Il peso clinico e sociale delle comorbosità
Cristina Mussini
Life expectancy from age 20-65 of people who
started antiretroviral
therapy in 2000-8 by CD4 cell count group at start of antiretroviral therapy
compared with that of UK population (2000-6
women and men)
BMJ 2011;343:d6016 doi:
10.1136/bmj.d6016
Componenti del costo annuale della cura dell’infezione da HIV a seconda dei CD4
Sloan CE et al. AIDS. 2012;26:45-56
L’invecchiamento della popolazione HIV positiva
COHERE in EUROCOORD
Median age 31 35 38 41 43 45 (years)
Tutto il mondo NON è paese
Estimates of HCV co-infection in PLHIV in Italy from cohorts’ data
Cohort Icona1 (%) Master2 % (N)
Estimated data in 94.146 PLHIV
linked to care
3PLHIV tested for HCV 75% (11.203)
70.609
PLHIV with anti HCV reactivity
29% (11241) 34% (8439)
21.791
PLHIV with HCV and cirrhosis in the
cohorts
(HCVAb+ & FIB4 >
3.25)
7.7% (3061) 7.8% (3475)
7.390
1. De Luca a et al CROI 2014, 2. Motta et al AIDS Res Ther 2012, 3. Notiziario ISS 2013
Changes in Causes of Death Over Time
1999-2000 (N=255) 2009-2011(N=548)
Weber R, et al. 19th IAC; Washington, DC; July 22-27, 2012; Abst. THAB03104.
Death rate fell from 17.4 deaths per 1000 py in 1999-2000 to 8.3 deaths in 2009-2011
11
Trends in the prevalence of cirrhosis, decompensated cirrhosis, HCC and mortality in 24,040 HIV –infected veterans during period
1996-06 presented according to HCV status
Ioannou V et al HEPATOLOGY 2013
The Treatment Cascade for People with Chronic Hepatitis C Virus Infection in the United States
This review identifies large gaps between current practice and treatment goals for people with chronic HCV infection, and highlights multiple
opportunities for improving engagement along the HCV treatment cascade.
Yehia B et al, CROI 2014
Modena HIV-HCV Cascade
Casi prevalenti al 01/01/2014
• Totale 1571: HCV Ab=498 (32%)
0 25 50 75 100
HCV-Ab HCV RNA+ Trattati SVR 498
414
209
111 53%
27%
Modena HIV-HCV
Cosa rimane da fare
Naive Experienced
Metavir Gt 2-3 Gt 1- 4 Gt 2-3 Gt 1- 4
F0-F1 21 68 5 33
F2 11 27 4 14
F3-F4 13 25 9 33
Gt 1a: 9 pts in lista OLT con SOF+RBV Gt 1b: 6 pts in CUP com SMP+DCV
Trattamenti attesi nel 2015: 80 (30%)
The following co-morbidities were analysed: Hypertension, Type 2 Diabetes, Cardiovascular Disease and Osteoporosis.
Pp prevalence was higher in cases than controls in all age strata (all p-values <0.001). Pp prevalence seen cases aged 41-50 was similar to that observed among controls aged >60 controls (p=0.282).
La prevalenza di polipatologie è più frequente nei soggetti HIV positivi rispetto ai negativi in ogni strato d’età
Guaraldi G. et al. CID 2011
Infarto del miocardio
La popolazione HIV+ è a maggior
rischio di IMA rispetto alla popolazione generale
Islam et al, HIV Medicine 2012
Results confirmed in Freiberg et al, JAMA Internal Med 2013 and Silverberg et al, JAIDS 2014
Cause di morte nella coorte D:A:D
7.9 (ATCC)
21Smith Lancet 2014
Cause of death Percentage
1AIDS-related 29
Liver-ralated 13
Non-AIDS cancers 15
CVD-related 11
Non-natural 10
Bacterial infections 7
Renal 1
Lactic acidosis/pancreatitis <0.5
Others/Unknown 15
Negli anni abbiamo imparato...
Klein et al. CROI 2014
1996-99 2000-03 2004-07 2008-09 2010-11 0
100 200 300 400
MIs per 100.000 py
HIV pos (n=24,768) HIV neg (n=257,600)
Multivariable Poisson model adjusted for age, sex, BMI, HIV risk, cohort, calendar year, race, family history of CVD, smoking, previous CVD event, TC, HDL, hypertension, diabetes.
Rischio relativo di IMA (95% CI)
Peggio Meglio
0.1 0.5 1 5 10
RR: 1.86 (1.31-2.65) Diabete (sì vs no)
RR: 1.30 (0.99-1.72) Ipertension (sì vs no)
Anamnesi familiare
Precedente malattia cardiovascolare
Sesso maschile
Età per 5 anni + vecchio
Fumo
RR: 1.40 (0.96-2.05) RR: 2.92 (2.04-4.18) RR: 2.13 (1.29-3.52) RR: 4.64 (3.22-6.69) RR: 1.32 (1.23-1.41)
Friis-Møller N et al. N Engl J Med. 2007;356:1723-1735.
