Contemporary Management of HIV.How Aging Affects ART Management.2018

Contemporary Management of HIV:
How Aging Affects ART Management
This program is supported by an independent educational
grant from ViiV Healthcare.

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Program Directors
Joseph J. Eron, Jr., MD
Professor of Medicine and
Epidemiology
University of North Carolina
School of Medicine
Director, AIDS Clinical Trials Unit
University of North Carolina
Chapel Hill, North Carolina
Princy N. Kumar, MD
Professor of Medicine and
Microbiology
Division of Infectious Diseases
Georgetown University Hospital
Division Chief
Division of Infectious Diseases
and Travel Medicine
Department of Internal Medicine
Medstar Georgetown University
Hospital
Washington, DC

Program Directors Disclosures
Joseph J. Eron, Jr., MD, has disclosed that he has received consulting
fees from Gilead Sciences, Janssen, Merck, and ViiV Healthcare and
funds for research support from Gilead Sciences, Janssen, and ViiV
Healthcare.
Princy N. Kumar, MD, has disclosed that she has received consulting
fees from Gilead Sciences, Theratechnologies, and ViiV Healthcare; has
received funds for research support from Gilead Sciences, Merck, and
ViiV Healthcare; and has ownership interest in Gilead Sciences, Johnson
& Johnson, Merck, and Pfizer.

Peer Review Disclosure
Barry S. Zingman, MD
Medical Director, AIDS Center
Clinical Director, Infectious Diseases, Moses Division
Professor of Medicine
Albert Einstein College of Medicine
Montefiore Medical Center
The University Hospital for Albert Einstein College of Medicine
Bronx, New York
Barry S. Zingman, MD, has no real or apparent conflicts of interest to
report.

Outline
 HIV and Aging
 ART Considerations in Aging Patients With HIV
 Preventive Care Considerations for Healthy Aging Patients With
HIV

Decreased Life Expectancy in Older HIV-Positive
Adults in Modern ART Era
 Population-based cohort study of survival in HIV-infected pts (n = 2440) and
uninfected controls matched by age and sex (n = 14,588) in Denmark
HIV-Negative
Controls
1996-2014
2006-2014
2000-2005
1996-1999
HIV-Positive Pts
1.00
0.75
0.50
0.25
0
ProbabilityofSurvival
50 60 70 80
Age (Yrs)
Legarth RA, et al. J Acquir Immune Defic Syndr. 2016;71:213-218. Slide credit: clinicaloptions.com

ATHENA: Older Pts Becoming More Prevalent in
the HIV-Infected Population
 Observational cohort of
10,278 HIV-infected pts in the
Netherlands
 Modeling study projections:
– Proportion of HIV-positive pts
≥ 50 yrs of age to increase
from 28% in 2010 to 73% in
2030
– Median age of HIV-positive
pts on combination ART to
increase from 43.9 yrs in
2010 to 56.6 yrs in 2030
Smit M, et al. Lancet Infect Dis. 2015;15:810-818.
ProportionofHIV-PositivePts
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
2010 2015 2020 20302025
> 70 yrs of age
60-70 yrs of age
50-60 yrs of age
40-50 yrs of age
30-40 yrs of age
< 30 yrs of age

AGEhIV: Older HIV-Infected Pts at Increased
Risk for Multiple Comorbidities
 Cross-sectional analysis of comorbidity prevalence in prospective cohort study of HIV-infected
pts (n = 540) vs controls (n = 524) 45 yrs of age or older
Schouten J, et al. Clin Infect Dis. 2014;59:1787-1797. Slide credit: clinicaloptions.com
0
20
40
60
80
100
45-49 50-54 55-59 60-64 ≥ 65
Pts(%)
HIV Infected
45-49 50-54 55-59 60-64 ≥ 65
HIV Uninfected
3+
2
1
0
Mean number of comorbidities
Number of participants
0.83
184
1.18
126
1.34
97
1.52
58
1.96
55
0.79
193
0.75
130
1.11
84
1.08
66
1.51
41
Age (Yrs)
Comorbidities, n

AGEhIV: Older HIV-Infected Pts at Increased
Risk for Multiple Comorbidities
 Cross-sectional analysis of comorbidity prevalence in prospective cohort study of HIV-
infected pts (n = 540) vs controls (n = 524) ≥ 45 yrs of age
Schouten J. Clin Infect Dis. 2014;59:1787-1797.
Pts(%)
50
30
20
10
0
40
P < .001
P = .018 P = .008 P = .044
HIV-uninfected pts
HIV-infected pts

Factors Related to Non-AIDS Comorbidities in
HIV-Infected Pts
Warriner AH, et al. Infect Dis Clin North Am. 2014;28:457-476. Slide credit: clinicaloptions.com
AGING
Chronic HIV infection
ART toxicity
HCV and other coinfections
Genetics
Obesity, exercise, diet,
smoking
Stress
Depression
Inflammation and fibrosis
Dyslipidemia
Insulin resistance
Decreased physical functioning
Cardiovascular
Renal
Metabolic
Functional
Neuropsychiatric
Factors Conditions End Organ Disease

HIV and Inflammation
 Hypothesis: HIV infection induces a persistent inflammatory
response, resulting in pathogenic responses and end-organ
disease
 Elevated levels of inflammatory markers, including IL-6,
associated with increased risk of non-AIDS comorbidities and
mortality in HIV-infected pts[1-4]
 ART partially reduces some inflammatory biomarker levels;
however, they may still remain elevated vs healthy HIV-
uninfected individuals[3,4]
1. Tenorio AR, et al. J Infect Dis. 2014;210:1248-1259. 2. So-Armah KA, et al. J Acquir Immune Defic
Syndr. 2016;72:206-213. 3. Nixon DE, et al. Curr Opin HIV AIDS. 2010;5:498-503.
4. Neuhaus J, et al. J Infect Dis. 2010;201:1788-1795.

