The "Silver Tsunami" Are We Ready? - Melanie Thompson, MD Principal Investigator AIDS Research Consortium of Atlanta @drmt on Twitter - CECentral

The “Silver Tsunami”
    Are We Ready?
      Melanie Thompson, MD
       Principal Investigator
AIDS Research Consortium of Atlanta
         @drmt on Twitter

Financial Disclosures
Dr Thompson's institution has received grants for research from
   CytoDyn, Cepheid, Frontier Biotechnologies, Gilead Sciences,
   GlaxoSmithKline, Merck & Co, and ViiV Healthcare. (Updated 04/1/21)

Learning Objectives
By the end of this presentation, the learner will be able to:
   1. Discuss 3 key challenges in the management of older people with HIV
   2. Assess for frailty in older persons with HIV
   3. Diagnose diabetes in a person with HIV

People with HIV are Living Longer!

CDC HIV Surveillance Report 2018 (updated 2020)

Aging is…
“Being nibbled to death by goldfish”
 ‐ My father in law, Richard Morris

We’ve put more effort into helping
folks reach old age than into helping
            them enjoy it.

       – Frank Howard Clark

Considerations for Aging with HIV
• Multimorbidity
    – Co‐morbidities including ASCVD, DM, frailty
    – Mental health/substance use issues
    – Organ demise: Hearing/vision loss, incontinence
•   Polypharmacy
•   Social isolation and loneliness
•   Stigma
•   Financial, housing, food insecurity; impact of social
    determinants of health

What I’m Not
Going to Talk
  About…

Multimorbidity is More Common in PWH
                        People With HIV   People Without HIV

   Cardiovascular
   Diabetes mellitus
   Chronic kidney ds
   Neurologic
   Osteoporosis
   Malignancy
   Depression

Schouten, CID, 2014

People with HIV are Living Longer
 But NOT Without Comorbidities

                          Marcus et al. JAMA Network Open. 2020 Jun (3)6

Multimorbidity in PWH on ART in the US:
                   2030 Projections
• The PEARL Model: ProjEcting Age, multimoRbidity and
  poLypharmacy
• NA‐ACCORD and CDC surveillance collaboration
• By 2030, 36% will have at least 2 comorbidities
   – Differences by age
   – Greatest increases among gay & bisexual men, esp Black/Hispanic;
     Hispanic persons who inject drugs & heterosexual women
• Increases in anxiety, depression, CKD, DM, MI
• Limitation: excludes transgender & AAPI persons
                                                Kasaie P et al. CROI 2021, Abstract 102.

Projected Burden of Multimorbidity by Age, 2030

                                Kasaie P et al. CROI 2021, Abstract 102.

Change in Prevalence of Comorbidities: 2020‐2030

                                     Kasaie P et al. CROI 2021, Abstract 102.

Rona
• 69 yo African‐American woman who moved from
  Memphis and has not been to clinic since January
  2020 “due to the pandemic.”
• She is coming back to reestablish care. Last CD4
  was 854/µL with HIV RNA < 50 c/mL.
• She has taken her HIV meds “mostly” regularly,
  but has missed some other meds because of cost
  and access issues.

Rona
• She has been observing coronavirus precautions, lives
  alone, is feeling increasingly isolated, and has not been
  vaccinated.
• She is drinking more alcohol than usual, has started
  smoking again, and has gained 27 pounds.
• She had one fall earlier this year, but had no injuries.
• She has “no energy,” gets “no exercise,” and doesn’t
  sleep well.

Problem List                      Medication List
HIV                               Elvitegravir/cobicistat/TAF/FTC
Hypertension                      Losartan/hydrochlorothiazide, metoprolol
Hyperlipidemia                    Rosuvastatin, ezetimibe
Diabetes mellitus                 Metformin (by endocrinologist)
Chronic kidney disease, stage 2   Lisinopril 5mg
Gastroesophageal reflux           OTC omeprazole BID (by GI doctor)
Osteoarthritis (knees)            OTC acetominophen, Goody’s Powder (at bedtime)
Osteopenia                        OTC calcium, magnesium, vitamin D
Seasonal allergic rhinitis        OTC diphenhydramine, fluticasone
Past deep vein thrombosis         Apixiban (by hospitalist in 2019)
Depression, anxiety               Escitalopram, clonazepam (by psychiatrist)
Insomnia                          Zolpidem, OTC melatonin

AND…
                      And…
Multivitamin with iron
Zinc (to prevent COVID)
Turmeric (for arthritis)
Apple cider vinegar (for BP)
Vitamin C – 4000 mg/day
Two supplements advertised on TV to “help
the brain”

Issues Associated with Polypharmacy

•   Inappropriate drugs, doses
•   Drug interactions: DON’T GUESS – LOOK IT UP!
•   Additive toxicities: nephrotoxic drugs, etc.
•   Risk of forgetting doses
•   Risk of missing prescriptions/skipping refills due to cost
•   Expense
•   “Overwhelmed” feeling of just too many pills!

