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5th International Workshop on Adverse Drug Reactions
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| Oral Presentations Plenary Session Abstracts P1 through P6 |
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| P1 | ATHEROSCLEROSIS AND THE PATHOGENESIS OF PLAQUE FORMATION Antiviral Therapy 2003; 8:L1 J-C Fruchart and P Duriez The amount of collagen in the lesion's fibrous cap depends upon its rate of biosynthesis stimulated by factors released from platelets (for example, transforming growth factor beta or platelet-derived growth factor), but inhibited by gamma interferon, a product of activated T cells. Degradation by matrix metalloproteinases also influences the level of collagen in the plaque's fibrous cap. Statins and fibrates decrease the risk of plaque disruption. |
| P2 | ADIPOSE TISSUE AND INSULIN RESISTANCE Antiviral Therapy 2003; 8:L1 K Frayn There is plenty of evidence for "metabolic inflexibility" of adipose tissue associated with insulin-resistant states such as obesity (large fat cells are inherently less active than small ones). Alternatively, in conditions with a deficiency of adipose tissue, such as lipodystrophy, there may simply not be sufficient adipose tissue to cope with incoming fat. This view, therefore, reconciles the fact that insulin resistance is associated both with an excess and a deficiency of adipose tissue. |
| P3 | THE ROLES AND MECHANISMS OF ADIPOCYTOKINES IN INSULIN RESISTANCE Antiviral Therapy 2003; 8:L2 T Yamauchi and T Kadowaki We propose that small adipocytes with increased expressions of insulin sensitizing hormones such as adiponectin as well as decreased expressions of adipokines causing insulin resistance such as TNFα are associated with insulin sensitivity, whereas hypertrophic adipocytes with decreased expressions of insulin sensitizing hormones as well as increased expressions of adipokines causing insulin resistance are associated with insulin resistance which may be a central mechanism to cause life style-related disease. |
| P4 | IN VITRO/IN VIVO CORRELATIONS AND OTHER MISADVENTURES IN PHARMACOLOGY Antiviral Therapy 2003; 8:L2 CW Flexner One possible solution involves a permeable hollow fibre cartridge system designed to mimic human pharmacokinetics. This system produces concentration–time curves identical to those seen in patients, and can also be used to assess protein binding effects. This model predicted the value of less frequent dosing of zidovudine and other antiretroviral nucelosides. This and other potential solutions to the problem of in vitro/in vivo correlation will be discussed. |
| P5 | MITOCHONDRIAL METABOLISM, ENERGY HOMEOSTASIS AND CELL DEATH Antiviral Therapy 2003; 8:L3 X Leverve The mechanism relating mitochondria and cell death still requires some clarification, but it is probable that the mitochondrial permeability transition pore (PTP) is involved via the release of cytochrome in the cytosol, which activates the caspase cascade. It is suggested that complex 1 plays a central role in the control of oxidative phosphorylation, ROS production and in the commitment to cellular death. Mild inhibition of complex 1 has been shown to interfere with ROS-related cell death. |
| P6 | PHARMACOGENOMICS: THE INHERITED BASIS FOR INTER-INDIVIDUAL DIFFERENCES IN DRUG RESPONSE Antiviral Therapy 2003; 8:L3 WE Evans The ultimate goal is to provide new strategies for discovery and optimization of drug therapy based on each patient’s genetic determinants of drug efficacy and toxicity. This presentation will use the TPMT polymorphism and thiopurine (e.g., azathioprine) therapy to illustrate the potential of pharmacogenomics to elucidate genetic determinants of drug response, and optimize the selection of drug therapy for individual patients |
| Hepatitis C Workshop Abstracts W1 through W2, page L4 |
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| W1 | ADVERSE EVENTS IN HIV/HCV-CO-INFECTED PATIENTS WITH INTERFERON α2B AND RIBAVIRIN (ANRS HC 02 – RIBAVIC TRIAL) Antiviral Therapy 2003; 8:L4 C Perronne, F Bani Sadr, P Morand, F Lunel, E Rosenthal, S Pol, P Cacoub and F Carrat on behalf of the RIBAVIC Study Group In co-infected patients, anti-HCV treatment is less tolerated leading to a high rate of treatment interruption. Co-administration of ribavirin and didanosine should be avoided. |
| W2 | RISK FACTORS FOR HEPATIC DECOMPENSATION IN CIRRHOTIC PATIENTS WITH HIV/HCV CO-INFECTION TREATED WITH PEGYLATED INTERFERON-α OR INTERFERON-α AND RIVBAVIRIN, OR PLACEBO Antiviral Therapy 2003; 8:L4 S Mauss1, D Larrey2, W Valenti3, F Torriani4, D Dieterich5, S. Passe, L Cupelli6, J Solsky6, J DePamphilis6 and the APRICOT Study Group The majority of risk factors associated with hepatic decompensation, however, are biological markers for advanced cirrhosis. Therefore, patients with early stage cirrhosis may not be at high risk of decompensation and should be considered for HCV treatment. |
| Session 1 Abstracts 1 through 4, pages L5 through L7 |
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| 1 | INDINAVIR-ASSOCIATED ENDOTHELIAL DYSFUNCTION IS ASSOCIATED WITH INCREASED PLASMA ADIPONECTIN LEVELS Antiviral Therapy 2003; 8:L5 SS Shankar, M Degawa-Yamauchi, RV Considine, HO Steinberg and MP Dubé In healthy non-obese HIV-negative volunteers, 4 weeks of daily IDV impairs endothelial function and is associated with increased plasma adiponectin levels. The correlation between these variables suggests that the IDV-induced elevation in adiponectin levels may be occurring as a protective response to damage initiated by the IDV-induced endothelial dysfunction. |
| 2 | CAROTID INTIMA-MEDIA THICKNESS IS MODERATELY INCREASED OVER TIME IN HIV-1-INFECTED PATIENTS Antiviral Therapy 2003; 8:L6 P Mercié1–3, R Thiébaut2,4, V Aurillac-Lavignolle2, JL Pellegrin1, MC Yvorra-Vives3, C Cipriano1,3, D Neau1, P Morlat1,2, JM Ragnaud1, M Dupon1, D Malvy1, S Lawson-Ayayi2, R Roudaut3 and F Dabis2 for the Groupe d’Epidemiologie Clinique du Sida en Aquitaine (GECSA) We hypothesize that chronic HIV infection and HAART use could promote atherosclerosis through several mechanisms; first, the higher prevalence of the atherogenic metabolic disorders and second, the immunological restoration and/or the stimulated CD4 cell increase able to produce CD40L, which is widely implicated in the progression of atherosclerosis. In this view, unstable atherosclerosis plaque should be investigated in order to better understand the pathophysiological mechanism of atherosclerosis and/or acute thrombotic events in HIV-infected patients. |
| 3 | EFFECTS OF HIV INFECTION, ANTIVIRAL TREATMENT AND BODY FAT CHANGES ON VLDL-APOLIPOPROTEIN-B METABOLISM Antiviral Therapy 2003; 8:L6 S Das1, M Stolinski2, W Jefferson2, N Jackson2, G Gilleran1, M O’Connor1, R Cramb1, M Umpleby2 and M Shahmanesh1 HIV infection itself increases the absolute VLDL apo-B secretion from the liver. These are not increased further by treatment with a protease inhibitor, nevirapine or efavirenz containing antiviral regimens. VLDL apo-B catabolic rates are not effected by HIV infection but are reduced by antiviral treatment, regardless of highly active antiretroviral therapy treatment regimens. This provides a possible mechanism for the increase in plasma lipid levels in HIV patients after starting highly active antiretroviral therapy. Data for IDL will be presented at conference. |
| 4 | EFFECTS OF EXERCISE TRAINING AND METFORMIN ON BODY COMPOSITION AND CARDIOVASCULAR INDICES IN HIV-INFECTED PATIENTS Antiviral Therapy 2003; 8:L7 SD Driscoll1, G Meininger1, M Lareau2, SE Dolan1, KM Killilea1, C Hadigan1, D Lloyd-Jones3, A Klibanski4, WR Frontera5 and S Grinspoon These data demonstrate that exercise training in combination with metformin significantly improves cardiovascular risk markers more than metformin alone in HIV-infected patients with fat redistribution and hyperinsulinaemia. Exercise training was well-tolerated and improved muscle strength and size, as well as aerobic fitness. Combined therapy in selected groups of HIV-infected patients may substantially alter cardiovascular risk. |
| Session II Abstracts 5 through 8, pages L8 to L9 |
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| 5 | INCREASED EXPRESSION OF 11β-HYDROXYSTEROID DEHYDROGENASE TYPE 1 IN SUBCUTANEOUS ADIPOSE TISSUE IN HIV-ASSOCIATED LIPODYSTROPHY Antiviral Therapy 2003; 8:L8 J Sutinen1,2, K Kannisto3, E Korsheninnikova4, T Nyman4, A Hamsten3, D Wake5, B Walker5 and H Yki-Jarvinen1,3 Increased expression of 11βHSD1 in adipose may contribute to insulin resistance in patients with HAART-associated lipodystrophy. |
| 6 | HIV PROTEASE INHIBITORS ACUTELY INHIBIT GLUCOSE-INDUCED INSULIN RELEASE FROM HUMAN PANCREATIC β CELLS Antiviral Therapy 2003; 8:L8 JC Koster1, M Remedi1, H Qiu2, CG Nichols1, and PW Hruz2 Taken together, these data suggest that therapeutic levels of the PIs are sufficient to inhibit glucose-induced insulin secretion in human islets in vitro and this inhibition is likely to contribute to the decreased β-cell response observed in PI-treated subjects. It remains to be determined whether block of glucose uptake (Glut3/Glut1) in human islets underlies impaired insulin, as is predicted for the rodent β-cell. |
| 7 | INDINAVIR INCREASES HEPATIC GLUCOSE PRODUCTION IN HEALTHY HIV-NEGATIVE MEN Antiviral Therapy 2003; 8:L9 MA Noor1, S Park2, GA Lee1, JM Schwarz1,2, J Lee2, M Wen2, JC Lo1, K Mulligan1, M Schambelan1 and C Grunfeld1 Four weeks of treatment with indinavir increases fasting HGP moderately and blunts the suppression of HGP by insulin. Glycogenolysis plays a major role in the increase in HGP in both fasting and hyperinsulinaemia. These results cannot be explained by an effect of indinavir on GLUT4 alone; therefore, other mechanisms must be involved. Hepatic insulin resistance contributes to the effects of indinavir on altered glucose metabolism. |
| 8 | LIPOLYSIS DIMINISHES AND GLUCOSE METABOLISM IMPROVES MODESTLY, BUT FAT DISTRIBUTION REMAINS UNCHANGED IN SEVERE LIPODYSTROPHIC HIV-1 INFECTED PATIENTS 96 WEEKS FOLLOWING PROTEASE INHIBITOR WITHDRAWAL Antiviral Therapy 2003; 8:L9 M van der Valk1, G Allick2, GJ Weverling3, JA Romijn4, MT Ackermans5, JMA Lange1,6, BLF van Eck-Smit7, C van Kuijk8, E Endert5, HP Sauerwein2 and P Reiss6 Ninety-six weeks of PI withdrawal in severe lipodystrophic HIV-1 infected patients resulted in a significant decrease in lipolysis and improvement in glucose oxidation. During fasting, but not during insulin-stimulation, glucose production was modestly reduced, while insulin-stimulated glucose disposal and fat distribution had not improved. Taken together, our data suggest that mechanisms additional to inhibition of GLUT-4 activity are responsible for the changes in glucose metabolism seen in HIV-infected patients with established lipodystrophy. |
| Session III Abstracts 9 through 12, pages L10 to L12 |
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| 9 | INCREASED IL-6 AND TNF-α EXPRESSION IS RELATED TO INCREASED APOPTOSIS AND DECREASED DIFFERENTIATION IN ADIPOSE TISSUE FROM PATIENTS WITH HIV-RELATED LIPOATROPHY Antiviral Therapy 2003; 8:L10 JP Bastard1,2, P Cervera1,2, V Jan1,2, M Maachi1,2, M Caron1,2, C Vigouroux1,2, H Vidal3, PM Girard1, P Levan1, W Rozenbaum1 and J Capeau1,2 We observed striking alterations in patients’ AT morphology as compared with controls: adipocytes of decreased size, increased apoptosis, increased stroma with fibrosis and vessels. Most of these alterations were related together. They were also related with altered differentiation. Moreover, IL-6 and TNF-α expression was increased in relation with altered differentiation and apoptosis. Since these two cytokines act at the level of AT through autocrine/paracrine mechanisms, these results argue for a deleterious role of AT cytokines not only in altered differentiation but also in increased apoptosis, which could be responsible for clinical lipoatrophy. |