Inflammation Associated With Disease in
Treated HIV Infection
 Mortality[1-4]
 Cardiovascular disease[5]
 Cancer[6]
 Venous thromboembolism[7]
 Type 2 diabetes[8]
 Radiographic emphysema[9]
 Renal disease[10]
 Bacterial pneumonia[11]
 Cognitive dysfunction[11]
 Depression[13]
 Functional impairment/frailty[14]
References in slidenotes. Slide credit: clinicaloptions.com

Case 1: ART-Naive Older Pt With
Comorbid Conditions

Case 1: Presentation
 60-yr-old white man presents for care after HIV diagnosis
Characteristic Finding
HIV-1 RNA  42,000 copies/mL
CD4+ cell count  225 cells/mm3
HLA-B*5701 status  Negative
Resistance/GT  No mutations
Blood pressure  145/86 mm Hg
BMI  27.5
Lipid profile  TC 196 mg/dL, LDL 125 mg/dL, HDL 25 mg/dL, TG 175 mg/dL
Renal markers  Serum Cr 1.5 mg/dL  eGFR 54 mL/min/1.73m2
Medications  Hydrochlorothiazide 25 mg QD  Simvastatin 10 mg QD
Other  Does not exercise  Smoker

CVD Mortality Higher in HIV-Infected Pts, Even
With Virologic Suppression
 Analysis of CVD-related mortality in HIV-infected pts in New York City HIV
Surveillance Registry 2001-2012 (N = 145,845)
– 71% male; median age: 49 yrs
 From 2001-2012, CVD mortality increased in HIV-infected pts (from 6% to
15%) while decreasing in the general population
 Age-adjusted rate of CVD mortality markedly decreased for HIV-infected pts
with virologic suppression
– HIV-1 RNA ≥ 400 copies/mL, 8.02/1000 PY
– HIV-1 RNA < 400 copies/mL, 3.99/1000 PY
– General population, 3.22/1000 PY
Slide credit: clinicaloptions.comHanna DB, et al. Clin Infect Dis. 2016;63:1122-1129.

Hypertension Is Increasing and More Prevalent
Among HIV-Infected Pts
 Analysis of HTN in HIV-infected pts in
UNC CFAR HIV Clinical Cohort,
1996-2013 (N = 3141)[1]
 Hypertension incidence
– 1996: 1.68 cases/100 PY
– 2013: 5.35 cases/100 PY
 Key risk factors
– Age – Obesity
– Diabetes – Renal insufficiency
– Nadir CD4+ cell count < 500 cells/mm3
 Analysis of HTN in HIV-infected (n =
527) and HIV-uninfected (n = 517)
persons in AGEhIV cohort[2]
 HTN rate higher among HIV-infected
vs HIV-uninfected persons
– 48% vs 36%; aOR: 1.65; 95% CI:
1.25-2.19
1. Okeke NL, et al. Clin Infect Dis. 2016;63:242-248.
2. van Zoest RA, et al. Clin Infect Dis. 2016;63:205-213.

START: Immediate vs Deferred ART by Age
 Subgroup analysis of START, in which HIV-infected, ART-naive adults with CD4+ cell count
> 500 cells/mm3 randomized to immediate or deferred* ART (N = 4685)
Molina JM, et al. IAC 2016. Abstract THAB0201. Slide credit: clinicaloptions.com
*Until CD4+ cell count ≤ 350 cells/mm3, AIDS-related event, or event requiring ART.
Mos
Aged < 30 Yrs
PtsWithSeriousAIDSor
Non-AIDS–RelatedEvent(%)
16
14
12
10
8
6
4
2
0
600 12 24 36 48
2.6
1.3
Immediate ART
Deferred ART
Aged 30-49 Yrs
16
14
12
10
8
6
4
2
0
600 12 24 36 48
3.3
1.3
Aged ≥ 50 Yrs
16
14
12
10
8
6
4
2
0
600 12 24 36 48
11.7
2.9

DHHS HIV Guidelines: ART Considerations for
Older Pts
 ART is recommended for all pts regardless of CD4+ cell count; especially important
for older pts due to
– Greater risk of serious non-AIDS complications
– Potentially a blunted immunologic response to ART
 Adverse drug events from ART and concomitant drugs may occur more frequently
in older HIV-infected pts
– Bone, kidney, metabolic, cardiovascular, and liver health should be monitored closely
 Polypharmacy is common in older HIV-infected pts
– Greater risk of drug–drug interactions
 HIV experts should collaborate with primary care providers and other specialists to
optimize the medical care of older HIV-infected pts with complex comorbidities
Slide credit: clinicaloptions.comDHHS Guidelines. October 2017.

