Transcript Slide 1

HIV 2012:
You are only as YOUNG as
your Immune System..
Daniel Nixon DO, PhD
Associate Professor of Medicine
Director – VCU HIV/AIDS Center (http://www.hivcenter.vcu.edu/)
[email protected] Office 804-828-4510
HIV…we now know where it came
from and when (slide from Paul Sharp’s 2006 CROI
lecture)
When? Between ~ 1884 and 1924
Nature. Oct 2, 2008
“Rumble in the Jungle”
Natural History of HIV: Focus on
Advanced HIV and Opportunistic Diseases
Shifting recommendations for “When to start
ART” – IAS USA panel, 1996-2010
> 500
VL>5K
VL>10K
350-500
VL>5K
VL>5K
200-350
<200
CD4
1996 1998 2000 2002 2004 2006 2008 2010
Guidelines 2012: When to Start ART
Guideline
HIV with
symptoms
or Hep B/C
Asymptomatic/No Hepatitis – CD4
<200
200-350
350-500
DHHS
Yes
Yes
Yes
Yes (mod Rec)
IAS-USA
Yes
Yes
Yes
Yes
BHIVA
Yes
Yes
Yes
Defer
EACS
Yes
Yes
Yes
Concider
WHO
Yes1
Yes
Yes
No
Mar2012
Feb2012
Oct2011
1initiate
at any CD4 if Hep B or active TB
Guidelines for the Use of Antiretroviral Agents in HIV-1Infected Adults and Adolescents - www.aidsinfo.nih.gov
Conflicting Evidence from Observational Studies for
Initiating ART with CD4 > 350
Comparison
CD4+ count strata
HR for death
NA ACCORD
<350 vs 350-500
350-500 vs > 500
1.7 (1.3 - 2.3)
1.9 (1.4 – 2.8)
ART CC
251-350 vs 351-450
1.1 (0.8 - 1.6)
351-450 vs 451-550
0.9 (0.6 - 1.4)
350 vs 500
1.0 (0.8-1.2)
HIV-Causal
• Kitahata MM et al, N Engl J Med 2009
• When to Start Consortium, Lancet 2009
• HIV Causal Collaboration, Annals Int Med, 2011
CD4 at Initiation of ARV Therapy
Predicts Extent of CD4 Recovery
• Median Peak CD4 was
progressively higher for specific
CD4 strata (p<0.001)
• Multivariate analysis: Increased
mortality with CD4 < 50 (HR=4.6)
and CD4 50-199 (HR=2.6)
compared to 350 cells/mm3
• Lower baseline CD4 at initiation
also associated with increased
risk of death from non-AIDSrelated causes
Median CD4+ cell count
• 1,378 Patients at 10 US Clinics
followed From 1996-2007
Palella F, et al. 17th CROI, 2010
Evidence from Randomized Trials for
Initiating Treatment at CD4 200-350
• CIPRA-HT001 – a single center trial in Haiti
– 2/3 of patients were clinical stage 2 or 3 and the median CD4+ count
at initiation in the deferred ART group was 166 cells/mm3 (IQR: 130,
190).
• SMART study - post-hoc analysis
– Only involved 477 patients and of these only 249 were ART-naïve.
• HPTN 052
– Deferral strategy was 200-250 cells; significant difference in
extrapulmonary TB; not powered to address survival (10 versus 13
deaths).
Continuous ART at CD4> 350 associated with decreased serious nonAIDS Events in Subset of “relatively” Naïve to ART in SMART
N
Rate
HR (DC/VS)
VS Group Deferred vs. Early
N
Rate
95% CI
P-value
15
4.8
4
1.1
4.4 [1.5, 13.2]
0.009
• OD fatal or non-fatal 11
3.5
3
0.8
4.4 [1.2, 15.8]
0.02
• Serious non-AIDS
12
3.9
2
0.5
7.1 [1.6, 31.5]
0.01
• Composite
21*
7.0
5
1.3
5.1 [1.9, 13.5]
0.001
DC Group
• OD or death
Emery et al, JID, April 2008
HPTN 052:
ART prevents HIV transmission
• 1763 discordant couples (one HIV-infected partner)
• Botswana, Brazil, India, Kenya, Malawi, South Africa, Thailand,
Zimbabwe (+ single US couple)
• CD4 count at entry: 350 – 550 cells/mm䔡
• Index case randomized to IMMEDIATE ART vs DEFERRED ART
– Deferral until CD4 count drops to < 250 cells/mm䔡or disease
– RESULTS:
• 1 new HIV infection in partners of those on ART
• 27 new HIV infections in partners of those deferring ART
• 96% efficacy of ART to prevent transmission in this
population!!
