Abstracts presented at the
13th International Workshop on Adverse Drug Reactions
and Co-morbidities in HIV
Rome, Italy, 14–16 July 2011
13th International Workshop on Adverse Drug Reactions and Co-morbidities in HIV v
ORGANIZING COMMITTEE
Chairs for 2011Kathleen Mulligan University of California at San Francisco, CA, USA Peter Reiss University of Amsterdam, Amsterdam, the Netherlands Giovanni Guaraldi University of Modena, Modena, Italy
Andrew Carr St Vincent’s Hospital, Sydney, Australia
Jacqueline Capeau Faculty of Medicine Saint Antoine, INSERM, Paris, France David Cooper University of New South Wales, Sydney, Australia
Stefan Mauss Center for HIV and Hepatogastroenterology, Düsseldorf, Germany Morrie Schambelan University of California at San Francisco, CA, USA
Ian Weller University College London Medical School, London, UK
SCIENTIFIC COMMITTEE
Georg Behrens Medical School of Hannover, Hannover, Germany Todd Brown Johns Hopkins University, Baltimore, MD, USA Judith Currier University of California, Los Angeles, CA, USA Gregory Dore University of New South Wales, Sydney, Australia Michael Dubé University of Southern California, Los Angeles, CA, USA
Julian Falutz Immune Deficiency Treatment Center, Montreal General Hospital, Montreal, Canada Steve Grinspoon Massachusetts General Hospital, Boston, MA, USA
Carl Grunfeld University of California Medical Center, San Francisco, CA, USA Donald Kotler Columbia University, New York, NY, USA
Jules Levin The National AIDS Treatment Advocacy Project, New York, NY, USA Jens Lundgren University of Copenhagen, Hvidovre, Denmark
Esteban Martínez IDIPAPS - Hospital Clinic, University of Barcelona, Barcelona, Spain Veronica Miller The George Washington University, Washington, DC, USA Graeme Moyle Chelsea and Westminster Hospital, London, UK Robert Munk AIDS INFO NET, Arroyo Seco, NM, USA Bill Powderly University College, Dublin, Ireland Massimo Puoti University Hospital, Brescia, Italy
Willy Rozenbaum Hôpital Tenon, Université Pierre et Marie Curie, Paris, France Pablo Tebas University of Pennsylvania, Philadelphia, PA, USA Sharon Walmsley University Health Network, Toronto, Canada Heiner Wedemeyer Hannover Medical School, Hannover, Germany Kevin Yarasheski Washington University, St Louis, MO, USA
PLENARY SPEAKERS
Paola Cinque San Raffaele Scientific Institute, Milan, Italy Göran Hansson Karolinska Institutet, Stockholm, Sweden
Jan Hoeijmakers, Erasmus University Medical Center, Rotterdam, the Netherlands Tom Hostetter Albert Einstein College of Medicine, New York, USA
Robert Ross Queen’s University, Kingston, Ontario, Canada George Schett University of Erlangen-Nuremberg, Erlangen, Germany
ORGANIZING SECRETARIAT
International Medical Press 36 St Mary at Hill London EC3R 8DU, UK Tel: +44 20 7398 0700 Fax: +44 20 7398 0701 www.intmedpress.com
E-mail: lipodystrophy@intmedpress.com
13th International Workshop on Adverse Drug Reactions and Co-morbidities in HIV xiii
PAGE TITLE AND PRESENTING AUTHOR ABSTRACT
ORAL PRESENTATIONS
Session 1
A3 Application of 16S ribosomal RNA gene-targeted pyrosequencing to O01 investigate the consequence of HIV disease and antiviral therapy on the
gut microbiome: a microbial (meta)genomic snapshot of duodenal biopsies, luminal aspirates, and stool pre- and post-treatment
CL Ellis