Resource: The Beers Criteria
• Potentially inappropriate medications for older adults
   – Due to intrinsic effects
   – Due to drug‐disease, drug‐syndrome interactions that may
     exacerbate the disease or syndrome
   – To be used with caution in older adults
• Medications that should be avoided or have their dosage
  reduced with varying levels of kidney function in older
  adults
• Potentially clinically important drug–drug interactions that
  should be avoided in older adults
                                                American Geriatric Society, 2019

Pocket
     Guide to
      Beers
     Criteria,
       2019
http://files.hgsitebuilder.com/hostgator257222/file/ags_2019_beers_pocket_printable_rh.pdf

Resource:
STOPP and
  START!

            https://jamanetwork.com/journals/jamaintern
            almedicine/fullarticle/227481

Drug Interactions: Don’t Guess!
• Cobicistat, ritonavir: strong CYP3A4 inhibitors, but somewhat
  different interactions (RTV also an inducer)
• PIs: darunavir, atazanavir: lots of interactions
• NNRTIs other than doravirine: CYP3A4 inducers; rilpivirine lowered
  by PPIs
• INSTIs: Polyvalent cations decrease absorption: Ca, Mg, Fe, Zn, Al
  especially when given together on empty stomach
   – Bictegravir: CYP3A4, UGT1A1; dolutegravir: minor CYPA4, UGT1A1
       • Rifampin/rifabutin (don’t use BIC; increase dose with DTG)
       • Metformin increased by BIC and DTG
• Look it up: www.hiv‐druginteractions.org

Drug‐Drug Interactions by Class
  ARV              Absorption                               Metabolism
            Incr Gastric    pg‐P        CYP          CYP             CYP            UGT1A1
                 pH                   Substrate    Inhibitor        Inducer
INSTI                       Most       Not RAL       EVG/c           EVG/c          Substrate
b/PI*            ATV         YES         YES          YES          Not COBI          Mixed
NNRTI            RPV                    YES        EFV, ETR      EFV, ETR, NVP
NRTI                       TAF, TDF                                                   ABC
*bPI = ATVr/c, DRVr/c

INSTIs only: Decreased concentrations with polyvalent cations: Ca, Mg, Fe, Zn, Al
Maraviroc: pg‐P & CYP substrate
Fostemsavir: Substrate of CYP inducers; inhibits OATP1B1/3 and BRCP

                                                    Adapted from DHHS ART Guidelines, Table 20

Resource: Liverpool HIV Drug Interactions

     www.hiv‐druginteractions.org

And back to Rona..
•   Review meds: doses, schedule, prescribers
     – OTC meds, & supplements; alcohol
•   Look for inappropriate or risky meds, doses
     – Clonazepam, zolpidem, diphenhydramine, alcohol increase risk of falls
     – Apixaban no longer needed
     – Supplements probably not needed
•   Look for drug‐drug, drug‐supplement, drug‐disease interactions
     – COBI increases metformin, rosuvastatin, fluticasone, apixiban, zolpidem,
       clonazepam (BIC & DTG also increase metformin!)
     – Polyvalent cations (Ca++ etc.) lower INSTI concentration when taken together
     – Chronic PPI increases bone loss
     – Goody’s powder = acetominophen + aspirin + caffeine: risk of bleeding,
       gastritis, and insomnia (and too much acetominophen!)

Medication List                              Changes/Strategy
Elvitegravir/cobicistat/TAF/FTC              Change to BIC/TAF/FTC
Losartan/hydrochlorothiazide, metoprolol     Monitor to adjust doses; lifestyle changes
Rosuvastatin, ezetimibe                      Monitor to adjust doses; lifestyle changes
Metformin (by endocrinologist)               Monitor glucose to adjust dose
Lisinopril 5mg
OTC omeprazole BID (by GI doctor)            H. pylori diagnosed & treated; address alcohol,
                                             dietary interventions
OTC acetominophen, Goody’s Powder (at HS)    Stop Goody’s Powder
OTC calcium, magnesium, vitamin D3           Proper spacing of Ca++, Mg++ re ART
OTC diphenhydramine, fluticasone             Loratadine (less sedative), stop fluticasone
Apixiban (by hospitalist in 2019)            D/C: no longer needed
Escitalopram, clonazepam (by psychiatrist)   Wean clonazepam; social interaction/therapy?
Zolpidem, OTC melatonin                      Avoid zolpidem; exercise & sleep hygiene

AND…
                      And…
Multivitamin with iron
Zinc (to prevent COVID)
Turmeric (for arthritis)
Apple cider vinegar (for BP)
Vitamin C – 4000 mg/day
Two supplements advertised on TV to “help
the brain”

Also Remember…
• General health assessments and screenings
• Cancer screening: breast, colon, lung, cervical, anal,
  prostate
• Vaccines! (SARS CoV‐2, flu, pneumonia, HAV, HBV, HPV)
   – Check CDC ACIP recommendations
• Special attention to social isolation, mental health,
  substance use
• Assess ability to participate in telehealth?

