Emerging comorbidities in the setting of long- term virological suppression

Antonella Castagna

San Raffaele Scientific Institute, Milan

Comorbidities in HIV Infection: a tangible problem

HIV-infected patients exhibit a worse cardiovascular risk profile after a first episode of acute coronary syndrome. Final results of long term follow up in the PACS-HIV study. F. Boccara

How much do smoking, hypertension and diabetes contribute to acute coronary syndrome in HIV-infected patients relative to uninfected patients? MC Sanchez

Development of a definition for Rapid Progression of renal disease in HIV-positive persons Lene Ryom (Nielsen)

Prevalence and risk factors of subclinical vertebral fractures in a cohort of HIV positive patients K. Luzi

ARV and comorbidities

•Bone Mineral Density (BMD) Analysis in Antiretroviral (ART)-Naïve Subjects Taking Lopinavir/ritonavir (LPV/r) Combined with Raltegravir (RAL) or Tenofovir/Emtricitabine (TDF/FTC) for 96 weeks in the PROGRESS Study Roula Qaqish

•Raltegravir as Replacement for PI- or NNRTI-Based ART in HIV-Infected Women with Lipohypertrophy: The Women, Integrase, and Fat Accumulation Trial Jordan E. Lake

Long-term immunological suppression

• Comorbidities as a Key Issue• Reasons for switching • Questions to face• Patient management

ARV switches in 12% of the undetectable patients since 2010

1-3 3-6 6-9 9-12 12-150

10

20

30

40

50

60

51%

23%

14%10%

3%

% o

f pati

ents

Virological Suppression (years)

Pooled ECHO and THRIVE Week 48 analysis:Most frequent treatment-related* grade ≥2 AEs†

Incidence, %RPV

N=686 EFV

N=682

P value TMC278 vs EFV

Any AE 16 31 <0.0001‡

Rash 1 8 <0.0001‡

Dizziness 1 6 <0.0001¶

Abnormal dreams/nightmares 1 4 0.005¶

Headache 2 2 #Insomnia 2 2 #Nausea 1 2 #

*Occurring in at least 2% of patients in either treatment group and excluding laboratory abnormalities reported as an AE; †Safety analyses performed using all available data, including beyond Week 48; ‡Fisher’s Exact test, predefined analysis for these AEs; ¶Fisher’s Exact test, post-hoc analysis; #Not determined because not predefined in this analysis

Significantly fewer grade 3 or 4 laboratory abnormalities for RPV (11%) vs EFV (18%)1

1Cohen C, et al. XVIIIth IAC 2010; Abstract THLBB206

Reasons for switching ARV

35,2

44,8

12,87,3

05

101520253035404550

Simplification Toxicity Treatmentfailure

Other causes

Per

cen

t

Cardiovascular risk associated with abacavir and tenofovir exposure in HIV-infected patients

0

3

6

9

12

15Abacavir

Tenofovir

Other ART

13.4

9.39.4

3.4 3.7 3.5

8.6

6.46.0

4.4

2.1 2.41.2 1.2 1.5

*

*

Crud

e ev

ent r

ate

(per

100

per

son-

year

s)

ANY CARDIOVASCULAR

EVENT

HEARTHFAILURE

CORONARY DISEASE

CEREBROVASCULARDISEASE

PERIPHERAL ARTERIALDISEASE

Choi AI. et al, AIDS 2011, 25: 1289-1298* P values were<0.01 compared to use of other ART

No association of Myocardial Infarction with Abacavir use: an FDA meta-analysis

Ding X, CROI 2011

Long-term glucose tolerance in highly experienced patients receiving NRTI-sparing regimens

BL Week 156 BL Week 15660

70

80

90

100

110

120

RED REM

Fasti

ng g

luco

se (m

g/dL

)

BL Week 156 BL Week 1560

30

60

90

120

RED REM

Fasti

ng in

sulin

(mg/

dL)

A.Bigoloni, abstract TUPE257 IAS 2011

RED (15 pts) = RAL, ETR, DRV/r REM ( 24 pts)= RAL, ETR, DRV/r

Diabetes diagnoses by OGTT in 5/39 patients

Percent changes in Lumbar Spine and Hip BMD for 4 Treatment Arms (substudy of ACTG A5202)

McComsey GA. et al, JID 2011: 203: 1791-1801

0 24 48 72 96 120 144 168 192-10

-5

0

5

10

EFV+TDF/FTC (N=57) EFV+ABC/3TC (N=60)

ATV/r+TDF/FTC (N=54) ATV/r+ABC/3TC (N=62)

Visit Week from Randomization

Spin

e BM

Dpe

rcen

t cha

nge

from

wee

k 0

0 24 48 72 96 120 144 168 192-10

-5

0

5

10

Visit Week from Randomization

Hip

BM

Dpe

rcen

t cha

nge

from

wee

k 0

96 weeks Bone Mineral Density (BMD) Analysis /Emtricitabine (TDF/FTC in the PROGRESS STUDY

 

CG, male, 48 years, HIV infection since 1988, DRV/r+TDF/FTC

• An ARV switch may be an opportunity for the patient

• There is a need to sign a new patient contract

Switches: questions to face

• Risks involved in continuing existing regimen

• Risk of encountering new toxicity• Risk of virological failure• Risk of resistance• Risk of viral escape in reservoirs• Rescue regimens in the case of failure• Patient management costs

Management of switch

Evaluate the weight of the potential comorbidity in the context of the patient’s global prognosis and the possible risk of developing other comorbidities

Discuss the risks/benefits of continuing the ongoing regimen or introducing a new regimen

Consider the active/proactive switch as part of the global treatment of the patient in terms of interventions and timing

Explain the expected outcome, and measure the observed effect in the right manner and at the right time