A3 Microbial translocation and metabolic and morphologic measures in O02 treated and untreated HIV infection
MP Dubé
A4 Tauroursodeoxycholic acid ameliorates ritonavir-induced ER stress and O03 insulin resistance
DN Reeds
A5 Abnormal reduction in serum FGF19 levels and in the expression of O04 receptors for FGF19/FGF21 in adipose tissue from HIV-infected patients
F Villarroya Session 2
A5 Plasma markers of bone loss and bone formation decrease with O05 intermittent antiretroviral therapy and predict change in bone
mineral density
J Hoy
A6 Lower fat mass and lower bone formation predict greater bone loss with O06 tenofovir in HIV-infected adults
A Carr
A7 Osteoporotic fracture risk associated with cumulative exposure to O07 tenofovir and other antiretroviral agents
R Bedimo
A7 Prevalence and risk factors of subclinical vertebral fractures in a cohort O08 of HIV positive patients
K Luzi Session 3
A8 Bone mineral density (BMD) analysis in antiretroviral (ART)-naive subjects O09 taking lopinavir/ritonavir (LPV/r) combined with raltegravir (RAL) or
tenofovir/emtricitabine (TDF/FTC) for 96 weeks in the PROGRESS Study
RB Qaqish
A9 Traditional risk factors overshadow HIV-related factors in predicting O10 vitamin D deficiency in HIV-infected children and young adults
AC Ross
ABSTRACT CONTENTS
Programme & Abstracts xiv
PAGE TITLE AND PRESENTING AUTHOR ABSTRACT
A9 Safety and efficacy of once-monthly dosing of vitamin D3 (50,000 IU) in O11 HIV-infected youth: Adolescent Trials Network Study 063
K Mulligan Session 4
A10 HIV-infected patients exhibit a worse cardiovascular risk profile after a O12 first episode of acute coronary syndrome. Final results of long term follow
up in the PACS-HIV study
F Boccara
A11 Antiretroviral therapy can be associated with increase in LDL O13 apolipoprotein-B residence time without increase in LDL-apo-B oxidation
and glycation
S Das
A12 Association of different lipid measures for atherogenic lipid fractions and O14 risk of coronary events in patients receiving combination antiretroviral
therapy: the Swiss HIV Cohort Study
HC Bucher
A13 How much do smoking, hypertension and diabetes contribute to acute O15 coronary syndrome in HIV-infected patients relative to uninfected patients?
M Calvo-Sánchez
A14 Changes in biomarkers in HIV-1-infected treatment-naive subjects treated O16 with tenofovir DF/emtricitabine plus atazanavir/ritonavir or
lopinavir/ritonavir for 96 weeks: the CASTLE biomarker substudy
G Moyle Session 5
A14 Development of a definition for rapid progression of renal disease in O17 HIV-positive persons
L Ryom
A15 Renal disease in HIV-infected children and adolescents participating in O18 THE
AF Camacho-Gonzalez
A16 Impact of tenofovir-associated renal dysfunction among HIV-infected O19 patients with low body-weight: a retrospective cohort study of the
Japanese patients
T Nishijima
A17 Effect on renal function of tenofovir co-administered with either O20 efavirenz or boosted lopinavir or boosted atazanavir: the Swiss HIV
Cohort Study
HC Bucher Session 6
A18 Raltegravir as replacement for PI- or NNRTI-based ART in HIV-infected O21 women with lipohypertrophy: The Women, Integrase, and Fat
Accumulation Trial
JE Lake
A18 Surrogate markers of visceral adipose tissue (VAT) in HIV-infected males: O22 how accurate are they?
