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1st International Workshop on Adverse Drug Reactions
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| Session One Lipid and glucose metabolism |
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| 001 | EFFECT OF HIV PROTEASE INHIBITORS ON IN VITRO ADIPOGENESIS AND IN VIVO FAT DEPOSITION Antiviral Therapy 1999; 4(Supplement 2):7 (abstract no. 001) J Lenhard, E Fuifine, M Paulik, D Croom, A Spaltenstein and J Weiel The results suggest that (i) the various PIs affect distinct metabolic pathways and (ii) environmental factors, such as retinoids and dietary fat, can influence the effects of PIs on fat metabolism. |
| 002 | LIPID METABOLISM AND LIPODYSTROPHIES Antiviral Therapy 1999; 4(Supplement 2):7 (abstract no. 002) Stephen L Sturley and Richard J Deckelbaum The critical role of the LRP in triglyceride metabolism was confirmed by tissue specific deletion or attenuation of the LRP. Under these circumstances, reduced LRP activity results in decreased lipoprotein-remnant clearance and two to three fold elevations in plasma triglyceride and cholesterol. This is very similar to the changes observed with HIV-PR therapy. This overview will summarise the basic concepts underlying lipodystrophies, with special emphasis on hypertriglyceridemias. |
| 003 | GLUCOSE TOLERANCE Antiviral Therapy 1999; 4(Supplement 2):8 (abstract no. 003) Katherine Samaras MBBS FRACP, Seng Khee Gan MBBS, FRACp, Donald Chisolm MBBS FRACP Hypotheses as to the mechanism include impairment of function due to excess fatty acid availability ("lipotoxicity"), damage from excess amylin secretion from the beta cell which accompanies the hyperinsulinaemia, or a genetic beta cell defect. Whatever the reason for impairment of beta cell function, the advent of hyperglycaemia causes a further deterioration ("glucotoxicity") which often causes a rapid progression to symptomatic hyperglycaemia. |
| Session Two Metabolic perturbations in HIV |
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| 004 | DYSLIPIDEMIA DUE TO HIV INFECTION AND ITS THERAPY Antiviral Therapy 1999; 4(Supplement 2):13 (abstract no. 004) Carl Grunfeld AZT treatment of therapy naïve patients with advanced HIV disease leads to decreased interferon and triglyceride levels. In contrast, treatment of HIV infected patients with HIV Protease Inhibitors (PI) induces a different profile. Triglyceride levels increase, the opposite of what was seen with AZT. LDL cholesterol levels increase to normal. HDL is not significantly changed. Using epidemiological data, the major risk of CAD is from the low level of HDL seen in HIV infection. PI induced increases in LDL and VLDL cholesterol also predict an increased risk of CAD events, but the predicted event rate is insignificant compared to the proven benefit of PI's in decreasing death and complications in AIDS. |
| 005 | ART-ASSOCIATED INSULIN RESISTANCE: FREQUENCY, POTENTIAL CAUSES AND POSSIBLE THERAPEUTIC INTERVENTIONS Antiviral Therapy 1999; 4(Supplement 2):13 (abstract no. 005) FD Goebel and R Walli (i) IR is frequently seen under ART, not restricted to the use of PI and commonly worsens over time. (ii) Treatment with insulin sensitizers (e.g. thiazolidinediones), and in some cases discontinuing PI, can ameliorate ART-associated IR. (iii) Besides other mechanisms, decreased expression of insulin receptors might contribute to ART-associated IR. |
| Session Three Wasting |
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| 006 | EFFECT OF RECOMBINANT HUMAN GROWTH HORMONE IN THE TREATMENT OF VISCERAL FAT ACCUMULATION INFECTION: INTERIM ANALYSIS Antiviral Therapy 1999; 4(Supplement 2):19 (abstract no. 006) ES Engelson, M Glesby, J Sheikhan, J Albu, J Wang, SB Heymsfield and DP Kotler These results indicate that visceral adipose tissue is labile and decreases during therapy with growth hormone in HIV-infected people, as it does in those with the metabolic syndrome X. Therapy is not associated with exacerbation of hyperlipidaemia, though it did lead to some hyperglycaemia. |
| 007 | TREATMENT OF WASTING Antiviral Therapy 1999; 4(Supplement 2):19 (abstract no. 007) K Mulligan Taken together, these studies demonstrate that HIV-infected individuals can regain weight and LBM under the proper therapeutic circumstances. The effects of reversal of wasting on survival and disease progression, long-term safety, and the potential value of these therapies in the treatment of fat redistribution remain to be determined. |
| Session Four Related symptoms |
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| 008 | GENETIC AND ACQUIRED LIPODYSTROPHY SYNDROMES Antiviral Therapy 1999; 4(Supplement 2):25 (abstract no. 008) A Garg Recently, patients infected with HIV, receiving therapy including HIV-1 protease inhibitors, have been reported to develop a lipodystrophy characterized by loss of sc adipose tissue from the extremities and face but excess fat deposition in the neck and trunk. The underlying mechanisms, however, of lipodystrophy in HIV-infected patients remain unknown. Current management of patients with lipodystrophy includes cosmetic surgery, diet and drug therapy for control of diabetes and dyslipidaemia. |
