1

HIV:

Bilan 2015 d’une nouvelle maladie silencieuse

Dr Matthias Cavassini

Service des Maladies Infectieuses, CHUV

Vieillir avec le VIH: Etat des connaissances

Les questions

Le nombre de “vieux” séropositifs augmente… source d’inquiétude ?

Vieillissement différent de la population générale ?

Implications médicales dans le suivi VIH, le traitement du VIH et la prévention du vieillissementdes patients infectés par le VIH ?

ATHENA: Older Pts Becoming More

Prevalent in the HIV-Positive Population

ATHENA: observational cohort of 10,278 HIV-positive pts in the Netherlands

Modeling study projections:

Proportion of HIV-positive pts ≥ 50 yrs of age to increase from 28% in 2010 to 73% in 2030

Median age of HIV-positive pts on combination ART to increase from 43.9 yrs in 2010 to 56.6 yrs in 2030 P

rop

ort

ion

of

HIV

-Po

sit

ive

Pts

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

02010 2015 2020 20302025

> 70 yrs of age

60-70 yrs of age

50-60 yrs of age

40-50 yrs of age

30-40 yrs of age

< 30 yrs of age

Smit M, et al. Lancet Infect Dis. 2015;15:810-818. Slide credit: clinicaloptions.com

http://www.clinicaloptions.com/oncology

Swiss HIV Cohort Study

Age distribution of active patients by year in the SHCS, 1992 - 2014

2004: 20 % were more than 50 years old

2014: 40% are more than 50 years old !

Decreased Life Expectancy in Older HIV+

Adults in Modern ART Era

Legarth RA, et al. J Acquir Immune Defic Syndr. 2016;71:213-218. Slide credit: clinicaloptions.com

HIV-Negative

Controls

1996-2014

2006-2014

2000-2005

1996-1999

Legarth RA, et al. J Acquir Immune Defic Syndr. 2016;71:213-218. Slide credit: clinicaloptions.com

HIV-Positive Pts

1.00

0.75

0.50

0.25

0

Pro

bab

ilit

y o

f S

urv

ival

50 60 70 80Age (Yrs)

http://www.clinicaloptions.com/oncologyhttp://www.clinicaloptions.com/oncology

En Suisse, l’espérance de vie des patients VIH +

âgé de 20 ans a presque rejoint celle de la

population générale.

Le nombre de “vieux” séropositifs augmente…

source d’inquiétude ?

http://www.google.ch/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&ved=0ahUKEwiVmdHbn_bSAhWL1BoKHbTBAYwQjRwIBw&url=http://www.redpepper.co.ug/hivaids-reducing-in-uganda-study/&psig=AFQjCNFJwWv9BSehAGs-VNJdg5gTrSgzQw&ust=1490689062178108http://www.google.ch/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&ved=0ahUKEwiVmdHbn_bSAhWL1BoKHbTBAYwQjRwIBw&url=http://www.redpepper.co.ug/hivaids-reducing-in-uganda-study/&psig=AFQjCNFJwWv9BSehAGs-VNJdg5gTrSgzQw&ust=1490689062178108https://www.google.ch/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjv5qvDofbSAhUD1xoKHYviAIwQjRwIBw&url=https://www.pinterest.com/pin/269934571385143390/&psig=AFQjCNH5r000uKMLvUdN5ta0bhWeVKRURA&ust=1490689492482798https://www.google.ch/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjv5qvDofbSAhUD1xoKHYviAIwQjRwIBw&url=https://www.pinterest.com/pin/269934571385143390/&psig=AFQjCNH5r000uKMLvUdN5ta0bhWeVKRURA&ust=1490689492482798

Schouten J, et al. Clin Infect Dis. 2014;59:1787-1797.