| 10 | EFFECTS OF NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS ON DIFFERENTIATION, RESPONSE TO INSULIN AND APOPTOSIS IN CULTURED ADIPOCYTES Antiviral Therapy 2003; 8:L11 M Caron1, M Auclair1, M Kornprobst1 and J Capeau1,2 Three of the NRTIs (ABC, ddI and 3TC) did not modify adipose cell functions, while d4T and ZDV decreased cell lipid content and mildly increased apoptosis. ZDV also induced insulin resistance. These results indicated that the thymidine analogues d4T and ZDV, but not the other NRTIs, presented some adverse effects in cultured adipocytes. |
| 11 | ALTERED ADIPOCYTOKINE GENE EX-PRESSION IN MURINE 3T3-F442A ADIPOCYTES TREATED WITH PROTEASE INHIBITORS AND NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS Antiviral Therapy 2003; 8:L11 SP Jones, O Janneh, DJ Back and M Pirmohamed Our data suggest that the PIs ritonavir and saquinavir have potent effects in up-regulating TNF-α and IL-6 mRNA levels, whilst decreasing adiponectin levels. The co-administration of the PPAR agonist rosiglitazone was found to partially attenuate the increased expression of TNF-α, but not IL-6 or adiponectin. Our results suggest that the metabolic abnormalities associated with PI use are, at least partially, related to effects on adipocytokine gene expression. |
| 12 | A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF ROSIGLITAZONE FOR PATIENTS WITH HIV LIPODYSTROPHY Antiviral Therapy 2003; 8:L12 C Hadigan1, S Yawetz2, A Thomas3, F Havers1, PE Sax2 and S Grinspoon1 Thiazolidinediones may provide an important therapeutic benefit. Studies are needed to identify optimal dose, duration of treatment, subpopulations most likely to benefit and choice of specific thiazolidinedione to minimize effects on cholesterol. |
| Session IV Abstracts 13 through 16, pages L12 to L15 |
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| 13 | RATES OF CHANGE IN BODY COMPOSITION AMONG ANTIRETROVIRAL-NAÏVE HIV-INFECTED PATIENTS RANDOMIZED TO A DIDANOSINE/STAVUDINE VERSUS ABACAVIR/LAMIVUDINE CONTAINING REGIMEN IN THE FLEXIBLE INITIAL RETROVIRUS SUPPRESSIVE THERAPIES (FIRST) STUDY (CPCRA 058) Antiviral Therapy 2003; 8:L12 JC Shlay1, F Visnegarwala2, G Bartsch3, J Wang4, WM El-Sadr5, C Gibert6, D Kotler4, C Grunfeld7 and S Raghavan5, for the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) Using basic anthropometric measurements, we found a significant difference in the rate of change in BMI, body cell mass, total body fat, body circumferences and skinfolds for didanosine/stavudine versus abacavir/lamivudine. This data supports a significantly greater subcutaneous fat loss in both peripheral and central sites in the didanosine/stavudine arm compared to the abacavir/lamivudine arm among antiretroviral-naïve patients treated with their first antiretroviral regimen. |
| 14 | ATAZANAVIR AND EFAVIRENZ, EACH COMBINED WITH FIXED-DOSE ZIDOVUDINE AND LAMIVUDINE, HAVE SIMILAR EFFECTS ON BODY FAT DISTRIBUTION IN ANTIRETROVIRAL-NAÏVE PATIENTS: 48-WEEK RESULTS FROM THE METABOLIC SUBSTUDY OF BMS AI424-034 Antiviral Therapy 2003; 8:L13 JG Jemsek1, E Arathoon2, M Arlotti3, C Perez4, N Sosa5, V Pokrovskiy6, M Giordano7, A Thiry7 and M Soccodato7 Atazanavir and efavirenz produced comparable and proportional effects on body fat distribution at 48 weeks when administered with fixed-dose zidovudine and lamivudine to antiretroviral-naïve patients. The pattern of fat increase observed on both regimens was consistent with weight gain and not with the patterns for central adiposity (disproportionate increase in truncal fat) or lipoatrophy (loss of appendicular fat) associated with the development of lipodystrophy. |
| 15 | TRUNK FAT IS CONSERVED WITH PI-BASED HAART, BUT NOT WITH NON-PI-BASED HAART, IN HIV-INFECTED WOMEN IN THE USA: DEXA SUB-STUDY IN THE WOMEN'S INTERAGENCY HIV STUDY Antiviral Therapy 2003; 8:L14 K Mulligan1, K Anastos2, R Freeman3, JE Justman4, P Wichienkuer1, E Robison3 and N Hessol1 Consistent with reports in men, lower levels of peripheral (leg) fat are seen in HIV-infected women on HAART, despite the high prevalence of obesity in this population. Conservation of trunk fat appears to be unique to PI-containing HAART. |
| 16 | LONG-TERM CHANGES IN LIPODYSTROPHY AFTER SWITCHING FROM THYMIDINE NUCLEOSIDE ANALOGUES TO ABACAVIR Antiviral Therapy 2003; 8:L15 A Martin1, A Carr2, C Ringland1, J Amin1, C Workman3, J Freund1, J Hoy4, N Doong5, D Smith1 and DA Cooper1,2 for the MITOX Study Group Lipoatrophy continued to improve for 2 years after switching stavudine or zidovudine therapy to abacavir, although this was not clinically evident in the majority of patients. |
| Session V Abstracts 17 through 20, pages L15 to L20 |
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| 17 | ANTIRETROVIRAL THERAPY WITH DIDANOSINE, STAVUDINE AND ZALCITABINE IS ASSOCIATED WITH DEPLETION OF MITOCHONDRIAL DNA IN THE LIVER Antiviral Therapy 2003; 8:L15 UA Walker1, J Bauerle1, M Laguno2, J Murillas2, S Mauss3, G Schmutz3, B Setzer1, R Miquel2, JM Gatell2 and J Mallolas2 Current treatment with didanosine, stavudine or zalcitabine is associated with decreased mtDNA in liver irrespective of cirrhosis and inflammation. This may be an important, but not exclusive, factor contributing to hyperlactataemia. |
| 18 | SUBCUTANEOUS FAT TISSUE MITOCHONDRIAL DNA DEPLETION AND ADIPOSE TOXICITY ARE STRONGLY ASSOCIATED WITH NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR (NRTI) THERAPY IN HIV-INFECTED PATIENTS Antiviral Therapy 2003; 8:L16 E Hammond, D Nolan, E McKinnon, I James and S Mallal These data indicate that adipocyte mtDNA depletion and mitochondrial toxicity are prominent in subcutaneous fat samples obtained from NRTI-treated individuals, providing a pathophysiological basis for the observed effects of NRTI choice and duration on lipoatrophy risk. |
| 19 | URIDINE PREVENTS AND TREATS mtDNA DEPLETION BY NRTI PYRIMIDINE ANALOGUES AND FULLY RESTORES MITOCHONDRIAL FUNCTION Antiviral Therapy 2003; 8:L17 UA Walker1, E Koch2, N Venhoff1, H Klinker3, P Langmann3, M Zilly3, J Schneider2 and B Setzer1 Uridine fully abrogates mitochondrial toxicity by NRTI-pyrimidines in a preventive and therapeutic setting. Uridine does not appear to interfere with the antiretroviral efficacy of NRTIs. Protective levels of uridine can be achieved in humans with Mitocnol, a new dietary supplement. |
| 20 | EFFECTS OF ZIDOVUDINE AND STAVUDINE ON KETONE BODIES AND LIPIDS IN MICE: POSSIBLE ROLE OF β-AMINOISOBUTYRIC ACID, A CATABOLITE OF THYMINE Antiviral Therapy 2003; 8:L17 C Maisonneuve1, K Begriche1, A Igoudjil1, P Letteron1, M-C Guimont2, D Pessayre1 and B Fromenty1 Altogether, our results suggest that the effects of zidovudine, stavudine and BAIBA on body fat depend on the nutritional state and the genetic/metabolic background of the animals. These data also suggest that BAIBA may mediate some of the metabolic effects induced by zidovudine and stavudine. Several of these effects could be related to increased fatty acid oxidation, but other mechanism(s) cannot be ruled out. |
| Section VI Abstracts 21 through 24, pages L18 to L20 |
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| 21 | UPDATED EXPERIENCE OF ABACAVIR HYPERSENSITIVITY GENETIC TESTING WITHIN THE MAJOR HISTOCOMPATIBILITY COMPLEX: ADDRESSING DIAGNOSTIC PRECISION AND PREDICTIVE VALUE Antiviral Therapy 2003; 8:L18 A Martin1, D Nolan1, S Gaudieri1,2, C Almeida1, F Carvalho1, C Witt3, D Sayer3, R Nolan3, S Herrmann1, F Christiansen2 and S Mallal1 Presence of HLA-B*5701 is highly predictive of abacavir HSR in the Western Australian HIV Cohort, with evidence that an abacavir-specific Class I-restricted immune response may involve the concurrence of HLA-B*5701 and a second locus within the central MHC that is carried on the 57.1 extended haplotype. |
| 22 | HIGH INCIDENCE OF PRE-ECLAMPSIA IN HIV-INFECTED PREGNANT WOMEN RECEIVING ANTIRETROVIRAL THERAPY Antiviral Therapy 2003; 8:L19 A Suy, O Coll, M Lonca, E Martinez, A Milinkovic, JM Gatell and JA Vanrell An unexpected high rate of pre-eclampsia has been identified in HIV-infected pregnant women in the past 2 years. If this trend is confirmed by other investigators, it may lead to change current recommendations on pregnancy in HIV-infected women. Studies of risk factors are under way. |
| 23 | REDUCED BONE DENSITY IN HIV-INFECTED WOMEN Antiviral Therapy 2003; 8:L19 SE Dolan, JS Huang, KM Killilea, MP Sullivan, N Aliabadi and S Grinspoon HIV-infected women demonstrate reduced bone density in comparison to age- and BMImatched female subjects of similar weight and racial composition. Increased bone resorption and altered nutritional status, hormonal function and body composition may contribute to the observed reduction in bone density in HIV-infected women. Consideration should be given to testing bone density in HIV-infected women with significant risk factors for osteopenia. |
| 24 | SAFETY OF NON-NUCLEOSIDE REVERSE TRANSCRIPTASE THERAPY: DATA FROM THE EuroSIDA STUDY Antiviral Therapy 2003; 8:L20 N Friis-MØller, O Kirk, P Reiss, A Mocroft, C Katlama, A Horban, D Banhegyi, J Gatell, B Clotet, AN Phillips and JD Lundgren for the EuroSIDA Study Group Among patients initiating NNRTI, discontinuation of therapy was more frequently observed for nevirapine than for efavirenz. Toxicity was the predominant reason for early and failure for late discontinuation. Few cases of severe clinical liver failure were observed on either drug. The majority of fatal liver failures occurred in patients co-infected with hepatitis C and/or B. |
| Poster Presentations Adipocyte Biology Abstracts 25 through 32, pages L23 to L27 |
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| 25 | EFFECTS OF HIV PROTEASE INHIBITORS IN HUMAN ADIPOSE TISSUE DIFFERENTIATION – INVOLVEMENT OF MATRIX METALLOPROTEINASES Antiviral Therapy 2003; 8:L23 V Bourlier1, A Zakaroff-Girard1, C Pizzacalla1, V Durand de Saint Front1, J Galitzky1, M Lafontan1 and A Bouloumié-Diehl2 HIV PIs treatment led to the reduction of human adipocyte differentiation as was observed with the MMP inhibitor batimastat treatment. Although PIs did not affect directly the activity of MMPs, our results suggest that the inhibitory effect of PIs on human adipocyte differentiation might be mediated through the specific reduction of the adipocyte-derived expression and secretion of MMP-9. |
| 26 | THE ROLE OF TUMOUR NECROSIS FACTOR ALPHA AND ANTIRETROVIRALS IN ADIPOCYTE APOPTOSIS IN VITRO Antiviral Therapy 2003; 8:L23 P Domingo, F Vidal, S Veloso, MA Sambeat, J Sirvent, J Vendrell, X Matias-Guiu, C Richart and JC Domingo Our results suggest that TNF-α is the driving force in subcutaneous adipocyte apoptosis, which occurs in the setting of FRS in HIV-1-infected patients on highly active antiretroviral therapy. |
| 27 | PREVENTION OF PROTEASE INHIBITOR-INDUCED ADIPOCYTE CYTOTOXICITY BY POLYUNSATURATED FATTY ACIDS AS A MODEL OF TREATMENT OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY-INDUCED LIPODYSTROPHY Antiviral Therapy 2003; 8:L24 JC Domingo1, B Cordobilla1, F Villarroya1, M Giralt1, MA de Madariaga1 and P Domingo2 These results (protected under a patent application by PE Brudy, SL) suggest the concept that n-3 and n-6 PUFAs treatment could inhibit adipocyte PI-induced cytotoxicity by suppressing the expression of SREBP-1 as well as having a well established role as ligands for peroxisome proliferators activated receptors. This might open up a new aspect of nutritional therapy application involving PUFAs as inhibitors of PI-induced lipid abnormalities. |