DHHS: First-line Therapy Recommendations
Third Agent NRTI Backbone Daily Tablets
INSTI-Based Regimens*
DTG ABC/3TC 1
DTG FTC/TAF or FTC/TDF 2
EVG/COBI FTC/TAF or FTC/TDF 1
RAL FTC/TAF or FTC/TDF 3
DHHS Guidelines. October 2017.
*Guidelines have not yet been updated to reflect February 2018 FDA approval of BIC/FTC/TAF.

BIC/FTC/TAF: Newest STR for HIV Treatment
 FDA approved February 2018
– Once-daily single-tablet regimen
Slide credit: clinicaloptions.comFDA BIC/FTC/TAF.
Key US Label Information
Indications
 For treatment-naive pts
 For pts who have been virologically suppressed for ≥ 3 mos, with no history of
treatment failure and no known resistance to individual components
Key DDIs
 Contraindicated with dofetilide or rifampin
 Take under fasting conditions 2 hrs before antacids containing Al/Mg or Ca
 Can be taken with other supplements containing calcium or iron with food
Dose
adjustments
 None required for pts with mild/moderate renal impairment; not recommended in pts
with CrCl < 30 mL/min

DHHS: Considerations for Initial ART Based on
Age-Related Comorbidity
Scenario
Consider
Avoiding
Options for Consideration*
Agent Caveat
CKD (eGFR
< 60 mL/min)
 TDF, especially
in RTV-
containing
regimens
 TAF
 ABC/3TC
 DRV/RTV + RAL
 LPV/RTV + 3TC
 If eGFR > 30 mL/min
 If HLA-B*5701 negative; 3TC requires dose
adjustment if CrCl < 50 mL/min
 If TAF or ABC cannot be used; if HIV-1 RNA
< 100,000 copies/mL and CD4+ cell count >
200 cells/mm3
 If TAF or ABC cannot be used; 3TC dose
adjustment if CrCl < 50 mL/min
Osteoporosis  TDF  TAF
 ABC/3TC  If HLA-B*5701 negative
CVD risk  ABC  DTG-, RAL-, or RPV-based regimens  If choosing boosted PI, ATV may be
preferable to DRV, but further study needed
Hyperlipidemia  PI/RTV or
PI/COBI
 EVG/COBI
 DTG-, RAL-, or RPV-based regimens
 TDF more favorable lipid effects vs
ABC or TAF
Slide credit: clinicaloptions.comDHHS Guidelines. October 2017.
*Guidelines have not yet been updated to reflect February 2018 FDA approval of BIC/FTC/TAF.

NEAT 022: Switch From Boosted PI to DTG in
Suppressed Pts With High CV Risk
 Randomized, open-label phase IV study in which pts with high CV risk* who were virologically
suppressed on a PI/RTV + 2 NRTIs were switched to DTG + 2 NRTIs† or continued PI/RTV + 2 NRTIs
(N = 415)
Gatell JM, et al. IAS 2017. Abstract TUAB0102. ClinicalTrials.gov. NCT02098837. Slide credit: clinicaloptions.com
*> 50 yrs of age and/or Framingham risk score > 10% at 10 yrs. †NRTIs to remain the same throughout study.
Virologic
Success‡
Virologic
Nonresponse
No
Virologic
Data
ITTPopulation(%)
Treatment difference: -2.1%
(95% CI: -6.6% to 2.4%)
4.9 4.4
100
80
60
40
20
0
93.1 95.2
2.0 0.5
DTG + 2 NRTIs
PI/RTV + 2 NRTIs
10
5
0
-5
-10
-15
-20
-25
DTG + 2 NRTIs
PI/RTV + 2 NRTIs
0.7
-8.7
-11.3
0.5
4.2
2.0 1.1
2.5
0.4
-18.4
-7.7 -7.0
TC Non–
HDL-C
TG LDL-C HDL-C TC/HDL
Ratio
P < .001
P < .001
P < .001
P < .001 P < .001
P = .286
MeanChange
FromBLtoWk48(%)
‡HIV-1 RNA < 50 copies/mL.
Wk 48 Virologic Efficacy Wk 48 Lipid Changes

ATHENA and Swiss HIV Cohort Studies:
Polypharmacy Among HIV-Infected Pts on ART
 5.2% of pts 50-64 yrs of age and 14.2% of pts
≥ 65 yrs of age received ≥ 4 meds other than ART
 Predicts that 20% of pts will be receiving
≥ 3 meds other than ART in 2030
Slide credit: clinicaloptions.com1. Smit M, et al. Lancet Infect Dis. 2015;15:810-818. 2. Hasse B, et al. Clin Infect Dis. 2011:53;1130-1139.
ATHENA Modeling Study[1]
16,000
14,000
12,000
10,000
8000
6000
4000
2000
0
People(n)
3+ comedications
2 comedications
1 comedication
No comedication
2010 2015 2020 2025 2030
Swiss HIV Cohort Study (N = 8444)[2]
Prospective Observational Study
< 50 Yrs 50-64 Yrs ≥ 65 Yrs
100
80
60
40
20
0
Participants(%)
n = 5761 n = 2233 n = 450
No comedication
1 comedication
2 comedication
3 comedications
4+ comedications