Prévalence des comorbidités dans 2 cohortes prospectiveshollandaises VIH pos. (n = 540) vs VIH neg (n = 524) ≥ 45 ans

Vieillir avec le VIH: addition de facteurs

LIFESTYLE

Normal Aging Process

Low CD4Untreated

HIV

Slide credit: clinicaloptions.com

HIV-Mediated

Inflammation

http://www.clinicaloptions.com/oncology

Comportements à risque chez les

personnes infectées par le VIH aux USA

Slide credit: clinicaloptions.com

General population[2,3]HIV-positive pts[1]

Pers

on

s (

%)

Prevalence of Alcohol, Cigarette, and Illicit Drug Use Among

HIV-Positive Pts vs General Population

*24% noninjection, 1.7% injection drug use in HIV-positive pts; illicit drug use for general population included marijuana,

cocaine, heroin, hallucinogens, inhalants, and nonmedical use of prescription-type pain relievers, tranquilizers, stimulants,

and sedatives.

100

60

40

20

0

80

Alcohol Use Cigarette Smoking Illicit Drug Use*

61.052.0

38.2

15.224.0

10.2

1. CDC.Behavioral and Clinical Characteristics of Persons Receiving Medical Care for HIV

Infection–Medical Monitoring Project, United States, 2013 Cycle (June 2013-May 2014).

2. 2. CDC. Summary Health Statistics for U.S. Adults: National Health Interview Survey, 2015.

3. Center for Behavioral Health Statistics and Quality. (2015). Behavioral health trends

in the United States: Results from the 2014 National Survey on Drug Use and Health.

http://www.clinicaloptions.com/oncology

Smoking is more frequent in the HIV infected

population

11

2015

HIV +

HIV -

Huber et al. Outcome of smoking cessation councelling…by HIV care physicians. HIV medicine, 2012: p.387-97

Smoking : why worry ?

12

Cardiovascular diseases

2-4 fold increase

Lung diseases

COPD: 1.2 x /10 x 10PY

Pneumonia: 2x increase

Cancers:

Lung: 3-16 fold increase

Mouth: 2-10 fold increase

Bladder: 2-4 fold increase

Other ‘deaths’:

Pregnancy loss

Taste

Erection

Nice skin

Osteoporosis

https://www.google.ch/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiy8LXwh7nPAhUCRhQKHeAFDAwQjRwIBw&url=https://www.theodysseyonline.com/whats-up-with-that-smoking&psig=AFQjCNFJOBOHdAvGL8FV_-k_Rn9OuO61tQ&ust=1475392599301393https://www.google.ch/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiy8LXwh7nPAhUCRhQKHeAFDAwQjRwIBw&url=https://www.theodysseyonline.com/whats-up-with-that-smoking&psig=AFQjCNFJOBOHdAvGL8FV_-k_Rn9OuO61tQ&ust=1475392599301393

Intervention should include

13

Brief advice to stop smoking

Assessment of the smoker’s interest in quitting

Offer of pharmacotherapy and councelling

Self help material

Referral to local programs

Après 2006…

PATHOGENESE

Comorbidities:

Cardiovascular disease, non-AIDS cancer,

kidney disease, liver disease, osteopenia/osteoporosis,

Neurocognitive disease

Adapted from: The end of AIDS: HIV infection as a chronic disease, Lancet 2013; 382: 1525-33

Inflammation Predicts Disease in Treated

HIV Infection

Mortality[1-4]

Cardiovascular disease[5]

Cancer[6,7]

Venous thromboembolism[8]

Type II diabetes[9]

Radiographic emphysema[10]

Renal disease[11]

Bacterial pneumonia[12]

Cognitive dysfunction[13]

Depression[14]

Functional impairment[15]

Slide credit: clinicaloptions.com

1.Kuller LH, et al. PLoS Med. 2008;5:e203.

2. Tien PC, et al. J Acquir Immune Defic Syndr.

2010;55:316-322.

3. Justice AC, et al. Clin Infect Dis. 2012;54:984-994.

4. Hunt PW, et al. J Infect Dis. 2014;210:1228-1238.

5. Duprez DA, et al. Atherosclerosis. 2009;207:524-529.

6. Breen EC, et al. Cancer Epidemiol Biomarkers Prev.

2011;20:1303-1314.