| 28 | MODE OF UPTAKE, ACCUMULATION AND INTRACELLULAR DISPOSITION OF ZIDOVUDINE IN CULTURED 3T3-F442A PREADIPOCYTES Antiviral Therapy 2003; 8:L24 O Janneh1, PG Bray2, A Owen1, DJ Back1 and M Pirmohamed1 The uptake, accumulation and efflux of ZDV in 3T3-F442A cells were energy-dependent and pH-sensitive. P-gp is one of the efflux transporters that significantly reduced the intracellular accumulation of ZDV and its metabolites. While the overexpression of multidrug transporters on adipocytes may potentially reduce the accumulation of antiretrovirals in adipocytes, thus minimizing toxicity (such as lipodystrophy), it could accelerate the acquisition of viral resistance. Indeed, targeted inhibition of P-gp may overcome this problem. This work was supported by Research grant from Bristol-Myers Squibb Virology, USA. |
| 29 | EXPERIMENTAL CHRONIC INFLAMMATION OF LYMPH NODES INDUCES THE FORMATION OF MORE ADIPOCYTES IN CONTIGUOUS ADIPOSE TISSUE Antiviral Therapy 2003; 8:L25 CM Pond, CA Mattacks and D Sadler We conclude that chronic immune stimulation of lymphoid tissues induces lipolysis and the formation of more adipocytes in the adjacent adipose tissue. These findings are consistent with the hypothesis that perinodal adipocytes interact locally with lymphoid tissues, and suggest mechanisms for the selective hypertrophy of lymphoid-containing adipose depots in HARS. The formation of additional adipocytes may explain why HARS reverses very slowly during interruptions to antiviral therapy, often not at all. |
| 30 | GATA-2 AND GATA-3 GENES ARE INVOLVED IN HUMAN ADIPOCYTE DIFFERENTIATION AND THEIR EXPRESSION IS ALTERED BY PROTEASE INHIBITORS Antiviral Therapy 2003; 8:L26 A Riva1, S Ammannato1, B Zanone Poma1, P Fedeli1, D Mologni1, L Rovati2, D Foschi3 and M Galli1 Our data demonstrate that the regulation of GATA-2 and GATA-3 protein is essential to human preadipocyte–adipocyte transition. The differentiation of primary preadipocytes in HIV-infected patients and in healthy controls is associated with down-regulation of GATA-2 expression and up-regulation of GATA-3. Protease inhibitors impair adipocyte differentiation at an early step of adipocyte differentiation probably interfering with GATA-2 expression. |
| 31 | DIFFERENTIAL EFFECT OF HIV PROTEASE INHIBITORS ON ADIPOGENESIS: INTRACELLULAR RITONAVIR IS NOT SUFFICIENT TO INHIBIT DIFFERENTIATION Antiviral Therapy 2003; 8:L26 C Vernochet1, S Azoulay2, D Duval2, R Guedj2, G Ailhaud1 and C Dani1 We showed for the first time that ritonavir accumulates into preadipocytes and adipocytes, suggesting a direct effect on intracellular targets. However, intracellular accumulation was clearly not sufficient, as Ob1771 cells remained resistant to the inhibitory effect of ritonavir. |
| 32 | HIV DRUGS ENTER HUMAN ADIPOCYTES AND INHIBIT DIFFERENTIATION OF PRECURSOR CELLS Antiviral Therapy 2003; 8:L27 C Vernochet1, S Azoulay2, D Duval2, R Guedj2, AM Rodriguez1, G Ailhaud1 and C Dani1 In conclusion, ritonavir and nevirapine accumulate in human preadipocytes and adipocytes, but only a direct effect of ritonavir is observed. As adipose tissue contains both preadipocytes and adipocytes, our results are consistent with a direct effect of PIs, which could lead to the development of a lipodystrophic syndrome. |
| Cardiovascular Diseases Abstracts 33 through 40, pages L28 to L32 |
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| 33 | CLINICAL CHARACTERISTICS AND MID-TERM PROGNOSIS OF ACUTE CORONARY SYNDROME IN HIV-INFECTED PATIENTS ON ANTIRETROVIRAL THERAPY: A 3-YEAR FOLLOW-UP STUDY Antiviral Therapy 2003; 8:L28 F Boccara1, C Smadja1, L Djaouti1, O Belliard1, W Rozenbaum2 and A Cohen1 This preliminary report highlights the risk of ACS and related complications in HIV-infected patients and raises questions regarding the implication of antiretroviral treatment. In order to evaluate the relationship between antiretroviral treatment, HIV disease and incidence and prognosis of ACS in HIV-infected patients, controlled and prospective studies are required. |
| 34 | ARE CORONARY HEART DISEASE AND PERIPHERAL ARTERIAL DISEASE ASSOCIATED WITH TOBACCO OR CANNABIS CONSUMPTION IN HIV-INFECTED PATIENTS ON PROTEASE INHIBITOR ANTIRETROVIRAL REGIMENS? Antiviral Therapy 2003; 8:L28 G Chêne1, B Ranque2, R Lassalle1, L Cuzin3, S Herson4, G Le Moal5, X Duval2, J-M Chapplain6, J-M Ragnaud7 and F Raffi8 for the APROCO (ANRS EP11) Study Group These data suggest that ageing and smoking are important risk factors for cardiovascular morbidity but the overall rate remains low, comparable with other observational cohorts of patients treated by PI. Smoking cessation should seriously be considered in these patients and should be added to the guidelines of optimal clinical management of HIV infection. |
| 35 | PREDICTORS OF ATHEROSCLEROSIS AND ATHEROSCLEROTIC PROGRESSION IN PATIENTS WITH HIV: THE ROLE OF TRADITIONAL AND IMMUNOLOGICAL RISK FACTORS Antiviral Therapy 2003; 8:L29 P Hsue1, J Lo1, A Franklin2, AF Bolger1, B Millabas2, JN Martin1, SG Deeks1 and DD Waters1 Carotid IMT is higher in HIV patients than in age-matched controls and progresses more rapidly than in published reports of HIV negative cohorts. In HIV patients, carotid IMT was associated with classic coronary risk factors, and nadir CD4 ≤200. These data suggest that immunodeficiency, along with traditional cardiac risk factors, contributes to atherosclerosis in HIV-infected individuals. |
| 36 | PULSE PRESSURE: ANOTHER CARDIOVASCULAR RISK FACTOR IN HIV-INFECTED PATIENTS? TRANSVERSAL STUDY IN A COHORT FROM A SINGLE INSTITUTION Antiviral Therapy 2003; 8:L30 R Palacios, J Santos, J Ruiz, M González and M Márquez The prevalence of an elevated PP in HIV-infected patients is high. HAART and HMX HIVrisk are associated with a high PP. But, in the multivariate analysis only age and sex were significant. Prospective studies to analyse the influence of this factor on the cardiovascular risk of HIV-infected patients are needed. |
| 37 | ATHEROGENIC LIPID PROFILE AND CARDIOVASCULAR RISK FACTORS IN HIV-INFECTED PATIENTS (NETAR STUDY) Antiviral Therapy 2003; 8:L30 J Santos, R Palacios, M Gonzalez, J Ruiz and M Marquez Tobacco use was the most frequent RF. ALP was associated with male sex, PI use and sexual HIV transmission. A high CVR was related with a lower nadir CD4 and sexual HIV transmission. Although the current global CVR of our patients is not high, bearing in mind the contribution of highly active antiretroviral therapy (HAART)-associated factors to the lipid profile and the high prevalence of some RF, it may increase in the future. |
| 38 | RISK FACTORS FOR MYOCARDIAL INFARCTION IN HIV-POSITIVE PATIENTS Antiviral Therapy 2003; 8:L31 E Quiros Roldan, C Torti, F Moretti, P Nasta, S Casari, F Paranonfo, MC Uccelli, MA Forleo and G Carosi Our data show that in HIV-infected patients, the CD4 T-lymphocyte count seems to have a role in the occurrence of MI. Moreover, PI use does not seem to have any negative impact on MI. |
| 39 | MEASUREMENT OF CD36 EXPRESSION ON MONOCYTES OF LONG-TERM HIGHLY ACTIVE ANTIRETROVIRAL THERAPY-TREATED HIV PATIENTS Antiviral Therapy 2003; 8:L31 J Roeling1, K Wendlandt1, C Huber2, S Hillebrand1, R Gruber1, F-D Goebel1 and B Banas1 As already discussed in the literature, different CD36 expression is seen in macrophages and PBMCs. Our findings show that, in HAART-treated HIV patients, CD36 expression is reduced on patient monocytes. Decreased CD36 expression might lead to impaired cholesterol uptake causing increased serum cholesterol concentration. This in turn might enhance transformation of macrophages to foam cells. In contrast to mouse macrophages, we cannot see an influence of PI on human monocytes. Therefore, further in vitro experiments with HAART-treated macrophages studying the CD36 expression will be performed. |
| 40 | HIGH PREVALENCE OF HYPERTENSION IN HIV-INFECTED PATIENTS Antiviral Therapy 2003; 8:L32 J Santos, R Palacios, J Ruiz, M Gonzalez and M Marquez The prevalence of SH and DH in our HIV-infected patients is high. Both SH and DH are associated with classic risk factors. It is important to measure blood pressure in these patients periodically. Although we have not observed any relation between HIV infection and/or HAART and SH/DH, prospective studies with a better analysis of their influence on blood pressure are needed. |
| Insulin Resistance/Diabetes Abstracts 41 through 47, pages L32 to L36 |
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| 41 | INCRETIN HORMONE RESPONSE TO ORAL GLUCOSE IS PRESERVED IN LIPODYSTROPHIC HIV PATIENTS WITH IMPAIRED GLUCOSE TOLERANCE Antiviral Therapy 2003; 8:L32 O Andersen1, SB Haugaard1,2, JJ Holst3, J Iversen1, UB Andersen4, JO Nielsen1 and S Madsbad2 GLP-1 secretion was not impaired in IGT LIPO. On the contrary, in IGT LIPO the incremental GLP-1 response was increased compared with NGT NONLIPO, perhaps reflecting a compensatory response rather than explaining the IGT. |
| 42 | ONE YEAR METABOLIC AND MORPHOLOGICAL FOLLOW-UP OF HIV-NAÏVE PATIENTS WITH OR WITHOUT TREATMENT Antiviral Therapy 2003; 8:L33 M Bentata1, M Taverna2, R Mansouri1, F Rouges1, P Honore1 and G Reach1 One year of PI combination therapy leads to a significant increase in fasting blood glucose, W/H ratio and LDL cholesterol that are not observed in the non-PI group. This delay could be too short to demonstrate the occurrence of insulin resistance according to the standard indices used. During the follow-up of untreated patients, the increase in hip circumference and the decrease in HDL cholesterol may suggest a specific role for HIV. |
| 43 | INCIDENCE OF PRE-DIABETES AND DIABETES IN THE MULTICENTER AIDS COHORT STUDY Antiviral Therapy 2003; 8:L33 TT Brown1, SR Cole2, X Li2, LA Kingsley3, FJ Palella4, SA Riddler3, BR Visscher5, JB Margolick2 and AS Dobs1 HIV+ men, on HAART at baseline, appeared to develop pre-diabetes and diabetes at a higher rate than HIV- men, independent of age and BMI. Additional follow-up is needed to confirm these findings and to disentangle the particular therapy or combination of therapies contributing to this apparent increased diabetes risk. |
| 44 | ROLE OF ADIPOCYTOKINES AND BODY FAT DISTRIBUTION IN INSULIN RESISTANCE IN HIV INFECTION Antiviral Therapy 2003; 8:L34 H Khatami1, K Mulligan1, JC Lo1, A Kanaya1, D Abrams1, P Havel2 , V Tai1 , M da Silva1 and M Schambelan1 In this group of HIV-infected men, we found that higher levels of trunk fat and lower levels of appendicular fat were independently associated with IR. Leptin and adiponectin had independent and opposite effects on IR. When evaluated by logistic regression, only adiponectin significantly attenuated the associations between both trunk and limb fat and insulin resistance. |
| 45 | PLASMA IL-18 IS ELEVATED IN HIV-INFECTED PATIENTS WITH LIPODYSTROPHY Antiviral Therapy 2003; 8:L35 B Lindegaard1,2, A-B Eg Hansen1, J Gerstoft1 and B Klarlund Pedersen1,2 Plasma IL-18 concentration is associated to the lipodystrophy syndrome in HIV-positive patients. In contrast to patients without HIV, IL-18 was not associated to any metabolic parameters. |
| 46 | IN VITRO MECHANISMS INVOLVED IN AMELIORATION OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY-ASSOCIATED INSULIN RESISTANCE USING THE AYURVEDIC MEDICINAL PLANT, MOMORDICA CHARANTIA Antiviral Therapy 2003; 8:L35 PV Nerurkar1,2, L Pearson1, K Adeli3, JE Frank4, R Yanagihara1 and VR Nerurkar1 Our data therefore suggests that BMJ will ameliorate HAART-associated insulin resistance, specifically through the MAP kinase pathway. |