Key Interactions: INSTI-Containing ART Regimens
 Consider www.hiv-druginteractions.org to assist with identifying potential
interactions for all regimens
Regimen Key Drug–Drug Interaction Considerations
All INSTIs[1]  Use caution with/avoid simultaneous polyvalent cation-containing antacids*
BIC/FTC/TAF[2]  Contraindicated with dofetilide or rifampin
DTG/3TC/ABC[1,3]
DTG + FTC/TDF or FTC/TAF[1,4]
DTG/RPV†[1,5]
 Dose adjust metformin (diabetes medication)
 Contraindicated with dofetilide
EVG/COBI/FTC/TDF[1,6]
EVG/COBI/FTC/TAF[1,7]
 Avoid lovastatin, simvastatin (lipid-lowering agents), salmeterol
(asthma/COPD medication)
 Avoid/use caution with inhaled, injected, or systemic steroids
RAL + FTC/TDF or FTC/TAF[1,8]  None notable aside from avoiding coadministration of polyvalent cation-
containing antacids
References in slidenotes. Slide credit: clinicaloptions.com
*BIC or DTG can be coadministered with Ca- or Fe-containing supplements if given with food. †Key DDIs with RPV: avoid PPIs (eg,
omeprazole, pantoprazole), dexamethasone.

Key Interactions: Boosted PI- or NNRTI-
Containing ART Regimens
Regimen Key Drug–Drug Interactions
ATV/RTV + FTC/TDF or
FTC/TAF[1-5]
DRV/RTV + FTC/TDF or
FTC/TAF[1,3-6]
 Avoid lovastatin, simvastatin (lipid-lowering agents), salmeterol
(asthma/COPD medication)
 Use caution with other lipid-lowering agents (eg, atorvastatin,
rosuvastatin, pravastatin)
 Use caution with/avoid specific antiarrhythmics (eg, amiodarone)
 Avoid PPIs (eg, omeprazole) with ATV
 Use caution with/avoid inhaled, injected, or systemic steroids
RPV/FTC/TDF[7]
RPV/FTC/TAF[8]
DTG/RPV*[10]
 Avoid PPIs (eg, omeprazole, pantoprazole), dexamethasone
EFV/FTC/TDF[1,9]  No notable comedications to avoid for EFV; consider alternative
corticosteroid to dexamethasone
Slide credit: clinicaloptions.comReferences in slidenotes.
*Key DDIs with DTG: Dose adjust metformin (diabetes medication).

Statins Decrease Immune Activation and Aortic
Plaque in Treated HIV Infection
 REPRIEVE: double-blind, randomized phase III trial of pitavastatin (planned
N = 6500) now enrolling[3]
sCD14 Declines
With Rosuvastatin[1]
Wks From Randomization
Plaque Regression
With Atorvastatin[2]
sCD14RelativeChange
FromWk0(%)
30
20
10
-40
-10
0 24 48
-20
0
-30
Placebo
Rosuvastatin
P = .002 P = .0056
ChangeinNoncalcified
PlaqueVolume(mm3)
20
10
-40
-10
-20
0
-30
Placebo
P = .03
Atorvastatin
40
1. Funderburg NT, et al. J Acquir Immune Defic Syndr. 2015;68:396-404.
2. Lo J, et al. Lancet HIV. 2015;2:e52-e63. 3. ClinicalTrials.gov. NCT02344290.

Approach to Lipid-Lowering (Statin) Therapy
 HIV-infected patients are at increased risk for ASCVD[1,2]
– ART can cause increases in triglycerides and total, VLDL, LDL, and HDL cholesterol
 Prescribing statins can be challenging due to DDIs, insulin resistance, adverse events, and
increased pill burden[1]
Aspect of Statin Therapy Recommendation
Goal of therapy  CVD risk reduction[1]
Screening
 A fasting lipid panel should be obtained in all newly diagnosed HIV-infected pts[1,3]
 Lipid screening annually[3]
Treatment
 Statin therapy is first-line therapy for elevated LDL-C and non-HDL-C[1]
 Moderate- or high-intensity statin therapy should be considered[1]
 Lifestyle therapy is the recommended first step[4]
Other  Patient-provider discussion is central to decisions on drug treatment[1]
References in slidenotes.

ASCVD Risk Estimator
 Consider tools.acc.org/ASCVD-Risk-Estimator/ to determine risk and recommendations
Slide credit: clinicaloptions.comtools.acc.org/ASCVD-Risk-Estimator/.
Case Pt 1

Slide credit: clinicaloptions.comDubé MP. Lipid management. 2015. p. 241-255.
PI- or COBI-Containing Regimens
High-Intensity Statin Moderate-Intensity Statin Low-Intensity Statin
Atorvastatin 20 mg Atorvastatin 10 mg Pravastatin 10-20 mg
Rosuvastatin 10-20 mg Rosuvastatin 5 mg Fluvastatin 20-40 mg
Pravastatin 40-80 mg* Pitavastatin 1 mg
Pitavastatin 2-4 mg
Simvastatin and lovastatin are contraindicated for pts receiving a PI, COBI, and/or RTV
*With darunavir, reduce pravastatin to 20-40 mg
NNRTI-, RAL-, or DTG-Containing Regimens
High-Intensity Statin Moderate-Intensity Statin Low-Intensity Statin
Atorvastatin 40-80 mg Atorvastatin 10-20 mg Pravastatin 10-20 mg
Rosuvastatin 20 mg Rosuvastatin 10 mg Fluvastatin 20-40 mg
Pravastatin 40-80 mg Pitavastatin 1 mg
Pitavastatin 2-4 mg Lovastatin 20 mg
Lovastatin 40 mg Simvastatin 10 mg
Simvastatin 20-40 mg
Suggested Statins in the Setting of ART
All doses daily.

