DNA DEPLETION IN CHILDREN Antiviral Therapy 2009; 14(Supp. 2):A64 (abstract no. P-46) C Morén1,3, A Noguera2, G Garrabou1,3, N Rovira2, M Nicolàs1,3, F Cardellach1,3, Ò Miró1,3 and C Fortuny2 The observed depletion in mtDNA content in HIV-infected children did not lead to differences in mtRNA levels or most part of MRC function. Homeostatic compensatory mechanisms at transcription level could explain the lack of correlation between mtDNA depletion and the totality of MRC functions. |
| P-47 | INCREASED MITOCHONDRIAL TOXICITY CORRELATES ADVERSE PERINATAL OUTCOME IN HIV-INFECTED WOMEN ON ANTIRETROVIRAL TREATMENT AND THEIR NEWBORN Antiviral Therapy 2009; 14(Supp. 2):A65 (abstract no. P-47 G Garrabou1, AS Hernandez2, C Moren1, M Nicolàs1, M López3, S Lopez1, A Gonce3, O Miro1 and O Coll3 Increased mtDNA depletion along pregnancy was found in HIV-infected women on HAART and their newborn accompanied with increased risk of adverse perinatal outcome. Further studies are needed to better understand materno-fetal morbidity associated with HIV and ARV exposure during gestation and whether mtDNA depletion could stand at the basis of mitochondrial dysfunction, cellular impairment and adverse perinatal results. |
| P-48 | DIDEXOXYNUCLEOSIDE-INDUCED SEVERE HYPERLACTATAEMIA IN WHITE EUROPEANS APPEARS NOT TO BE CAUSED BY A COMMON INHERITED MTDNA MUTATION Antiviral Therapy 2009; 14(Supp. 2):A65 (abstract no. P-48) A Arenas-Pinto1, I Weller1, R Ekong2, A Grant3, P Reiss4, R Weber5, N Bradman2 and C Ingram2 We did not find an association between mtDNA polymorphisms and the occurrence of HL/LA in white European patients exposed to dideoxynucleosides. Our data suggest that there is no single mutation encoded in the mitochondrial genome that predisposes patients to HL/LA. |
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