• Recognizes increased ASCVD risk in persons with
  HIV
  – 1.5‐2x increase in MI, stroke, heart failure
  – Increased pulmonary HTN, blood clots, sudden death
• Addresses pathophysiology, screening, treatment
• Includes link to patient perspective from PLWH
                                            Feinstein, Circulation, 2019

Contribution
 to MI Risk in                         CKD, Stage 4
    PWH                                CD4 < 200/µL
(NA‐ACCORD)                            HIV‐RNA > 400c/mL                HCV

When obesity
included:

DM significant            Elev
HIV‐RNA not      Smoke?   Tot    HTN
significant               Chol

                                                           Althoff, Lancet HIV, 2020

ASCVD Risk
Assessment and
   Treatment
Two approaches
• High risk
• Low‐moderate risk
            Feinstein, Circulation, 2019

High Risk Approach
• Known clinical ASCVD, or
• LDLc ≥ 190 mg/dL (untx), and/or
• Age 40‐75 with diabetes
  mellitus
                 OR
• Calculated high ASCVD risk by
  risk calculator tools
• Presence of HIV‐related or 2018
  ACC/AHA “risk enhancers”
                                    Feinstein, Circulation, 2019

If YES: Consider adjusting risk upward; may be 1.5‐2x higher
                                              Feinstein, Circulation, 2019

But also…
• Control risk factors other than lipids
   –   Smoking, smoking, smoking!
   –   Diabetes mellitus
   –   Hypertension
   –   Obesity ‐ encourage exercise and diet: education!
• Statin (without hyperlipidemia)?
   – Wait for REPRIEVE trial…
• Consider role of mental health in being able to address
  general health issues: holistic approach needed

Oahunbade, et al, JAHA, March 23, 2021

Smoking and Cancer in PLWH
• Smoking: up to ¾ of PLWH
• Cancer burden attributable to
  smoking
  – Lung cancer: 94%
  – Other ‘smoking related’ cancers
    (esophageal, oral, etc.): 31%
  – Anal cancer: 32%
  – All cancer: 9%
                                      Altekruse, AIDS, 2018

Diabetes Mellitus: ADA Definition (2021)
• Hemoglobin A1C ≥ 6.5%
   – "In conditions associated with an altered relationship between A1C
     and glycemia, such as …HIV….only plasma blood glucose criteria
     should be used to diagnose DM.” Likely only applies when on ART.
• Fasting plasma glucose ≥ 126 mg/dL, confirmed by repeat
• Plasma glucose ≥ 200 mg/dL 2 hrs after 75 g oral glucose
  tolerance test
• Random plasma glucose ≥ 200 mg/dL with polyuria and
  polydipsia

                                              ADA. Diabetes Care 2021;44(Suppl. 1):S15–S33.

A1C May Under‐ or Overestimate Glycemia Depending on ART

•   A1C underestimated glycemia on NNRTIs, but overestimated on PIs
•   Tenofovir (TDF) had no effect; INSTIs were not tested
•   Unlike in MACS study, HIV itself did not affect A1C levels in this cohort
                                                     Eckhardt, et al. AIDS Patient Care & STDs, 2012

Patel, Epidemiology of Sarcopenia and Frailty, 2016

Three Tools for Assessing Frailty
• Fried’s Frailty Phenotype
   – 5 physical variables
• Short Physical Performance Battery (SPPB)
   – 3 physical tasks
• Frailty Index
   – 40 physical, psychological, social/functional variables

Fried’s Frailty Phenotype

                Requires dynomometer

                              Fried, J of Gerontology, 2001

Frailty Phenotype as a Predictor
Frailty phenotype
predicts
• Death

      Fried, J of Gerontology, 2001

Frailty Phenotype as a Predictor
Frailty phenotype
predicts
• Death
• Worsening
  disability
• Incident fall
• 1st hospitalization
                        Frailty phenotype was more common in
                             women and African‐Americans

                                               Fried, J of Gerontology, 2001

Frailty: Short Physical Performance Battery
                     (SPPB)
3 physical tasks:
• Repeated chair
  stands (sit then
  stand 5 times)
• Balance tests
• 4‐meter (10‐foot)
  walk test
                      geriatrictoolkit.missouri.edu/SPPB‐Score‐Tool.pdf; Greene, AIDS, 2014

Frailty Index
• Relates deficit accumulation to risk of death
• 40 variables
   – Physical: e.g. walk outside < 3d/wk; wt loss > 5 kg/yr
      • Comorbid diseases, without regard to severity
   – Psychological: feel depressed, happy, lonely, etc.
   – Social/Functional: help bathing, dressing, eating, etc.
• Scored between 0‐1 = deficits/variables
   – < 0.08 = robust; ≥ 0.25 = frail
                                                   Searle, BMC Geriatrics, 2008.