| 009 | MITOCHONDRIAL TOXICITY OF NUCLEOSIDE ANALOGUE REVERSE TRANSCRIPTASE INHIBITORS Antiviral Therapy 1999; 4(Supplement 2):25 (abstract no. 009) K Brinkman The most serious presentation of mitochondrial toxicity is (fatal) lactic acidosis, presenting with abdominal discomfort, nausea and vomiting, followed by tachypnoea and rapid deterioration. This toxicity occurs after months of NRTI therapy, and persons who have suffered other NRTI toxicity appears to be at increased risk. Early recognition is essential and NRTIs have to be stopped immediately. Co-factor supplements, like riboflavin, co-enzyme Q and L-carnitine can be beneficial. |
| Session Five Recent cohort studies: The evolution of a case definition for lipodystrophy |
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| 010 | LIPODYSTROPHY IN HIV: A COMMUNITY PERSPECTIVE Antiviral Therapy 1999; 4(Supplement 2):33 (abstract no. 010) B Cheng Lipodystrophy has become a major interest of researchers worldwide and multiple strategies are being tested to treat it. The patient community is increasingly well informed about the problem and anxiously awaiting additional information from Project Inform and other information providers before choosing personal strategies for coping. |
| 011 | A SYNDROME OF LIPODYSTROPHY (LD), LACTIC ACIDAEMIA AND LIVER DYSFUNCTION ASSOCIATED WITH HIV NUCLEOSIDE ANALOGUE REVERSE TRANSCRIPTASE INHIBITOR THERAPY: CONTRIBUTION TO PI-RELATED LD SYNDROME Antiviral Therapy 1999; 4(Supplement 2):33 (abstract no. 011) A Carr1, J Miller2, M Law2 and DA Cooper1,2 A syndrome of LD, constitutional symptoms, lactic acidaemia and hepatic dysfunction can complicate long term NRTI therapy. Both PI and NRTI therapy, particularly if associated with lactic acidaemia, can contribute to HIV LD syndrome, but PI therapy and NRTI therapy cause distinguishable clinical and metabolic features. |
| 012 | CLINICAL AND LABORATORY CHARACTERISTICS OF LIPODYSTROPHY IN A FRENCH COHORT OF HIV-INFECTED PATIENTS TREATED WITH PROTEASE INHIBITORS Antiviral Therapy 1999; 4(Supplement 2):34 (abstract no. 012) W Rozenbaum, S Gharakhanian, Y Salhi, N Adda, T Nguyen, C Vigouroux and J Capeau HIV-related lipodystrophy syndrome includes a variety of clinical and biological manifestations, which can be included in a case definition. Different subtypes can be distinguished. The natural history of this syndrome deserves prospective follow up. |
| 013 | DEVELOPMENT OF CASE DEFINITIONS AND CRITERION FOR RHEUMATIC DISEASES: LESSONS FOR STUDYING THE EPIDEMIOLOGY OF LIPODYSTROPHY, IN HIV Antiviral Therapy 1999; 4(Supplement 2):34 (abstract no. 013) Matthew H. Liang, MD, MPH For large-scale epidemiologic studies, the requirement for expensive imaging, laboratory tests or expert physical examination can be unpractical and prohibitively expensive. |
| Poster Session Abstracts | |
| 014 | DESCRIPTION OF LIPODYSTROPHY IN THE HIV OUTPATIENT STUDY (HOPS) Antiviral Therapy 1999; 4(Supplement 2):39 (abstract no. 014) DJ Ward1, KM Delaney2, AC Moorman3, K Lichtenstein4, F Palella5, B Young4, KC WOOd6, SD Holmberg3 and the HOPS Investigators We characterized physical manifestations of lipodystrophy in a large cohort of HIV-infected individuals and propose a stratified case definition that corresponded well with laboratory evidence of elevation in blood lipids. These limitations have been overcome with casefinding survey tools with sufficient sensitivity to screen individuals for further evaluation. SLE was the first disease so studied; Reiter's and the connective tissue diseases as a group have also case-finding techniques developed. Most of them are indeed based on self-reported versions of the ACR criteria. |
| 015 | FACTORS INFLUENCING THE EVOLUTION OF PLASMA TRIGLYCERIDE IN THE ERA OF HAART, AQUITAINE COHORT, 1996-1998 Antiviral Therapy 1999; 4(Supplement 2):40 (abstract no. 015) R Thiébautl,2, D Malvyl,2, P Mercie2,3, V Daucourt1,3, C Marimoutou1,3 and F Dabis1 for the Groupe d'Epidemiologie Clinique du Sida en Aquitainel,3 (GECSA) As reported before the era of HAART, AIDS stage is associated with an increase of TG as with male gender and age. We confirm also the increase of TG with PI. Adjusting for PI use, nucleoside analogues are not significantly associated with TG. |
| 016 | PREVALENCE OF LIPODYSTROPHY AND RELATION WITH CLINICAL, ANTHROPOMETRIC DATA AND TREATMENT, AQUITAINE COHORT, 1999 Antiviral Therapy 1999; 4(Supplement 2):40 (abstract no. 016) V Daucourt1,2, R Thiébaut1,3, P Mercié2,3, D Malvy2,3, D Neau2,3, F Bonnal2,3, C Marimoutou1,2 and F Dabis1 for the Groupe d'Epidémiologie du SIDA en Aquitaine1,2 (GECSA) Our systematic approach allows us to conclude there is a high frequency of clinically defined LD including among patients not treated with PIs. LDs are associated with important anthropometric modifications, in particular for patients presenting peripheral adiposity or mixed syndromes. |
| 017 | LIPODYSTROPHY, GLUCOSE AND LIPID METABOLISM DYSFUNCTIONS, AQUITAINE COHORT, 1999 Antiviral Therapy 1999; 4(Supplement 2):41 (abstract no. 017) R Thiébaut1,2, V Daucourt1,3, D Malvy1,2, N Bernard2,3, S Farbos4, J Ceccaldi5, P Morlat2,3 and JM Ragnaud2,3 for the Groupe d'Epidémiologie Clinique du Sida en Aquitaine1,3 {GECSA} Lipid and glucose metabolism abnormalities are more frequent in LD patients (HI, IR, HTG) with various ARV regimens and are particularly frequent in patients presenting single or mixed peripheral adiposity. |
