1. HIV Alert: Management of Older Patients
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3. Faculty
David A. Wohl, MD Professor of Medicine School of Medicine Site Leader, AIDS Clinical Trials Unit-Chapel Hill University of North Carolina at Chapel Hill Director, North Carolina AIDS Training and Education Center Chapel Hill, North Carolina Co-Director, HIV Services North Carolina Department of Correction Raleigh, North Carolina

4. Faculty Disclosure Information
David A. Wohl, MD, has disclosed that he has received consulting fees from Bristol Myers-Squibb, Gilead Sciences, and Janssen and funds for research support paid to his university from Gilead Sciences and ViiV.

5. Aging With HIV Infection
The Numbers: Epidemiology of aging among those with HIV infection
The Reasons: Drivers of aging and frailty
The Response: Practical approaches to prevent/minimize age-related conditions and avoid frailty
Slide credit: clinicaloptions.com

6. Proportion of HIV-Positive Pts
ATHENA: Older Pts Becoming More Prevalent in the HIV-Positive Population
ATHENA: observational cohort of 10,278 HIV-positive pts in the Netherlands
Modeling study projections:
Proportion of HIV-positive pts ≥ 50 yrs of age to increase from 28% in to 73% in 2030
Median age of HIV-positive pts on combination ART to increase from 43.9 yrs in to 56.6 yrs in 2030
> 70 yrs of age yrs of age
50-60 yrs of age
40-50 yrs of age yrs of age
< 30 yrs of age
1.0
0.9
0.8
0.7
0.6
Proportion of HIV-Positive Pts
0.5
0.4
ART, antiretroviral therapy.
0.3
0.2
0.1
2010
2015
2020
2025
2030
Slide credit: clinicaloptions.com
Smit M, et al. Lancet Infect Dis. 2015;15:

7. Decreased Life Expectancy in Older HIV+ Adults in Modern ART Era
1.00
HIV-Negative Controls
0.75
Probability of Survival
0.50
HIV-Positive Pts
0.25 50 60 70 80
Age (Yrs)
Slide credit: clinicaloptions.com
Slide credit: clinicaloptions.com
Legarth RA, et al. J Acquir Immune Defic Syndr. 2016;71:
Legarth RA, et al. J Acquir Immune Defic Syndr. 2016;71:

8. The Facts About Aging With HIV
People living with HIV now have life expectancies that are very close to that of people without HIV
But people with HIV have a greater risk for conditions that are associated with getting older
The reasons why HIV-positive people suffer more from these conditions are debated, but all agree that lifestyle plays a role
Although aging with HIV is inevitable, the course of aging can be influenced by actions
eg, healthy diet, exercise
Slide credit: clinicaloptions.com

9. High Risk Behaviors in Persons With HIV Infection
100
Prevalence of Alcohol, Cigarette, and Illicit Drug Use Among
HIV-Positive Pts vs General Population 80
General population[2,3]
HIV-positive pts[1]
61.0 60
52.0
Persons (%)
38.2 40
24.0 20
15.2
10.2
References 1. CDC. Behavioral and Clinical Characteristics of Persons Receiving Medical Care for HIV Infection–Medical Monitoring Project, United States, 2013 Cycle (June 2013-May 2014). HIV Surveillance Special Report 16.
2. CDC. Summary Health Statistics for U.S. Adults: National Health Interview Survey, 2015.
3. Center for Behavioral Health Statistics and Quality. (2015). Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and
Health.
Alcohol Use
Cigarette Smoking
Illicit Drug Use*
*24% noninjection, 1.7% injection drug use in HIV-positive pts; illicit drug use for general population included marijuana, cocaine, heroin, hallucinogens, inhalants, and nonmedical use of prescription-type pain relievers, tranquilizers, stimulants, and sedatives.
CDC.Behavioral and Clinical Characteristics of Persons Receiving Medical Care for HIV Infection–Medical Monitoring Project, United States, 2013 Cycle (June 2013-May 2014).
2. CDC. Summary Health Statistics for U.S. Adults: National Health Interview Survey, 2015.
3. Center for Behavioral Health Statistics and Quality. (2015). Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health.
Slide credit: clinicaloptions.com

