Еxpert faculty use case-based examples to examine considerations for aging patients with HIV. Topics include ART modification, bone loss, renal impairment, cardiovascular risk, and cognitive decline.

1. Confronting the Challenges of HIV Care in an
Aging Population
Supported by an educational grant from
ViiV Healthcare

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Slide credit: clinicaloptions.com

3. Faculty
Daniel R. Kuritzkes, MD
Chief, Division of Infectious Diseases
Brigham and Women’s Hospital
Harriet Ryan Albee Professor of Medicine
Harvard Medical School
Boston, Massachusetts
Christian B. Ramers, MD, MPH
Associate Clinical Professor
Division of Infectious Diseases
Department of Medicine
UC San Diego School of Medicine
La Jolla, California
Assistant Medical Director
Division of Research/Special Populations
Family Health Centers of San Diego
San Diego, California

4. Faculty Disclosures
The faculty reported the following financial relationships or relationships
to products or devices they or their spouse/life partner have with
commercial interests related to the content of this CME/CE activity:
Daniel R. Kuritzkes, MD, has disclosed that he has received consulting fees
from AbbVie, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, and ViiV
Healthcare and funds for research support from Gilead Sciences, Merck, and
ViiV Healthcare.
Christian B. Ramers, MD, MPH, has disclosed that he has received consulting
fees from AbbVie and Gilead Sciences; funds for non-CME/CE services from
AbbVie, Gilead Sciences, Merck, and ViiV Healthcare; and funds for research
support from Gilead Sciences.

5. Bone and Renal Considerations

6. Patient Case 1
 63-yr-old woman receiving EFV/FTC/TDF
‒ Stable use of this regimen since
diagnosis 13 yrs ago
‒ HIV-1 RNA consistently undetectable
(< 20 copies/mL)
 No history of AIDS or HIV-related
complications
‒ Has been experiencing mild sleep
disturbance
 Her internist has retired; you are asked
to take over her care
Parameter Lab Value
CD4+ cell count, cells/mm3
 Current
 Nadir
640
280
Blood pressure, mm Hg 140/88
CrCl, mL/min 50
Proteinuria by dipstick 2+
T-score by DXA -2.1
Slide credit: clinicaloptions.com

7. Noninferior Efficacy Across Phase III ART Switch Studies
1. Kityo. CROI 2018. Abstr 500. 2. Johnson. JAIDS. 2019;81:463. 3. van Wyk. IAS 2019. Abstr WEAB0403LB.
4. Llibre. Lancet. 2018;391:839. 5. Orkin. Lancet HIV. 2017;4:e195. 6. DeJesus. Lancet HIV. 2017;4:e205. Slide credit: clinicaloptions.com
Study Switch to Comparator
HIV-1 RNA Endpoint at Wk 48, %
< 50 c/mL ≥ 50 c/mL
Study 1961[1] BIC/FTC/TAF
(n = 234)
EVG/COBI/FTC/(TAF or TDF) or ATV + RTV + FTC/TDF
(n = 236)
96 vs 95 2 vs 2
DRIVE-SHIFT[2] DOR/3TC/TDF
(n = 447)
Boosted PI, EVG/COBI, or NNRTI + 2 NRTIs
(n = 223)
91 vs 95* 2 vs 2*
TANGO[3] DTG/3TC
(n = 369)
3-drug or 4-drug TAF-based ART
(n = 372)
93 vs 93 < 1 vs < 1
SWORD-1/2[4] DTG + RPV
(n = 513)
NNRTI, INSTI, or PI + 2 NRTIs
(n = 511)
95 vs 95 < 1 vs 1
Study 1216[5] RPV/FTC/TAF
(n = 316)
RPV/FTC/TDF
(n = 314)
94 vs 94 1 vs 0
Study 1160[6] RPV/FTC/TAF
(n = 438)
EFV/FTC/TDF
(n = 437)
90 vs 92 1 vs 1
Listed studies not head to head. *Value given for comparator arm from Wk 24; patients were subsequently switched to DOR/3TC/TDF.