| 018 | CASE REPORT OF LIPODYSTROPHY OBSERVATIONS IN PATIENTS NAÏVE OF PROTEASE INHIBITOR TREATMENT, AQUITAINE COHORT, 1999 Antiviral Therapy 1999; 4(Supplement 2):42 (abstract no. 018) P Mercié1,2, D Malvy2,3, V Daucourt1,3, H Dutronc1,2, D Lacoste1,2, M Dupon1,2, JL Pellegrin1,2 and R Thiebaut2,3 for the Groupe d'Epidémiologie du SIDA en Aquitaine1,3 {GECSA} LD can be observed in a substantial number of patients naïve of PI. The implication of lamivudine and stavudine in LD recently suggested was not confirmed in our study, in which LD was observed in patients treated with many different antiretroviral combinations. |
| 019 | PROTEASE INHIBITORS AND NUCLEOSIDE ANALOGUE REVERSE TRANSCRIPTASE INHIBITORS INTERACT TO CAUSE SUBCUTANEOUS FAT WASTING IN PATIENTS WITH HIV INFECTION Antiviral Therapy 1999; 4(Supplement 2):42 (abstract no. 019) S Mallal1, M John1, C Moore1,2, I James2 and E Mckinnon2 The wasting of fat from the subcutaneous compartments of the face, limbs and central abdomen occurring in HIV-infected patients cannot be explained by PIs alone. NRTIs appear to cause slowly progressive fat loss, which is accelerated by the addition of protease inhibitor therapy. HAART regimens containing stavudine cause faster fat loss and an earlier onset of clinically apparent wasting compared to those containing zidovudine. |
| 020 | INCIDENCE OF FAT TISSUE ABNORMALITIES IN PROTEASE INHIBITOR-NAÏVE PATIENTS TREATED WITH NRTI COMBINATIONS Antiviral Therapy 1999; 4(Supplement 2):43 (abstract no. 020) M Galli1, AL Ridolfo1, C Gervasoni1, L Ravasio1, F Adorni2 and M Moroni1 Incidence of AFTD is high also in PI-naïve subjects treated with double NRTI combinations. The risk of developing AFTD is higher in women. |
| 021 | CONSIDERATIONS IN THE DEVELOPMENT OF A CASE DEFINITION FOR HIV/HAART-ASSOCIATED LIPODYSTROPHY SYNDROME Antiviral Therapy 1999; 4(Supplement 2):44 (abstract no. 021) J Falutz and D Turcot Given the gender and HAART profile-based differences and similarities in clinical and laboratory features in HAL cases and controls, these variables among others, need to be considered in the development of a case definition. |
| 022 | THE SALSA (SELF-ASCERTAINED LIPODYSTROPHY SYNDROME ASSESSMENT) COHORT: ABNORMALITIES IN CASES COMPARED TO CONTROLS Antiviral Therapy 1999; 4(Supplement 2):44 (abstract no. 022) N Muurahainen1, J Falutz2, G Santos3, R Pettit1, M Kleintop1, M Glesby4, D Kotler1 and the SALSA Investigators Group Although HIV-positive 'cases' report more abnormalities than gender-matched HIV-positive and healthy controls, controls also report abnormalities. Additional multivariate analyses and studies employing more objective measures of fat distribution (ongoing) are needed to more fully elucidate a case definition for LD syndrome(s). |
| 023 | A CROSS-SECTIONAL STUDY OF METABOLIC DISORDERS AND LIPODYSTOPHY IN HIV-INFECTED PATIENTS TREATED WITH ANTIRETROVIRAL COMBINATION THERAPY INCLUDING PROTEASE INHIBITORS (PI) WITHIN A PHASE IV COHORT STUDY OF PI: APROCO-ANRS EP11 Antiviral Therapy 1999; 4(Supplement 2):45 (abstract no. 023) Aproco Study Group on Metabolic Complications1 This preliminary data confirm the high prevalence of lipodystrophy in HIV-infected patients treated with PI containing regimen. They allow to describe clinical and associated metabolic disorders. This large cohort will led us to determine risk factors and relationship between different abnormalities. |
| 024 | REVERSIBILITY OF PERIPHERAL FAT WASTING (LIPOATROPHY) ON STOPPING STAVUDINE THERAPY Antiviral Therapy 1999; 4(Supplement 2):45 (abstract no. 024) T Saint-Marc and JL Touraine These non-randomized data suggest that ceasing stavudine therapy for 6 months resulted in improvements in metabolic and body fat abnormalities induced by stavudine. The reversibility of the symptoms further support the potential role of stavudine in the pathogenesis of a peripheral fat wasting syndrome. |
| 025 | CHANGES IN BODY FAT DISTRIBUTION IN 154 HIV-INFECTED MALE PATIENTS TREATED WITH COMBINED ANTIRETROVIRAL THERAPY Antiviral Therapy 1999; 4(Supplement 2):46 (abstract no. 025) T Saint-Marc, M Partisani, I Poizot-Martin, F Bruno and 0 Rouvière Three different syndromes must be distinguished: (i) a syndrome of fat depletion characterized by a decrease in abdominal and midthigh SQAT which could be related to the use of stavudine; (ii) a syndrome of fat redistribution combining loss of SQAT and increase in VAT related to an unusual side-product of effective virus control; and (iii) a syndrome of subcutaneous fat disposition reflecting increase in caloric intake after HAART was begun. |
| 026 | LIPODYSTROPHIC SYNDROMES IN A COHORT OF HIV-1-INFECTED PATIENTS RECEIVING HAART WITH A PROTEASE INHIBITOR Antiviral Therapy 1999; 4(Supplement 2):47 (abstract no. 026) JP Viard and B Rakotoambinina In conclusion, length of nucleoside exposure before HAART may be a risk factor for lipoatrophy, whereas elevation of blood lipids is seen independently of lipodystrophy and may be dependent on PI exposure. |
