judith schouten on behalf of the age h iv study group
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Comorbidity and ageing with HIV A prospective comparative cohort study. XIX International AIDS Conference July 26 th 2012, Washington DC. Judith Schouten on behalf of the AGE h IV study group. Background & Rationale. - PowerPoint PPT PresentationTRANSCRIPT
Judith Schoutenon behalf of the AGEhIV study group
XIX International AIDS Conference July 26th 2012, Washington DC
Comorbidity and ageing with HIVA prospective comparative cohort study
Background & Rationale
• Combination antiretroviral therapy (cART): decline in AIDS-associated morbidity and mortality
• Life-expectancy: still shorter than expected, particularly when cART started late1
• Large proportion of HIV-patients: broad range of comorbidities2
1 Bhaskaran K, Hamouda O, Sannes M, et al. JAMA 2008 Jul 2;300(1):51-9. 2 Hasse B, Ledergerber B, Furrer H, et al. Clin Infect Dis 2011 Dec;53(11):1130-9.
Are age-related comorbidities more prevalent and/or occurring at a younger age in HIV-infected individuals
as compared to in HIV-uninfected individuals?
Design & Study population
Prospective comparative cohort study (started October 2010)
Prevalence (and incidence) of age-associated non-communicable comorbidities (AANCC) and their risk factors in persons ≥45 yrs
Participants:
• HIV-1-infected: from the HIV outpatient clinic at the Academic Medical Center (Amsterdam)
• HIV-1-uninfected: from the Amsterdam Municipal Health Service sexual health clinic, and the ongoing Amsterdam Cohort Studies on HIV/AIDS
Statistical analysis
Preliminary comparison of prevalence of AANCC using currently available baseline data
Multivariable ordinal logistic regression (proportional odds model) to assess the contribution of HIV and traditional risk factors towards AANCC
Outcome measure: Number of AANCC per participant
Covariates explored: age, gender, ethnicity, packyears of smoking, alcohol abuse, substance abuse (XTC, cocaine, cannabis), BMI, sexual orientation (MSM), HIV-status
Comorbidities analyzed
In addition, objective assessment of:• Hypertension:
3 measurements with a 1-minute interval;RR ≥140 and/or ≥90 in all 3 measurements
• Chronic Obstructive Pulmonary Disease: 3 forced expiratory measurements; FEV1/FVC < 0.7 in all 3 measurements
• Diabetes mellitus:HbA1c (IFCC) ≥ 48 mmol/mol and/or Glucose (non-fasting) ≥ 11.1 mmol/L and/orGlucose (fasting) ≥ 7.0 mmol/L
• Reduced renal function:eGFR (CKD-EPI) < 60 mL/min
• Osteoporosis:DXA T-score < -2.5 SD
Hypertension
Angina pectoris
Myocardial infarction
Peripheral arterial insufficiency
Cerebrovascular disease
Diabetes mellitus type 2
Chronic Obstruct Pulm Disease
Chronic liver disease
Reduced renal function
Cancer
Atraumatic fracture/osteoporosis
• Data on the following AANCC were available for analysis• Most of the AANCC were identified as self-reported by participants using a
standardized questionnaire (validation in progress)
Demographic and HIV characteristics
HIV neg(n=452)
HIV pos(n=489) p-value
Age (years) 51.5 (47.5-57.6) 52.9 (48.1-59.8) 0.009 Male gender 83.8% 89.4% 0.013Dutch 82.1% 75.1% 0.037MSM 63.5% 68.5% 0.105Years of known HIV-1 seropositivity (years) 12.2 (6.5-17.3)Mean CD4 count in year prior to enrollment (cells/mm3) 573 (436-748)
Nadir CD4 count (cells/mm3) 210 (130-310)Undetectable during year prior to enrollment 85.0%Prior AIDS 30.1%
On cART
91.2%• 74% started Rx-naive • 26% started ART-exp.