START Study
HIV-infected individuals who are ART-naïve with
CD4+ count > 500 cells/mm3
Early ART Group
Deferred ART Group
Initiate ART immediately
following randomization
Defer ART until the CD4+ count
declines to < 350 cells/mm3 or
AIDS develops
N=2,000
N=2,000
What to Start 2012:
DHHS Initial ART Recs
NNRTI based
Protease-Inhibitor
based
Integrase Inhibitor
based
Pregnant Women
• Efavirenz1 +
Tenofovir/Emtricitibine
(TDF/FTC) daily
• Atazanvir or Darunavir with
low dose Ritonavir “boosting
agent”+ TDF/FTC daily
• Raltegravir bid + TDF/FTC
daily
• Lopinavir/Ritonavir bid + AZT
and Lamiviudine bid
1. EFV NOT to be used during the 1st trimester of pregnancy or in
women who are not using effective and consistent contraception.
HIV drugs and especially protease
inhibitors have many Interactions..
Statins
Interacting Protease
Inhibitor
Prescribing recommendation
Atorvastatin
Tipranavir/r
Avoid concurrent administration
Lopinavir/r
Use with caution and lowest dose
Darunavir/r
Fosamprenavir
Fosamprenavir/r
Saquinavir/r
Do not exceed 20 mg
atorvastatin
Statins
Nelfinavir
Do not exceed 40 mg
atorvastatin
Fluvastatin
No data available
Lovastatin/Simvastatin
Contraindicated
Pitavastatin
Atazanavir/r
Darunavir/r
Lopinavir/r
No dose limitations
Pravastatin
Darunavir/r
Lopinavir/r
No dose limitions
Rosuvastatin
Atazanavir/r
Lopinavir/r
Do not exceed 10mg
Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and
Adolescents. March 29, 2012. www.aidsinfo.nih.gov.
FDA drug safety communication, March 1, 2012, www.fda.gov
Patients Have Changed Since the
Adoption of HAART
Survival From Age 25 Years
Probability of Survival
1
0.75
Population
Controls
0.5
Late HAART
(2000-2005)
0.25
Early HAART
(1997-1999)
Pre-HAART
(1995-1996)
0
25
30
35
40
45
50
55
60
65
70
Age
(years)
Cumulative survival curve for HIV-infected persons (without hepatitis C coinfection)
and persons from the general population.
N=383,862 (HIV-infected patients, n=3990; General population controls, n=379,872)
Lohse N, et al. Ann Int Med. 2007
HIV - the Good News & the Bad
• Antiretroviral drugs have tripled average life
expectancy over the last decade, by reducing
opportunistic infections, however:
•
– In ART era only ~10% deaths in HIV infected clinical trials subjects
were due to AIDS defining illnesses.
Non-AIDS malig ~ 21%
CVD ~ 9%
Liver Disease ~ 9%
Non-AIDS Infection ~8%
In addition to reducing AIDS/Death, ART
reduces serious Non-AIDS Outcomes
No. of Patients
Rate
with Events DC VS
Endpoints
Hazard Ratio
(95% CI)
Major CVD, hepatic
or renal disease
CVD+
104
1.8
1.1
1.7
79
1.3
0.8
1.6
Hepatic (Cirrhosis)
17
0.3
0.2
Renal (ESRD)
11
0.2
0.1
Non-AIDS Malig++
47
0.8
0.5
Other non-AIDS death
51
0.9
0.5
186
3.2
2.0
Any of the above
+ MI (clinical or silent), stroke, surgery for CAD
++ Except non-melanoma skin
0.1
1.4
4.5
1.4
1.8
1.6
1
10
Favors DC Favors VS
The SMART Study Group. N Engl J Med 2006
INFLAMMATION??