| 027 | DXA ANALYSIS OF THE ASSOCIATION BETWEEN PROTEASE INHIBITOR USE AND FAT DISTRIBUTION IN HIV-INFECTED ADULTS Antiviral Therapy 1999; 4(Supplement 2):48 (abstract no. 027) A Shevitz, AY McDermott, T Knox, R Roubenoff, J Kehayias and S Gorbach Therefore, regional DXA analysis demonstrated that PI use is associated with more trunk fat and less appendicular fat in men and women, without differences in total body composition or weight. |
| 028 | EFFECT OF INITIATING INDINAVIR THERAPY ON GLUCOSE METABOLISM IN HIV-INFECTED PATIENTS: RESULTS OF MINIMAL MODEL ANALYSIS Antiviral Therapy 1999; 4(Supplement 2):48 (abstract no. 028) MP Dubé1, R Aqeel2, H Edmondson-Melançon1, D Johnson1 and TA Buchanan2 During 8 weeks of indinavir-based therapy, fasting glucose increased and insulin sensitivity decreased. Pancreatic B cell responsiveness did not manifest a normal increase in insulin release to compensate for the insulin resistance. This combination of insulin resistance and inadequate B cell response may explain the hyperglycemia and other metabolic abnormalities seen in some PI-treated patients. |
| 029 | INVESTIGATIONS INTO THE PROPOSED MECHANISMS OF HIV-ASSOCIATED PERIPHERAL LIPODYSTROPHY, HYPERLIPIDAEMIA AND INSULIN RESISTANCE Antiviral Therapy 1999; 4(Supplement 2):49 (abstract no. 029) GJ Stevens, M Chen, R Grecko, A Lankford, C Lee, J Harr and PW Rose The lack of significant homology between CRABP1 and HIV-1 protease together with the lack of CYP3A4 involvement in retinoic acid isomerization demonstrate that mechanisms other than those previously proposed may be involved in the metabolic effects. Recent studies have also implicated reverse transcriptase inhibitors as possible causative agents. Studies to investigate the effects of RTIs on adipocyte differentiation and lipolytic activity are in progress. |
| 030 | INCIDENCE OF LIPODYSTROPHY IN START (SELECTION OF THYMIDINE ANALOG REGIMEN THERAPY) STUDIES Antiviral Therapy 1999; 4(Supplement 2):49 (abstract no. 030) E Dale1, J Mauney1, K Uffelman1, M Stevens2 and R Grosso2 Based on this ad hoc analysis, there do not appear to be clinically significant differences in the incidence of lipodystrophy among stavudine and zidovudine treatment groups. |
| 031 | A MULTICENTRE, RANDOMIZED, OPEN-LABEL, COMPARATIVE TRIAL OF THE CLINICAL, IMMUNOLOGICAL AND VIROLOGICAL BENEFIT OF SWITCHING THE PI BY NEVIRAPINE IN HAART-EXPERIENCED PATIENTS SUFFERING LIPODYSTROPHY Antiviral Therapy 1999; 4(Supplement 2):50 (abstract no. 031) L Ruiz1, E Negredo1, A Bonjoch1, R Paredes1, J Romeu1, G Sirera1, RC Fumazl, L Zamora2 and B Clotet1 for the LD Study Group After 12 weeks, patients on HAART with LD and undetectable plasma VL who switched to didanosine/stavudine/nevirapine maintained HIV-l suppression, reduced CHOL and TG levels and improved quality of life and self-perception of LD changes. |
| 032 | THE FREQUENCY OF RASH DURING THE INITIAL USE OR UPON RECHALLENGE WITH NEVIRAPINE AND DELAVIRDINE Antiviral Therapy 1999; 4(Supplement 2):50 (abstract no. 032) JG O'Brien1, M Gangar1, G Arias1 and CA1,2,3Kemper Neither HIV status, CD4 count, nor plasma HIV RNA levels were significant predictors for the development of rash. Fever preceded rash in 21 % of patients receiving nevirapine. Drug was discontinued in 19% of patients receiving nevirapine and 24% receiving delavirdine because of rash. Rash recurred in 80% of patients who were rechallenged with the same agent and in 67% of patients crossed-over to the alternate agent, suggesting that there is probably little value in attempting to retreat patients with cutaneous reactions, even with the alternate agent, except in those patients with limited treatment options. |
| 033 | ALTERATIONS IN PLASMA TRIGLYCERIDES LEVELS DURING TREATMENT WITH THREE DIFFERENT PROTEASE INHIBITOR REGIMENS: A RANDOMIZED STUDY Antiviral Therapy 1999; 4(Supplement 2):51 (abstract no. 033) BT Røge, TL Katzenstein and J Gerstoft Ritonavir-containing regimens caused a sustained elevation of PT. Indinavir did not significantly increase PT. |
| 034 | AMPRENAVIR: A NEW PROTEASE INHIBITOR WITH A FAVOURABLE METABOLIC PROFILE Antiviral Therapy 1999; 4(Supplement 2):52 (abstract no. 034) L Pedneault1, C Hanson1, P Nacci2, A Fetter2, J Millard1 and M Rogers1 Amprenavir is a new PI with a favourable metabolic profile. Marked elevations in TG, GL and CH levels were infrequent. However, slight elevations in TG levels were observed more frequently with dual PI regimens. Our data suggest that previous treatment history might be predictive of FR. |
| 035 | SERUM LIPID LEVELS IN HIV-POSITIVE ADULTS DURING SAQUINAVIR-CONTAINING COMBINATION THERAPY Antiviral Therapy 1999; 4(Supplement 2):52 (abstract no. 035) P Skolnik1, P Siemon-Hryczyk2, J Drake3, F Duff2 and N Buss4 In these studies, glucose levels appeared unaltered during antiretroviral therapy. Dual PI regimens appeared to affect lipid markers more than single PI regimens. Accepting the limitations of cross-study comparisons, a tentative ranking of the PI-containing regimens studied, based on their effects on serum lipids, is saquinavir SGC <saquinavir SGC plus nelfinavir (1250 mg) <saquinavir SGC plus ritonavir (400 mg). The clinical implications of these observations remain to be established. |