CDC STEDI

            https://www.cdc.gov/steadi/index.html

Frailty is Dynamic!
          Interventions to Prevent Frailty
•   Exercise, strength and balance training
•   Social interaction
•   Healthy diet
•   Preventative health care and screening
•   Management of medications
•   Smoking cessation

Screening for HIV‐Associated Neurocognitive Disorders

Screening tools have variable sensitivity/specificity
•   Mini‐mental state examination (MMSE)
•   International HIV dementia scale (IHDS)
•   Montreal cognitive assessment (MoCA)
•   Simioni symptom questionnaire (SSQ)
•   Cognitive assessment tool‐rapid version (CAT‐rapid)

                                             Joska, AIDS Behavior, 2016

Screening for HIV‐Associated Neurocognitive Disorders

Screening for HIV dementia
   – IHDS + CAT‐rapid = most sensitive/specific
Screening for asymptomatic/mild HAND
   – No screener had adequate sensitivity/specificity: need
     full neuropsych testing
   – MoCA often used in clinic
Don’t forget reversible causes … syphilis, thyroid
disease, B12 deficiency, depression
                                                  Joska, AIDS Behavior, 2016

Screening for Mental Health and Substance Use Issues

• Depression and substance use are common; screening is
  uncommon
• Easy screening tools available (and reimbursable!)
• Depression ‐ PHQ 2 and 9; Anxiety ‐ GAD‐2 and 7
   – PHQ‐2: Over the last 2 weeks, how often have you been bothered by
     the following: (score 0‐3)
       • Little interest or pleasure in doing things
       • Feeling down, depressed or hopeless
• Alcohol Use: CAGE and AUDIT
• Drug Use: TICS, opioid risk tool

                          National HIV Curriculum: https://www.hiv.uw.edu/page/mental‐health‐screening/phq‐2

Tools for Screening
      National HIV Curriculum
      • https://www.hiv.uw.edu

https://www.hiv.uw.edu/page/mental‐health‐screening/phq‐2

The Social Isolation Score (SIS)
Visits from close family
Visits from close friends
Number of close family/friends
Use of self‐help or support group in last year
Volunteer work or involvement in community organization
Frequency of attendance to religious events
Relationship status
Living alone
                                  Greysen et al., Journal of American Geriatrics Society, 2013

PLWH ≥ 65 yo
 are 2‐7 times
more likely to
  experience
     social
isolation than
those who are
     HIV ‐

                 Greysen et al., Journal of American Geriatrics Society, 2013

Social Isolation Is Associated with Increased Mortality

                                                    Not Isolated
                                                    SIS < 4

                                                    Isolated
                                                    SIS ≥ 4

                                  Greysen et al., Journal of American Geriatrics Society, 2013

Stigma Kills!
• HIV status
• LGBTQ+
  discrimination
• Ageism
• Substance use
• Race/ethnicity

What Do
   Guidelines
     Say?
    IAS‐USA 2020

JAMA. doi:10.1001/jama.2020.17025

What Do Guidelines Say?
                                   EACS 2020
 • Manage polypharmacy

 • Assess for and manage frailty: Frailty Phenotype (Fried) and Frailty Index

https://www.eacsociety.org

What Do Guidelines Say?
                         DHHS 2021 (from 12/2019)
• Section on “HIV and the Older Person”
• Attention to polypharmacy & multimorbidity
  management
• Refer those with progressive neurocognitive
  defects for neurologic assessment and
  neuropsychiatric testing
• Drug‐drug interactions tables focused on ART
  DHHS. Guidelines for the Use of Antiretroviral Agents in Adults & Adolescents Living with HIV
  https://clinicalinfo.hiv.gov/en/guidelines

FINALLY! An Update!

              Thompson M, et al. CID, 6NOV2020 ; also
              www.hivma.org under “Guidelines”

What Do Guidelines Say?
             HIVMA/IDSA Nov. 2020
• Recommendations focused on preventing,
  detecting & managing multimorbidity
• Section on metabolic & noncommunicable
  comorbidities including drug interactions
• Neurocognitive assessment recommended
  based on symptoms
                             Thompson M, et al. CID, 6NOV2020 ; also
                             www.hivma.org under “Guidelines”

Patient
Centered Care
Coordination
  for Older
    PLWH
                Slide: HealthHIV

Thank You!
•   Colleagues whose research I have presented
•   Research participants
•   Guidelines panels
•   People living with HIV who have had the
    resilience to become the survivors who inspire
    us today!