J Falutz
13th International Workshop on Adverse Drug Reactions and Co-morbidities in HIV xv
PAGE TITLE AND PRESENTING AUTHOR ABSTRACT
A19 Results from the pooled DEXA substudies of the double-blind, randomised, O23 Phase III trials comparing rilpivirine (RPV, TMC278) versus efavirenz (EFV)
in treatment-naive, HIV-1-infected adults
P Tebas
A20 The influence of HLA supertype on thymidine analogue induced body O24 composition changes in STEAL
DV Cordery
POSTER PRESENTATIONS
Adipocyte biology
A25 Lipomatosis in HIV-1-infected patients: comparative analysis of the P01 molecular signature in ‘buffalo hump’ and lipomas at distinct anatomical
sites
M Giralt Aging & associated disorders
A27 Cost of non-infectious co-morbidities in patients with HIV P02
G Guaraldi
A27 Premature decline of serum total testosterone in human immunodeficiency P03 virus (HIV) infected men with HIV-related lipodystrophy in the highly active
antiretroviral therapy (HAART) era: a cross-sectional observational study
G Guaraldi
A28 Prevalence of sarcopenia defined by skeletal muscle mass and function in P04 an urban cohort of older HIV-infected patients under care
P Wasserman Body composition
A29 Longitudinal relationships between self-reported body fat changes and P05 physical and mental health-related quality of life in the Multicenter AIDS
Cohort Study (MACS)
TT Brown
A29 Metabolic risk factors in responders to tesamorelin, a growth hormone- P06 releasing factor (GRF) analogue, in HIV-infected patients with excess
abdominal fat
J Falutz
A30 Coronary artery calcification is associated with femoral but not with P07 lumbar spine mineral density
G Guaraldi
A31 The Metabolic Abnormalities, Telmisartan, and HIV Infection (MATH) Trial P08
JE Lake
A31 Peripheral intermuscular adipose tissue and intramyocellular lipids: other P09 fat compartments implicated in HIV-associated lipodystrophy changes
seen on switching from thymidine analogues to tenofovir
A Milinkovic
A32 Lipodystrophy, is it still relevant? P10
J Price
Rome, Italy, 14–16 July 2011
Programme & Abstracts A30
Method: Two Phase III multicenter, randomized,
double-blind, trials, consisting of 26-week, placebo-controlled primary intervention phase followed by 26-week exten-sion phase were conducted. Data from the two studies were pooled. In the per-protocol population, 402 HIV patients with excess abdominal fat were treated with tesamorelin for the main phase (26 weeks) and 176 patients for both phases (52 weeks). Statistical analy-ses were performed on combined results from the two trials using ANCOVA models for efficacy and some safety parameters.
Results: Dropout rates were similar in treatment
and placebo groups. At week 26, 68.8% (n=232) of tesamorelin-treated patients vs 32.6% (n=56) of pla-cebo-treated patients were categorized as responders (P 0.001). 72.4% of patients treated with tesamor-elin for 52 weeks were categorized as responders. Changes from baseline (mean [standard deviation]) in tesamorelin-treated responders versus non-responders are shown in Table 1 for the main and the extension phases.
Distress due to belly image as assessed by patients was also improved in VAT responders at week 26 (score change: 15.53 vs 3.40 [P 0.001]). FBG and insulin were unchanged in responders and deteriorated in non-responders.
Conclusion: This analysis revealed a significantly
greater responder rate in tesamorelin-treated patients compared to placebo. FBG and insulin were unchanged in the responders but deteriorated in non-responders. These data show that no clinically significant changes in glucose parameters occurred in the large majority of HIV patients with excess abdominal fat respond-ing to tesamorelin, with significant reductions in VAT. Moreover, significant benefits in metabolic risk factors accrued. These data provide important new evidence for the clinical utility and metabolic benefits of strate-gies to reduce VAT by augmenting the biological secre-tion of GH.