| 036 | LIPID PROFILES IN PATIENTS ON RITONAVIR/INDINAVIR-CONTAINING SALVAGE REGIMENS Antiviral Therapy 1999; 4(Supplement 2):53(abstract no. 036) M Youle1, A Mocroft1, M Johnson1, S Madge1, D Ross1, I Tierney1, M Fisher2 and S Randerson2 Switching from other PI-containing regimens to ritonavir/indinavir is associated with a significant rise in serum lipids directly related to the dose of ritonavir. |
| 037 | THE PREVALENCE OF LIPODYSTROPHY IN AN HIV-INFECTED OUTPATIENT POPULATION Antiviral Therapy 1999; 4(Supplement 2):54(abstract no. 037) V Carter, F Adams, J Hoy, I Nyulasi and A Mijch The prevalence of lipodystrophy is 70% according to the definition used. Adverse effects of PIs include hypertriglycerideaemia and lowering of HDL levels. This male HIV-infected population have multiple risk factors for the development of CVD. Anthropometric measures underestimate the percentage total body fat compared to DEXA. |
| 038 | PRECOCIOUS LESIONS OF THE CAROTID VESSELS IN HIV-1-INFECTED PATIENTS TREATED WITH PROTEASE INHIBITORS Antiviral Therapy 1999; 4(Supplement 2):54 (abstract no. 038) P Maggi1, G Fiorentino1, A Saracino1, C Fico3, F Perilli2, A Lillo2, G Regina2 and G Angarano1 This preliminary report showed an higher than expected prevalence of precocious lesions of the carotid vessels. Previous drug addiction could represent an important predisposing factor. Further studies are warranted to confirm these observations. |
| 039 | LACK OF CLINICAL LIPODYSTROPHY IN PATIENTS RECEIVING EFAVIRENZ PLUS NRTIs IN STUDY 006 Antiviral Therapy 1999; 4(Supplement 2):55 (abstract no. 039) R Stryker1, D Skiest2, K Tashima3, S Staszewski4, SA Villano5, DF Labriola5, NM Ruiz5 and the Study 006 Investigator Team5 No cases of probable clinical lipodystrophy were observed in the efavirenz plus NRTIs arm of study 006. |
| 040 | ONE YEAR EFFECTS OF SWITCHING FROM HIV-1 PIs TO NEVIRAPINE ON METABOLIC ABNORMALITIES Antiviral Therapy 1999; 4(Supplement 2):55 (abstract no. 040) JM Gatell, I Conget, L Lozano, R Casamitjana and E Martinez Our data confirm the long-term positive effects of replacing PIs by nevirapine on metabolic abnormalities while maintaining suppression of viral replication. |
| 041 | NRTI-INDUCED MITOCHONDRIAL TOXICITY AS AN AETIOLOGY FOR FAT REDISTRIBUTION SYNDROME Antiviral Therapy 1999; 4(Supplement 2):56 (abstract no. 041) TN Kakuda, RC Brundage, PL Anderson and CV Fletcher We hypothesize that NRTIs may precipitate FRS. This hypothesis does not exclude other factors such as HIV protease inhibitors or other factors that may exacerbate this condition. Future studies are needed to elucidate the cause(s) of FRS. |
| 042 | TWO CASE REPORTS OF UNUSUAL LIPOMATOUS GROWTHS ASSOCIATED WITH COMBINATION ANTIRETROVIRAL THERAPY Antiviral Therapy 1999; 4(Supplement 2):56 (abstract no. 042) D Milano1, JB Finkelstein3, DC Cerriero1 and L Fontana2 Presence of lipomas in the subcutaneous compartment suggests (i) an altered mechanism for growth stimulation; (ii) protected compartment in the presence of peripheral fat depletion; or (iii) different molecular/genetic make-up of the lipocytes within a lipoma. Of interest is the regression of the lipoma in patient 1 with rhGH therapy, coinciding with reduced abdominal girth and presumably, regression of mesenteric fat. |
| 043 | RITONAVIR USE AND HYPERLIPIDAEMIA IN HIV-INFECTED PATIENTS Antiviral Therapy 1999; 4(Supplement 2):57 (abstract no. 043) F Terheggen,EJG Sijbrands, K Brinkman, HM Weigel and PHJ Frissen Hyperlipidaemia occurred in a significant proportion of ritonavir treated HIV patients. C-peptide prior to treatment, HIV-1 risk factor (infection not by intravenous drug use) and prior use of PIs were predictive for the development of hyperlipidaemia. Despite the marked hypertriglyceridaemia (<20 mmol/l in three patients) no clinical sequelae i.e. pancreatitis were observed. Follow-up was too short to assess long-term effects, i.e. atherosclerosis. |
| 044 | EFFECT OF FENOFIBRATE ON HYPERLIPIDEMIA IN HIV-INFECTED PATIENTS Antiviral Therapy 1999; 4(Supplement 2):58 (abstract no. 044) D Lee, WC Mathews, S Hsia, S Basinger and E,Barber (i) Fenofibrate may be useful in the treatment of both hypertriglyceridaemia and hypercholesterolaemia in the HIV population. Further prospective studies are needed to evaluate the safety, efficacy and drug interactions of fenofibrate in this population. |
| 045 | MULTICENTRE PROSPECTIVE COHORT STUDY TO EVALUATE THE SAFETY PROFILE OF HAART IN HIV OUTPATIENTS: 1 YEAR FOLLOW-UP RESULTS Antiviral Therapy 1999; 4(Supplement 2):58(abstract no. 045) S Mateu on behalf of the Barcelona Antiretroviral Surveillance Study (BASS) Group ADR is a major cause of treatment discontinuation in patients on HAART, accounting for almost half of treatment modifications. Long-term data are needed in order to assess the impact of ADR on patient care. |