| 47 | ASSOCIATION OF HIV-PROTEASE INHIBITORS WITH INSULIN RESISTANCE IS RELATED TO POTENCY OF INHIBITION OF GLUT4 AND GLUT1 ACTIVITY IN ADIPOCYTES AND MYOCYTES Antiviral Therapy 2003; 8:L36 S Wang, R Mulvey, C Elosua, OP Flint and RA Parker Inhibition of glucose uptake varied among the PIs according to relative expression of the two major glucose transporters of fat and muscle, GLUT4 (insulin-responsive) and GLUT1. At concentrations near Cmax, indinavir strongly inhibited GLUT4 but not GLUT1, lopinavir and ritonavir moderately inhibited both GLUT4 and GLUT1, and nelfinavir, saquinavir and amprenavir weakly inhibited both isoforms. Atazanavir exhibited the least inhibition of both GLUT4 and GLUT1 in all the models. The data support the current hypothesis that direct GLUT inhibition by some PIs contributes to peripheral insulin resistance in highly active antiretroviral therapy (HAART). Since glucose uptake supplies precursors for adipocyte triglyceride synthesis, this mechanism could contribute to lipoatrophy. Together with the proteasome/ lipogenesis hypothesis, these data support atazanavir's favourable metabolic profile seen in the clinic. |
| Mitochondrial Disorders Abstracts 48 through 61, Pages L37 to L45 |
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| 48 | IS NUCLEOSIDE ANALOGUE-ASSOCIATED PERIPHERAL NEUROPATHY A CUMULATIVE TOXIC PROCESS? Antiviral Therapy 2003; 8:L37 A Arenas-Pinto, K Bhaskaran, D Dunn and IVD Weller We found no evidence of a cumulative toxicity in any of the study arms. Age and CD4 were independently associated with peripheral neuropathy. |
| 49 | DECLINED MITOCHONDRIAL DNA LEVELS IN PERIPHERAL BLOOD MONONUCLEAR CELLS DUE TO HIV INFECTION CAN FURTHER DECLINE OR RISE DEPENDING ON THE MITOCHONDRIAL TOXICITY OF THE USED ANTIVIRAL DRUG COMBINATION Antiviral Therapy 2003; 8:L37 M P de Baar1, I Dobbelaer1, EC Timmermans1, K Smolders1, M Casula2, M Buitelaar1, M Westrop1, B van Gemen1 and A de Ronde1 We conclude that measuring mtDNA levels in PBMCs is a powerful tool to assess and monitor the effects of HIV and antiviral drugs on the mitochondria. As HIV infection itself can cause mtDNA decline, the more toxic therapies will lead to a further decline of the mtDNA levels, possibly leading to severe adverse effects. The observed rise in mtDNA levels during therapy is probably due to recovery from HIV infection combined with less toxicity of the antiviral drug combinations itself. The consequences of these observations for the prediction on the development of adverse effects are being investigated in clinical studies. |
| 50 | EFFECTS OF THE TREATMENT BY NUCLEO-SIDE REVERSE TRANSCRIPTASE INHIBITORS ON MITOCHONDRIAL FUNCTION OF SUPERFICIAL AND DEEP ADIPOSE TISSUES OF RATS Antiviral Therapy 2003; 8:L38 C Deveaud, B Beauvoit and M Rigoulet Our working hypothesis is that higher sensitivity of superficial adipose tissue towards NRTIs is linked to its lower mitochondrial enzymatic equipment. Metabolic consequences of this higher sensitivity of superficial adipose tissue are now under investigation. |
| 51 | SYMPTOMATIC HYPERLACTATAEMIA IN HIV PATIENTS ON ANTIRETROVIRAL THERAPY: A CASE CONTROL STUDY Antiviral Therapy 2003; 8:L39 A Dos Santos, Y Gérard, Y Yazdanpanah, S Deuffic-Burban, F Ajana, X de la Tribonnière, P Choisy and Y Mouton Lactate monitoring should be evaluated in the presence of symptoms or such risk factors. This study also clarifies the respective role of each dual combination of nucleoside analogues in the occurrence of HL, among the most prescribed drugs. |
| 52 | MITOCHONDRIAL TOXICITY AUTHENTIFIED BY RESPIRATORY CHAIN DYSFUNCTION IN HIV-INFECTED PATIENTS TREATED BY NUCLEOSIDES WITH SYMPTOMATIC HYPERLACTATAEMIA Antiviral Therapy 2003; 8:L39 A Nguyen-Wartel1, C Goujard1,4, A Slama2, C Pinganaud1, M Tardieu3,4, JF Delfraissy1,4 and J Gasnault1,4 All patients presenting with symptomatic hyperlactataemia in our cohort, except one, had respiratory chain complex impairment in PBL by a direct method. Although the results for mtDNA are controversial, our results could sustain the hypothesis of a direct nucleoside mitochondrial toxicity. |
| 53 | DEFECTIVE MITOCHONDRIAL BIOGENESIS WITH ALTERED ADIPOSE TISSUE DIFFERENTIATION IN PATIENTS WITH HIV-RELATED LIPODYSTROPHY Antiviral Therapy 2003; 8:L40 C Jardel1, C Barthelemy2, V Jan3, JP Bastard3, S Chapin1, P Levan4, J Capeau3 and A Lombes2 Mitochondrial alteration with decreased mtDNA and defective mitochondrial biogenesis in addition to altered differentiation are present in lipoatrophic patients' adipose tissue. A synergistic effect of the diverse therapeutic compounds on adipose tissue differentiation, mitochondrial biogenesis and mtDNA maintenance is proposed. |
| 54 | DOES HIV INFECTION BY ITSELF HAVE ANY EFFECT ON MITOCHONDRIAL DNA CONTENT? Antiviral Therapy 2003; 8:L40 S López1, Ò Miró1, E Martínez2, E Pedrol3, A Beato1, E Deig3, JM Gatell2, J Casademont1 and F Cardellach1 We demonstrate that mtDNA depletion can be promoted by the proper HIV infection or concomitant conditions. Further investigations are necessary to elucidate the mechanisms implicated, although several hypotheses around the HIV infection-derived apoptotic processes induced by the mitochondrial pathway have been invoked. |
| 55 | EFFECTS OF SWITCHING TO A HIGHLY ACTIVE ANTIRETROVIRAL THERAPY REGIMEN CONTAINING TENOFOVIR ON DIVERSE MITOCHONDRIAL PARAMETERS Antiviral Therapy 2003; 8:L41 S López1, E Negredo2, O Miró1, L Ruiz2, B Clotet2, J Casademont1 and F Cardellach1 The switch to a HAART schedule containing tenofovir seems to be safe from the mitochondrial toxicity point of view. |
| 56 | A 13C-METHIONINE BREATH TEST DETECTS DRUG RELATED MITOCHONDRIAL TOXICITY IN HIV-INFECTED PATIENTS Antiviral Therapy 2003; 8:L41 L Milazzo1, O Sangaletti2, M Piazza1, M Moroni1 and A Riva1 13C-methionine breath test showed mitochondrial function impairment in asymptomatic antiretroviral treated HIV-positive patients and particularly in those with symptoms of drug-related mitochondrial toxicity. This non-invasive test can be used to monitor ART mitochondrial toxicity in vivo and to discover early and asymptomatic damage to the respiratory chain. |
| 57 | INCREASED APOPTOSIS IN SKELETAL MUSCLE, HIGHLY ACTIVE ANTIRETROVIRAL THERAPY AND LIPODYSTROPHY Antiviral Therapy 2003; 8:L42 O Miró1, S López1, J Fernández-Solá1, E Martínez2, E Pedrol3, A Milinkovic, J Casademont1 and JM Gatell2 Patients on HAART exhibit increased apoptosis in skeletal muscle, which seems to be greater in those patients developing LD. |
| 58 | TIME ON ANTIRETROVIRAL THERAPY AND MITOCHONDRIAL DNA CONTENT AND CYTOCHROME C OXIDASE ACTIVITY Antiviral Therapy 2003; 8:L43 O Miro1, S Lopez1, E Martinez2, E Pedrol3, J Casademont1 and F Cardellach1 Antiretroviral therapies are associated with both, mtDNA depletion and COX inhibition. The time receiving any NRTI, irrespective of the specific drug, seems to be the factor more closely related to such mitochondrial toxicities. |
| 59 | IMMUNOSUPPRESSIVE EFFECT OF MTDNA DEPLETION BY D-DRUGS IN HEALTHY HUMAN LYMPHOCYTES Antiviral Therapy 2003; 8:L43 B Setzer1, M Schlesier1, AK Thomas2 and UA Walker1 Didanosine and to a lesser extent zalcitabine, but not stavudine, mediate a time- and concentration-dependent mtDNA depletion in lymphocyte mitochondria (CD8 being more sensitive than CD4 lymphocytes), along with respiratory chain dysfunction and reduced proliferation after mitotic stimuli. The data indicate a potential immunosuppressive effect of d-drugs on healthy lymphocytes, to which reduced de novo synthesis of pyrimidines by a defect in the respiratory chain-dependent dihydroorotate dehydrogenase may contribute. |
| 60 | EFFECTS OF DIFFERENT ANTIRETROVIRAL TREATMENTS ON MITOCHONDRIAL DNA LEVELS IN PBMCs OF HIV-INFECTED PATIENTS Antiviral Therapy 2003; 8:L44 P Tebas, K Mondy, A De Ronde, E Rooj, MP de Baar, K Henry, W Powderly, S Claxton and KE Yarasheski mtDNA copy number increases to more normal levels with effective antiretroviral therapy. However, we found that therapy that effectively suppressed viral replication (stavudine + didanosine + indinavir ±hydroxyurea) resulted in a decline of mtDNA copy number per cell. Switches of the non-NRTI component of the regimen did not have an effect on mtDNA. The Primagen assay can be useful in monitoring mtDNA and mitochondrial toxicity in PBMCs. |
| 61 | THE EFFECT OF LONG-TERM STORAGE ON MEASURED PLASMA LACTATE CONCENTRATIONS. FURTHER RESULTS FROM ACTG STUDY A5099 Antiviral Therapy 2003; 8:L45 R Zackin1, D Kitch1, RG Gibson2, B Alston3, K Mulligan4, and MP Dubé2 Storage of NaF/KOx plasma of up to 24 months had no significant effect on lactate measurements. While clinically relevant shifts in population means did occur in POST samples at some early time-points, no obvious trends were observed. It is acceptable to handle samples in this manner for later analysis. |
| Lipid Disorders Abstracts 62 through 74, Pages L45 to L52 |
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| 62 | PHYSIOLOGICAL GROWTH HORMONE REPLACEMENT IMPROVES FASTING LIPID KINETICS IN PATIENTS WITH HIV LIPODYSTROPHY SYNDROME Antiviral Therapy 2003; 8:L45 J Shi, S D’Amico, K Rehman, M Maldonado, F Jahoor and A Balasubramanyam Physiological GH replacement improves fasting lipid kinetics and plasma free fatty acids concentrations in patients with HLS and GH deficiency. The lack of concomitant improvement in plasma triglyceride and total cholesterol levels suggests that additional interventions that target the defective lipid kinetics in the fed state may be required to normalize the abnormal lipoprotein patterns. Studies combining physiological GH replacement with isocaloric, low-fat diets are warranted. |
| 63 | MARKED IMPAIRMENT OF DIETARY TRIGLYCERIDE DISPOSAL CONTRIBUTES TO HYPERTRIGLYCERIDAEMIA IN HIV LIPODYSTROPHY SYNDROME Antiviral Therapy 2003; 8:L46 RV Sekhar, D Iyer, J Gaubatz, K Rehman, M Maldonado, HJ Pownall, F Visnegerwala, F Jahoor and A Balasubramanyam Patients with HLS have markedly impaired disposal of dietary triglyceride. Specifically, nonoxidative disposal of absorbed dietary triglyceride is severely restricted, leading to elevations in both chylomicron- triglyceride and VLDL-trigylceride plasma concentrations after consumption of a meal. These elevated levels persist even after an overnight fast. Thus, a severe defect in dietary triglyceride disposal contributes to the hypertriglyceridaemia associated with HIV lipodystrophy. |
| 64 | LIPID IMPROVEMENT WITH ATAZANAVIR THERAPY IN AN ANTIRETROVIRAL-EXPERIENCED POPULATION: EXPERIENCE IN THE ATAZANAVIR EARLY ACCESS PROGRAM Antiviral Therapy 2003; 8:L46 RB Corales1, C Coffey1, F Gordon1, SM Fine1, ML Christie1, KM Mang1, WM Valenti1, JF Maa2, G Thal2 and J Tudor2 In this site’s atazanavir EAP experience with 29 patients, atazanavir-based highly active antiretroviral therapy was efficacious and showed significant lipid benefits in antiretroviral-experienced patients who were failing previous highly active antiretroviral therapy and/or had dyslipidaemia. |
| 65 | EFFECT OF TENOFOVIR, ZIDOVUDINE, AND STAVUDINE ON ADIPOCYTE MITOCHONDRIAL DNA, VIABILITY AND LIPID METABOLISM Antiviral Therapy 2003; 8:L47 OP Flint, R Mulvey, C Elosua, S Wang and RA Parker Significant reductions in mtDNA were only observed following inhibition of adipocyte function (stavudine, tenofovir), or in the absence of any effect on adipocyte function (zidovudine). These results are not consistent with NRTI inhibition of mtDNA synthesis as a mechanism for the induction of lipoatrophy. Further, in contrast to reported results in undifferentiated, proliferating cells, mtDNA synthesis is impaired by moderate levels of tenofovir, but only by extremely high concentrations of stavudine or zidovudine in our fully differentiated adipocyte model. |