Inflammatory Biomakers are Elevated with
HIV (SMART) compared to non-HIV (MESA)
Neuhaus J et al. JID 2010
SMART Nested Case Control
Biomarker Study (85 cases/170con)
Conditional logistic used to estimate ORs
for mortality (lowest quartile as reference)
Adjusted OR consider covariates
corresponding to: age, race, ART, HIV
RNA, CD4+ count, BMI, total/HDL
cholesterol, smoking, diabetes, Hep B/C
co-infection, use of lipid and BP lowering
medication
Baseline Biomarkers and All Cause Mortality
Adjusted
Un-adjusted
OR (4th/1st)
P-value
OR (4th/1st)
P-value
hs-CRP
2.0
0.05
3.1
0.02
Amyloid A
2.2
0.07
3.1
0.05
Amyloid P
0.7
0.39
1.1
0.78
IL-6
8.3
<0.0001
12.4
<0.0001
D-dimer
12.4
<0.0001
41.2
<0.0001
F1.2
1.0
0.92
1.3
0.64
Marker
Kuller L et al, PLoS Med 2008
D-dimer: Effect of ART Interruption (DC) for Participants on
ART and with an HIV-RNA ≤ 400 copies/mL
0.8
DC Group
Median (IQR) D-dimer (µg/mL)
VS Group
P<0.001 (27% increase in DC)
0.6
0.4
0.2
0
Baseline
Month 1
Kuller L et al, PLoS Med 2008
D-dimer: Effect of ART Initiation (VS) for
Participants Not on ART at Entry
Stored plasma for 254 subjects (126 DC arm, 128 VS arm), naïve to ART or off ART
>6 mo analyzed for IL-6, hs-CRP, & D-dimer (baseline, mo 2 & 6)
DC Group
Median (IQR)D-dimer (µg/mL)
1
VS Group
P=0.002
P<0.001
0.5
(22% lower for VS)
0
Baseline
Month 2
Baker JV et al. JAIDS 2010
Month 6
Inflammatory or Coagulopathy Biomarkers Associated
with Mortality in RCTs of HIV-infected Individuals
Biomarker
Odds ratios*: 1st vs 4th Quartile
Effect of HAART
Other HIV disease
Associations
D-dimer
12.4 (SMART), 2.4 (FIRST) 2.6
(Phidisa)
Decreases
CVD
hs-CRP
2.0 (SMART), 2.1 (FIRST), 3.6
(Phidisa)
No decrease
CVD, OD
IL-6
8.3 (SMART), 1.8 (FIRST), 3.8
(Phidisa), 1.5** (ACTG 384 and 5015 )
May decrease
CVD, OD
sCD14
6.0 (SMART)
Unknown
Microbial translocation
• While HAART partially reduces some
biomarker levels, they still remain elevated
compared with healthy non-HIV infected
individuals
But where would the inflammation be
coming from??
Infection destroys gut-associated lymphoid
tissue within 4 weeks of infection
-> Recovery is impaired, even with ART..
Brenchley JM et al J Exp Med. 2004
HIV-induced gut CD4+ T-cell depletion leads to
LPS/microbial translocation into the circulation
-> CHRONIC IMMUNE ACTIVATION
Brenchley, JM et al. Nature Medicine 2006
Excessive CD8+T-cell stimulation and
activation predicts CD4+ depletion and AIDS
• CD8+ T-cell activation is predictive of HIV disease
progression, independent of HIV viral load
(Giorgi JV et al. JID 1999
Calbone J et al. AIDS 2000)
• Patients with HIV viremia fully suppressed by ART
that have blunted CD4 recovery show continued
CD8+ T-cell activation
(Anthony KB et al. JAIDS. 2003, Hunt PW et al. JID 2003)
• Elite controllers not on ART with undetectable HIV
RNA & CD4 depletion have CD8+ T-cell activation
(Hunt PW et al. JID 2008)
– Note: that CD8 “activation” refers to expression of cell
surface markers (e.g. CD38 and HLA-DR)..in REALITY, the
CD4/CD8 cells are hypoactive/anergic functionally in
setting of HIV infection
“Inflamm-aging”
- Francesch C. et al. Ann NY Acad Sc 2000
De Martinis M et al. Exp and Mol Path 2006
HIV and “Inflamm-aging”
• HIV infection shares numerous clinical similarities w/ aging
– increased incidence of CVD, malignancy, infection, and chronic viral
reactivation, sarco/osteopenia, neurocognitive decline, & frailty
HIV and “Inflamm-aging”
• HIV infection shares numerous clinical similarities w/ aging