| 046 | LIPODYSTROPHY SYNDROME IN PATIENTS WITH PRIMARY HIV INFECTION ON LONG TERM ANTIRETROVIRAL THERAPY Antiviral Therapy 1999; 4(Supplement 2):59(abstract no. 046) J Miller1, D Smith2, P Grey2, S Emery1, A Carr3, J Anderson4, R McFarlane4, W Genn4 and DA Cooper1 Features of LD syndrome are common in patients with PHI treated with antiretroviral therapy. There is an association with duration of PI therapy but can occur in patients who are PI-naïve. |
| 047 | INCREASED APO B SYNTHESIS AND DEFECTIVE DELIPIDATION OF TRIGLYCERIDE-RICH VLDL ARE POTENTIAL MECHANISMS OF ART-ASSOCIATED DYSLIPIDAEMIA Antiviral Therapy 1999; 4(Supplement 2):59(abstract no. 047) M Schmitz, G Michl, R Walli, T Demant and FD Goebel These data indicate that increased triglycerides are primary due to reduced rates of VLDL transfer into denser lipoproteins implying a lower rate of lipoprotein lipase mediated delipidation. In addition, total Apo B synthesis was increased and shifted towards triglyceride rich VLDL1. Overall, this lipoprotein profile in patients with ART-associated dyslipidaemia implies an increased risk for cardiovascular events. |
| 048 | LIPODYSTROPHY AND METABOLIC CHANGES IN HIV-INFECTED PATIENTS TREATED WITH OR WITHOUT PIs Antiviral Therapy 1999; 4(Supplement 2):60(abstract no. 048) F Boufassa1, A Dulioust2, C Gouiard1, AS Lascaux3, M Feneant-Thibault1 and the LipoSud Study Committee In this preliminary analysis, significant differences were found in fasting metabolic disorders among patients treated with PI compared to those who were not. The major objective of this study is to define factors influencing the occurrence of lipodystrophy and dyslipidaemia in a large population of HIV-infected patients. |
| 049 | PREVALENCE OF LIPODYSTROPHY AND METABOLIC ABNORMALITIES IN RELATION WITH ANTIRETROVIRAL REGIMENS FOR THE TREATMENT OF HIV INFECTION Antiviral Therapy 1999; 4(Supplement 2):60(abstract no. 049) A Duran, N Flaster, E Keszberg, G Sequeira and M Losso Although we did not find significant differences in cholesterol and trygliceride values between those who receive PICR and who receive other treatments, those who developed LD showed the greatest incidence of abnormal values. The fact that the percentage of patients with LD diagnosis in our cohort was lower than in previous reports is probably related to our strict criteria in defining this syndrome. |
| 050 | SAFETY AND TOLERABILITY OF ANTIRETROVIRAL THERAPY IN THE BRITISH COLUMBIA DRUG TREATMENT PROGRAM Antiviral Therapy 1999; 4(Supplement 2):61 (abstract no. 050) V Montessori, N Jahnke, B Yip, RS Hogg, MV O'Shaughnessy and JSG Montaner As more effective ARV becomes available, safety and tolerability of treatment is becoming of increasing importance. Although some antiretroviral agents may be associated with detrimental effects, such as anaemia, the overall benefit of effective therapy may be protective. |
| 051 | REPLACING A PI WITH EFAVIRENZ FOR MANAGEMENT OF PI TOXICITY Antiviral Therapy 1999; 4(Supplement 2):62 (abstract no. 051) M Harris, G Larsen, M Bell and JSG Montaner The strategy of replacing a PI with efavirenz within a combination regimen may improve PI toxicity and maintain virological control in selected patients. Formal clinical trials addressing this issue are underway. |
| 052 | ABACAVIR HYPERSENSITIVITY REACTIONS IN THE CLINIC Antiviral Therapy 1999; 4(Supplement 2):62 (abstract no. 052) M Harris, G Larsen, M Bell and JSG Montaner Physicians should maintain a high index of suspicion for abacavir hypersensitivity reactions. As a result, while true hypersensitivity reactions may have a frequency of up to 5%, a greater proportion of patients (10-12% in our series) will suspend all or part of their antiretroviral therapy due to suspicious symptomatology. Discontinuation of abacavir as a result of true or suspected hypersensitivity reactions is a relatively common occurrence among treatment-experienced patients on multi-drug regimens. |
| 053 | BODY FAT REDISTRIBUTION IN PERSONS ON NON-PI-CONTAINING REGIMENS Antiviral Therapy 1999; 4(Supplement 2):63(abstract no. 063) G Moyle, N Dent and C Baldwin A syndrome indistinguishable from PI-associated lipodystrophy may be observed in individuals on PI-sparing regimens. Prior PI therapy may represent a risk factor for this phenomenon. Additionally, a clinical picture of lipodystrophy without marked lipid or insulin abnormalities may be observed. Investigation for other causes of fat redistribution may be worthwhile. |
| 054 | LIPID ELEVATIONS DURING NON-NUCLEOSIDE RTI (NNRTI) THERAPY: A CROSS-SECTIONAL ANALYSIS Antiviral Therapy 1999; 4(Supplement 2):63 (abstract no. 054) GT Moyle and C Baldwin Cholesterol values in the intervention range are commonly observed during NNRTI therapy and may be more common with EFV. No specific NA appeared associated with an increased risk of abnormal lipids. Prior therapy with PI may predispose patients to elevated cholesterol during NNRTI therapy. |
| 055 | CHANGES IN VISCERAL ADIPOSE TISSUE AND BLOOD LIPIDS IN PERSONS REPORTING FAT REDISTRIBUTION SYNDROME SWITCHED FROM PI THERAPY TO EFAVIRENZ Antiviral Therapy 1999; 4(Supplement 2):64 (abstract no. 055) GJ Moyle, C Baldwin, S Comitis, N Dent and BG Gazzard Plasma levels of lipids do not correlate with visceral fat storage. Lipid levels may rise after substitution of a PI with efavirenz. Changes in cholesterol levels in patients substituting a PI with efavirenz may represent movement of lipids to or from visceral stores. Virological control is maintained in NNRTI-naïve persons with viral loads <500 copies/ml substituting a PI for efavirenz. |