7. Borges ÁH, et al. AIDS. 2013;27:1433-1441.

8. Musselwhite LW, et al. AIDS. 2011;25:787-795.

9. Brown TT, et al. Diabetes Care. 2010;33:2244-2249.

10. Attia EF, et al. Chest. 2014;146:1543-1553.

11. Gupta SK, et al. HIV Med. 2015;16:591-598.

12. Bjerk SM, et al. PLoS One. 2013;8:e56249.

13. Burdo TH, et al. AIDS. 2013;27:1387-1395.

14. Martinez P, et al. J Acquir Immune Defic Syndr.

2014;65:456-462.

15. Erlandson KM, et al. J Infect Dis. 2013;208:249-2

http://www.clinicaloptions.com/oncology

16

27 350 cas VIH +

55 109 contrôles

La Trithérapie est bonne

pour votre cœur !

HIV-1 RNA Suppression and Cancer

Park LS et al. 2015 International Conference on Malignancies in

AIDS and Other Acquired Immunodeficiencies. Oral presentation.

AIDS Defining

500

400

300

200

100

0

30

20

10

0

IR

IRR

P < .0001

Virus-Related NADC

400

300

200

100

0

8

6

4

0

IR

IRR

P < .0001

2

Nonvirus NADC

1000

750

500

250

0

2.0

1.5

1.0

0

IR

IRR

P < .0008

0.5

HIV positive, unsuppressed

HIV positive, early suppressed

HIV positive, long-term suppressed

HIV negative

IRR

Slide credit: clinicaloptions.com

http://www.clinicaloptions.com/oncology

Adherence:

100 % vs < 100 %

Activity Preserves Lean Mass and

Function

40-yr-old 70-yr-old

sarcopenic

66-yr-old

runner

76-yr-old

farmer

Slide credit: clinicaloptions.comCourtesy of Dr. Todd Brown

Schäfer et al. High prevalence of physical inactivity

among patients from the Swiss HIV Cohort Study.

AIDS care, 2017, p.1-6

http://www.clinicaloptions.com/oncologyhttps://www.google.ch/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjenajotPbSAhUIrRoKHbqoAZsQjRwIBw&url=https://www.acefitness.org/blog/5071/anti-aging-benefits-of-exercise&psig=AFQjCNG0ykfkHC_SZn7bsA15IIpSytSmQQ&ust=1490694724287882https://www.google.ch/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjenajotPbSAhUIrRoKHbqoAZsQjRwIBw&url=https://www.acefitness.org/blog/5071/anti-aging-benefits-of-exercise&psig=AFQjCNG0ykfkHC_SZn7bsA15IIpSytSmQQ&ust=1490694724287882

Vieillir avec le VIH…

1. C’est possible…enfin…bonne nouvelle !

2. Plus à risque de développer des problèmes de santé liés à l’âge

3. Les raisons de développer ces problèmes sontmultifactorielles (comportement, VIH, inflammation, toxicité médicamenteuse)

4. On ne peut éviter de vieillir, mais on peut agir sur le comportement, le VIH et peut-être aussil’inflammation.

Impact du vieillissement sur le traitement

du VIH

Comorbidités (rénale, hépatique, vasculaire, os)

Poly-médications

Interactions médicamenteuses, adhésions

Usage des comprimés uniques pas toujours adapté

Incapacité à adapter le dosage

DHHS Considerations for Initial ART

Based on Age-Related Comorbidity

Slide credit: clinicaloptions.comDHHS Guidelines. July 2016.