10. Aging With HIV: Factor Stacking
HIV-Mediated Inflammation
Untreated HIV
Low CD4
LIFESTYLE
Normal Aging Process
Slide credit: clinicaloptions.com

11. Inflammation Predicts Disease in Treated HIV Infection
Mortality[1-4]
Cardiovascular disease[5]
Cancer[6,7]
Venous thromboembolism[8]
Type II diabetes[9]
Radiographic emphysema[10]
Renal disease[11]
Bacterial pneumonia[12]
Cognitive dysfunction[13]
Depression[14]
Functional impairment[15]
References
1. Kuller LH, et al. PLoS Med. 2008;5:e203.
2. Tien PC, et al. J Acquir Immune Defic Syndr. 2010;55:
3. Justice AC, et al. Clin Infect Dis. 2012;54:
4. Hunt PW, et al. J Infect Dis. 2014;210:
5. Duprez DA, et al. Atherosclerosis. 2009;207:
6. Breen EC, et al. Cancer Epidemiol Biomarkers Prev. 2011;20:
7. Borges ÁH, et al. AIDS. 2013;27:
8. Musselwhite LW, et al. AIDS. 2011;25:
9. Brown TT, et al. Diabetes Care. 2010;33:
10. Attia EF, et al. Chest. 2014;146:
11. Gupta SK, et al. HIV Med. 2015;16:
12. Bjerk SM, et al. PLoS One. 2013;8:e56249.
13. Burdo TH, et al. AIDS. 2013;27:
14. Martinez P, et al. J Acquir Immune Defic Syndr. 2014;65:
15. Erlandson KM, et al. J Infect Dis. 2013;208:
1.Kuller LH, et al. PLoS Med. 2008;5:e203.
2. Tien PC, et al. J Acquir Immune Defic Syndr. 2010;55:
3. Justice AC, et al. Clin Infect Dis. 2012;54:
4. Hunt PW, et al. J Infect Dis. 2014;210:
5. Duprez DA, et al. Atherosclerosis. 2009;207:
6. Breen EC, et al. Cancer Epidemiol Biomarkers Prev. 2011;20:
7. Borges ÁH, et al. AIDS. 2013;27:
8. Musselwhite LW, et al. AIDS. 2011;25:
9. Brown TT, et al. Diabetes Care. 2010;33:
10. Attia EF, et al. Chest. 2014;146:
11. Gupta SK, et al. HIV Med. 2015;16:
12. Bjerk SM, et al. PLoS One. 2013;8:e56249.
13. Burdo TH, et al. AIDS. 2013;27:
14. Martinez P, et al. J Acquir Immune Defic Syndr. 2014;65:
15. Erlandson KM, et al. J Infect Dis. 2013;208:249-2
Slide credit: clinicaloptions.com

12. AGEhIV: Comorbidity Distribution
Cross-sectional analysis of comorbidity prevalence in prospective cohort study of HIV-infected pts (n = 540) vs controls (n = 524) ≥ 45 yrs of age 50
P < .001
HIV-uninfected pts
HIV-infected pts 40 30
Pts (%) 20
CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; CVD, cardiovascular disease; FX, fractures; HTN, hypertension; MI, myocardial infarction; PAD, peripheral artery disease. 10
P = .044
P = .018
P = .008
HTN MI
PAD
CVD
CKD
Angina
T2DM
COPD
Non-AIDS Cancer
Osteoporosis/ FX
Slide credit: clinicaloptions.com
Schouten J, et al. Clin Infect Dis. 2014;59:

13. START: Reduced but Persistently High Risk of AIDS Event With Early ART10
Immediate ART
Deferred ART
~ 1% of immediate ART arm had an AIDS event by Yr 5 8 6
Cumulative Percent With an Event 4 2 6 12 18 24 30 36 42 48 54 60
ART, antiretroviral therapy.
Mos
72% reduced risk of serious AIDS events with immediate ART
INSIGHT START Study Group. N Engl J Med. 2015;373: Lundgren J, et al. IAS Abstract MOSY0302.
Slide credit: clinicaloptions.com