| 056 | AN INCREASE IN ABDOMINAL GIRTH ON PROTEASE INHIBITOR THERAPY IS ASSOCIATED WITH VISCERAL OBESITY AND METABOLIC DISTURBANCES THAT CLOSELY RESEMBLE SYNDROME X Antiviral Therapy 1999; 4(Supplement 2):64 (abstract no. 056) L Kosmiski, D Kuritzkes, K Lichtenstein, K Greenberg, J Ehrlich and RH Eckel An increase in abdominal girth on PI therapy is associated with marked visceral obesity and metabolic disturbances, including insulin resistance, that closely resemble syndrome X. Marked visceral adiposity is present in the absence of a high waist circumference and early evidence of CHD was present. |
| 057 | IMPACT OF PI-SPARING HAART REGIMENS ON ADHERENCE, QUALITY OF LIFE AND EMOTIONAL STATUS OF HIV-POSITIVE PATIENTS SUFFERING LIPODYSTROPHY Antiviral Therapy 1999; 4(Supplement 2):65(abstract no. 057) CR Fumaz1, A Tuldrà1, MJ Ferrer2,R Paredes1 and B Clotet2 After a switch to PI-sparing HAART, ADH was not affected and QL improved. The initial decay and subsequent recovery in ES may reflect a process of adaptation to the new syndrome. |
| 058 | INCIDENCE OF METABOLIC CHANGES AND LIPODYSTROPHY IN TWO TRIALS COMPARING DOUBLE VERSUS TRIPLE ANTIRETROVIRAL THERAPY IN EARLY HIV DISEASE Antiviral Therapy 1999; 4(Supplement 2):66 (abstract no. 058) F Garcia, M Ortega, A Cruceta, C Tortajada, A Soriano, L Zamora, JM Mira, T Pumarola and JM Gatell for the Spanish EARTH Studies There were no significant changes in fasting cholesterol, triglycerides and glucose levels after 1 year of double or triple antiretroviral therapy, except in the group receiving stavudine/lamivudine/ritonavir. Clinical lipodystrophy was exceptional in these trials. Incidence of metabolic abnormalities may be lower in early stages of HIV-1 disease. |
| 059 | A STUDY OF THE EFFECTIVENESS OF REGULAR EXERCISE ON LEAN BODY MASS, BODY CELL MASS AND QUALITY OF LIFE IN PEOPLE LIVING WITH HIV/AIDS Antiviral Therapy 1999; 4(Supplement 2):66 (abstract no. 059) S Tenzif1, J Austin1, P Ford2 and G Robinson3 The results suggest that regular cardiovascular and resistance training may maintain or increase BCM, LBM, and QOL in PHAs. |
| 060 | LIPID ABNORMALITIES IN HIV-1-POSITIVE PATIENTS TREATED WITH PROTEASE INHIBITORS Antiviral Therapy 1999; 4(Supplement 2):67 (abstract no. 060) G Behrens1, HH-J Schmidt2, J Genschel2, A Dejaml, R Haas2, M Stoll1, MP Mann2 and RE Schmidt1 The frequency of hyperlipidaemic risk factors was surprisingly high in the studied group, which in turn may explain the proposed increased risk of atherogenesis in HIV-1 protease inhibitor-treated patients. Therefore, HIV-1 protease inhibitor-treated subjects should also be evaluated for their lipoprotein pattern, which may require antihyperlipidaemic interventions. |
| 061 | PERSON-TIME ANALYSIS COMPARING RATES OF ADVERSE EVENTS POSSIBLY RELATED TO INCREASED LIPIDS BETWEEN NELFINAVIR AND CONTROL PATIENTS IN FIVE CLINICAL TRIALS Antiviral Therapy 1999; 4(Supplement 2):67(abstract no. 061) K Cormier, R Lewis and NJ Clendeninn Among 1229 HIV-positive patients in five clinical trials (505, 506, 511, 534, 542) the median duration on nelfinavir was 12.4 months (range 0.2-19.6 months). Rates, among both nelfinavir patients and controls, were low for all AEs. One unconfirmed MI was reported in 1129 person-years on nelfinavir (0.89 per 1000 person-years); none was reported in 105 person-years on control. Six cases of fat redistribution were reported in 1130 person-years on nelfinavir (5.31 per 1000 person-years); one case was reported in 104 person-years on control (9.59 per 1000 person-years). There was no statistically significant association between nelfinavir use and any AE under investigation. |
| 062 | EVIDENCE FOR LIPODYSTROPHIC SYNDROME IN HIV-INFECTED CHILDREN Antiviral Therapy 1999; 4(Supplement 2):68 (abstract no. 062) D Jaquet, M Levine, E Ortega, M Polak and C Lévy-Marchal Our preliminary data confirm that morphological and metabolic changes occur in HIV-infected children and suggest that: (i) lipodystrophy is seen in nearly 50% of the children; and (ii) morphological changes are associated with metabolic disorders. Altogether, the clinical features in children look similar to those observed in adults. A larger study population is required to precisely characterize the lipodystrophic syndrome in children. A longitudinal follow-up is necessary to define the evolution and consequences of the metabolic disorders. |
| 063 | ABNORMALITIES IN HIV-ASSOCIATED LIPODYSTROPHY SYNDROME THAT VARY BY WEIGHT STATUS Antiviral Therapy 1999; 4(Supplement 2):68 (abstract no. 063) N Muurahainen1, R Pettit1, D Kotler2, 1 Falutz3, G Santos4,M Kleintop1, M Glesby2 and SALSA Investigators Group Buffalo hump is more common in overweight patients. Other abnormalities are also significantly associated with weight status (BMI) in patients with HALS. These preliminary findings may help explain some of the variability in abnormalities reported in different cohort studies of this syndrome. |