– increased incidence of CVD, malignancy, infection, and chronic viral
reactivation, sarco/osteopenia, neurocognitive decline, & frailty
• HIV infection results in T-cell activation and Immunosenescence
– In both aging and HIV infection, this leads to an elevated proportion of
CD28(-), CD57(+), memory CD8+ T cells characterized by reduced
capacity to produce IL-2, Incr IL-6, apoptosis resistance, & shortened
telomers
– Up to half of peripheral CD8+ T-cells are activated in HIV+ individuals,
compared with < 10% in healthy HIV - people
HIV and “Inflamm-aging”
• HIV infection shares numerous clinical similarities w/ aging
– increased incidence of CVD, malignancy, infection, and chronic viral
reactivation, sarco/osteopenia, neurocognitive decline, & frailty
• HIV infection results in T-cell activation and Immunosenescence
– In both aging and HIV infection, this leads to an elevated proportion of
CD28(-), CD57(+), memory CD8+ T cells characterized by reduced
capacity to produce IL-2, Incr IL-6, apoptosis resistance, & shortened
telomers
– Up to half of peripheral CD8+ T-cells are activated in HIV+ individuals,
compared with < 10% in healthy HIV - people
• HIV+ individuals (median age, 56 years) with good immune
reconstitution and viral suppression had T-cell similarities to older
(median age, 88 years) HIV- individuals (Desai SR et al. CROI 2009)
HIV and “Inflamm-aging”
• HIV infection shares numerous clinical similarities w/ aging
– increased incidence of CVD, malignancy, infection, and chronic viral
reactivation, sarco/osteopenia, neurocognitive decline, & frailty
• HIV infection results in T-cell activation and Immunosenescence
– In both aging and HIV infection, this leads to an elevated proportion of
CD28(-), CD57(+), memory CD8+ T cells characterized by reduced
capacity to produce IL-2, Incr IL-6, apoptosis resistance, & shortened
telomers
– Up to half of peripheral CD8+ T-cells are activated in HIV+ individuals,
compared with < 10% in healthy HIV - people
• HIV+ individuals (median age, 56 years) with good immune
reconstitution and viral suppression had T-cell similarities to older
(median age, 88 years) HIV- individuals (Desai SR et al. CROI 2009)
• As with increased CD8+ T-cell activation, increased senescence
(reduced CD28 expression on CD8+ & CD4+ T cells) associated
with more rapid HIV disease progression (Cao W et al. JAIDS 2009)
CMV and “Inflamm-aging”
• CMV+ adults over ~ 65y/o have a much greater expansion
of CD28- cells than age-matched CMV- controls
– many of these cells reflect the oligoclonal expansion of CMVspecific T cells
Hadrup SR et al. J Immuno 2006, Ouyang Q et al. J Clin Immuno 2003
Almanzar G et al. J Virol 2005
CMV and “Inflamm-aging”
• CMV+ adults over ~ 65y/o have a much greater expansion
of CD28- cells than age-matched CMV- controls
– many of these cells reflect the oligoclonal expansion of CMVspecific T cells
Hadrup SR et al. J Immuno 2006, Ouyang Q et al. J Clin Immuno 2003
Almanzar G et al. J Virol 2005
• Clinical significance of these findings is not clear,
however, it has already been shown that:
– CMV+ older persons are less likely to respond to vaccines
than age-matched, CMV- persons
Trzonkowski P et al. Vaccine 2003
– CMV-associated changes in the immune system are predictive
of early mortality among older persons
Hadrup SR et al. J Immuno 2006, Wikby A et al. J Gerontol 2005
CMV & the Swedish OCTO and
NONA studies
• 231/240 individuals
– mean age of ~ 90 years
– followed longitudinally x 4+yrs
– Grouped by Immune Risk
Profile
.