Case 1: Take-Home Points
Observation Recommendations
HIV-infected pts have
increased CVD risk
 Virologic suppression can reduce CVD risk
 Controlling other metabolic comorbidities (many of which occur more
frequently in HIV-infected pts) can also reduce the risk of CVD
 HTN, T2DM, CKD, lipid abnormalities
 Lifestyle modification (exercise, diet, smoking cessation) may also
reduce risk
ART can increase dyslipidemia
 Manage lipids with statin therapy; consider potential DDIs with boosted
PI- or COBI-containing regimens
Numerous challenges exist in
treating HIV infection in aging
pts
 Assess comorbidities and potential interplay with ART regimens
 Bone, lipid, or cardiovascular abnormalities can be exacerbated by
specific therapeutics
 Consider polypharmacy and potential DDIs

Case 2: Aging Patient Developing
Comorbidities on ART

 62-yr-old, HIV-infected white man returns for routine visit
Current ART regimen/HIV status  Stable suppression on EFV/FTC/TDF for 12 yrs; current HIV-1 RNA undetectable
CD4+ cell count  425 cells/mm3; nadir count 50 cells/mm3
Comorbidities  Hypertension and hyperlipidemia, both controlled
Vital signs  Temp 98.6ºF; pulse 80 and regular, BP 130/76 mm Hg, RR 12
Weight  160 lbs (lost 10 lbs in last yr)
Other
 Reports low energy and fatigue;
wants to sleep all the time
 Denies depressed mood, easy
bruisability, hair loss
 No fevers/chills/night sweats
 No lymphadenopathy or edema
 Normal urine function
 Normal lab values: CBC, CMP, thyroid
studies, B12 level
 Colonoscopy 2 yrs ago: normal
 No STIs; HAV and HBV immune; HCV
Ab negative

The Concept of Frailty
 Multisystem clinical syndrome that reflects biological rather than chronological age; regarded as
an end-stage state[1]
 Associated with loss of functional homeostasis, inability to recover fully after stressors, and
morbidity and excess mortality[1]
 Other tools: FRAIL Scale, Study of Osteoporotic Fractures (SOF) index, Clinical Frailty Scale[3-5]
Slide credit: clinicaloptions.comReferences in slidenotes.
Fried Frailty Phenotype[2]
Frailty Characteristic Clinical Criteria*
Shrinking Unintentional weight loss (> 10 lbs) in prior year, sarcopenia
Muscle weakness Poor grip strength (lowest quintile by sex, BMI)
Poor endurance/exhaustion Self-reported exhaustion
Slowness Walking time per 15 ft (slowest quintile by sex, height)
Low activity Low kcal/week expenditure (lowest quintile by sex)
*Frailty defined as presence of ≥ 3 criteria; prefrailty as presence of 1-2 criteria.

Frailty More Prevalent in HIV-Infected vs
HIV-Uninfected Persons
 Assessment of frailty* in HIV-infected (n = 521) and -uninfected (n = 513) pts in AGEhIV cohort
 Frailty/prefrailty associated with HIV infection, advanced age, smoking, chronic HCV infection, depression,
low BMI,† and waist-to-hip ratio
Slide credit: clinicaloptions.comKooij KW, et al. AIDS. 2016;30:241-250.
Frailty Prevalence by Age/HIV Status Individual Frailty Criteria
*Using Fried frailty phenotype. †In HIV-infected patients only.
Nonfrail
Prefrail
Frail
0
20
40
60
80
100
Pts(%)
HIV Status
Age (Yrs)
0
5
10
15
20
HIV infected
HIV uninfected
Pts(%)
25
30
P < .001
P < .001P < .001
P < .001
P = .04
- +
45-50 50-55 55-60 60-65 > 65
- + - + - + - +

Frailty Associated With Increased Risk of
Hospitalization
 Prospective evaluation of frailty in HIV-infected pts (N = 445)[1]
– Frailty prevalence: 9%
– Predictors of frailty: higher number of comorbidities and past OIs, increased
depressive symptoms, antidepressant use, lower serum albumin, unemployment
– Frailty associated with excess hospitalizations and longer inpatient hospital stays
 ALIVE: evaluation of frailty in HIV-infected (n = 417) and -uninfected
individuals (n = 886)[2]
– Frailty prevalence: 12.1% overall; 13.4% among HIV-infected pts
– Frailty significantly associated with all-cause hospitalization rates (HR: 1.41; 95%
CI: 1.06-1.87; P < .05)
1. Önen NF, et al. J Infect. 2009;59:346-352.
2. Piggott DA, et al. J Gerontol A Biol Sci Med Sci. 2017;72:389-394.

