Workshop 1: “L’anziano”Moderatori: E. Sagnelli, F. SuterDiscussant: F.v. Schloesser

Come cominciare, quali farmaci e come risponde l’anzianoS. Lo Caputo

Age and Natural History of HIV

• Immune system wanes with age• Older age associated with faster progression to

clinical AIDS and death (pre-HAART)[1-3]

• Mixed data in HAART era– Some studies suggest association of age with

poorer outcomes[4,5]

– Others show that with effective treatment, no effect of age[6,7]

1. Babiker AG, et al. J Clin Epidemiol. 2001;54(suppl 1):S16-S24. 2. Carre N, et al. AIDS. 1994;8:797-802. 3. Phillips AN, et al. J Acquir Immune Defic Syndr. 1991;4:970-975. 4. Grabar S, et al. AIDS. 2004;18:2029-2038. 5. Kauffman GR, et al. Arch Intern Med. 2003;163:2187-2195. 6. Smith CJ, J Infect Dis. 2004;190:1860-1868. 7. Porter K, et al. Lancet. 2003;362:1267-1274.

Impact of age on HAART response

Favours young

Favours old No difference

Total no. of studies

CD4 response

4 1 4 9

Virological response

1 3 6 10

Note: Data based largely on small non-randomised trials

Based on interpretation of following studies. Manfredi R, Chiodo F. AIDS 2000;14:1475–7; Viard JP, et al. J Infect Dis 2001;183:1290-4. Knobel H, et al. AIDS 2001;15:1591–3; Yamashita TE, et al. AIDS 2001;15:735–46; Manfredi R, et al. J AIDS 2003;33:112–4; Tumbarello M, et al. AIDS 2003;17:128–31; Goodkin K ,et al. AIDS 2004;18(Suppl 1):S87–98; Grabar S, et al. AIDS 2004;18:2029–38; Tumbarello M, et al. MBC Infect Dis 2004;4:46–56; Based on Gebo KA. Drugs Aging 2006: 23(11):897–913, with addition of: Sabin CA et al. CROI 2007, Poster 528 and Cuzin L, et al. Clin. Infect Dis. 2007:45:654–7

Total population 3015 patients , <50 years 2614 (86.7%), > 50 years 401 (13.3%)

CD4 cell reconstitution is significantly slower than in younger patients, despite a better virologic response

This impaired immunologic response may explain their higher risk of clinical progression

Ten age strata were chosen: less than 2, 2–5, 6–12, 13–17, 18–29, 30–39 (reference group), 40–49, 50–54, 55–59 and 60 years or older; those aged 6 years or more were included in multivariable analysesThe four youngest age groups had 223, 184, 219 and 201 individuals and the three oldest age groups had 2693, 1656 and 1613 individuals. Precombination antiretroviral therapy CD4 cell counts were highest in young children and declined with age.

Better virological responses but poorer immunological responses in olderindividuals, together with low precombination antiretroviral therapy CD4 cell counts, may place this group at increased clinical risk.

Unadjusted and adjusted hazard ratios of the impact of age on time to (a) confirmed virological response and (b) confirmed immunological response

•Retrospective analysis of an observational clinical cohort.

•670 younger patients (<40 years) and 149 older patients (>50years)

•Older patients were more likely to be started on an NNRTI-based regimen than were younger patients (41.6 vs. 29.0%, P<0.01)

•The Johns Hopkins University AIDS Service

•HAART initiation dates between 13 December 1995 and 9 February 2006. Median followup time after HAART initiation was 46.1 months

•Time to virologic suppression after HAART initiation was shorter in older patients•CD4 response did not differ by age. •Older patients had feweropportunistic infections, but survival was shorter

Older patients more likely to achieve HIV-1 RNA <500 copies/mL

• Kaiser Permanente study compared patients 40-49 yoa and ≥50 yoa to patients 18-39 yoa• Patients >50 yoa more likely to achieve HIV-1 RNA <500 copies/mL vs patients 18-39 yoa, even when adjusting

for comorbidities• Adherence major advantage for older patients

Silverberg MJ. Arch Intern Med. 2007;167(7):684-691.

≥50 years

40-49 years

CI, confidence interval;HR, hazard ratio; yoa, years of age

1.3

0.6

0.7

0.8

0.9

1.0

1.1

1.21.15

0.97

0.95

1.03

0.97

1.15

0.97

1.07

HR

(95

% C

I)

Model: Age Age + Adherence

Age + Modified Charlson

Comorbidity

All Predictors

Older Age and the Response to and Tolerabilityof Antiretroviral TherapyMichael J. Silverberg,, Wendy Leyden,; Michael A. Horberg,

ARCH INTERN MED/VOL 167, APR 9, 2007

2259 patients aged 18 to 39 years (reference group), 1834 patients aged 40 to 49 years, and 997 patients 50 years or older enrolled in an integrated health care system (from KPNC HIV registry).

Despite a higher risk of adverse events, patients 50 years or older sustained high therapy adherence to maintain improved virological outcomes and to compensate for their early blunted CD4 T-cell count response compared with younger patients.

Age and toxicity in the first year of HAART (UK-CHIC)

• 8708 naïve patients initiating HAART, 1998-2005 in 13 UK centres

• 2650 (30%) discontinued at least one drug for non-virological failure reasons

• Discontinuing was associated with:– Younger age (<30; RH 1.12)– Older age (>50; RH 1.14)

• Strong association between older age and:– Increased cholesterol– decreased haemoglobin– Increased triglycerides

Sabin et al, HIV Medicine, 2008

0

10

20

30

40

50

18-35 36-50 >50

NRTIs+EFV NRTIs+LPV/r NRTIs+NVP NRTIs+oPI/r

n.casi: 518 612 126

%

Cambiamenti nella scelta del regime terapeutico iniziale nella coorte ICONA dal 2001 al 2010Associazione tra regimi terapeutici ed età all’inizio della terapia

Anni

P value <0.001

HIV Management in aging

• Starting HAART:– start HAART earlier in the older?

• Increased risk of disease progression to AIDS• Increased risk of co-morbidities• Maintain higher CD4 count

• Choosing HAART:– regimens to avoid toxicities that overlap with ageing?

• CVD, bone disease– chose HAART regimens

that penetrate the CNS?

Age and HAART

• Specific regimen are not influenced by age• Effect of age on antiviral response also

variable– Adherence may be greater in older patients

• Antiretroviral tolerability decreases with age• ART-induced organ toxicities may exacerbate

preexisting age-related conditions• Close monitoring is required to detect any

emerging problems

AZT

DDI

3TC

TDF

ABC

FTC

D4T

TRV

CBV

KVX

NVP

EFV

ETV

SQV

LPV

TPV

FPV

DRV

ATV

RTV

IDV

NFV

RAL

ENF

VCV

MVC