| 66 | INCREASES IN BLOOD CHOLESTEROL AND TRIGLYCERIDES AMONG PERSONS WITH HIV/AIDS ON HIGHLY ACTIVE ANTIRETROVIRAL THERAPY COMPARED WITH POPULATION NORMS Antiviral Therapy 2003; 8:L48 AR Levy1, U Iloeje2, RS Hogg1,3, L McCandless3, PR Harrigan3, J Mukherjee2, G Bondy3, B Yip3, MV O'Shaughnessy3 and JS Montaner3 One unintended effect of HAART is to raise harmful blood lipids relative to population norms. This effect seems to be greater on triglycerides than on cholesterol. Insofar as triglycerides may contribute to an increased risk for cardiovascular disease, steps should be taken to reduce triglycerides among persons using HAART. |
| 67 | LACK OF CORRELATION BETWEEN SREBF1 GENOTYPE AND HYPERLIPIDAEMIA IN HIGHLY ACTIVE ANTIRETROVIRAL THERAPY-TREATED INDIVIDUALS Antiviral Therapy 2003; 8:L48 DA Katz, A Yang, MS King, L Han, JD Isaacson, T Mueller, DR Grimm and SC Brun A smaller study previously suggested that variation in SREBF1 is predictive for hyperlipidaemia in HAART-treated HIV-positive patients, but these results were not confirmed in this larger, prospective trial. |
| 68 | TRANSCRIPTIONAL PROFILES SUPPORT PROTEASOME MODULATION HYPOTHESIS FOR LIPID DISTURBANCES OF CURRENT HIV-PROTEASE INHIBITORS AND LIPID NEUTRALITY OF ATAZANAVIR Antiviral Therapy 2003; 8:L49 RA Parker, WP Yang, S Wang, W Fenderson, R Mulvey, N Laing and OP Flint Results support the hypothesis that PIs dysregulate lipogenic pathways in adipose and liver through a common mechanism involving partial inhibition of proteasome activity, altering turnover of key nuclear transcription factors controlling lipogenic pathways, such as SREBPs. The impact on lipid metabolism differs for hepatocytes (increased lipid production) and adipocytes (diminished fat storage). This would promote hyperlipidaemia and lipoatrophy, and along with glucose transport inhibition contribute to insulin resistance. The data are consistent with the dyslipidaemia of several PIs and the favourable lipid profile of atazanavir in the clinic. |
| 69 | EFFECTS OF AN INDINAVIR/RITONAVIR-BASED DUAL PROTEASE INHIBITOR REGIMEN ON THE LIPID PROFILE OF HIV-INFECTED PATIENTS Antiviral Therapy 2003; 8:L49 H Wilson, S Rawlins, L Ma, R Petruschke and M Abramson We performed an exploratory analysis of changes in lipids among patients enrolled in studies of an indinavir/ritonavir regimen. |
| 70 | THE PREVALENCE OF HYPERLIPIDAEMIA IN PATIENTS CO-INFECTED WITH HEPATITIS C AND HIV Antiviral Therapy 2003; 8:L50 E Phillips, R Saskin and J Raboud Patients who were co-infected are less likely than non-co-infected HIV patients to have elevated cholesterol or triglyceride and hence have less exposure to lipid-lowering agents. The lower incidence of hyperlipidaemia in the co-infected group may relate in part to the degree of liver dysfunction and lower cumulative antiretroviral exposure. |
| 71 | RETROSPECTIVE ANALYSIS OF COST AND RESOURCE USE IN THE MANAGEMENT OF HIV-ASSOCIATED DYSLIPIDAEMIA Antiviral Therapy 2003; 8:L51 A Richter1, M Pladevall2, JE Lafata2, R Manjunath1, N Markowitz3, UH Iloeje4, W Irish1, H Xi2, J Simpkins2 and I Brar3 Dyslipidaemia has been presumed to have minimal impact on medical costs. However, our study shows that dyslipidaemia is associated with nonnegligible increases in overall medical costs for HIV patients. |
| 72 | IMPACT OF PROTEASE INHIBITOR THERAPY ON NUMBER OF CASES AND COSTS OF DYSLIPIDAEMIA IN HIV-INFECTED PATIENTS Antiviral Therapy 2003; 8:L51 A Richter1, W Irish1, JE Lafata2, M Pladevall2, LJ McQuay1, H Xi2, N Markowitz3, I Brar3, R Manjunath1, J Simpkins2, U Kumar3, MA Ramos3 and UH Iloeje4 PI usage is significantly associated with dyslipidaemia in HIV-infected patients. Patients with dyslipidaemia incur significantly greater costs even after controlling for duration of PI use. The incremental cost associated with dyslipidaemia was greater in PI users than non-PI users. |
| 73 | THE RELATIONSHIP BETWEEN FAT DISTRIBUTION AND VLDL AND IDL METABOLISM IN HIV-INFECTED ADULTS Antiviral Therapy 2003; 8:L52 S Das1, M Stolinski2, W Jefferson2, N Jackson2, G Gilleran1, M O’Connor1, R Cramb1, M Shahmanesh1 and M Umpleby2 Our result suggests that changes in body fat distribution are associated with alteration in VLDL and IDL apo-B clearance from plasma. |
| 74 | EFFECT OF SHORT-TERM ROSIGLITAZONE TREATMENT ON LIPID KINETICS IN PATIENTS WITH HIV LIPODYSTROPHY SYNDROME Antiviral Therapy 2003; 8:L52 F Visnegarwala, J Shi, S D'Amico, F Jahoor, K Rehman, K Ellis, M Maldonado and A Balasubramanyam Short-term treatment with rosiglitazone decreases lipolysis, a fundamental defect in HIV lipodystrophy in conjunction with favourable trends in the body composition measurements. |
| Body Composition Abstracts 75 through 103, Pages L53 to L70 |
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| 75 | REPRODUCIBILITY AND USE OF 3-D LASER SURFACE SCANS FOR THE ASSESSMENT OF FACIAL LIPOATROPHY Antiviral Therapy 2003; 8:L53 P Benn1, S Eccles2, C Ruff3, J Cartledge1, V Sauret3, A Copas4, A Linney3, IG Williams4 and SG Edwards1 3-D laser surface scans of the face are reproducible in patients with and without LA. This technique is able to detect significant volume change following an intervention and may provide an objective means of monitoring facial LA. Further longitudinal studies are needed. |
| 76 | STAVUDINE HAS AN EXCELLENT LONG-TERM SAFETY AND TOXICITY PROFILE WHEN USED AS A FIRST-LINE AGENT EARLIER IN DISEASE WITH HIGHER NADIR CD4 CELL COUNTS AND PERCENTAGES Antiviral Therapy 2003; 8:L54 P Greiger-Zanlungo1,2, G Blick2, Z Arzu1,2 and T Garton2 d4T has an excellent safety/toxicity profile with significantly less LD and PN when used as the first-line thymidine ARV earlier in HIV disease with higher nadir CD4% and CD4#>350. When used as a second-line ARV following AZT, LD was significantly increased and associated with lower nadir CD4% and # and HCV co-infection. |
| 77 | TOWARDS A RELIABLE DEFINITION OF HIV-LIPODYSTROPHY: A STUDY OF THE LIPODYSTROPHY QUESTIONNAIRE Antiviral Therapy 2003; 8:L54 RB Cavalcanti, J Raboud and S Walmsley These results suggest that there is at best moderate agreement between ratings of lipodystrophy for individual items of the LQ, both when comparing physician ratings with self-reports and when assessing inter-physician agreement. This implies that, as a measure of HIV-LD, individual components of the LQ have sub-optimal reliability. When testing the standard used in the Case Definition Study we found modest agreement between physicians, suggesting fair reliability. Detailed scoring instructions for raters may improve reliability of the LQ. |
| 78 | SIGNIFICANT CORRELATION BETWEEN LOW NADIR CD4 AND THE INCIDENCE OF FAT WASTING BUT NOT LIPODYSTROPHY WITHOUT FAT WASTING Antiviral Therapy 2003; 8:L55 CM Dezii1, KA Lichtenstein2, J Maa1 and SL Hodder1 These data suggest a significant association between lower nadir CD4, lower nadir BMI and white race with the incidence of fat wasting. Low CD4 nadir was not associated with lipodystrophy without fat wasting. Individuals in whom antiretroviral therapy is instituted at higher CD4 counts may exhibit a lower incidence of lipodystrophy. |
| 79 | DEXA-DERIVED LIPODYSTROPHY INDEX: AN OBJECTIVE MEASURE OF ALTERED FAT MASS IN HIV-POSITIVE PATIENTS ON HIGHLY ACTIVE ANTIRETROVIRAL THERAPY Antiviral Therapy 2003; 8:L56 J Falutz and L Rosenthall As recently reported, we also found that loss of FM was the predominant body composition change in patients with features of HAL. Determination of easily obtained, objectively derived, imaging based measures incorporating alterations in regional FM accurately identifies the majority of patients with perceived body shape changes. Further studies are required to define the optimal derived measurement and its role in studying the lipodystrophy syndromes. |
| 80 | AUTOLOGOUS FAT TRANSFER FOR TREATING FACIAL WASTING IN HIV-RELATED LIPODYSTROPHY: EXPERIENCE OF 53 TREATED PATIENTS Antiviral Therapy 2003; 8:L56 G Guaraldi1, D De Fazio2, R Rondina3, G Orlando1, R Murri4, A Grisotti2, G Nardini1, M Callegari2, I De Lorenzi2, M Blini2, M Pecorari1, B Beghetto1, R Covezzi1, R Esposito1 and A Wu5 Our results showed that autologous fat transplant is effective and durable both evaluated with objective measures and with subjective evaluations. ABCD and Beck depression scale are a useful tool to identify patients who may benefit from surgery. |
| 81 | FAT ACCUMULATION OF THE CHEEKS AFTER AUTOLOGOUS FAT TRANSFER FOR TREATING FACIAL WASTING IN HIV-RELATED LIPODYSTROPHY Antiviral Therapy 2003; 8:L57 G Guaraldi1, D De Fazio2, G Orlando1, R Murri3, A Wu4 and R Esposito1 Our observations suggest that fat atrophy or hypertrophy is unlikely to depend only on paracrine factors, such as cytokine signals. In fact, paracrine factors were present in the body site in which alteration appeared, but relapse occurred in a different area. Adipocyte receptors and mitochondrial toxicity-related mechanisms may explain the present findings: receptor expression as well as mtDNA may be transferred from the donor to the recipient site, remaining sensitive to the same lipohypertrophy determinants. Another, not mutually exclusive hypothesis, is that cheeks lipohypertrophy may be the result of expansion of brown fat transferred with the intervention. The clinical implication is that when autologous fat transplant is chosen for face atrophy treatment, the preferred subcutaneous adipose graft site should be abdomen or groin. |
| 82 | BREAST ENLARGEMENT IN MALE HIV-INFECTED PATIENTS Antiviral Therapy 2003; 8:L57 M Garcia1, E Martinez1, P Domingo2, JL Blanco1, A Biglia1, A Milinkovic1, A Leon1, M Lonca1, M Laguno1, J Mallolas1 and JM Gatell1 Breast enlargement in HIV-infected patients is a rare condition. It is an heterogeneous entity with different clinical and laboratory characteristics. Although spontaneous improvement may occur, withdrawal of potentially implicated drugs and testosterone therapy may be useful therapeutic options. |
| 83 | LACK OF BENEFIT IN LIPODYSTROPHY AFTER REPLACING PROTEASE INHIBITORS BY NON-NUCLEOSIDES: 48 WEEKS RESULTS IN A PROSPECTIVE TRIAL Antiviral Therapy 2003; 8:L58 T García-Benayas1, F Blanco1, J De la Cruz2, V Soriano1 and J González-Lahoz1 Replacement of PI by NNA does not improve LD body-shape changes assessed by anthropometry measurements after a 12 month follow-up period. Moreover, worsening in limbs peripheral lipoatrophy may occur, most likely reflecting the involvement of nucleoside analogues through mitochondrial toxicity of subcutaneous fat. |
| 84 | RECOMBINANT HUMAN GROWTH HORMONE ENHANCES PATIENT-REPORTED BODY IMAGE AND IMPROVES QUALITY OF LIFE IN HIV-ASSOCIATED ADIPOSE REDISTRIBUTION SYNDROME Antiviral Therapy 2003; 8:L59 DP Kotler1, R Turner2, M Su3, M Testa3, M Thompson4, J Gertner5 and N Muurahainen5 on behalf of the STARS Trial Investigator Group Treatment with rhGH significantly reduced VAT and improved body image, psychological distress and overall QOL. Reversals following drug reassignment further established the link between HARS and patient-reported outcomes. |
