Download HIV Related Comorbidities

Aging, Inflammation, and Organ
Damage in HIV+ Patients
Jean-Pierre Routy, MD
Graeme Moyle, MD
Bill Powderly, MD
Philippe Morlat, MD
Metabolism
• Visceral damage
– Because patients are living longer
– Damage associated with both aging and antiretroviral
therapy (ART) use
• HIV related inflammation
– Can cause organ damage
– May not be the ONLY source of organ damage
• Treatment and aging both affect health
Inflammatory Damage as a
Multifactorial Issue
• Patients are not just affected by HIV, they are also
– Getting older
– Getting lifestyle diseases
• Risk factors, before HIV infection, play a major role in
disease formation
– Smoking
– Heart disease
• Antiretroviral (ARV) therapy may only be a minor risk
factor for organ damage in most HIV+ patients
Look at the Whole Patient
• Don’t just assess HIV and treatment
• Remember the role lifestyle plays and other factors
such as
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Smoking
Alcohol use
Heart disease
Diet
Age
A broad, holistic approach is important
for patient health
Amsterdam Aging Cohort - AGEhIV
NEW FROM AIDS 2012
• HIV+ population vs. similar HIV - controls
– 74.5 % of HIV+ patients and 61.6% of controls reported
≥1 age-associated, non-communicable condition
(AANCC)
– HIV+ had significantly more AANCC (1.4 vs. 1) in every
age group
– Burden of AANCC in HIV+ patients was similar to that
seen in HIV – controls, who were 5 years older
• Traditional risk factors played an important role
Source: Schouten, J. et al. Comorbidity and aging in HIV-1 infection:
the AGEhIV Cohort Study. AIDS 2012 Abstract: THAB0205
Who is at risk?
• After CD4 count is normalized, mortality and
morbidity risk normalizes as well
• There may only be a subset of HIV+ patients at an
increased risk for aging diseases
– Late diagnoses
– Treatment with older Antiretroviral (ART) medication
– Those who have not achieved optimal immune
recovery
Patient Factors, Host Factors, and Virus
• Antiretroviral (ART) therapy shouldn’t take all the
blame for metabolic and inflammatory effects
– Relevant in subset of patients
• Risk factors may be more important
• Avoid drugs that might accentuate any risk
associated with patient behaviors, such as smoking
Inflammation, T-Cell Recovery, and CVD
• SMART Study
– When HIV is uncontrolled
• More inflammation
• More endothelial damage
• Increased cardiovascular disease (CVD) risk
– Treating patients earlier may reduce these types
of damages
• Might increase drug-associated damage
• However, there probably is less negative impact than
what would be caused by waiting to treat the patient
PI & Cardiovascular Risk
• Ritonavir
– Dose-dependent dyslipidemia
• Not all protease inhibitors (PI) are associated with
increased risk of myocardial infarction (MI)
– Lopinavir and ritonavir are associated
– Indinavir is associated, alone or in combination
– Atazanavir is NOT associated, alone or in combination
• Inappropriate to claim a class effect
Mechanisms of PI Effect on CVD
• Biological pathways for cardiovascular effect
– Dyslipidemia
– Insulin Resistance
• Kaletra (lopinavir + ritonavir), Indinavir
• Protease inhibitors (PI) choices vary with
– Ease of use
– Side effects
Not all choices will be suitable for all patients
Use of Statins in HIV+ Patients
• HIV is considered a risk factor for cardiovascular
disease (CVD) in France
– Affects guidelines for statin use
– Drugs started earlier in HIV+ patients
Obesity, HIV, and CVD
• Diabetes
– More related to
• Lifestyle
• Obesity epidemic
– Treatment may contribute through
• Direct biological effects on insulin resistance
• Making people feel healthier and therefore eat more
– HIV is a risk factor but it isn’t the dominant issue
However…
• Some people do quickly gain weight after starting ART
– Tends to be central
– Kicks-in metabolic syndrome
• Certain drug choices are associated with insulin
resistance
– Indinavir
– Ritonavir
– Lopinavir/ritonavir
• Raltegravir and maraviroc are NOT associated with
insulin resistance
• C-reactive protein
– Increases in lopinavir/ritonavir (Kaletra) patients
– Decreases with raltegravir
Specific Drug Choices Matter
• Drug choices can affect
– Insulin resistance
– Inflammatory markers
– Lipid markers
• Cumulative exposure to thymidine analogues is a
risk factor, including from past use
Immunometabolics
• Not a lot of data
• Inflammation is related to atherosclerosis
– Unknown whether only specific inflammation is a risk
– Research needed to determine affect of generalized
HIV-mediated inflammation
• Inflammation caused by HIV-associated infections is
also a potential concern
Don’t Forget the Benefits of Treatment
• Treatment is a good thing for patients
• Early treatment may be even better
– Reduces systemic inflammation
• Try not to get caught up in potential risk factors of
treatments, that are helping patients live longer
and healthier lives, than they would otherwise
• HIV treatment may also improve overall health,
through increased monitoring, when compared to
HIV patients
Patients Age 50
• Start statins
• Bone scan
• Coronary calcium scores
• Full health check
• Aggressive intervention for conditions of aging
Co-infection - Hepatitis C
• Major source of
– Cardiovascular risk
– Renal risk
• Hepatitis C virus (HCV) viremia
– Contributes to significant clinical outcomes
HIV and Kidney Disease
• Some drugs affect renal function
– Tenofovir (TDF)
• Tubulopathies
– Certain protease inhibitors (PIs)
TDF and PIs may be particularly dangerous in
combination
Tools for Monitoring Kidney Disease
• Calculated GFR (glomerular filtration rate)
– Based on creatinine levels
– May not always be an accurate assessment of kidney
function
– Certain ART medications elevate creatinine, without
affecting filtration rate
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Dolutegravir (investigational integrase inhibitor)
Ritonavir
Cobicistat (investigational enhancer)
Rilpivirine
• Need new ways to assess kidney function
Monitoring Kidney Disease
• Don’t forget non-HIV related factors that can affect
kidney function such
– Hypertension etc…
• eGFR does not do an effective job of monitoring
tubular damage, which is the concern with many
HIV medications
Take Home Message
• Global improvement in HIV management
– Patients are living longer
– Relatively minor non-inflammatory events
• Medication is better than HIV
– However, new drugs may complicate follow-up, even
as they improve outcomes
Good news!
Patients aren’t sick because of immunodeficiency
The Difficulty in Treating HIV
• Non-communicable diseases and HIV infection must
be closely monitored for clinical care
• Must back-off from a sole focus on infectious disease
• Integrating systems of whole-health care, can improve
quality of life
• Oversight is important
When treating HIV infected patients, you must
always remain aware of the importance of drugdrug interactions, and immunological concerns