ABSTRACT P07
Antiviral Therapy 2011; 16 Suppl 2:A30
Coronary artery calcification is associated with femoral but not with lumbar spine mineral density
A Bellasi1, S Zona2, G Orlando2, F Carli2, S Cocchi2,
G Ligabue3, V Richira4, P Bagni2, P Raggi5,
G Guaraldi2
1Nephrology, Dialysis and Hypertension Department, S Orsola-Malpighi, Bologna, Italy; 2Metabolic Clinic, Infectious and Tropical Diseases Unit, Department of Medicine, University of Modena and Reggio Emilia, Modena, Italy; 3Radiology Unit, Department of Imaging, University of Modena and Reggio Emilia, Modena, Italy; 4Division of Endocrinology, Department of Emergency Medicine, University of Modena and Reggio Emilia, Modena, Italy; 5Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA, USA
Background: Vascular calcification (VC) of the
coro-naries (CAC) is associated with a high risk of cardio-vascular (CV) events and poor survival. A large body of evidence suggests the existence of a link between bone demineralization and VC. We aimed at testing the asso-ciation between CAC and bone mineral density (BMD) in a large cohort of HIV-infected patients.
Materials: We assessed simultaneously CAC as well
as lumbar and femoral BMD in a large cohort of 681 consecutive HIV-infected patients by means of car-diac CT and DEXA. Logistic regression analysis was used to determine the association between low femo-ral and lumbar spine BMD (defined as BMD below the 25th percentile of the study cohort distribution) and extensive CAC (defined as CAC greater than 100 Agatston Unit)
Results: Patients with CAC 100 were older, more likely to be male, diabetic and overweight. In contrast, a bet-ter renal function and a lower CV risk profile was note among patients without extensive CAC 100. At univari-able analyses, a trend toward low femoral (14.26 vs 22.6,
P=0.10) but not lumbar spine BMD (15 vs 16, P=0.95)
was noted. Adjustments for factors associated with either
Week 26 Week 52 VAT (%) -27.4 (14.0) vs 9.8 (14.9)1 -31.1 (16.8) vs 8.1 (13.8)1 WC (cm) -4.2 (5.7) vs -0.4 (4.4)* -4.7 (6.4) vs -1.0 (4.9)* TG (mg/dl) -50 (147) vs -12 (105)* -68 (159) vs 3 (102)* IGF-I (ng/ml) 136 (106) vs 85 (104)* 91 (100) vs 76 (138) FBG (mg/dl) 1 (16) vs 5 (14)* -1 (14) vs 8 (17)* Insulin (µIU/ml) -1.0 (24.7) vs 5.6 (13.2)* -2.5 (18.7) vs 4.8 (17.5)* HbA1c (%) 0.07 (0.34) vs 0.27 (0.41)* 0.03 (0.32) vs 0.18 (0.46)* Table 1. (Abstract P06)
Data are mean (SD).*P 0.05. 1Analysis not done.
Rome, Italy, 14–16 July 2011
13th International Workshop on Adverse Drug Reactions and Co-morbidities in HIV A31
CAC or BMD revealed a significant association between CAC and femoral but not lumbar spine BMD. Indeed, patients with extensive CAC had a twofold higher risk of having a low femoral BMD (OR: 2.24; 95% CI: 1.08–4.65; P=0.03) after adjustment for age, sex, diabe-tes, BMI, Framingham risk score, estimated glomerular filtration rate (by EPI equation), protease inhibitor expo-sure and CD4 nadir.
Conclusion: Current results show that CAC is
independ-ently associated with low BMD in HIV infected patients. Further studies are needed to elucidate the mechanisms that link bone demineralization and VC deposition and whether therapies that impact BMD might also attenu-ate VC progression in HIV-infected patients.
ABSTRACT P08
Antiviral Therapy 2011; 16 Suppl 2:A31
The Metabolic Abnormalities, Telmisartan, and HIV Infection (MATH) Trial
JE Lake1, CH Tseng1, F Wu1, JS Currier1 1University of California, Los Angeles, CA, USA
Background: Visceral adipose tissue (VAT)
accumula-tion in the setting of HIV infecaccumula-tion and ART is not fully understood, and treatment options remain limited. Tel-misartan, an angiotensin receptor blocker and PPAR-G agonist, has been shown to decrease VAT in HIV-unin-fected subjects. This study examines the effects of stand-ard-dose telmisartan on adipose tissue (AT) volumes and metabolic parameters in HIV-infected patients with lipohypertrophy.