Scenario ART-Specific Consideration

Consider Avoiding Options

CKD (eGFR

< 60 mL/min)

TDF, especially in RTV-

containing regimens

TAF (if eGFR > 30 mL/min)

ABC/3TC (if HLA-B*5701 negative; if HIV-1 RNA

> 100,000 c/mL, do not use with EFV or ATV/RTV;

3TC dose adjustment if CrCl < 50 mL/min)

DRV/RTV + RAL (if HIV-1 RNA < 100,000 c/mL and

CD4+ cell count > 200 cells/mm3)

LPV/RTV + 3TC (3TC dose adjustment if CrCl

< 50 mL/min)

Osteoporosis TDF TAF

ABC/3TC (if HLA-B*5701 negative; if HIV-1 RNA

> 100,000 c/mL, do not use with EFV or ATV/RTV)

CVD ABC

LPV/RTV

Hyperlipidemia PI/RTV or PI/COBI

EFV

EVG/COBI

DTG

RAL

Consider TDF over ABC or TAF

http://www.clinicaloptions.com/oncology

Drugs for Common Conditions in the

Aging That May Interact With ART

Comorbidity Comorbidity

Drugs

Interacting ARVs

T2DM Metformin DTG/3TC/ABC,[1] DTG + FTC/TDF or FTC/TAF,[2-4]

EVG/COBI/FTC/TDF,[5] EVG/COBI/FTC/TAF[6]

GERD Antacid

PPI

All[1-8]

ATV/RTV + FTC/TDF or FTC/TAF,[3,4,9] DRV/RTV +

FTC/TDF or FTC/TAF[3,4,10] RPV + FTC/TDF or

FTC/TAF[11,12]

CVD Statin,

Antiarrhythmic

EVG/COBI/FTC/TDF,[5] EVG/COBI/FTC/TAF[6]

ATV/RTV + FTC/TDF or FTC/TAF,[9,3,4]

DTG/3TC/ABC[1]

COPD Beta-agonist

Glucocorticoid

EVG/COBI/FTC/TDF,[5] EVG/COBI/FTC/TAF[6]

ATV/RTV + FTC/TDF or FTC/TAF,[2,3,9] DRV/RTV +

FTC/TDF or FTC/TAF[3,4,10]

DHHS Guidelines. July 2016. Slide credit: clinicaloptions.com

http://www.clinicaloptions.com/oncology

VIH et vieillissement*: recherche SHCS

Poly-médication1

Adhésion2

Os 3

Cardiovasculaire 4

Neurocognitif 5

Reins 6

Metabolic & Aging

Cohort (M&A)NAMACO

n=983 patients

Metabolic

(Fasting + urine)

n=2000

CCTA

n= 450

1 Marzolini et al. Antiv.Ther. 2010, p.413-23.2 Kamal et al. CROI 2017, poster 4683 Mueller et al. AIDS 2010, p.1127-34; Junier et al. Open inf. Dis forum, 20164 Glass et al. HIV Med 2006, p.404-10; Bucher et al.Antiv Ther.2010,p.31-40. ;Nüesch et al. JAIDS 2013, p.396-404; Carballo et al.

Aids Res and Ther. 2015, e-collection5 Metral et al. CROI 2017, poster 362

* Hasse et al. CID 2011, p.1130-39

Conclusions

Compréhension globale médicale du patient

Décisions thérapeutiques en conséquences

Communication et coordination des soins avec d’autres spécialistes et médecin traitant

Promotion de la santé = changement du style de vie

Back up slides

Statins Decrease Immune Activation and

Aortic Plaque in Treated HIV Infection

REPRIEVE: double-blind, randomized phase IV trial of pitavastatin (planned N = 6500) now enrolling[3]

1. Funderburg NT, et al. J Acquir Immune Defic Syndr. 2015;68:396-404.

2. Lo J, et al. Lancet HIV. 2015;2:e52-e63.

3. ClinicalTrials.gov. NCT02344290. Slide credit: clinicaloptions.com

sCD14 Declines

With Rosuvastatin[1]

Wks From Randomization

Plaque Regression

With Atorvastatin[2]

sC

D1

4 R

ela

tive

Ch

an

ge

Fro

m W

k 0

(%

)

30

20

10

-40

-10

0 24 48

-20

0

-30

Placebo

Rosuvastatin

P = .002 P = .0056

Ch

an

ge

in

No

nc

alc

ula

ted

Pla

qu

e V

olu

me

(m

m3) 20

10

-40

-10

-20

0

-30

Placebo

P = .03

Atorvastatin

40

http://www.clinicaloptions.com/oncology