8. DRIVE-AHEAD: Neuropsychiatric Events
With First-line DOR/3TC/TDF vs EFV/FTC/TDF
Orkin. Clin Infect Dis. 2019;68:535. Slide credit: clinicaloptions.com
*Statistical testing not prespecified for these secondary categories.
P < .001
P < .001
P = .033
Dizziness Sleep Disorders/
Disturbances
Altered
Sensorium
Psychosis and
Psychotic
Disorders*
Depression and
Suicide/Self-
Injury*
Patients(%)
8.8
12.1
4.4 4.1
0.3
37.1
25.5
8.2
6.6
1.1
DOR/3TC/TDF
EFV/FTC/TDF40
30
20
10
0

9. TANGO: Renal and Bone Changes
With Switch to DTG/3TC
9
van Wyk. IAS 2019. Abstr WEAB0403LB. Slide credit: clinicaloptions.com
Continue TAF-based ART (n = 371)Switch to DTG/3TC (n = 369)
Plasma/Serum Markers Serum Bone Turnover Markers
eGFR From Cr
(CKD-EPI),
mL/min/
1.73 m2
Cr,
µmol/L
eGFR From
Cystatin C
(CKD-EPI), mL/
min/1.73 m2
Osteocalcin Procollagen
1 N-terminal
Propeptide
Type 1
Collagen C-
telopeptide
Bone-Specific
Alkaline
Phosphatase
AdjustedMeanΔFromBLatWk48
AdjustedMeanΔfromBLatWk48(μg/L)
10
5
0
-5
-10
6.67
2.19
-7.8
-3.0
0.1
-1.6
Urine Markers
Protein:Cr,
g/mol
RBP:Cr,
µg/mmol
β2M:Cr,
mg/mmol
ΔFromBLatWk48(%)
20
10
0
20
-2.9
1.6
6.3 6.7
-2.7
-7.8
14
12
8
2
-2
-4
P < .05
P < .001
-0.03 -0.34
-1.15
0.69
9.3
6.4
P < .05
0.0602 0.031010
10
6
4
0
P < .001
P < .001

10. SWORD-1/2: Renal and Bone Changes
With Switch to DTG + RPV
 70% to 73% of patients were receiving TDF at screening
 Greater decline in proteinuria (ie, urine RBP and β2M) with DTG/RPV vs continued BL ART
Llibre. Lancet. 2018;391:839. Slide credit: clinicaloptions.com
Osteocalcin Procollagen Type 1
N-terminal Propeptide
Type 1 Collagen
C-telopeptide
Bone-Specific Alkaline
Phosphatase
*NNRTI, INSTI, or PI + 2 NRTIs.
P < .0001 for comparison between arms of change from BL to Wk 48 at each marker.
DTG + RPV Continue BL ART*
BL
Wk 48
BL
Wk 48
MeanSerum
Concentration(µg/L)
60
50
40
30
20
10
0
MeanSerum
Concentration(µg/L)
0.8
0.6
0.4
0.2
0
15.9
12.9
16.2 17.1
23.8
19.0
24.0 23.1
53.0
45.6
55.3 54.7
0.66
0.49
0.69
0.63

11. -80
Study 1961: Quantitative Proteinuria by BL Regimen
With Switch to BIC/FTC/TAF in Women
11
No TDF at Baseline
Slide credit: clinicaloptions.com
MedianΔFromBLatWk48,%
(IQR)
UACR,
mg/g
RBP:Cr,
μg/g
β2M:Cr,
μg/g
UACR,
mg/g
RBP:Cr,
μg/g
β2M:Cr,
μg/g
TDF at Baseline
P = .40 P < .001 P < .001
MedianΔFromBLatWk48,%
(IQR)
Switch to BIC/FTC/TAF Continue BL ART*
*EVG/COBI/FTC/(TAF or TDF) or ATV + RTV + FTC/TDF.
120
100
80
60
40
20
0
-20
-40
-60
-80
10
-29
20
-27
-9-4
P = .090 P = .14 P = .19
120
100
80
60
40
20
0
-20
-40
-60
0
-7
17
711
-4
BL Ratio6.5 6.7 129.6 117.0 138.9 150.0 6.5 6.2 94.1 95.1 87.2 86.9BL Ratio
Kityo. CROI 2018. Abstr 500.

