CD4 nadir and antiretroviral exposure predict premature polypathology onset

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1 CD4 nadir and antiretroviral exposure predict premature polypathology onset Guaraldi Giovanni Metabolic Clinic Infectious and Tropical Disease Unit University of Modena and Reggio Emilia, Modena, Italy

2 HIV & Ageing: evidence for a phenotype Polypathology Disability Frailty

3 Aim of the Study Hp: We hypothesized that the increased prevalence of Non-Infectious Co-Morbidities (NICM) observed among HIV-related patients, when compared to the general population, is the result of premature aging among HIV infected persons Obj: The objective was to compare the prevalences of and risk factors for common age-related co-morbidities among HIV infected persons versus matched controls

4 Materials and Methods A cross-sectional, retrospective, case-control study using data from patients who were observed from 2002 to 2009 Cases: 2854 HIV+ on ART Consecutive pts attending the MC (805 from Modena HIV Clinic) Controls: 8562 age, sex, race and geografical areamatched adults selected by CINECA ARNO Observatory database CINECA ARNO Observatory database aggregate vital statistics, health and social indicators including: general practitioner's prescriptions, hospital admissions and discharges, diagnosis tests and diagnostic examinations prescriptions. It is active since 1986, collecting data from a population of 11 million of inhabitants from 32 Health Units in Italy indivduals were recruted

5 Materials and Methods End points: 1. Non Infectious Co-Morbidities (NICM) including: CVD, Htn, T2DM, renal failure, fractures Anamnestic/diagno stic Drug tracing ICD9 Drug tracing 2. Poly-pathology (Pp) was defined as the association of 2 or more NICM

6 Results Baseline characteristics It was assumed that controls never had CD4+ nadir <200 cell/μl

7 Result Probability of Non Infectious Co-Morbidities (NICM)

8 Non Infectious Co-morbidities risk in cases and controls Renal failure T2 Diabetes Mellitus Bone fracture Hypertension Cardiovascular Disease All p< 2.2e-16

9 Poly-patology prevalence in cases and controls, stratified by age categories Pp 3.9% 9.0% 20.0% 46.9% Pp 0.5% 1.9% 6.6% 18.7% Pp prevalence was higher in cases than controls in all age strata (all p-values <0.001) Pp prevalence seen cases aged was similar to that observed among controls aged controls (p=0.282)

10 Polypathology risk and age Risk of polypathology according to age HIV-infected (cases) Controls Descriptive representation of the difference between the 2 curves on the horizontal sense: how older are controls than cases, depending on an equal incidence of Pp, per fixed values of estimated probability

11 Association among Non Infectious Co-morbidities Age età e Gender sesso f A grapho Model was used to verify the hypothesis that the four NICM diabetes mellitus, CVD, bone fracture and renal failure were statistically independent after adjustment for gender, age and the presence of hypertension b ipertensione Hypertension fratture a Bone fractures d cvd.tot CVD c diabete T2DM g insuf.renale Renal failure The log-linear model specifying this hypothesis provides a very good fit of the data

12 Probability of polypathology by age among persons with hypertension and without hypertension Poplypathology including Hypertension Poplypathology not including Hypertension HIV-infected (cases) Controls Htn is the necessary ingredient to develop Pp

13 Independent Predictors of Polypathology: Multivariable logistic regression model ß St.error P-value Age, per 1 yr of increase <0.001 Gender (male) <0.001 CD4+ nadir <200 cell/μl <0.001 ARV exposure, per 1 yr of increase <0.001

14 Limitations There may have been inherent differential sensitivities in our ability to detect co-morbidities among cases versus controls since our methods of NICM discernment were, by necessity, different for these two patient groups. The cross-sectional nature of our study implies the possibility that a survival bias may have occurred in which patients with better prognoses were selected out, especially in the higher age group categories.

15 Is MC cohort representative of HIV clinic patients?

16 Discussion Age-related NICM and Pp were significantly more common among HIV infected patients than persons in the general population within each age stratum studied. Hypertension appear to the epidemiological link among NICM Pp prevalence among among HIV-infected persons anticipated Pp prevalence in the general population by 10 years HIV- specific factors (lower nadir CD4 nadir and more prolonged ART exposure) are independent predictors of Pp Earlier NICM screening is warranted for HIV-infected patients.

17 Biological age is increased in HIV infected patients 53.50% 46.50% CAC > 0 CAC = 0 Increased Vascular Age Below expected Vascular Age Expected Vascular Age We observed an average increase of 15 (range 1-43) years compared to their chronological age. The only predictor of increase coronary age was current CD4 Guaraldi G, Clin Infect Dis (11):

18 HIV & Ageing: Next steps to evidence for a phenotype Disability Polypathology Frailty Research questions: 1.Does Pp has the same impact on disability and frailty as in the general population? 2.Is the HIV aged individual frail or fit?

19 Acknoledgments Menozzi M, Zona S Garlassi E, Orlando G Carli F, Cocchi S Berti A Rossi E De Rosa M Palella F Thank you for your attention