14. START: Serious Non-AIDS Events
39% reduced risk of serious non-AIDS events with immediate ART 10
Immediate ART
Deferred ART 8 6
Cumulative Percent With an Event 4 2 6 12 18 24 30 36 42 48 54 60
ART, antiretroviral therapy; KS, Kaposi sarcoma; TB, tuberculosis.
Outcome HR
TB 0.29
Bacterial infection 0.38
KS 0.09
Lymphoma 0.30
Non-AIDS cancer 0.50
Mos
INSIGHT START Study Group. N Engl J Med. 2015;373: Lundgren J, et al. IAS Abstract MOSY0302.
Slide credit: clinicaloptions.com

15. HIV-1 RNA Suppression and Cancer
AIDS Defining
Virus-Related NADC
500 30
400 8
P < .0001
P < .0001
400
300 6 20
300 IR
IRR IR
200 4
IRR
200 10
100
100 2
Nonvirus NADC
HIV positive, unsuppressed
HIV positive, early suppressed
HIV positive, long-term suppressed
HIV negative
IRR
1000
2.0
P < .0008
IR, incidence rate; IRR, incidence rate ratio; NADC, non-AIDS defining cancer.
750
1.5 IR
500
1.0
IRR
250
0.5
Park LS et al International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies. Oral presentation.
Slide credit: clinicaloptions.com

16. Frailty, Disability, and Functional Impairment in Older HIV Pts
Impairment (body function):
Osteoarthritis
Impairment:
History, exam, x-ray
Limitations (activity):
Slow chair rise time,
slow gait
Limitations:
Short Physical Performance Battery Timed walk
Frailty (vulnerability):
Slow walking speed, low activity, fatigue
Frailty:
Fried’s frailty phenotype
Disability:
Activities of daily living, independent activities of daily living
Disabilities (participation):
Requires cane but ramp into home and no stairs in home
Slide credit: clinicaloptions.com
Erlandson KM, et al. Curr HIV/AIDS Rep. 2014;11:

17. Frailty Risk Factors in Aging HIV-Positive Patients
Risk Factors (OR: Frail vs Nonfrail)
HR: 3.9
P = .002
Frail (n = 33)
Prefrail (n = 185)
Nonfrail (n = 141)
HR: 3.9
P < .001
HR: 3.6
P = .001
HR: 3.3
P = .004
HR: 3.7
P = .004
Incidence (%)
CVD, cardiovascular disease.
Slide: Risk Factors for Frailty in Aging HIV-Positive Patients
In addition, to CD4 counts <200 cell/mm3, frailty was strongly associated with comorbidity, lifestyle, and poor outcomes (hospitalizations, falls [data not shown]).1
Reference
Erlandson KM, Allshouse A, Duong S, et al. Prevalence and risk factors for frailty in HIV- 1 infected individuals on suppressive antiretroviral therapy. Program and abstracts of the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention; July , 2011 Rome, Italy. Abstract TuPE124.
HR: 5.1
P = .007
HR: 3.5
P = .022
HR: 3.8
P = .067
CVD
Viral
Hepatitis
Diabetes
Neurologic
Disease
Psychiatric
Disease
Unhealthy
Weight
Arthritis
Osteoporosis
Slide credit: clinicaloptions.com
Erlandson KM, et al. IAS Abstract TuPE124.

18. Relative Risk of MI, Stroke Declining for HIV Pts in Recent Yrs
MI Rates by HIV Status[1]
Kaiser Permanente cohort in California (N = 282,368)
Lower MI incidence likely due to CVD risk factor reduction, lipid- friendly ART, reduced immunodeficiency[1,2]
HIV+ pts with recent CD4+ cell count ≥ 500 c/mm3 or HIV-1 RNA < 500 c/mL not at significantly greater risk vs HIV- individuals after adjustment for stroke risk factors[3,4]
However, recent CD4+ cell count < 200 c/mm3 associated with increased risk
400
HIV+
HIV-
300
200
MIs per 100,000 PY
100 Yr
Stroke Rates by HIV Status[3]
250
HIV+
HIV-
200
ART, antiretroviral therapy; CVD, cardiovascular disease; MI, myocardial infarction; PY, patient-years.
References
1. Klein DB, et al. CROI Abstract 737.
2. Klein DB, et al. Clin Infect Dis. 2015;60:
3. Marcus JL, et al. CROI Abstract 741.
4. Marcus JL, et al. AIDS. 2014;28:
150
MIs per 100,000 PY
100 50 Yr
Slide credit: clinicaloptions.com
References in slidenotes.