12. Study 1160
Studies 1216 and 1160: Bone Changes
With Switch to RPV/FTC/TAF
Hagins. HIV Med. 2018;19:724. Slide credit: clinicaloptions.com
Switch to RPV/FTC/TAF
MeanBMDΔFromBL,%(95%CI)
Study 1216
Wk
MeanBMDΔFromBL,%(95%CI)
Continue RPV/FTC/TDF Switch to RPV/FTC/TAF Continue EFV/FTC/TDF
3
2
1
0
-1
Hip
1.62
-0.61
P < .001
3
2
1
0
-1
Spine
2.04
-0.25
P < .001
96BL 724824
Wk
3
2
1
0
-1
Hip
1.83
-0.62
P < .001
3
2
1
0
-1
Spine
1.70
0.13
P < .001
96BL 724824

13. Key Take-home Messages
 Multiple options available when switching ART to reduce toxicity
‒ Ample data from large clinical trials demonstrating noninferior virologic
efficacy of diverse switch regimens
‒ Allows for individualization of regimen choice based on patient need
 2-drug regimens offer a newer potential way to reduce toxicity, are
emerging as an acceptable strategy
Slide credit: clinicaloptions.com

14. Cardiovascular Complications

15. Patient Case 2
 57-yr-old white male receiving
DRV/COBI + FTC/TDF
‒ Diagnosed in 2008 with
HIV-1 RNA 78,000 copies/mL,
CD4+ cell count 190 cells/mm3
‒ Initiated boosted PI due to
concerns regarding adherence
 Smokes 1 pack of cigarettes per
day, has for ~ 35 yrs
 No current comedications
Parameter Lab Value
Cholesterol, mg/dL
 Total
 LDL
 HDL
243
159
31
Hemoglobin A1c 5.9
Blood pressure, mm Hg 129/86
10-yr ASCVD risk score, % 20.6
Slide credit: clinicaloptions.com

16. < 40
NA-ACCORD: Increased MI Risk Among PLWH
General population
(ARIC, n = 14,308)
PLWH
(NA-ACCORD, n = 29,169)
Characteristic
Adjusted IRR for MI
(95% CI)
HIV infection 1.21 (1.02-1.45)
Age (vs 40-49 yrs)
 50-59 yrs
 ≥ 60 yrs
1.72 (1.39-2.13)
2.97 (2.38-3.71)
Female sex 0.60 (0.54-0.66)
Black race 0.90 (0.81-1.00)
Ever smoker 1.53 (1.38-1.71)
Hypertension 1.80 (1.63-1.99)
Diabetes 2.51 (2.22-2.84)
Total cholesterol ≥ 240 mg/dL 1.51 (1.36-1.67)
MI Incidence by Age
Age (Yrs)
Slide credit: clinicaloptions.comDrozd. JAIDS. 2017;75:568.
P < .05 for all values except black race.
IncidenceRate/1000PY
40-49 50-59 ≥ 60
14
12
10
8
6
4
2
0

17. D:A:D Study: Increased CVD Risk With Boosted PIs
 Increased CVD risk with RTV-boosted DRV in unadjusted and multivariate analyses
Slide credit: clinicaloptions.comRyom. Lancet HIV. 2018;5:e291.
RTV-Boosted ATV RTV-Boosted DRV
CVDIncidenceRate,
Events/1000PYFU(95%CI) Unadjusted Incidence of CVD Stratified by Cumulative PI Use
20
15
10
5
1
0
0 0-1 1-2 2-3 3-4 4-5 5-6 > 6
Cumulative Yrs of Exposure
Events, n
PYFU
824
163,785
75
12,886
49
7631
41
6369
26
6144
46
5757
34
4898
62
9278
0 0-1 1-2 2-3 3-4 4-5 5-6 > 6
Cumulative Yrs of Exposure
909
185,246
52
8845
51
6591
44
5285
39
4100
17
2940
18
1768
27
1975

18. Elevated Smoking Prevalence in Persons Living With HIV
 Smoking rate is 2-3 x higher in persons living with HIV[1-4]
 Reasons include[2-4]:
‒ ↑ anxiety and other mental illnesses
‒ ↑ alcohol and illicit drug use
‒ ↑ sociodemographic stressors
‒ ↑ risk-taking behaviors and impulsiveness
‒ False perception of smoking risks
‒ Smoking cessation remains low priority among HIV care providers
1. Ranjit. F1000Res. 2018;7:718. 2. Mdodo. Ann Intern Med. 2015;3:335. 3. Giles. AIDS Res Ther. 2018;15:26. 4. Fuster. HIV Med. 2009;10:614. Slide credit: clinicaloptions.com