Frailty Risk Factors in Aging HIV-Positive Pts
Slide credit: clinicaloptions.comErlandson KM, et al. IAS 2011. Abstract TUPE124.
Incidence(%)
Diabetes
Frail (n = 33)
Prefrail (n = 185)
Nonfrail (n = 141)
Risk Factors (OR: Frail vs Nonfrail)
Neurologic
Disease
Psychiatric
Disease
CVD Unhealthy
Weight
Arthritis Osteoporosis Viral
Hepatitis
HR: 5.1
P = .007
HR: 3.9
P < .001
HR: 3.9
P = .002
HR: 3.8
P = .067
HR: 3.7
P = .004
HR: 3.6
P = .001
HR: 3.5
P = .022
HR: 3.3
P = .004
0
20
40
60
80

Returning to Case 2: Recent Fracture and
Diminished Bone Health
 62-yr-old pt returns for a visit; has suffered a wrist fracture in a fall
Current ART regimen/HIV status  Stable suppression on EFV/FTC/TDF for 12 yrs; current HIV-1 RNA undetectable
Comorbidities  Hypertension and hyperlipidemia, both controlled
Vital signs  Temp 98.6ºF; pulse 80 and regular, BP 130/76 mm Hg, RR 12
Weight  160 lbs (lost 10 lbs in last yr)
Other
 Reports low energy and fatigue;
wants to sleep all the time
 Denies depressed mood, easy
bruisability, hair loss
 No fevers/chills/night sweats; no
lymphadenopathy or edema
 Normal urine function and lab values
 No STIs; HAV and HBV immune; HCV
Ab negative
Bone health
 Recently suffered a wrist fracture in a fall
 DXA T-scores: L-spine: -2.6; femoral neck: -2.7; hip: -2.6

Fracture Prevalence Is Increased in Older HIV-
Infected Pts
 Meta-analysis: HIV-positive pts had 6.4-fold increased risk of low BMD and 3.7-fold
increased risk of osteoporosis[1]
 8525 HIV-infected pts compared with 2,208,792 uninfected pts in Partners HealthCare
System, 1996-2008[2]
Women Men
Age (Yrs)
7.0
6.0
5.0
4.0
3.0
2.0
1.0
0
FracturePrevalence/
100Persons
30-39 40-49 50-59 60-69 70-79
P = .002
(overall comparison)
HIV
Non-HIV
HIV
Non-HIV
Age (Yrs)
7.0
6.0
5.0
4.0
3.0
2.0
1.0
0
FracturePrevalence/
100Persons
20-29 30-39 40-49 50-59 60-69
P < .0001
(overall comparison)
1. Brown TT, et al. AIDS. 2006;20:2165-2174. 2. Triant V, et al. J Clin Endocrinol Metab. 2008;93:3499-3504.

ART Considerations for Pts With Bone
Complications
 DHHS considerations[1]
– Consider avoiding TDF: associated with greater decrease in BMD along
with renal tubulopathy, urine phosphate wasting, and osteomalacia
– Consider ABC/3TC or FTC/TAF
 Significantly greater BMD loss with PI-based regimens vs RAL-based
regimens (when used with FTC/TDF)[2]
 DTG/ABC/3TC associated with less bone turnover vs EFV/TDF/FTC[3]
 DTG/RPV: FDA approved in November 2017 as potential switch
regimen for pts with virologic suppression on current ART, no drug
resistance, and no history of VF[4]
1. DHHS Guidelines. October 2017. 2. Brown TT, et al. J Infect Dis. 2015;212:1241-1249.
3. Tebas P, et al. AIDS. 2015;29:2459-2464. 4. DTG/RPV [package insert]. 2018. Slide credit: clinicaloptions.com

 Randomized study comparing switch to non–TDF-based ART vs continuing TDF-based ART +
zoledronic acid* (5 mg IV at Mos 0 and 12) in pts with low BMD† and virologic suppression on TDF-
based ART (N = 87)
ZEST: Zoledronic Acid vs TDF Switching to
Improve BMD in Pts Receiving TDF-Based ART
Slide credit: clinicaloptions.comHoy J, et al. IAS 2017. Abstract WEAB0106LB.
Outcome, 24 Mos
Continue
TDF + ZOL
(n = 43)
TDF Switch
(n = 42)
P
Value
Femoral neck BMD ∆
from BL, %
4.1 2.1 .03
Total hip BMD ∆ from
BL, %
4.6 2.6 .009
Fractures (events), % 2 17 .03
Fractures (pts), % 2 10 .20
Mean eGFR ∆ -6.0 3.3 .003
*Calcium and vitamin D supplementation (as indicated) were also provided. †T-score ≤ -1.0 at spine (L1-L4) or left femoral neck by DXA.
‡Primary endpoint, ITT population.
Lumbar Spine BMD Change at 24 Mos‡
ChangeinBMDFromBL(%)
8
6
4
2
0
0 12 24
Mos
6.1
7.4
2.9 2.9
P < .001
P < .001
Continue TDF + ZOL
TDF switch
 Potential limitations: study conducted before TAF available; possible AE concerns with long-term use of
bisphosphonates

Recommendations for Evaluation of Bone
Disease in HIV
Brown TT, et al. Clin Infect Dis. 2015;60:1242-1251. Slide credit: clinicaloptions.com
HIV-Infected Population Assessment Monitoring
Men 40-49 yrs of age
Premenopausal women
≥ 40 yrs of age
 Assess risk of fragility
fracture using FRAX
 For pts with FRAX score ≤ 10%,
monitor FRAX in 2-3 yrs
 For pts with FRAX score > 10%,
perform DXA
Men ≥ 50 yrs of age
Postmenopausal women
Pts with fragility fracture
history, receiving chronic
glucocorticoids, or at high
risk of falls
 Assess BMD using DXA
 For pts with advanced osteopenia,
monitor DXA in 1-2 yrs
 For pts with mild or moderate
osteopenia, monitor DXA in 5 yrs
 For pts started on bisphosphonates
(significantly reduced BMD or
fracture history), repeat DXA in 2 yrs