19. Activity Preserves Lean Mass and Function
40-yr-old
70-yr-old
sarcopenic
66-yr-old
runner
76-yr-old
farmer
Slide credit: clinicaloptions.com
Courtesy of Dr. Todd Brown

20. Change in Noncalculated Plaque Volume (mm3) Wks From Randomization
Statins Decrease Immune Activation and Aortic Plaque in Treated HIV Infection
sCD14 Declines
With Rosuvastatin[1]
Plaque Regression
With Atorvastatin[2] 30
Placebo
Rosuvastatin
P = .03 40 20 20 10 10
sCD14 Relative Change
From Wk 0 (%)
-10
Change in Noncalculated Plaque Volume (mm3)
P = .0056
-20
P = .002
-10
-30
-20
-40
-30 24 48
Change in non-calcified plaque volume (mm3)
-40
Wks From Randomization
Placebo
Atorvastatin
REPRIEVE: double-blind, randomized phase IV trial of pitavastatin (planned N = 6500) now enrolling[3]
1. Funderburg NT, et al. J Acquir Immune Defic Syndr. 2015;68:
2. Lo J, et al. Lancet HIV. 2015;2:e52-e63.
3. ClinicalTrials.gov. NCT
Slide credit: clinicaloptions.com

21. ART Considerations in Older Pts
Comorbidities
Polypharmacy
Drug–drug interaction, dosing, adherence challenges
Renal or hepatic impairment
Alterations in pharmacokinetics, potential for drug toxicity
Challenges with single-tablet regimens
Inability to alter single component dosing
Difficulty swallowing large tablets
ART, antiretroviral therapy.
Slide credit: clinicaloptions.com

22. DHHS: Key Considerations When Caring for Older HIV-Infected Pts
DHHS has included older adult pts as a separate special population with the following recommendations:
ART is recommended in all pts, regardless of CD4+ cell count, but is especially important in older pts
ART-associated AEs may occur: monitor bone, kidney, metabolic, CV, and liver health
Increased risk of drug–drug interactions between ARV drugs and other medications
HIV experts and primary care providers should work together to manage complex comorbidities
Counseling to prevent secondary transmission of HIV
AE, adverse event; ART, antiretroviral therapy; ARVs, antiretroviral; CV, cardiovascular; DHHS, US Department of Health and Human Services.
Slide credit: clinicaloptions.com
DHHS Guidelines. July 2016.

23. July 2016 Updates on Recommended Regimens for First-line ART
DHHS[1]
Recommended regimens include 3 INSTIs and 1 boosted PI
Primary change since Jan update is addition of TAF/FTC
IAS-USA[2]
All recommended regimens include INSTI + TAF/FTC or ABC/3TC
Major changes since update include removal of NNRTIs, boosted PIs, and TDF
Regimen
DHHS[1]
IAS-USA[2]
DTG/ABC/3TC
DTG + TAF/FTC
DTG + TDF/FTC
EVG/COBI/TAF/FTC
EVG/COBI/TDF/FTC
RAL + TAF/FTC
RAL + TDF/FTC
DRV + RTV + TAF/FTC
DRV + RTV + TDF/FTC
3TC, lamivudine; ABC, abacavir; COBI, cobicistat; DRV, darunavir; DTG, dolutegravir; EVG, elvitegravir; FTC, emtricitabine; IAS-USA, International Antiviral Society-USA; RAL, raltegravir; RTV, ritonavir; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate.
Preferred/recommended
Alternative
1. DHHS Guidelines. July 2016.
2. Günthard HF, et al. JAMA. 2016;316:
Slide credit: clinicaloptions.com

