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Transcript of HIV 2012: You are only as YOUNG as your Immune System.. Daniel Nixon DO, PhD Associate Professor of...
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HIV 2012: You are only as YOUNG as
your Immune System..
Daniel Nixon DO, PhDAssociate Professor of Medicine Director – VCU HIV/AIDS Center (http://www.hivcenter.vcu.edu/)
[email protected] Office 804-828-4510
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HIV…we now know where it came from and when (slide from Paul Sharp’s 2006 CROI
lecture)
When? Between ~ 1884 and 1924Nature. Oct 2, 2008
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“Rumble in the Jungle”
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Natural History of HIV: Focus on Advanced HIV and Opportunistic Diseases
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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
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Guidelines 2012: When to Start ART
Guideline HIV with symptoms or Hep B/C
Asymptomatic/No Hepatitis – CD4
<200 200-350 350-500
DHHSMar2012 Yes Yes Yes Yes (mod Rec)
IAS-USA Yes Yes Yes Yes
BHIVAFeb2012 Yes Yes Yes Defer
EACSOct2011 Yes Yes Yes Concider
WHO Yes1 Yes Yes No
1initiate at any CD4 if Hep B or active TBGuidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents - www.aidsinfo.nih.gov
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Conflicting Evidence from Observational Studies for Initiating ART with CD4 > 350
Comparison CD4+ count strata HR for death
NA ACCORD <350 vs 350-500 1.7 (1.3 - 2.3) 350-500 vs > 500 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)
HIV-Causal 350 vs 500 1.0 (0.8-1.2)
• Kitahata MM et al, N Engl J Med 2009 • When to Start Consortium, Lancet 2009• HIV Causal Collaboration, Annals Int Med, 2011
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CD4 at Initiation of ARV Therapy Predicts Extent of CD4 RecoveryCD4 at Initiation of ARV Therapy Predicts Extent of CD4 Recovery
• 1,378 Patients at 10 US Clinics followed From 1996-2007
• 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-AIDS-related causes
Med
ian
CD
4+ c
ell c
ou
nt
Palella F, et al. 17th CROI, 2010
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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).
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Continuous ART at CD4> 350 associated with decreased serious non-AIDS Events in Subset of “relatively” Naïve to ART in SMART
DC Group VS GroupHR (DC/VS)
Deferred vs. EarlyP-valueN Rate N Rate 95% CI
• OD or death 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]
0.001Emery et al, JID, April 2008
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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!!
•
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START Study
HIV-infected individuals who are ART-naïve with CD4+ count > 500 cells/mm3
Early ART Group
Initiate ART immediately following randomization
N=2,000
Deferred ART Group
Defer ART until the CD4+ count declines to < 350 cells/mm3 or
AIDS develops
N=2,000
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What to Start 2012: DHHS Initial ART Recs
NNRTI based • Efavirenz1 + Tenofovir/Emtricitibine (TDF/FTC) daily
Protease-Inhibitor based
• Atazanvir or Darunavir with low dose Ritonavir “boosting agent”+ TDF/FTC daily
Integrase Inhibitor based
• Raltegravir bid + TDF/FTC daily
Pregnant Women • 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.
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HIV drugs and especially protease inhibitors have many Interactions..
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
Statins Interacting Protease Inhibitor
Prescribing recommendation
Atorvastatin Tipranavir/r
Lopinavir/r
Darunavir/rFosamprenavir
Fosamprenavir/rSaquinavir/r
Nelfinavir
Avoid concurrent administration
Use with caution and lowest dose
Do not exceed 20 mg atorvastatin
Do not exceed 40 mg atorvastatin
Fluvastatin No data available
Lovastatin/Simvastatin Contraindicated
Pitavastatin Atazanavir/rDarunavir/rLopinavir/r
No dose limitations
Pravastatin Darunavir/rLopinavir/r
No dose limitions
Rosuvastatin Atazanavir/rLopinavir/r
Do not exceed 10mg
Statins
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Survival Trends in HIV-infected Patients Have Changed Since the
Adoption of HAART
Survival Trends in HIV-infected Patients Have Changed Since the
Adoption of HAART
Lohse N, et al. Ann Int Med. 2007
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)
Survival From Age 25 Years
1
0.75
0.5
0.25
0
25 30 35 40 45 50 55 60 65 70
Age (years)
Pro
ba
bil
ity
of
Su
rviv
al
Population
Controls
Late HAART (2000-2005)
Early HAART (1997-1999)
Pre-HAART (1995-1996)
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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%
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In addition to reducing AIDS/Death, ART reduces serious Non-AIDS Outcomes
No. of Patients with EventsEndpoints
Major CVD, hepatic or renal disease 104 1.8 1.1CVD+ 79 1.3 0.8
Hazard Ratio (95% CI)
RateDC VS
Renal (ESRD) 11 0.2 0.1
1.4Hepatic (Cirrhosis) 17 0.3 0.2
0.1 1 10
1.4
4.5
1.7
Non-AIDS Malig++ 47 0.8 0.5
1.8
1.6
Favors DC Favors VS
Other non-AIDS death 51 0.9 0.5
Any of the above 186 3.2 2.0
1.6
+ MI (clinical or silent), stroke, surgery for CAD++ Except non-melanoma skin
The SMART Study Group. N Engl J Med 2006
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INFLAMMATION?? Inflammatory Biomakers are Elevated with HIV (SMART) compared to non-HIV (MESA)
Neuhaus J et al. JID 2010
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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
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Baseline Biomarkers and All Cause Mortality