Methods: 35 HIV-infected men and women with HIV-1
viral loads 48 copies/ml on ART and central fat accu-mulation (defined for women/men as: waist circum-ference 94/95 cm or a waist-to-hip ratio 0.88/0.94) received open-label telmisartan 40 mg daily for 24 weeks. AT volumes were quantified at 0 and 24 weeks by L4-L5 single slice CT scans. Waist circumference and waist:hip ratios were performed by a single operator using standardized technique. Fasting serum lipids, glu-cose and hs-CRP were obtained. 35 subjects provided 80% power to detect a 10% decrease in VAT over 24 weeks (two-sided alpha 0.05).
Results: 15 women and 20 men were enrolled and
com-pleted the 24-week protocol. At entry (mean or %): age 49; 43% Hispanic, 34% Black, 23% White; 91% non-smokers; CD4 635 cells/mm3; BMI 34.6; 51% PI, 20% NNRTI, 26% RAL, 74% TDF, 66% FTC. After 24 weeks, no significant improvement in VAT was observed, although participants lost a mean of 3.3% (95% CI -11.9%, 5.42%; P=0.45). A significant loss of both total (TAT; 4.2%; 95% CI -8.6, -0.21; P=0.04) and
subcutaneous (SAT; 3.4%; 95% CI -6.41%, -0.46%;
P=0.03) AT was observed. A concomitant decrease in
both waist and hip circumference accompanied SAT loss without an overall change in waist: hip ratio, VAT:TAT ratio, weight or BMI.
This study was not powered to detect differences between subgroups, however women lost 5.2% VAT (P=0.48), while men lost 1.9% (P=0.73). SAT and VAT loss was greater for subjects with BMIr30 at baseline (SAT: 5.6% vs 1.0%, P=0.12; VAT: 6.2% vs 0.02%,
P=0.49).
No significant change in lipids, glucose or hs-CRP was observed. The average decrement in systolic/diasto-lic BP over 24 weeks was 7/5 mmHg, similar to that seen in HIV-negative subjects. No related Grade 3 or 4 adverse events occurred.
Conclusions: Telmisartan was extremely well-tolerated.
No significant loss of VAT was demonstrated. However, an overall loss of VAT was observed, and greater losses may have been seen with continued follow-up. SAT loss has not been observed with telmisartan in the HIV-negative population. These findings warrant continued investigation of telmisartan’s effects on AT depots in HIV-infected patients with lipodystrophy, including the potential for differential responses to treatment by sex.
ABSTRACT P09
Antiviral Therapy 2011; 16 Suppl 2:A31
Peripheral intermuscular adipose tissue and intramyocellular lipids: other fat compartments implicated in HIV-associated lipodystrophy changes seen on switching from thymidine analogues to tenofovir
A Milinkovic1,2, AI García1,2, R Sandoval1,2,
M del Amo1,2, J Pomes1,2, X Tomas1,2, J Mallolas1,2 1Hospital Clinic, Barcelona, Spain; 2Biomedical Engineering Department, University of Barcelona, Spain
Background: Subcutaneous adipose tissue (SAT)
decreases and that visceral abdominal fat (VAT) increases in HIV-associated lipodistrophy, measured by DEXA and CT scan. Decreased intermuscular adipose tissue (IMAT) and an elevation of intramyocellular lipid (IMCL) accumulation measured by magnetic reso-nance (MR) have also been described. No longitudinal studies have been reported evaluating any correlation between adipose tissue compartments, their association with metabolic parameters and the effects of switching from thymidine analogues (TA) to tenofovir disoproxil fumarate (TDF)-containing regimens.
Methods: 28 HIV-infected patients, 22 men and 6
women with moderate to severe lipoatrophy receiving