Pawelec G et al. Immuno Reviews 2005
T-cells are not the only problem…
HIV infection Associated w/ BOTH Adaptive
and Innate Immune System Activation
• Excess CD4 and CD8 T-cell activation observed in
patients with HIV
– Increased CD8 HLA-DR/CD38 expression associated with rapid
CD4 loss, impaired CD4 recovery, poor immunologic responder
on ART, & accelerated immune senescence
• Excess B-cell activation observed in patients w/ HIV
– Hypergammaglobulinemia, Autoantibodies
• Excess Platelet activation observed in patients w/ HIV
– Increased expression of TF, P-selectin, sCD40
• Excess Monocyte/Macrophage activation w/ HIV
– Increased expression of TF, CD14/sCD14
– NOTE: CMV infection of monocytes  differentiation to
proinflammatory “M1” macrophages (Chan G et al. J Immun 2008)
Macrophage Activation and
HIV-Associated Vascular Disease
Moore KJ
Cell 2011
HIV+ persons are at 2-fold 
risk for CHD “risk equivalent”
Freiberg CROI 2011
CHD Risk Factors:
Traditional and HIV-specific
Age
Gender
HIV Infection
Antiretroviral
Therapy
Family
History
Smoking
CHD Risk
Hypertension
Lipids &
Lipoproteins
Metabolic Disease
(hyperglycemia, insulin
resistance, and obesity)
Endothelial
Injury and
Inflammation
Biomarkers and Cardiovascular Disease:
SMART: HDL, D-dimer, IL-6, CRP, & NT-pro-B BNP
associated with CVD
•
Baseline hsCRP (p<0.0001), IL-6
(p<0.0001), & D-dimer (p=0.0008)
elevated in CVD cases
•
Total HDL (p<0.0001) was reduced
in CVD cases
– HDL negatively associated with Ddimer and IL-6 (R= -0.25)
•
N-terminal pro-B-type Natriuretic
Peptide elevated in CVD
(OR highest vs. lowest quartile – adjusted =
2.3, P =0.02)
Duprez D.A. et al. Atherosclerosis 2009
Duprez D.A. et al. 17th CROI 2010
Modulating Immune Activation:
Aspirin
Population
ASA
dose
Design
CRP
IL-6
TNF-α
Chronic stable angina
300mg
Placebo
controlled


--
Metabolic syndrome
300mg
Placebo
controlled



Metabolic syndrome
100mg
Placebo
controlled

NS
NS
Post-myocardial
infarction
160mg
vs. warfarin

--

Diabetes (Type 2)*
300/100m Dose
g
comparison
NS*
NS*
--
Healthy volunteers
325mg
NS
NS
NS
Cross-over
*Levels declined after starting aspirin but did not reach significance for either dose (n=20/arm)
Circulation 1999, Diab. Ob. Met 2008, JPP 2009, AJC 2003, AJC 2003
Relative Risk of MI by baseline CRP
Stratified by Aspirin (325mg QOD) versus Placebo
Ridker et. al. NEJM 1997
However, A 2009 Lancet Meta-analysis of RCTs found that:
Aspirin is of uncertain net value as primary prevention of vascular disease
Modulating Immune Activation:
ACTG A5275 - Atorvastatin
•
Why look at statins in (non-hyperlipidemic) HIV+ patients?
–
–
–
–
•
Blocking HMG-CoA reductase with a statin reduces activation of GTPbinding proteins RAS and Rho - “molecular switches” that regulate
transcription of inflammatory response genes
Statins inhibit expression of IL-6 (hs- CRP), TF (d-dimer), sCD14, and TNF-a
Statins decrease CD8+ T-cell activation
Statins reduce these biomarkers in numerous settings (e.g. sepsis,
pneumonia, influenza, COPD, hepatocellular CA, CVD)
JUPITER Study
–
Rosuvastatin decreased mortality and venous thrombotic disease in
subjects with hsCRP>2 mg/L and “normal” LDL (<130 mg/dl)
–
Individuals achieving hsCRP < 2 mg/L (entry criteria >2) had 62% decrease
in events
•Ridker
et al. NEJM 2008, Ridker et al. Lancet 2009
AMI rate per 10,000 p-y
MI Rates by SBP & HIV Status in
VACS
1000
HIV(-)
HIV(+)
800
600
400
200
0
<120
120-124 125-129 130-134 135-139 140-144 145-149 150-154 155-159
>160
.