19. Danish HIV Cohort Study: Impact of Smoking on MI Risk
MI Incidence, Stratified by Smoking Status
CumulativeIncidence
PLWH Control PLWH Control
Ever
Smoking
If All Current
Smokers Stopped
Population-AttributableFraction,
%(95%CI)
Rasmussen. Clin Infect Dis. 2015;60:1415. Slide credit: clinicaloptions.com
*First of: 1/1/1999, HIV diagnosis date, date of first available smoking
status data, date reaching 40 yrs of age, or date of immigration.
Yrs Since Index Date*
Current smokers
(HIV+ vs control)
aIRR: 2.83
Former smokers
(HIV+ vs control)
aIRR: 1.78
100
80
60
40
20
0
72
24
42
21
MIs Associated With Smoking
0.05
0.04
0.03
0.02
0.01
0
0 2 4 6 8
HIV+, current smokers
HIV+, previous smokers
HIV+, never smokers
Control, current smokers
Control, previous smokers
Control, never smokers

20. D:A:D Study: Impact of Smoking on MI Risk
Slide credit: clinicaloptions.comPetoumenos. HIV Med. 2011;12:412.
*Adjusted for age, sex, cohort, yr, family history of CVD, diabetes, time updated lipid measurements, and systolic blood pressure.
Adjusted Risk of MI by Smoking Status in PLWH*
Stopped Smoking During Follow-up
Never
Smoked
Current
Smoking
< 1 yr 1-2 yrs 2-3 yrs 3+ yrs
5.0
2.5
0.5
Previous
Smoking
AdjustedIncidenceRate/1000PY

21. Relative CVD Risk Reduction With Different Interventions
Slide credit: clinicaloptions.comPetoumenos. HIV Med. 2014;15:595.
After smoking cessation
After reducing cholesterol 1 mmol/L
After reducing systolic BP 10 mm Hg
Modeled Impact of Modifying Risk Factors
on CVD Risk in PLWH
CVD risk in PLWH
RelativeHazard
Age (Yrs)
6
5
4
3
2
1
40 45 50 55 60 65

22. Relative CVD Risk Reduction With Different Interventions
Slide credit: clinicaloptions.comSmit. Clin Infect Dis. 2018;66:743.
ReductioninCases(%)
Earlier HIV
Diagnosis and
Treatment
Avoiding cART
With Increased
CVD Risk
Smoking
Cessation
Monitoring/
Tx of HTN and
Dyslipidemia
Joint
Intervention
20
0
25
15
35
30
10
5
Modeled Average Annual Reduction in CVD Cases

23. Smoking Cessation in PLWH
 Cessation rates very low (3% to 5%) when patients attempt on their own[1]
 PLWH less likely than general population to successfully quit smoking
‒ 32.4% vs 51.7%, respectively, in cross-sectional surveys[2]
‒ 4.2 mean prior attempts to quit in 1 study of PLWH in San Francisco[3]
Slide credit: clinicaloptions.com
1. Hughes. Addiction. 2004;99:29. 2. Mdodo. Ann Intern Med. 2015;162:335. 3. Humfleet. AIDS Educ Prev. 2009;21:54. 4. AAFP.
Pharmacologic Product Guide: FDA-Approved Medications for Smoking Cessation. Updated January 17, 2019. 5. Ledgerwood.
Nicotine Tob Res. 2016;18:2177. 6. Mercié. Lancet HIV. 2018;5:e126. 7. Wilkes. Int J Chron Obstruct Pulmon Dis. 2008;3:45.
Agent[4,5] Mechanism Typical Duration Efficacy
Nicotine
replacement
Binds nicotine receptor 8-24 wks Limited data in PLWH
Varenicline Binds nicotine receptor 12-24 wks 15% at 12 mos in PLWH[6]
Bupropion
Norepinephrine/dopamine
reuptake inhibitor
7-12 wks
(6 mos max)
Limited data in PLWH
~ 20% at 12 mos in general population[7]
DDI risk with PIs, NNRTIs

24. Key Take-home Messages
 PLWH have an increased risk of multiple adverse CV outcomes vs
general population (eg, MI, hypertension, peripheral artery disease)
‒ Interventions to reduce CVD risk in PLWH are often underutilized
 Smoking, which occurs more frequently among persons with vs without
HIV, increases CVD risk
‒ Smoking cessation is potentially one of the highest impact interventions,
reducing CVD and cancer risk