Un-adjusted Adjusted
Marker 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
Kuller L et al, PLoS Med 2008
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D-dimer: Effect of ART Interruption (DC) for Participants on ART and with an HIV-RNA ≤ 400 copies/mL
0
0.2
0.4
0.6
0.8
DC Group
VS Group
Baseline Month 1
Med
ian
(IQ
R)
D-d
imer
(µ
g/m
L)
P<0.001 (27% increase in DC)
Kuller L et al, PLoS Med 2008
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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)
0
0.5
1
Med
ian
(IQR
)D-d
imer
(µg/
mL)
Baseline Month 6Month 2
P<0.001P=0.002
DC Group
VS Group
Baker JV et al. JAIDS 2010
(22% lower for VS)
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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
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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
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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
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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
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“Inflamm-aging” - Francesch C. et al. Ann NY Acad Sc 2000
De Martinis M et al. Exp and Mol Path 2006
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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
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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
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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)
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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)
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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 CMV-
specific T cells Hadrup SR et al. J Immuno 2006, Ouyang Q et al. J Clin Immuno 2003 Almanzar G et al. J Virol 2005
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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 CMV-
specific 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
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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
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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)
•
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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
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CHD Risk Factors:Traditional and HIV-specific
CHD Risk
HIV Infection
AntiretroviralTherapy
Lipids & Lipoproteins
EndothelialInjury and
Inflammation
Hypertension
Smoking
Metabolic Disease(hyperglycemia, insulin resistance, and obesity)
Age Gender FamilyHistory
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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 D-
dimer 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 2009Duprez D.A. et al. 17th CROI 2010
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Modulating Immune Activation:
AspirinPopulation ASA
doseDesign 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)* 300/100mg
Dose comparison
NS* NS* --
Healthy volunteers 325mg Cross-over NS NS NS
Circulation 1999, Diab. Ob. Met 2008, JPP 2009, AJC 2003, AJC 2003
*Levels declined after starting aspirin but did not reach significance for either dose (n=20/arm)
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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 diseaseHowever, A 2009 Lancet Meta-analysis of RCTs found that: Aspirin is of uncertain net value as primary prevention of vascular disease
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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 GTP-
binding 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
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MI Rates by SBP & HIV Status in VACS
<120 120-124 125-129 130-134 135-139 140-144 145-149 150-154 155-159 >160 .0
200
400
600
800
1000
HIV(-) HIV(+)
Systolic BP (mmHg)
AMI r
ate
per 1
0,00
0 p-
y
Armah & Freiberg CROI 2012
SBP Category (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
* Adjusted for age, race/ethnicity, diabetes cholesterol, smoking, HCV, BMI, renal disease, and cocain/EtOH
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Brusselle et al. Lancet 2011
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Macrophage Activation and HIV-Associated Pulmonary Disease
• 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
• HIV and Matrix MP co-localize to areas of empysema at autopsy
Crothers K et al. Am J Resp Crit Care Med 2011
VA Cohort (n=100,000 matched)
Yearsly MM et al. Diag Mol Path 2005
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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
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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
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Biomarker DC-arm VS-arm p-value forInteraction
OR (95% CI)a p-value OR (95% CI)
p-value
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
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)
Sandler N. et al J. Infect Dis. 2011
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Model of HIV induced “Aging”
Desai S and Landay A Curr HIV/AIDS Rep 2010
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Model of VIRAL induced “Aging”
Activated Macrophages and T-cells produce IL-6, MMP, etc. in brain, bone, lung, liver, vasculature ~ tissue level
HCVCMV
Bact 16sDNA
LPS
CMV
HIV
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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
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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
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THANK YOU for your ATTENTION!