Frailty is more prevalent among
HIV-infected vs HIV-uninfected
individuals
 Assess pts for frailty; consider Fried Frailty Phenotype or
other available tests
Fracture prevalence and low
BMD common among pts with
HIV
Some ART regimens have larger
impact on BMD loss than others
 Assess pts for BMD loss or risk of bone disease depending
on risk factors
 For pts at risk for or with BMD loss or bone disease,
consider ART modifications
 Backbone: consider FTC/TAF or ABC/3TC vs
FTC/TDF
 Greater BMD loss observed with PI-based regimens vs
RAL-based regimens

Case 3: Preventive Care Considerations for
Healthy Older Patients With HIV

 55-yr-old white man transfers care from another state
HIV status
 Stable suppression for 15 yrs on
RAL + FTC/TDF; current HIV-1 RNA
undetectable
Family history
 Father died from stroke at age 76
 Mother breast cancer survivor at
age 75; has T2DM and
hyperlipidemia
 Healthy sister age 57
Social
 Lives with HIV+ husband; sexually
active with husband only
 Smokes on weekends/at bars
 Alcohol daily 1-2 glasses of wine
with dinner; no illicit drug use
Additional
findings
 Excellent tolerability to HIV meds
 Reports irritability because of job
stress but sleeping well
 Reports 25-lb weight gain in past 2
yrs; stopped exercising because of
injury to ankle and never resumed
 No fevers/chills/night sweats; no
lymphadenopathy
 No pulmonary or cardiovascular
complaints; no edema
 Normal urine function and bowel
habits

 55-yr-old white man transfers care from another state
Physical exam
 Vital signs: temp 98.6ºF; pulse rate 80 and regular, BP 146/88 mm Hg,
RR 12, weight 205 lbs, BMI 30.1
 PE unremarkable
Laboratory values
 Normal lab values: CBC, CMP (except glucose 108 mg/dL)
 TC 205 mg/dL, LDL 124 mg/dL, HDL 30 mg/dL, TG 255 mg/dL
 STI testing negative
 HAV and HBV immune; HCV Ab negative
ASCVD 10-yr risk  20.2%

Keeping Healthy HIV Pts Healthy: How to Beat
Inflammation and Limit Comorbidities
 Adhere to HIV medications
 Quit smoking
 Refine diet and maintain normal weight
– For obese individuals, a hypocaloric diet can reduce inflammation[1]
 Exercise
– Study of sedentary HIV-infected pts on ART (N = 49) found that 60 mins
brisk walking ± 30 mins strength training 3 times/wk for 12 wks improved
functional status and reduced inflammatory markers/immune activation[2]
 Reduce alcohol intake; avoid drugs
1. Hermsdorff HH, et al. Endocrine. 2009;36:445-451.
2. Bonato M, et al. BMC Infect Dis. 2017;17:61.

HIV Infection Lowers Threshold at Which
Alcohol Causes Harm
 Study of alcohol intake and mortality or physiologic injury in HIV-infected (n
= 18,145) and HIV-uninfected (n = 42,228) individuals in the Veterans Aging
Cohort Study
– 76% of HIV-infected pts with HIV-1 RNA < 500 copies/mL
 Threshold for association between alcohol and mortality differed by HIV
status
Slide credit: clinicaloptions.comJustice AC, et al. Drug Alcohol Depend. 2016;161:95-103.
HIV Status Threshold, Drinks/Mo Mortality, HR (95% CI)
Infected ≥ 30 1.30 (1.14-1.50)
Uninfected ≥ 70 1.13 (1.00-1.28)
 Similarly, lower alcohol threshold for physiologic injury (eg, falls, fractures) in
HIV-infected pts

START: Cancer Events With Immediate vs
Deferred ART
INSIGHT START Group. N Engl J Med. 2015;373:795-807. Lundgren J, et al. IAS 2015. Abstract MOSY0302.
Cancer Event, n
Immediate
ART
(n = 2326)
Deferred
ART
(n = 2359)
Total 14 39
Kaposi sarcoma 1 11
Lymphoma, NHL + HL 3 10
Prostate cancer 2 3
Lung cancer 2 2
Anal cancer 1 2
Cervical or testis
cancer
1 2
Other types* 4 9
*Immediate ART: squamous cell carcinoma, plasma cell myeloma, bladder cancer, fibrosarcoma. Deferred ART: gastric
adenocarcinoma, breast cancer, ureteric cancer, malignant melanoma, myeloid leukemia, thyroid cancer, leiomyosarcoma, liver
cancer, squamous cell carcinoma of head and neck.
Time to Cancer Event
10
8
6
4
2
0
Cumulative%WithEvent
0 12 24 36 48 60
Mo
Deferred ART
Immediate ART
Rate/100 PY: immediate, 0.20; deferred, 0.56
(HR: 0.36; 95% CI: 0.19-0.66; P = .001)