Systolic BP (mmHg)
<120
120-139
<140 (on Rx)
≥140
aHR for HIV uninfected
ref
1.1
1.2
1.4
aHR for HIV infected
ref
1.7
2.8
2.8
SBP Category
(mmHg):
* Adjusted for age, race/ethnicity, diabetes cholesterol, smoking, HCV, BMI, renal disease, and cocain/EtOH
Armah & Freiberg CROI 2012
Brusselle et al. Lancet 2011
Macrophage Activation and
HIV-Associated Pulmonary Disease
VA Cohort (n=100,000 matched)
•
Alveolar Macrophage expression of
Matrix MP from HIV+ smokers w/ early
emphysema >> than in HIV- smokers
w/ early emphysema
– Kaner RJ et al. J. Leuk Bio 2009
•
Crothers K et al. Am J Resp Crit Care Med 2011
HIV and Matrix MP co-localize to
areas of empysema at autopsy
Yearsly MM et al. Diag Mol Path 2005
Macrophage Activation and
HIV-Associated Bone Density Loss
• HIV infection associated
with an increased risk (~3X
higher that HIV neg) of
osteopenia, fracture, and
avascular necrosis of bone
• Bone is an immunologically
rich tissue & activated
macrophages, T-cells,
osteoclasts, & inflammatory
cytokines play a central role
in accelerated bone loss
Mansky KC Clin Interventions in Aging 2010
HIV and Osteopenia – Some Issues
•
•
•
•
•
•
DXA Scanning if >50 y/o (McComskey et al. CID 2010)
Quit Smoking and Drinking (>3drinks/d)!
Treat Hypogonadism or Hypothyroidism
Weight Bearing Exercise
Safe Home
Vit D – treating low Vit D (<25 ng/dl) reasonable
– Efavirenz is associated with reduction in 25-hydroxy vit D levels
– Limited data on vitamin D supplementation in HIV-positive
patients have shown transient, beneficial effects on PTH, but no
effects on BMD.
• Bisphosphonates effective (6 RCTs)
– Treat with t-score ≤ 2.5 or -1.0-2.5 with FRAX 10 year fracture
prob score >20 (NOF 2008)
• Protease Inhibitors and Tenofovir as Risks?
– Avoid starting protease inhibitors if possible with t-score ≤ 2.5
Macrophage Activation and
HIV-Associated Mortality
Only sCD14 levels* (a marker of monocyte/macrophage
activation) are associated with mortality among microbial
translocation biomarkers
*after adjustment for other risk factors/biomarkers 1st/4th OR = 4.1 (p=0.02)
Biomarker
DC-arm
VS-arm
p-value
for
Interacti
on
OR (95% CI)a
p-value
OR (95%
CI)
pvalue
sCD14 (x106 pg/ml)
3.5 (1.5,8.3)
0.004
2.0
(0.8,5.4)
0.15
0.43
LPS (pg/ml)
1.0 (0.6,1.7)
0.96
0.7
(0.3,1.7)
0.40
0.63
I-FABP (pg/ml)
0.9 (0.4,2.1)
0.84
2.3
(0.6,8.8)
0.19
0.58
16S rDNA (copies/l)
0.9 (0.3,2.2)
0.90
0.5
(0.2,1.4)
0.21
0.26
EndoCAb (MMU/ml)
1.1 (0.8,1.6)
0.49
0.9
(0.5,1.4)
0.66
0.57
Sandler N. et al J. Infect Dis. 2011
Model of HIV induced “Aging”
Desai S and Landay A Curr HIV/AIDS Rep 2010
Model of VIRAL induced “Aging”
CMV
HCV
CMV
LPS
HIV
Bact 16sDNA
Activated Macrophages and T-cells produce IL-6, MMP, etc.
in brain, bone, lung, liver, vasculature ~ tissue level
Take Home Points
• Chronic antigen (HIV, LPS, CMV, HCV, etc.) stimulation
leads to excessive stimulation/activation of ALL arms of
the immune system
• Chronic immune activation leads to an immune system
more likely to cause tissue inflammation & less likely to
do its job! This has implications that extend well
beyond HIV!
– Premature aging – senescence and hypofunction of
the immune system
– Progression to AIDS
– End organ damage
• Inflammation correlates with many bad outcomes
– Treating HIV helps & should be done but doesn’t
entirely halt this problem
– Numerous strategies to modulate immune
activation/inflammation under study
Take Home Points
• Inflammation also increased by:
– Smoking: e.g. a study found that HIV - women
who stopped smoking showed decreased levels
of CRP, IL-6, TNF-alpha within weeks after quitting
– Diet / Obesity: adipocytes are “cytokine
factories”
– Other common disease processes like diabetes
• Role of PCP: Managing these sources of
inflammation, CVD risk reduction (e.g. BP, ASA,
Statin), alcohol cessation, expanded cancer and
bone density screening, helping with adherence,
watch drug-drug interactions, & STD risk reduction
• Don’t forget routine OPT-OUT HIV testing.. Inpatient,
outpatient, ED
THANK YOU for your
ATTENTION!