25. Mental Health and Neurocognitive Disorders

26. Patient Case 3
 67-yr-old MSM currently receiving DTG + FTC/TAF + DRV/COBI
‒ HIV diagnosed in late 1980s
‒ Nadir CD4+ cell count of 125 cells/mm3
‒ Started dual NRTI therapy in 1995; multiple ART regimens since
‒ History of multi-dermatomal zoster and recurrent bacterial pneumonia
 Presents with concerns of cognitive decline, increasing isolation, and
depressive symptoms
 Notes he increasingly loses keys, forgets where he parked, and finds
himself in a room having forgotten what he was doing
Slide credit: clinicaloptions.com

27. Patient Case 3
 History of hypogonadism, peripheral
neuropathy, major depression/anxiety
with insomnia, hyperlipidemia, and
hypertension
 Quit smoking 5 yrs ago (25 pack-yrs),
social alcohol and marijuana use, and
history of recreational stimulants
 Physical examination reveals 10-lb
weight loss in last 6 mos, subtle buccal
fat wasting, and flat affect with poor
eye contact
‒ Alert and oriented x 3
Current Medications (+ ART) Dose
Gabapentin 300 mg TID
Testosterone cypionate 200 mg IM Q2W
Sertraline 50 mg PO QD
Clonazepam as needed for
anxiety
0.5 mg PO BID
Zolpidem as needed for insomnia 10 mg PO QHS
Parameter Lab Value
CD4+ cell count, cells/mm3 360
HIV-1 RNA, copies/mL < 20
PHQ-9 15*
Slide credit: clinicaloptions.com
*No suicidal ideation.

28. HIV-Associated Neurocognitive Disorders
 HAND represent a spectrum of
severity with variable prevalence
in ART-treated individuals
 In the modern cART era,
approximately one half of
patients have some degree of
neurocognitive impairment
Antinori. Neurology. 2007;69:1789. Saylor. Nat Rev Neurol. 2016;12:234. Heaton. Neurology. 2010;75:2087. Slide credit: clinicaloptions.com
cART Era
HAD
MND
ANI
No
Impairment
Pre-cART Era
HAD
ANI
MND
No
Impairment
‒ HIV-associated dementia (HAD) is less prevalent than it used to be
‒ Milder forms are more prevalent, including asymptomatic neurocognitive
impairment (ANI) and mild neurocognitive disorder (MND)

29. Risk Factors and Pathogenesis of HAND
 Risk factors associated with
HAND include:
‒ Nadir CD4+ cell count
< 200 cells/mm3, advanced
age, illicit drug use, HCV
coinfection, cerebrovascular
risk, sleep disorders, psychiatric
comorbidities
 Pathogenesis incompletely
understood
‒ Inflammation and neurotoxicity
‒ Brain as reservoir for HIV
persistence
‒ Abnormal glutamate
homeostasis
‒ Low-level HIV escape in CNS
‒ Neurotoxicity of ART
Saylor. Nat Rev Neurol. 2016;12:234. Heaton. Neurology. 2010;75:2087. Slide credit: clinicaloptions.com

30. Challenges in Clinical Management of HAND
 Significant overlap of related clinical syndromes (polypharmacy,
Alzheimer’s dementia, substance abuse–related impairment,
depressive symptoms)[1,2]
 Imprecise tools for diagnosis[3]
 Evidence-based treatment guidelines lacking
 Inconsistent findings regarding CNS penetration effectiveness ̶ tailored
regimens[1,4,5]
 Role of CNS toxicity of ART agents unclear[1,4,5]
1. Saylor. Nat Rev Neurol. 2016;12:234. 2. Justice. AIDS. 2018;32:739. 3. Fazeli. J Clin Exp Neuropsychol.
2017;39:842. 4. Marra. AIDS. 2010;23:11. 5. Smurzynski. AIDS. 2011;23:357. Slide credit: clinicaloptions.com

31. Key Take-home Messages
 Neurologic decline in aging patients with HIV is multifactorial and
relatively prevalent
 The clinical manifestations of neurocognitive ailments have changed in
the cART era (shifting toward MND and ANI)
 Clinical management remains a challenge; more research is needed

32. clinicaloptions.com/hiv
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