HIV and Cancer
 Assessment of malignancy in HIV-infected pts in EuroSIDA (N = 15,648)
Slide credit: clinicaloptions.comShepherd L, et al. HIV Med. 2016;17:590-600.
Malignancy Type Malignancy Risk Factors
Infection-related
malignancies
 Hodgkin/non-Hodgkin lymphoma (EBV)
 Hepatocellular carcinoma (HBV/HCV)
 Kaposi sarcoma (HHV-8)
 Anal, cervical, vulvar, vaginal, penile, stomach, and
oral cancers (HPV)
 Age
 Lower CD4+ cell count
 HBV coinfection
 Detectable HIV-1 RNA
 Prior ADM
Infection-
unrelated
malignancies
 Lung cancer
 Prostate cancer
 Colorectal cancer
 Breast cancer
 Age
 Lower CD4+ cell count
 HBV coinfection
 Current smoking

D:A:D: Impact of Smoking Cessation on Cancer
Incidence in HIV-Infected Pts
 Baseline characteristics: 72.5% male; 20.8% prior AIDS; 46% current smoker; 20% exsmoker; 31%
never smoked; median age: 40 yrs (IQR: 34-46); median CD4+ cell count: 444 cells/mm3 (IQR: 295-632)
 Pts followed for median of 9 yrs (IQR: 6-11)
Shepherd L, et al. CROI 2017. Abstract 131.
Adjusted Rate Ratios for Specific Cancers in 35,424 HIV+ Pts With 285,103 PYFU
Smoking Status Smoking-
Unrelated Cancer
Smoking-Related
Cancer (Excl. Lung)
Lung Cancer
Never (reference)
Current smoker
Ex at baseline
Ex: < 1 yr
Ex: 1-2 yrs
Ex: 2-3 yrs
Ex: 3-5 yrs
Ex: > 5 yrs
Adjusted Rate Ratio (95% CI)
0.5 1 2
P trend
= .04
P trend
= .04
P trend
= .13
0.5 1 2 4 1 2 4 8 16 32

Cancer Prevention
 Encourage smoking cessation
 Provide hepatitis and HPV vaccinations
 Advise sunscreen and avoidance of sun overexposure
 Screening:
– Yearly cervical and anal Pap tests as indicated[1]
– Colon cancer screening at age 50[1]
– Breast cancer screening every other year at age 50[2,3]
– Prostate screening risks and benefits discussed at age 50[2,4]
– If hepatitis B or C positive, screen for liver cancer[1]

Screening With Low-Dose CT Reduces Lung
Cancer Mortality in High-Risk Pts
 N = 53,454 persons at high risk for lung
cancer at 33 US medical centers, 2002-
2004[1]
– Randomized to 3 annual low-dose CT
screening vs single-view chest x-ray
– Low-dose CT reduced RR lung cancer
mortality by 20% (95% CI: 6.8% to 26.7%;
P = .004) and RR all-cause mortality by
6.7% (95% CI: 1.2% to 13.6%; P = .02)
 USPSTF recommends annual low-dose
CT screening in adults aged 55-80 yrs who
have a 30 pack-yr smoking history and
currently smoke or quit smoking within the
past 15 yrs[2]
1. National Lung Screening Trial Research Team, et al. N Engl J Med. 2011;365:395-409.
2. USPSTF. Lung Cancer Screening Guidelines. 2013.
Cumulative Numbers of Lung Cancers
and Deaths From Lung Cancer
800
CumulativeNo.
ofLungCancers
600
400
0
200
1000
0 1 2 3 4 5 6 7 8
Low-dose CT
Chest radiography
400
CumulativeNo.of
LungCancersDeaths
300
200
0
100
500
0 1 2 3 4 5 6 7 8
Yrs Since Randomization
Low-dose CT
Chest radiography
1200

CT Screening for Lung Cancer in HIV-Infected
Smokers
 Prospective CT screening in 224 HIV-positive current or former
smokers aged ≥ 25 yrs detected 1 lung cancer in 678 PYFU
– Median age: 48 yrs (IQR: 44-53); median CD4+ nadir: 179 cells/mm3
(IQR: 61-332)
Hulbert A, et al. J Thorac Oncol. 2014;9:752-759.
Characteristics Adjusted OR for Lung Cancer 95% CI P Value
Increasing age 1.08 1.01-1.15 .02
Increasing pack-yrs 1.09 1.04-1.15 < .0001
Decreasing CD4+ nadir 1.006 1.002-1.01 .006
Increased SD/TLV 1.23 1.03-1.47 .02
Factors Associated With Lung Cancer on Multivariate Regression

ANRS EP48 HIV CHEST: CT Screening for Lung
Cancer in HIV-Infected Smokers
 Prospective CT screening in 442 HIV-positive smokers aged
≥ 40 yrs with CD4+ nadir < 350 cells/mm3 detected 9 lung
cancers
– Median follow-up time after CT: 24.4 mos (IQR: 22.8-26.4)
– Median age: 49.8 yrs (IQR: 46.3-53.9); median CD4+ nadir:
168 cells/mm3 (IQR: 75-256)
 6 of 9 lung cancers detected by CT were detected at early
disease stage
Makinson A, et al. AIDS. 2016;30:573-582. Slide credit: clinicaloptions.com

Healthy aging pts with HIV
should be encouraged to
maintain health and be
aware of increased risk of
HIV-specific comorbidities
 Adhere to HIV medications
 Quit smoking
 Maintain normal weight
 Exercise
 Reduce alcohol intake; avoid drugs
Cancer risk should be
managed in HIV-infected pts
and screening provided
 Encourage smoking cessation
 Provide hepatitis and HPV vaccination
 Provide cancer screening as indicated

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