Years since start of first ART (years) 11.2 (5.5-14.9)
Data presented as median (IQR) or percentage as appropriate
Comorbidity risk factors
HIV neg(n=452)
HIV pos(n=489) p-value
Smoking (packyears) 3.0 (0.0-18.5) 7.6 (0.0-31.0) <0.001
Currently smoking 23.9% 31.9% 0.006
Heavy daily drinking 6.9% 3.5% 0.019
Daily to monthly use of cannabis and/or XTC and/or cocaine 17.5% 17.6% 0.965
BMI (kg/m2) 24.5 (22.9-27.0) 24.1 (22.3-26.7) 0.021
Blood pressure systolic (mmHg) 133 (125-143) 135 (126-147) 0.028
Blood pressure diastolic (mmHg) 79 (72-85) 82 (75-89) <0.001
Data presented as median (IQR) or percentage as appropriate
Comorbidity prevalence
HIV neg(n=452)
HIV pos(n=489) p-value
≥1 AANCC (%) 60.4% 74.4% <0.001
Number of AANCC (mean (SD)) 0.9 (0.95) 1.4 (1.27) <0.001
Comorbidity in relation to age
Comorbidity in relation to age
Comorbidity in relation to age
Comorbidity distribution
*
Risk factors for comorbidity• Multivariable ordinal logistic regression model
• BMI, use of XTC/cocaine/cannabis/alcohol, ethnicity and sexual orientation (MSM) were not found to be independent risk factors
Risk factors for comorbidity• Multivariable ordinal logistic regression model
• BMI, use of XTC/cocaine/cannabis/alcohol, ethnicity and sexual orientation (MSM) were not found to be independent risk factors
OR 2.1
Risk factors for comorbidity• Multivariable ordinal logistic regression model
• Adding estimated duration of HIV infection to the model
Risk factors for comorbidity• Multivariable ordinal logistic regression model
• Adding estimated duration of HIV infection to the model
OR 1.16
Risk factors for comorbidity• Multivariable ordinal logistic regression model
• Adding duration of ART exposure to the model
Risk factors for comorbidity• Multivariable ordinal logistic regression model
• Adding duration of ART exposure to the model
OR 1.35
The role of AGE accumulation
• AGEs = Advanced Glycation Endproducts• Non-enzymatic glycation of proteins/lipids/DNA• AGE accumulation is influenced by age, smoking, inflammation, renal
function, diabetes• Level of AGEs increases with age (ageing biomarker?)• AGEs in the skin measured with skin autofluorescence (AGE-reader)• Measured AGE-values were compared to existing reference values,
according to age, gender and smoking1
1 Koetsier M, Lutgers HL, de Jonge C, et al. Diabetes Technol Ther 2010 May; 12(5); 399-403.
The role of AGE accumulation
The role of AGE accumulation
The role of AGE accumulation
The role of AGE accumulation• Adding excess AGE accumulation to the model (per 10% above the reference AGE value)
The role of AGE accumulation• Adding excess AGE accumulation to the model (per 10% above the reference AGE value)
OR 1.08
Conclusions
• AANCC were significantly more prevalent amongst HIV-positives compared to uninfected controls of similar age
• (Longer duration of) being HIV infected / exposure to cART were associated with a higher prevalence of AANCC(in a cohort almost exclusively on cART)
• HIV-positive participants consistently had excess accumulation of AGEs
• Excess accumulation of AGEs was independently associated with a higher prevalence of AANCC (causality cannot be established in a cross-sectional analysis)
AgehIV Study Team
Academic Medical CenterP. Reiss (PI) F.W. WitM. van der Valk J. Schouten K. KooijB.C. Elsenga A. Henderiks
Public Health Service AmsterdamM. Prins (co-PI)I.G. StolteM. Martens J. BerkelS. MollA. van RoosmalenG.R. Visser
HIV Monitoring Foundation F. de Wolf S. Zaheri Y.M. Ruijs L. GrasA. KesselringAmsterdam Institute of Global Health and DevelopmentM. HeidenrijkR. Meester F. Janssen Financial support:The Netherlands Organisation for Health Research and Development (ZonMW) grant nr. 300020007 & Stichting AIDS Fonds grant nr. 2009063Additional unconditional grants from: Gilead Sciences Boehringer Ingelheim ViiV Healthcare Abbott
Janssen PharmaceuticalsMerck & CoBristol Myers Squibb
AgehIV Study Team: additional collaborators
AMC Dept. of Infectious Diseases S.E. Geerlings, J.M. Prins, J.T. van der Meer, F.J. Nellen, M.H. Godfried, T. van der Poll, M. van Vugt, W.J. Wiersinga, H.E. Nobel, J. van Eden, M. Mutschelknauss-Rikken, A. van Hes, A. Westerman, F. Pijnappel
Experimental Immunology & Lab Viral ImmunopathogenesisN. Kootstra, J. Hamann, E. van Leeuwen, M. Joerink, A.B. van ‘t Wout, H. Schuitemaker, P. Baars, R. Lutter
CardiologyJ. de Jong
Vascular medicineB.J. van den Born, E. Stroes, B. van den Bogaard, E. de Groot
EndocrinologyM. Serlie, P. Bisschop, P. Lips (VUMC)
OncologyD. Richel
Geriatric medicineS. de Rooij
Nuclear medicine B. van Eck-Smit, M. de Jong
Pulmonary medicine R. van Steenwijk, E. Dijkers
Nefrology J. Willemsen, R. Krediet
Gastro-enterology E. Dekker
Psychology P. Nieuwkerk
Sexuology R. van Lunsen, M. Nievaard
Neurology P. Portegies
Neuropsychology B. Schmand
Neuroradiology C. Majoie, M. Caan, T. Su, F. Vos
Ophthalmology F. Verbraak, N. Demirkaya
Psychiatry E. Ruhé, I. Visser
HIV Vereniging Nederland M. Mulder
And of course many thanks to all study participants!