| 85 | PSYCHOMETRIC PROPERTIES OF A LIPODYSTROPHY SCALE Antiviral Therapy 2003; 8:L59 D Lee, P Patel, J Epp, SM Basinger, WC Mathews and E Barber The patient and clinician self-administered Owen Clinic LD scale was found to be highly reliable and useful in the assessment of LD. Our data suggests that the evaluation of LD should be multidimensional and that three different scales should be used independently to evaluate fat loss, fat accumulation and retinoid effects often associated with LD. |
| 86 | ANTHROPOMETRIC ASSESSEMENT AND FOLLOW-UP OF LIPODYSTROPHY IN HIV-INFECTED CHILDREN Antiviral Therapy 2003; 8:L60 M Beregszaszi1, S Blanche2, C Dollfus3, M Levine4, S Deghmoun1, N Bellal2, JL Bresson6, D Chevenne5, R Hankard7, M Houang3 and C Levy-Marchal1 LPD develops in HIV-infected children and measures of skinfold thickness may be very contributive to objectively assess LPD. LPD was not significantly associated with metabolic disturbances in children. Over 1 year the different features of LPD and metabolic disturbances were fairly stable, indicating that, once developed, these complications are not very rapidly progressive. |
| 87 | STRONG ASSOCIATION BETWEEN BUFFALO HUMP AND HIGH SERUM INSULIN CONCENTRATIONS IN HIV-INFECTED INDIVIDUALS Antiviral Therapy 2003; 8:L61 PWG Mallon1,2, H Wand1, M Law1, J Miller3, DA Cooper1,2 and A Carr2 These results suggest an association between BH and antiretroviral therapy with this subgroup of patients at higher risk for hypertension and hyperinsulinaemia. |
| 88 | IMPACT OF STRUCTURED THERAPY INTERRUPTION ON BODY COMPOSITION OF CHRONICALLY HIV-INFECTED PATIENTS: PRELIMINARY 1-YEAR RESULTS Antiviral Therapy 2003; 8:L61 A Milinkovic, E Martinez, S Vidal, JL Blanco, M Lonca, F Garcia, J Fernandez, A Cruceta, A Leon, M Laguno, J Mallolas, JA Arnaiz, F Pons and JM Gatell Interruption of antiretroviral therapy for at least 6 months had a positive impact on body composition in a population of patients with good control of HIV infection. The impact on body fat was more obvious in patients with lipoatrophy. |
| 89 | COMPUTERIZED TOMOGRAPHY FINDINGS OF FACIAL LIPOATROPHY IN HIV-INFECTED PATIENTS Antiviral Therapy 2003; 8:L61 J Berenguer, T Pujol, A Tomaselo, J Fontdevila, A Milinkovic and E Martinez Facial lipodystrophy in HIV-infected patients affects predominantly the superficial facial soft tissues instead of the buccal fat pat. |
| 90 | IMPROVEMENTS IN DEXA AND CT SCAN VALUES AFTER A SWITCH FROM STAVUDINE TO ABACAVIR OR ZIDOVUDINE DO NOT CORRELATE WITH ANTHROPOMETRIC MEASUREMENTS AT 48 WEEKS Antiviral Therapy 2003; 8:L62-L63 G McComsey1, V Williams2, D Ward3, T File4, T Lonergan5, P Shalit6, R Fisher2 and J Hernandez2, for the TARHEEL Study Team. Subjects with LA showed progressive gains in body fat by DEXA and CT scan through week 48 when stavudine was replaced with either abacavir or zidovudine. There was little or no correlation between DEXA or CT scan changes and anthropometric measurements, suggesting that more sensitive methods than anthropometric measurements are needed to quantify changes in fat in patients with LA. |
| 91 | PROSPECTIVE ASSESSMENT OF BODY COMPOSITION IN ANTIRETROVIRAL-NAÏVE HIV-INFECTED ADULTS STARTING ANTIRETROVIRAL THERAPY Antiviral Therapy 2003; 8:L63 A Milinkovic1, S Vidal1, L Bianchi1, C Ayuso1, P Domingo2, M Gomila2, JM Gatell1 and E Martinez1 Slight fat increases and fat-free mass decreases were observed in this cohort after 1 year of antiretroviral therapy. Several baseline and drug factors were associated with a higher impact on body composition. |
| 92 | COMPARATIVE ASSESSMENT OF OBJECTIVE METHODS FOR THE MEASUREMENT OF BODY FAT Antiviral Therapy 2003; 8:L63 A Milinkovic1, S Vidal1, L Bianchi1, C Ayuso1, P Domingo2, M Gomila2, JM Gatell1 and E Martinez1 In general, techniques measuring similar compartments were fairly well correlated. CT scan and DEXA were the techniques more correlated for the measurement of abdominal fat. |
| 93 | RECOMBINANT HUMAN GROWTH HORMONE EFFECTS ON BODY COMPOSITION OF HIV WASTING PATIENTS IN THE HIGHLY ACTIVE ANTIRETROVIRAL THERAPY ERA Antiviral Therapy 2003; 8:L64 D Kotler1, J Gertner2, E Daar3, JC Melchior4, G Moyle5, F O'Brien2 and E Svanberg6 r-hGH (Serostim®), 6 mg DD was superior to 6 mg AD on body weight and body composition of HIV wasting patients in the HAART era. 6 mg AD was slightly better tolerated than 6 mg DD. |
| 94 | LIMB FAT MASS AT BASELINE IS NOT ASSOCIATED WITH BASAL OR GROWTH HORMONE-STIMULATED GAINS IN PHYSICAL WORK OUTPUT IN HIV-ASSOCIATED WASTING Antiviral Therapy 2003; 8:L65 GJ Moyle, F O’ Brien, E Svanberg and JM Gertner These data do not support the hypothesis that mitochondrial damage might constitute a common aetiology underlying reduced PF and poor muscular function in HIV-associated weight loss and peripheral fat wasting. |
| 95 | LONGITUDINAL EFFECTS ON SUBCUTANEOUS FAT MASS OF INITIATING OR SWITCHING STAVUDINE- AND ZIDOVUDINE-BASED ANTIRETROVIRAL THERAPY Antiviral Therapy 2003; 8:L65 I James, D Nolan, E Hammond, E McKinnon and S Mallal Choice of d4T versus AZT in the first HAART regimen, and in subsequent switching strategies, is associated with differential effects on fat wasting over time. These drug-specific effects may manifest through NRTI-associated mitochondrial DNA depletion and adipose tissue mitochondrial toxicity. |
| 96 | ASSOCIATION BETWEEN HIV DISEASE CHARACTERISTICS WITH TOTAL AND REGIONAL BODY COMPOSITION LEVELS IN ANTIRETROVIRAL-NAÏVE MEN AND WOMEN Antiviral Therapy 2003; 8:L66 S Raghavan1, C Mullin2, G Bartsch2, J Wang3, D Kotler3, J Shlay4, C Gibert5, C Grunfeld6 and A Carr7 (CPCRA) Prior AIDS is associated with lower subcutaneous fat levels in central and peripheral regions in both men and women except for abdominal skinfolds and waist fat area in men. Women tend to experience greater changes than men with specific reference to body mass index, total body fat and subcutaneous fat levels, where as men tend to experience greater difference in body cell mass in association with prior AIDS. |
| 97 | IS LIPODYSTROPHY ASSOCIATED TO POORER QUALITY OF LIFE IN HIV-1-INFECTED PATIENTS? Antiviral Therapy 2003; 8:L66 A Rousaud1, J Blanch2, E Martínez3, E De Lazzari4, J-M Peri2, A Milinkovic3, J-L Blanco3 and J-M Gatell3 We did not find differences in overall QoL between patients according the presence or not of lipodystrophy. However, we noted that some patient-related characteristics were associated with a greater impact on QoL. |
| 98 | SHORT-TERM EFFECT OF BASELINE CD4 AND HIV-1 RNA ON LEAN BODY MASS GAIN FOLLOWING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY Antiviral Therapy 2003; 8:L67 CM Shikuma1, R Zackin2, D Mildvan3, F Sattler4, P Nyangweso2 and K Mulligan5 for the ACTG 892 Team In this large group of subjects, initiation of HAART was associated with only modest gains in weight and LBM, with the greatest increases occurring in subjects who showed greater degrees of immunological and virological compromise at baseline. LBM gain was associated with improved functional performance. |
| 99 | RISK FACTORS FOR BODY FAT COMPOSITION CHANGES IN PATIENTS TREATED WITH LOPINAVIR/RITONAVIR OR NELFINAVIR Antiviral Therapy 2003; 8:L68 B da Silva, M King, P Cernohous, C Kelly, R Tressler and S Brun Through 96 weeks, no difference in rates of body fat changes was observed in pts treated with LPV/r (15%) or NFV (14%). Fat loss was the most common event, but 95% of pts in the analysis received d4T, which has been associated with this event. BL glucose, race, gender and alcohol use were significant risk factors for fat redistribution, but on-treatment lipid and glucose elevations were not, suggesting pretreatment metabolic disorders may play a role in body composition changes. |
| 100 | BODY SHAPE ABNORMALITIES IN HIV-INFECTED PATIENTS AND ANTIRETROVIRAL TREATMENT: ARE DRUGS ASSOCIATED? Antiviral Therapy 2003; 8:L68 M Torralba1, S Azriel2, R Rubio1, L Tamargo1, V Moreno1, F Pulido1, G Martínez2 and F Hawkins2 Lipodystrophy is a complication occurring frequently in our cohort, which follows similar patterns to those described in other series. In this study, length of treatment, age and treatment with d4T are independent factors for lipodystrophy development, but not therapy with PI. |
| 101 | EFFECT OF RECOMBINANT HUMAN GROWTH HORMONE ON THE ACTIVITY OF ANTIRETROVIRAL AGENTS AGAINST WILD-TYPE AND RESISTANT HIV-1 Antiviral Therapy 2003; 8:L69 MA Wainberg1, BG Brenner1, JM Gertner2, S Kenley2 and C Olivier3 r-hGH did not affect the anti-HIV effects of commonly used antiretroviral drugs in PMBCs. These tissue culture data support the hypothesis that the use of r-hGH in HIV-infected people who are undergoing active antiretroviral therapy does not promote viral replication. |
| 102 | PROSPECTIVE EVALUATION OF LEPTIN AND ADIPONECTIN LEVELS IN HIV-INFECTED PATIENTS INITIATING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY Antiviral Therapy 2003; 8:L69 SL Walmsley, A Foster, R. Calvacanti, K Logue, A Azad, A Cheung and J Raboud Log leptin levels are highly correlated with BMI and regional fat and decrease in association with peripheral fat loss. Leptin levels are increased in pts with elevated TG independent of ARV. The changes in leptin levels with fat loss and metabolic changes could be either the consequence or the cause of the abnormalities. |
| 103 | Abstract withdrawn |
| Clinical Management of ADRs Abstracts 104 through 117, Pages L70 to L78 |
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| 104 | EVALUATION OF DIARRHOEA IN PATIENTS AFTER SUBSTITUTION OF NELFINAVIR WITH LOPINAVIR/RITONAVIR Antiviral Therapy 2003; 8:L70 E Bargman1, R Rode2, SL Green3, BM Rodwick4, R Eng5, G Levy Hara6, P Gargalianos-Kakolyri7, V Boix8, Y Shen2, MP Luo2, J Sylte2 and R Tressler2 for the M00-267 (PLATO) Study Group Subsitution of nelfinavir with LPV/r resulted in a decrease or resolution of diarrhoea, and improved tolerability (ASDM) and QOL (MOS-HIV), while maintaining or improving viral control. No new onset SE was reported by ≥5% of patients. |
| 105 | DIETARY SUPPLEMENTATION WITH PROBIOTICS, SOLUBLE FIBRE AND L-GLUTAMINE REDUCES DIARRHOEA IN HIV+ MEN RECEIVING NELFINAVIR OR LOPINAVIR/RITONAVIR Antiviral Therapy 2003; 8:L71 CR Heiser1, JT Barrett2, JA Ernst3, N French4, R Slotten4, T Klein4, R McAllister2, M Russert5 and GJ Kelliher6 Probiotics, soluble fibre and L-glutamine significantly reduce diarrhoea for subjects receiving nelfinavir or lopinavir/ritonavir. Improvement was seen in subjects who were not controlling diarrhoea with loperamide alone. Dietary methods to treat HIV diarrhoea are effective and clinically significant. |
| 106 | EVALUATION OF SIDE EFFECTS IN PATIENTS AFTER SUBSTITUTION OF THEIR PROTEASE INHIBITOR/NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR WITH LOPINAVIR/RITONAVIR Antiviral Therapy 2003; 8:L71 D Bassetti1, Y Shen2, AR Minguez3, RW Presnell4, M Mogyoros5, R Scott6, MT Bloch7, C Dominguez8, A Rubin2, R Rode2, MP Luo2 and R Tressler2 for the M00-267 (PLATO) Study Group SE observed at baseline were consistent with the known safety profiles for the baseline PI/NNRTI. Approximately 80% of patients who substituted their PI/NNRTI with lopinavir/ritonavir experienced improvement in their primary SE, while maintaining or improving viral control. Diarrhoea was the only new onset symptom reported by ≥5% of patients. |
| 107 | EVALUATION OF COLEMAN’S LIPOSTRUCTURE FOR TREATMENT OF FACIAL LIPODYSTROPHY IN HIV PATIENTS RECEIVING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY Antiviral Therapy 2003; 8:L72 M Burnouf1, M Buffet1, M Schwarzinger2, P Roman1, M Prevot1, P Bui1, I Gorin1, N Franck1 and N Dupin1 This 1-year evaluation of the impact of Coleman’s lipostructure for correction of facial lipodystrophy in HIV-infected patients proved the good efficiency of this treatment when measured conservatively by agreement on improvement by three independent specialists and demonstrates satisfaction in 93% of patients. |