| 064 | HIV-PROTEASE INHIBITOR DECREASES INSULIN-STIMULATED GLUCOSE TRANSPORT IN SKELETAL MUSCLE Antiviral Therapy 1999; 4(Supplement 2):69 (abstract no. 064) LA Nolte, KE Yarasheski, K Kawanaka and JO Holloszy Insulin stimulation of phosphatidylinositol 3-kinase activity and phosphorylation of protein kinase B/Akt were not decreased in muscles incubated with 20 μM indinavir, suggesting that indinavir may inhibit GLUT4 translocation or activity, rather than insulin signalling. |
| 065 | STAVUDINE USE IS NOT ASSOCIATED WITH AN INCREMENTAL RISK OF HYPERLIPIDAEMIA DURING TREATMENT WITH HIV-1 PROTEASE INHIBITORS Antiviral Therapy 1999; 4(Supplement 2):70 (abstract no. 065) FWNM Wit, EH Gisolf, LMM Oostweegel, GJ Weverling, JMA Lange, P Reiss and SA Danner Similar elevations of TG and total chol occurred in both arms. The addition of stavudine was not associated with an incremental risk of hyperlipidaemia. |
| 066 | TREATMENT WITH DELAVIRDINE IN COMBINATION WITH NRTIs AND/OR PIs IS NOT ASSOCIATED WITH LIPODISTROPHY OR METABOLIC LIPID/GLUCOSE DISTURBANCES Antiviral Therapy 1999; 4(Supplement 2):70 (abstract no. 066) M Para1, B Conway2, D Kuritzkes3, J Eron4, L Wathen5, C Greenwald5, L Paxton5, C Pietrantoni5, J Lee5 and W Freimuth5 Results from multiple clinical protocols indicate that there is no apparent significant risk of developing lipodystrophy, metabolic lipid disorders, or elevation of glucose, triglycerides, or cholesterol when delavirdine is added to NRTI and/or PI combination therapy compared to control combinations. |
| 067 | CONTRIBUTION OF NRTIs COMBINATIONS ON LIPODYSTROPHY AND IMPACT OF THERAPY SWITCHING Antiviral Therapy 1999; 4(Supplement 2):71 (abstract no. 067) Polo R, Verdejo J, Martinez S, Martinez-Olaiz S, Gonzalez M, Gomez-Cano M, Gonzalez-Lahoz J The significant differences on LD incidence among the groups suggest NRTIs must have some impact in the emergence of LD. The strongest effect on LD development was shown by the stavudine+ didanosine combination (88.2 %) in contrast with zidovudine+lamivudine group (2.2%). The switch of therapy in the 10 patients from stavudine+didanosine to zidovudine+lamivudine led to significant improvements (as early as 12 weeks) on triglyceride levels and anthropometric measurements which continued to improve at 24 weeks. Further research is warranted. |
| 068 | PROSPECTIVE FOLLOW-UP OF A PI SUBSTITUTION FOR EFAVIRENZ IN PATIENTS WITH HIV-RELATED LIPODYSTROPHY SYNDROME Antiviral Therapy 1999; 4(Supplement 2):71 (abstract no. 068) W Rozenbaum1, N Adda1, T Nguyen1, Y Salhi1, C Vigouroux2, J Capeau2 and S Gharakhanian1 Switching PI therapy to efavirenz in patients with HRLS did not lead to significant differences in clinical and metabolic abnormalities after three months. Three patients reached end points: two for side effects and one for virological failure. |
| 069 | CAUSES OF ELEVATION OF LACTIC ACID LEVEL IN HOSPITALIZED HIV-INFECTED PATIENTS Antiviral Therapy 1999; 4(Supplement 2):72 (abstract no. 069) W Tantisiriwat, P Tebas, L Polish, E Casabar, W Powderly and C Pichtenbaum Elevation of lactic acid level is an uncommon condition in admitted HIV infected patients. Sepsis is the most common cause. Lactic acidosis syndrome secondary to antiretroviral medication is an infrequent cause of elevation of lactic acid level. Aetiology of unexplained lactic acidosis in the setting of antiretroviral therapy needs further investigation. |
| 070 | HEPARIN-RELEASABLE LIPOPROTEIN LIPASE ACTIVITY IS REDUCED IN HIV PI-ASSOCIATED HYPERTRIGLYCERIDAEMIA Antiviral Therapy 1999; 4(Supplement 2):72 (abstract no. 070) KE Yarasheski, P Tebas, D Marin, S Lassa-Claxton, WG Powderly and CF Semenkovich Decreased LPL activity in the peripheral tissues appears to contribute to HIV PI-associated hypertriglyceridaemia. We hypothesize that the insulin resistance associated with HAART plus PI therapy reduces heparin-releasable LPL activity. This contributes to the hyper-triglyceridaemia associated with HAART plus PI therapy. |
| 071 | CLINICAL FACTORS RELATED TO THE SEVERITY OF FAT REDISTRIBUTION IN THE HIV OUTPATIENT STUDY (HOPS) Antiviral Therapy 1999; 4(Supplement 2):73 (abstract no. 071) K Lichtenstein1, D Ward2, K Delaney3, A Moorman4, F Palella5, B Young1, K Wood6, S Holmberg3 and the HOPS Investigators Independent associations exist between fat redistribution and factors which include but are not limited to protease inhibitor therapy, particularly time since HIV diagnosis, immune factors, age, and various classes of antiretroviral drugs, which suggest that causes of this syndrome are multifactorial. |
| 072 | TREATMENT WITH HIV-1 PROTEASE INHIBITORS IS ASSOCIATED WITH IMPAIRED GLUCOSE TOLERANCE, BETA-CELL FUNCTION AND LIPID METABOLISM Antiviral Therapy 1999; 4(Supplement 2):73 (abstract no. 072) G Behrens1, A Dejam1, HH-J Schmidt3 H-J Balks2, G Brabant2, T Körner1, M Stoll1, RE Schmidt1 Combination drug regimens including PI are accompanied by IGT, hyperproinsulinemia as an indicator for beta-cell dysfunction, and lipid abnormalities proven to be significant risk factors for coronary heart disease. Moreover, PI may have impact on processing of proinsulin to insulin. |
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