D:A:D: Fattori di rischio cardiovascolare
tradizionali nella popolazione HIV+
Anche le arterie sono infiammate
Subramanian et al JAMA 2012
Come nelle altre patologie infiammatorie croniche
Meta-analysis showing the effect size (Cohen’s D) of the difference in CIMT between patients with rheumatic disease and control subjects.
Tyrrell et al Arterioscler Thromb Vasc Biol. 2010;30:1014-26.
Martinez et al., AIDS 2010
SPIRAL Study
Cambiare la terapia può avere un ruolo….
… ma smettere di fumare diminuisce il rischio cardiovascolare molto di più
*Adjusted for: age, cohort, calendar yr, antiretroviral treatment, family history of CVD, diabetes, time- updated lipids and blood pressure assessments.
Never Smoked Previous Current Baseline Smoking
< 1 yr 1-2 yrs 2-3 yrs 3+ yrs Stopped Smoking During Follow-up 5
IRR of MI*
1
0.5
1.73
3.40
3.73
3.00 2.62
2.07
D:A:D Study
Petoumenos et al. HIV Medicine 2011
Incidence ratio risk
Fratture e bassa densità minerale
ossea
La BMD diminuisce con l’età
Age, years
Orwoll ES, Klein RF, Endocr Rev, 1995: 16: 87-118
Fratture patologiche aggiustate per età
0 1 2 3 4 5 6 7 8
18-29 30-39 40-49 50-59 60-69 ≥70
Age at Cohort Entry (Years)
Fracture Rate (per 1,000 patient-years)
Vertebral Hip
Wrist Total
General population1
1Data from Triant V, et al., JCEM 2008;93: 3499–3504
Menopausa nelle donne HIV+
Menopausa precoce (< 40 aa)
P=0.04
Schoenbaum et al . Clin Infect Dis 2005.
Women living with HIV were 73% more likely to experience early onset of menopause, compared with HIV-uninfected women (P=0.024) (46 vs 47)
n=303 n=268
26%
10%
0%
5%
10%
15%
20%
25%
30%
HIV infected HIV uninfected
Perdita di BMD con l’inizio della terapia:
~2-6% a 48-96 settimane
Author, y N Wks ART-type Study outcomes
Gallant, 2004 602 144 TDF vs. d4T Spine :TDF-2.2% ; d4T:-1.0%
Hip : TDF: -2.8%; d4T:-2.4%
Tebas, 2007 157 96 NFV vs EFV 2.5% decrease in total BMC Bonnet, 2007 74 36 PI vs non-PI 0.8% decrease in lumbar BMD Brown, 2009 106 96 LPV/r vs AZT/3TC/EFV 2.5% loss in total BMD
Duvivier, 2009 71 48 PI vs Non-PI Spine: -4.1% , Hip: -2.8%
van Vonderen, 2009
50 104 AZT/3TC/LPV/r v NVP/LPVr Fem Neck: -6.3% v -2.3%
Spine: -5.1 v -2.6 %
Moyle, 2009 385 48 TDF v ABC Hip: ABC:-1.9%; TDF: -3.6%
Spine: ABC: -1.6%; TDF -2.4%
McComsey, 2010
258 96 TDF v ABC ATV/r vs EFV
Hip: ABC:-2.2%; TDF: -4.0%
Spine: ABC: -1.8%; TDF -3.8%
Hip: ATV/r:-3.5%; EFV: -3.5%
Spine: ATV/r:-3.0%; EFV: -2.0%
Huang, 2010 753 96 TDF v AZT v d4T LPV/r v EFV
Total BMD: TDF: -3%; v AZT: -1.75% v d4T:
-2%Difference LPV/r vs EFV: -0.5%
Qaqish, 2011 160 96 LPV/r+RAL v LPV/r+TDF/FTC Total BMD: +0.68 v -2.5%
Tebas, 2011 349 96 RPV vs EFV (+NRTI) Total BMD: -1.5% vs -1.5%
Moyle, 2011 224 96 ATV/r v LPV/r (+TDF/FTC) Total BMD: -3% v -4%
Liu AY. Et al, PLoS ONE 6(8): e23688. doi:10.1371/journal.pone.0023688 (2011)
TDF monoterapia in vivo
ACTG 5142: BMD alla settimana 96
% Cha nge in BMD from B as eline
LPV/ TDF
Observed Changes (as treated)
Huang J. WAIDS 2010. Vienna. WEAB0304
Costi per Fx di Femore e per Infarto Miocardico in Italia, 2007
Piscitelli P, Osteoporos Int 2007
Frattura di Femore Infarto Miocardico
Costi diretti 394.000.000 270.000.000 Riabilitazione 412.000.000 260.000.000 Pensione invalidità 108.000.000 NA
Costi indiretti 161.000.000 530.000.000
Totale 1.075.000.000 1.060.000.000
N° Ricoveri 80804 72575
I. O . N.
C A.