| 108 | IMPACT OF ADIPONECTIN, C-REACTIVE PROTEIN AND LEPTIN ON THE HIV LIPODYSTROPHY CASE DEFINITION Antiviral Therapy 2003; 8:L73 R Puls1, ML Munier1, K McGhie2, I Chadborn1, S Emery1, AD Kelleher1,2, M Law1 and A Carr2 for the HIV Lipodystrophy Case Definition Study Group ADP and C-RP, but not leptin, levels were altered in a diverse sample of patients with LD. ADP could be included in both the primary LDCD, as well as a non-imaging LDCD, but the accuracy of neither CD was improved. ADP could not substitute for DEXA and CT-derived imaging data in the primary LDCD. |
| 109 | SATISFACTION AND OUTCOMES OF PATIENTS ATTENDING A MULTI-DISCIPLINARY LIPODYSTROPHY/METABOLIC CLINIC Antiviral Therapy 2003; 8:L73 G Frize1, K Gibson2, G Scullard1, C de Souza1 and A Hughes1 Very high rates of satisfaction with the clinic were reported along with high rates of sustained behavioural changes in diet and exercise and perceived improvements in managing lipodystrophy. This provides evidence that the multidisciplinary approach is very effective in reducing the impact of lipodystrophy. |
| 110 | ATTITUDES AND PERCEPTIONS OF PATIENTS WITH FACIAL LIPOATROPHY BEFORE AND AFTER INTERVENTION USING POLYLACTIC ACID Antiviral Therapy 2003; 8:L74 G Frize, A Hughes, G Scullard, N Hanna and C de Souza High levels of reported distress and concerns over the impact of facial changes are present in these participants. The intervention was viewed optimistically and participants believed it would reduce psychological distress. Satisfaction with the intervention was high with the majority of patients perceiving it as the most effective intervention for this problem. |
| 111 | APPROPRIATE INCREASE IN IGF-I AND IGFBP3 DURING GH TREATMENT IN HIV-POSITIVE SUBJECTS WITH WASTING AND LIPOHYPERTROPHY Antiviral Therapy 2003; 8:L74 JM Gertner1, D Bock1, N Muurahainen1, F O’Brien1 and E Svanberg2 Endogenous growth hormone (GH) secretion and the response of the GH/insulin-like growth factor (IGF) axis to exogenous GH in HIV/AIDS vary considerably. |
| 112 | MECHANICAL AND ULTRASOUND-ASSISTED LIPOSUCTION FOR TREATING SUBCUTANEOUS FAT ACCUMULATIONS IN HIV-RELATED LIPODYSTROPHY: EXPERIENCE OF 33 TREATED PATIENTS Antiviral Therapy 2003; 8:L75 G Guaraldi1, D De Fazio2, G Orlando1, R Murri3, A Grisotti2, G Nardini1, M Callegari2, I De Lorenzi2, M Blini2, M Pecorari1, B Beghetto1, R Covezzi1, R Esposito1 and A Wu4 Our results showed that all the mentioned surgical procedures were safe. Different techniques are necessary according to the content of fibrous material present in the context of lipomas. A high number of relapse was present and evident in cases of no exposure to protease inhibitors after surgery also. Patient satisfaction was good after surgery but reintervention is needed in the majority of the cases. |
| 113 | TREATMENT OF FACIAL LIPOATROPHY BY INJECTION OF AUTOLOGOUS ADIPOSE TISSUE Antiviral Therapy 2003; 8:L76 J Fontdevila, A Milinkovic, E Martinez, T Sik Yoon, JM Gatell and JM Serra Autologous fat injection is a satisfactory and affordable option to treat facial lipoatrophy if enough subcutaneous fat exists. The effectiveness of the technique seems to be higher in females. Long-term follow-up is needed to assess the potential risk of fat reabsorption. |
| 114 | ATORVASTATIN AND PRAVASTATIN FOR HYPERCHOLESTEROLAEMIA IN HIV-POSITIVE PATIENTS RECEIVING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY Antiviral Therapy 2003; 8:L76 NP Smith, MR Nelson, GJ Moyle and BG Gazzard Both A and P decrease serum cholesterol in HIV-positive patients receiving HAART. The effects are similar. There was no clear difference in effect on PI-containing regimes as compared to non-PI regimes between treatment groups. |
| 115 | ROSIGLITAZONE TREATMENT OF HIV-ASSOCIATED LIPODYSTROPHY SYNDROME: IMPACT ON THE BIOAVAILABILITY OF ANTIRETROVIRAL COMPOUNDS Antiviral Therapy 2003; 8:L77 M Oette1, K Göbels1, M Kurowski2, A Kroidl1, T Feldt1, M Wettstein1 and D Häussinger1 Treatment with 4 mg of RSG for combined LDS is likely to reduce the bioavailability of nevirapine. Thus, routine therapeutic drug monitoring is recommended for patients treated with nevirapine and RSG to avoid sub-optimal drug levels of ARV. RSG can be safely co-administered in patients on a therapy consisting of efavirenz, ritonavir-boosted lopinavir or nelfinavir. Due to singular measurement, no recommendation can be given for saquinavir. No serious adverse event was seen under RSG co-medication in a dosage of 4 mg. |
| 116 | INCREASED BIOAVAILABILITY OF NELFINAVIR 625 MG TABLET AND THE POTENTIAL IMPACT ON ADVERSE EXPERIENCES Antiviral Therapy 2003; 8:L77 P Hsyu, C Petersen, E Pun and E Daniels At steady state, the 625 mg tablet of NFV produces higher systemic concentrations and appears to have better bioavailability than the 250 mg tablet. NFV concentrations in the AUC group >61 mg.h/l (containing NFV levels comparable to those achieved with the 625 mg tablet) did not result in unexpected AEs or clinical lab changes. The impact on efficacy of increased NFV concentrations achieved using the 625 mg tablet is under investigation. |
| 117 | LIPOATROPHY SEVERITY INDEX: A QUANTITATIVE SCORE FOR FACIAL ATROPHY TO EVALUATE TREATMENT WITH POLYMETHYLMETHACRYLATE Antiviral Therapy 2003; 8:L78 MS Serra and LKM Oyafuso LASI seems to be a good tool for estimating the magnitude of facial lipoatrophy, as well as for evaluating the treatment response among persons submitted to facial implants. This index seems to be helpful for comparing different techniques and products used for treatment of facial lipoatrophy and should be applied in different settings by other researchers. |
| Cohort Studies Abstracts 118 through 125, Pages L78 to L82 |
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| 118 | FACTORS ASSOCIATED WITH SELF-REPORTED ADVERSE EVENTS THAT HAVE A HIGH OR VERY HIGH IMPACT ON EVERY DAY LIFE Antiviral Therapy 2003; 8:L78 E Guitton1 and E Trenado2 Further studies are needed to confirm these results and eventually to try to understand why women and persons out of work are at higher risk to declare some adverse events to have a high or very high impact on every day life. |
| 119 | IMPROVEMENT IN LIPID LEVELS IN ANTIRETROVIRAL- EXPERIENCED HIV-INFECTED PATIENTS WHO ARE FAILING THERAPY AND ARE SWITCHED TO AN ATAZANAVIR-CONTAINING REGIMEN Antiviral Therapy 2003; 8:L79 K Lichtenstein1, N Clumeck2, N Bellos3, C Rodriguez4, V Estrada5, K Gialelis6, S Sankoh7 and E Ledesma8 In ARV-experienced patients who failed prior PI-containing regimens, treatment with atazanavir, or atazanavir in combination with ritonavir or saquinavir, plus NRTIs, is associated with a more favourable lipid profile than lopinavir/ritonavir plus NRTIs, with a reduced need for lipid-lowering therapy. Atazanavir is an option for ARV-experienced patients for whom PI therapy is desirable and hyperlipidaemia-associated cardiovascular risk is a consideration. |
| 120 | A PROSPECTIVE COHORT STUDY ON THE RISK OF LIPODYSTROPHY IN HIV-1- INFECTED PATIENTS TREATED WITH HIGHLY ACTIVE ANTIRETROVIRAL THERAPY NOT CONTAINING PROTEASE INHIBITORS Antiviral Therapy 2003; 8:L80 E Martinez1, L Bailey2, A Milinkovic1, JL Blanco1, M Lonca1, M Laguno1, A Leon1, J Mallolas1, AN Phillips2 and JM Gatell1 The risk factors associated with the development of lipodystrophy in ART-naïve HIV-1-infected patients who are treated with PI-sparing regimens are complex. Of all variables investigated in these analyses that can be identified before they start therapy, age and triglyceride level emerged as strong predictors of lipodystrophy. There was also some evidence that stavudine might also be involved in the development of lipodystrophy. This information may help clinicians to tailor regimens to those who indicate an increased susceptibility to the development of this unpleasant side-effect as a result of older age or abnormal triglyceride concentrations at baseline. |
| 121 | RISK OF METABOLIC ABNORMALITIES IN HIV-INFECTED PATIENTS STARTING LOPINAVIR-RITONAVIR CONTAINING ANTIRETROVIRAL THERAPY: A PROSPECTIVE COHORT STUDY Antiviral Therapy 2003; 8:L80 E Martinez1, P Domingo2, MJ Galindo3, A Milinkovic1, JA Arroyo2, F Baldovi3, E de Lazzari1 and JM Gatell1 The risk of developing diabetes, hypertrigliceridaemia or hypercholesterolaemia warranting therapeutic intervention with lopinavir/ritonavir-containing HAART depends on the baseline values of these metabolic parameters. These findings may have important clinical implications on prescribing lopinavir/ritonavir. |
| 122 | CLINICAL CLASSIFICATION OF FACIAL LIPOATROPHY IN HIV-INFECTED PATIENTS Antiviral Therapy 2003; 8:L81 J Fontdevila, A Milinkovic, E Martinez,T Sik Yoon, JM Gatell and JM Serra This classification can be successfully and easily used in daily practice. At the moment, female patients who ask for a plastic surgeon’s help are less affected and their progression to a final grade is longer, less frequent or slower. Studies had been undertaken to confirm establishing this grading system, using comparative objective measurements. |
| 123 | DISCORDANT TREATMENT OF HYPERLIPIDAEMIA IN A COHORT OF HIV SEROPOSITIVE AND SERONEGATIVE MEN Antiviral Therapy 2003; 8:L81 WF Pewen, BC Calhoun and LA Kingsley The prevalence of hyperlipidaemia is approximately 50% greater in SP. However, we observe a twofold disproportionate rate of treatment, with SP far more likely to receive treatment for hyperlipidaemia. |
| 124 | CAUSES OF DEATH OF HIV-INFECTED PATIENTS IN THE HIGHLY ACTIVE ANTIRETROVIRAL THERAPY ERA Antiviral Therapy 2003; 8:L82 B Roca, RE Rovira, AP Perez and B Cabestany In the era of HAART, the most prevalent cause of death in patients with HIV infection is cirrhosis of the liver. Inadequate treatment and death because of classic opportunistic infections are also common. |
| 125 | EVALUATION OF CUTANEOUS CROSS-TOXICITY BETWEEN EFAVIRENZ AND NEVIRAPINE-CONTAINING REGIMENS IN CLINICAL PRACTICE Antiviral Therapy 2003; 8:L82 M Torralba1, M Neira2, R Rubio1, MJ López-Pedraza2, L Tamargo1, V Moreno1 and JR Costa1 Cutaneous toxicity is a frequent adverse event related to NNRTI. Patients who have a rash with NNRTI have greater possibilities of getting a new rash with the next NNRTI. |
| Hepatotoxicity Abstracts 126 through 128, Pages L83 to L84 |
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| 126 | HEPATOTOXICITY OF RITONAVIR-BOOSTED INDINAVIR (IDV/R 800/100 MG TWICE DAILY) AND SAQUINAVIR (SAQ/R 1000/100 MG TWICE DAILY) IN A PHASE IV, RANDOMIZED, OPEN-LABEL, AND MULTICENTRE TRIAL IN ADULT HIV-1 INFECTION: THE MaxCmin1 TRIAL Antiviral Therapy 2003; 8:L83 JD Lundgren1, A Hill2, Z Fox1, N Clumeck3, JN Bruun4, J Benetucci5, I Cassetti6, P Vernazza7, A Rieger8 and UB Dragsted1 on behalf of the MaxCmin1 Trial Group The reported hepatitis prevalence was relatively low. Bilirubin elevation was seen in the IDV/r arm. No clinically significant excess hepatotoxicity was seen in hepatitis patients compared to the overall study population during r-tx. |
| 127 | A RETROSPECTIVE COHORT STUDY OF LIVER TOXICITY IN HEPATITIS B AND C HIV CO-INFECTED PATIENTS IN THE HIV ONTARIO OBSERVATIONAL DATABASE Antiviral Therapy 2003; 8:L84 E Phillips1,2, J Raboud2,3 and R Saskin3 A high proportion of HIV patients co-infected with HBV and HCV have serious elevations in transaminases which may be related to both type and cumulative exposure to ART. Patients exposed to boosted PI regimens, ddI and d4T appear to be at heightened risk, and patients on nelfinavir-based regimens without previous exposure to other PIs or ddI/d4T at lower risk, for serious hepatotoxicity. |