24. DHHS Considerations for Initial ART Based on Age-Related Comorbidity
Scenario
ART-Specific Consideration
Consider Avoiding
Options
CKD (eGFR < 60 mL/min)
TDF, especially in RTV-containing regimens
TAF (if eGFR > 30 mL/min)
ABC/3TC (if HLA-B*5701 negative; if HIV-1 RNA > 100,000 c/mL, do not use with EFV or ATV/RTV; 3TC dose adjustment if CrCl < 50 mL/min)
DRV/RTV + RAL (if HIV-1 RNA < 100,000 c/mL and CD4+ cell count > 200 cells/mm3)
LPV/RTV + 3TC (3TC dose adjustment if CrCl < 50 mL/min)
Osteoporosis
TDF
TAF
ABC/3TC (if HLA-B*5701 negative; if HIV-1 RNA > 100,000 c/mL, do not use with EFV or ATV/RTV)
CVD
ABC
LPV/RTV
Hyperlipidemia
PI/RTV or PI/COBI
EFV
EVG/COBI
DTG
RAL
Consider TDF over ABC or TAF
3TC, lamivudine; ABC, abacavir; ART, antiretroviral therapy; ATV, atazanavir; CKD, chronic kidney disease; COBI, cobicistat; CrCl, creatinine clearance; CVD, cardiovascular disease; DHHS, US Department of Health and Human Services; DRV, darunavir; EVG, elvitegravir; FTC, emtricitabine; RAL, raltegravir; RTV, ritonavir; TDF, tenofovir disoproxil fumarate.
Slide credit: clinicaloptions.com
DHHS Guidelines. July 2016.

25. Drugs for Common Conditions in the Aging That May Interact With ART
Comorbidity
Comorbidity Drugs
Interacting ARVs
T2DM
Metformin
DTG/3TC/ABC,[1] DTG + FTC/TDF or FTC/TAF,[2-4] EVG/COBI/FTC/TDF,[5] EVG/COBI/FTC/TAF[6]
GERD
Antacid
PPI
All[1-8]
ATV/RTV + FTC/TDF or FTC/TAF,[3,4,9] DRV/RTV + FTC/TDF or FTC/TAF[3,4,10] RPV + FTC/TDF or FTC/TAF[11,12]
CVD
Statin,
Antiarrhythmic
EVG/COBI/FTC/TDF,[5] EVG/COBI/FTC/TAF[6] ATV/RTV + FTC/TDF or FTC/TAF,[9,3,4] DTG/3TC/ABC[1]
COPD
Beta-agonist
Glucocorticoid
EVG/COBI/FTC/TDF,[5] EVG/COBI/FTC/TAF[6]
ATV/RTV + FTC/TDF or FTC/TAF,[2,3,9] DRV/RTV + FTC/TDF or FTC/TAF[3,4,10]
3TC, lamivudine; ABC, abacavir; ART, antiretroviral therapy; ARV, antiretroviral; ATV, atazanavir; COBI, cobicistat; COPD, chronic obstructive pulmonary disease; CVD, cardiovascular disease; DRV, darunavir; DTG, dolutegravir; EVG, elvitegravir; FTC, emtricitabine; GERD, gastroesophageal reflux disease; PPI, proton pump inhibitor; RTV, ritonavir; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate.
References
DTG/3TC/ABC [package insert]
DTG [package insert]
FTC/TDF [package insert]
FTC/TAF [package insert]
EVG/COBI/FTC/TDF [package insert]
EVG/COBI/FTC/TAF [package insert]
RAL + FTC/TAF [package insert]
RAL + FTC/TDF [package insert]
ATV [package insert]
DRV [package insert]
RPV/FTC/TDF [package insert]
RPV/FTC/TAF [package insert]
DHHS Guidelines. July References in slidenotes
Slide credit: clinicaloptions.com

26. 4 Fundamental Components of Geriatric Primary Care
Comprehensive assessment
Creation, implementation, and monitoring of plan of care
Communication among and coordination with care providers
Promotion of active engagement in care (pt and family caregiver)
Slide credit: clinicaloptions.com
Boult C, et al. JAMA. 2010;304:

27. Conclusions Aging is a natural and expected process
For many reasons, people living with HIV have a higher risk for many age-related health problems
However, many of these comorbid conditions can be prevented or reversed by actions taken by the pt and the provider
HIV care must start to incorporate principles of geriatric medicine to meet needs of older patients
Recognition of drivers of frailty (physical, mental, chemical) is essential to applying appropriate interventions
ART selection should take into account the pt’s comorbidities and potential for drug interactions and adverse events
ART, antiretroviral therapy.
Slide credit: clinicaloptions.com

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