17,5 15,1
19,9
2,4 3,8
15,7 19,6
12,8 17,8
23,6
7,1
1,4 17,8
9,3
14,4
9,3 19,6
5,1
1 34
15,5
0 5 10 15 20 25 30 35
< 50 (n=581) 51-60 (n=140) > 60 (n=97)
cerebro-vascular Diabetes Hypertension Miocardial infacrction Lypodistrophy eGFR <60
Non AIDS-Defining Malignancies
Icona: prevalenza di differenti co-morbosità non-AIDS correlate a seconda dell’età nel
paziente naive
ICONA Foundation. Internal data
I. O . N.
C A.
5,8
8 9,6
41,5
20,7
9,8
6,2 11
12,4
1,1
25,3 24,9
11,7 10,3
7,6 11,4
1,6 14,1
36,9
11,9
0 5 10 15 20 25 30 35 40 45
< 50 (n=916) 51-60 (n=273) > 60 (n=184)
Cerebrovascular Diabetes Hypertension Miocardial infarction Lypodistrophy eGFR <60
Non AIDS-Defining Malignancies
Icona: prevalenza di differenti co-morbosità non-AIDS correlate a seconda dell’età nel paziente trattato
ICONA Foundation. Internal data
EuroSIDA: Kaplan-Meier Progression to CKD
EuroSIDA Study:
Risk for Chronic Kidney Disease
Kirk, O et al. 17th CROI 2010. Abstract 107LB
A 65 anni il filtrato glomerulare si riduce di
circa il 30% e ogni anno successivo si riduce di un ulteriore 1-2%
Brenner and Rector's The Kidney, 9th Edition
Tumori non-AIDS definenti
Per alcuni il rischio è
maggiore, per altri minore
Cancer Nb study SIR (95% CI) Heterogeneity
HL (EBV) 6 19 (13-27) <0.001
Ano (HPV) 5 47 (22-100) <0.001
Fegato (HBV/HCV) 5 7.5 (4.2-14) <0.001
Polmone 6 3.5 (2.6-4.6) <0.001
Mammella 6 0.6 (0.5-0.8) 0.003
Prostata 5 0.6 (0.4-0.7) 0.08
Shiels et al. JAIDS 2009; 52:611-22
.
Frequenti tumori non-AIDS definenti
Hodgkin
IRR (95%CI) N=149
Polmone*
IRR (95%CI) N=207
Fegato +
IRR (95%CI) N=119
Ultimo CD4
>500
350-500 200-350 100-200 50 -100 <50
1.0
1.2 (0.7-2.2) 2.2 (1.3-3.8) 4.8 (2.8-8.3) 7.7 (3.9-15.2) 5.4 (2.4-12.1)
1.0
2.2 (1.3-3.6) 3.4 (2.1-5.5) 4.8 (2.8-8.0) 4.9 (2.3-10.2) 8.5 (4.3-16.7)
1.0
2.0 (0.9-4.5) 4.1 (2.0-8.2) 7.3 (3.5-15.3) 6.6 (2.4-17.6) 7.6 (2.7-20.8)
Model adjusted on age, sex and risk, and migration from SubSaharan Africa
* Independent of smoking or + independent of HBV/HCV infection in sensitivity analyses
Cancro anale
Ano
IRR (95%CI) N=74
Tempo con CD4<200 (per anno)
1.3 (1.2-1.5)
Tempo con HIV-RNA >
100,000 copie/mL (per anno)
1.2 (1.1-1.4)
Model adjusted on age, sex and risk, and migration from SubSaharan Africa
Rischio quando i CD4 sono >=500/mm3
Kaiser permanente HL Anale Polmone Fegato
RR in HIV+ with recent CD4 >=
500/mm3 compared with HIV-
13.5 (7.2–25.1)
33.8 (17.8–64.3)
1.2 (0.7–1.9) 1.0 (0.4–2.4)
Silverberg et al, Cancer Epidemiol biomarkers Prev 2011 Hleyhel et al, AIDS 2014
FHDH ANRS CO4 HL Anale Polmone Fegato
SIR in HIV+ with recent CD4 >= 500/mm3 for more than 2 years compared with HIV-
9.4 (7.9-16.8)
- 0.9 (0.6-1.3) 2.4 (1.4-4.1) Age, sex and race adjusted
Age and sex adjusted