| 128 | FATTY LIVER AND ANTIRETROVIRAL THERAPY IN HIV-POSITIVE PATIENTS CO-INFECTED WITH HEPATITIS B VIRUS OR HEPATITIS C VIRUS Antiviral Therapy 2003; 8:L84 MB Ristig1, HL Wang2, P Tebas1, J Aberg1, WG Powderly1, J Crippin3 and M Lisker-Melman3 In this case series there was no significant correlation between fatty liver and exposure to d4t or any ART. The rate of fatty liver appeared similar between HBV and HCV. BMI was a stronger predictor of fatty liver in HIV-positive subjects. |
| Other Toxicities Including Neurological Complications and Hypersensitivity Abstracts 129 through 143, Pages L85 to L93 |
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| 129 | FREQUENCY OF SERIOUS PSYCHIATRIC ADVERSE EVENTS WITH EFAVIRENZ Antiviral Therapy 2003; 8:L85 M Allin1, I Reeves2, M Tennant-Flowers2 and I Everall1 Dramatic and life-threatening psychiatric side effects, including psychosis, depressed mood and suicidal and homicidal ideation are rare but significant side effects of efavirenz. Clinicians should be aware of these potential complications and consider withdrawal of the drug and urgent referral to specialist service should they arise. These complications may occur in individuals without prior psychiatric history. It may be wise to avoid efavirenz in individuals with a history of self-harm or suicide attempts. Larger studies will be required to identify the factors that predispose certain individuals to such adverse events. |
| 130 | NEUROPSYCHOLOGICAL DISTURBANCES AND PHARMACOKINETIC LEVELS IN PATIENTS RECEIVING EFAVIRENZ: A PILOT STUDY Antiviral Therapy 2003; 8:L86 JL Blanco1, T Raspall2, Y Lopez-Pua3, M Sarasa3, E Martinez1, A Biglia1, A Milinkovic1, M Laguno1, A Blanco3, A Leon1, M Lonca1, F Garcia1, JM Miro1, T Boget2, J Blanch2, M Salamero2, X Carne3, JM Gatell1 and J Mallolas1 According our data we couldn’t find any relationship between efavirenz plasma levels and impairment of the neuropsychological functions when using the previously described tests. |
| 131 | ANTIRETROVIRAL MEDICATIONS AND NEUROPSYCHIATRIC ASSESSMENTS IN PAEDIATRIC PATIENTS WITH HIV Antiviral Therapy 2003; 8:L86 J Caballero1,3, S Benavides1,3, KI Koranyi1,2, MT Brady1,2 and MC Nahata1,3 Lamivudine and ritonavir were associated with ADHD in this patient population. Aggression appears to be more evident in children with HIV who had a positive in utero illicit drug exposure. |
| 132 | PREVALENCE AND TREATMENT OF ANAEMIA WITH EPOETIN α IN THE HIGHLY ACTIVE ANTIRETROVIRAL THERAPY ERA Antiviral Therapy 2003; 8:L87 H Grossman1 and GJ Leitz2 Two separate trials evaluating the dosing of epoetin alpha have demonstrated that correction of anaemia using epoetin alpha once weekly is effective in HIV-infected patients. Further research on optimal dosing (e.g., once every 2 or 3 weeks) of epoetin α in this patient population is ongoing. |
| 133 | IMPROVING QUALITY OF LIFE IN ANAEMIC, HIV-INFECTED PATIENTS DURING THE HIGHLY ACTIVE ANTIRETROVIRAL THERAPY ERA Antiviral Therapy 2003; 8:L87 H Grossman1 and GJ Leitz2 Correcting anaemia with epoetin α in HIV-infected patients resulted in improved energy and activity levels, as well as improved overall QOL. |
| 134 | DIAGNOSIS OF ABACAVIR HYPERSENSITIVITY REACTIONS AMONG PATIENTS NOT RECEIVING ABACAVIR IN TWO BLINDED STUDIES Antiviral Therapy 2003; 8:L88 J Hernandez, A Cutrell, T Bonny, S Castillo, C Brothers, J Hee, W Powell and T Scott Diagnosis of hypersensitivity reaction to abacavir occurred in 2 to 3% of subjects not receiving abacavir in double-blinded studies. Most cases had rash alone or rash accompanied by non-specific, mild symptoms. These data underscore the importance of assessing hypersensitivity reactions to abacavir as a multi-symptom syndrome and suggest that hypersensitivity reactions to abacavir may be overdiagnosed, particularly in the presence of rash due to other agents. However, when a distinction cannot be made, abacavir should be discontinued. |
| 135 | FALSE ELEVATION OF CA 15.3 TUMOUR MARKERS IN PATIENTS UNDER HIGHLY ACTIVE ANTIRETROVIRAL THERAPY: CASE REPORT AND AIM OF THE STUDY Antiviral Therapy 2003; 8:L88 M Blanc, S Gauchez, B Colombe and P Leclercq These preliminary results suggest that elevation of CA 15.3 levels in patients under HAART might be interpretated with caution. Clinicians must not worry women before a gradual increase of CA 15.3 at successive dosage. Cautions must be highlightened for use of tumour markers in HAART-treated patients with treatment or surveillance of breast cancer. Mechanisms of these abnormal CA 15.3 levels in HAART patients aren’t elucidated, although they could possibly be caused by interaction with cytochrome P450, specific hepatic impairment or steatohepatitis. |
| 136 | ANAEMIA PREVALENCE AMONG HIV PATIENTS: ANTIRETROVIRAL THERAPY AND OTHER RISK FACTORS Antiviral Therapy 2003; 8:L89 TS Wills1, G Leitz2, JP Nadler1, S Powers1, C Somboonwit1, A Vincent1, K Marino2, E Naik1, N Khan1, N Almyroudis1 and B Laartz1 In this study of HIV-positive patients in the HAART era, the overall prevalence of anaemia was 30.3% (54.0% in women, 20.2% in men). Risk of anaemia was greatest among those with CD4 <50 cells/mm3, women, African Americans, and zidovudine-containing HAART. |
| 137 | PANCREATIC TOXICITY ASSOCIATED WITH THE CO-ADMINISTRATION OF DIDANOSINE AND TENOFOVIR Antiviral Therapy 2003; 8:L89 A Milinkovic, A Ravasi, M Tuset, J Mallolas, JL Blanco, M Laguno, JB Perez-Cuevas, O Sued, A Biglia, F Garcia, JM Miro, JM Gatell and E Martinez The co-administration of didanosine, even with a reduction of dose, and tenofovir may lead to an increased risk of pancreatitis. These findings support the investigation of a further didanosine dosage adjustment, and a close monitoring for potential didanosine-associated adverse effects when co-administered with tenofovir. |
| 138 | SLEEP QUALITY AND BRAINWAVE PATTERNS DURING EFAVIRENZ THERAPY Antiviral Therapy 2003; 8:L90 GJ Moyle, C Fletcher and BG Gazzard Efavirenz is associated with sleep and concentration disturbances that persist in many individuals to 12 weeks after commencement of therapy. |
| 139 | SUBCLINICAL HYPOTHYROIDISM IN HIV-POSITIVE PATIENTS: IS IT IATROGENIC OR HIV-RELATED? Antiviral Therapy 2003; 8:L91 T Quirino1, M Bongiovanni1, E Ricci2, P Bonfanti1, E Chebat3, C Martinelli1, L Valsecchi1, S Carradori1, S Landonio1, T Bini1, A Gabbuti1, R Giuntini1, C Gulisano1 and GM Vigevani1 The frequency of subclinical hypothyroidism was comparable in naïve and HAART-treated patients. Together with the fact that no risk factors were significantly related to the pathology, this casts doubt on the causal role of HIV infection in this disorder. |
| 140 | RENAL FUNCTION BEFORE AND AFTER TENOFOVIR DISOPROXIL FUMARATE Antiviral Therapy 2003; 8:L91 B Roca, RE Rovira, B Cabestany, AP Perez, JM Ventura and JA Ferrero In this cohort, no change in renal function is observed 3 months after starting treatment with tenofovir. |
| 141 | EVALUATION OF TOXICITY AND ADVERSE EVENTS RELATED TO EFAVIRENZ AND NEVIRAPINE CONTAINING REGIMENS IN CLINICAL PRACTICE Antiviral Therapy 2003; 8:L92 M Torralba1, M Neira2, R Rubio1, MJ López-Pedraza2, L Tamargo1 and JR Costa1 Adverse events are common with both treatments. Treatment interruption due to rash was more frequent in NVP cohort than EFV cohort although, overall, the EFV-containing regimen was interrupted more frequently than the NVP-containing regimen. |
| 142 | METABOLIC AND VASCULAR RISK FACTORS ASSOCIATED WITH HIV DEMENTIA IN OLDER SEROPOSITIVE PATIENTS Antiviral Therapy 2003; 8:L92 VG Valcour1, CM Shikuma1, B Shiramizu1, M Watters1, P Poff1, O Selnes2 and N Sacktor2 These preliminary results suggest vascular and metabolic risk factors may be associated with dementia in older HIV-positive individuals and should be evaluated further. Fasting laboratory values are now being acquired for all patients in the cohort to facilitate further analysis. |
| 143 | INAPPROPRIATELY LOW SEX-HORMONE BINDING GLOBULIN WITH SEVERELY DEPLETED TOTAL TESTOSTERONE IN TWO HIV-INFECTED PATIENTS ON TRANSDERMAL TESTOSTERONE REPLACEMENT THERAPY, RECOMBINANT GROWTH HORMONE AND OXANDROLONE Antiviral Therapy 2003; 8:L93 P Wasserman, S Segal-Maurer and DS Rubin Patients 1 and 2 had low testosterone levels in spite of exogenous testosterone replacement. Discontinuation of oxandrolone in both patients, and rGH in patient 1, led to normalization of testosterone levels in patient 1 and the return of morning erections in patient 2. As prior postulated, it is possible that first pass metabolism of orally administered oxandrolone decreased hepatic synthesis of SHBG, allowing exogenously supplied testosterone to be excreted. We report the first association of long-term oxandrolone use, diminished SHBG and low testosterone levels. Further work is necessary to elucidate the relationship. |
| Bone Disease Abstracts 144 through 148, Pages L94 to L96 |
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| 144 | COMBINED USE IN HIV-INFECTED WITH BONE MASS LOSS OF CALCITONIN AND ALENDRONATE Antiviral Therapy 2003; 8:L94 A Bazarra1 and A Castro2 It is necessary to carry out a wider and longer study, among HIV patients, but it seems that alendronate contributes advantages to decrease bone mass loss, at least at lumbar spine, without calcitonin. Osteoporosis is a multifactorial disease, maybe its best treatment and prevention is combining several drugs and attitudes. It would be good to test several adjusted doses to decrease side effects. These results can be interesting for the HIV-infected, who have a lot of medication. |
| 145 | GENDER AS A RISK FOR LOW BONE DENSITY IN PAEDIATRIC COHORT VERTICALLY INFECTED WITH HIV Antiviral Therapy 2003; 8:L94 R Rosso1, M Vignolo2, A Parodi2, S Grassi2, A Di Biagio1, G Aicardi2 and D Bassetti1 QUS measurements in HIV patients fell below mean values of controls: this effect tends to become more pronounced with longer therapy duration and not with the type of therapy. Gender seems to be a further risk factor for bone problems. QUS is useful and non-invasive in HIVpp follow-up. |
| 146 | OSTEOPENIA/OSTEOPOROSIS IN HIGHLY-EXPERIENCED HIV-INFECTED PATIENTS Antiviral Therapy 2003; 8:L95 E Seminari, L Galli, A Rubinacci, A Galli, G Fusetti, A Soldarini and A Castagna Half of advanced HIV-infected highly pretreated subjects had BML that is associated to a complex biochemical frame highly suggestive of a high bone turnover state that might have clinical relevance. High OPG level should indicate a protective response to counteract osteoclastogenesis activation by factors not yet identified and not reflected by circulating RANKL. |
| 147 | BONE MINERAL DENSITY EVOLUTION IN HIV-INFECTED PATIENTS Antiviral Therapy 2003; 8:L95 M Torralba1, S Azriel2, R Rubio1, L Tamargo1, V Moreno1, F Pulido1, E Jódar2 and F Hawkins2 HIV-infected patients following a stable antiretroviral treatment present moderate osteopenia without signs of accelerated BMD loss after 12 months of monitoring. BMI, weigh and length of treatment were associated with low bone mass. |
| 148 | LONGITUDINAL CHANGES OF BONE MINERAL DENSITY AND METABOLISM IN ANTIRETROVIRAL-TREATED HIV-INFECTED CHILDREN Antiviral Therapy 2003; 8:L96 A Vigano, I Zamproni, S Beccio, R Bianchi, V Giacomet and S Mora Our data confirm the presence of low BMD and bone metabolism derangement in HIVinfected children, and they indicate only a partial improvement during HAART. The role of possible therapeutic approach to restore bone mass and metabolism should be assessed in paediatrics. |
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