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Longevity, health, and well-being in our patients

Prasanna Jagannathan, M.D.

Assistant Professor

Division of HIV, ID, and Global Medicine

UCSF

Disclosures and Acknowledgements

No Disclosures

Goals: Life expectancy and wellness in HIV

Mind the (life expectancy) gap HIV in 2016 What makes up the gap?

Some strategies to narrow the gap

Mind the (quality of life) gap! What makes up the gap?

Some strategies to narrow the gap

Case 1: C.C.

55 yo man with HIV receiving primary care at Ward 86, ZSFG

HIV: Diagnosed 1990, CD4 nadir 50, now in low 200s History of thrush, no other OIs

ART: VL suppressed since 2003 2001-03: Trizivir + TFV

2003-08: EFZ + TFV + 3TC + DDI

2008-current: atripla

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Case 1: C.C.

PMH:

HCV Genotype 1a Portal HTN on imaging (esophageal varices)

h/o seizures (?ETOH-related)

h/o depression (not on treatment)

SH: Stays in his home most of the day caring for very ill partner

Substances:

ETOH: up to 6 pack of beer per night

Smokes ½ - 1 ppd

If you are this patient’s PCP in 2016: What are you most worried about?

0A B C D E

A) Curing his HCV

B) Poor immune recovery/Modernizing his ART

C) Alcohol use

D) Smoking cessation

E) Lack of physical activity

F) Something else

CC’s priorities

Resources to support care of his partner

Tobacco Has cut back and quit a few times, but always

resumes (partner also smokes)

HCV (once INF-sparing regimens became available)

Cutting back on his drinking (for his partner)

Life expectancy in HIV 2016: Closing the gap (Kaiser data)

*Marcus et al JAIDS 1 Sep 2016

N=24768HIV-infected

N=257600HIV-uninfected

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What is the major driver of the persistent gap in life expectancy?

A) HBV/HCV co-infection

B) HIV-associated malignancies

C) Late ART initiation/immune activation

D) Drug/alcohol use

E) Smoking

F) Something else

0A B C D E F

Life expectancy in HIV 2016: Closing the gap

*Marcus et al JAIDS 1 Sep 2016

Smoking in HIV-infected individuals

Prevalence in HIV-infected: 40-70% General population prevalence 20% HIV-infected also significantly less likely to quit

Several studies link smoking in PLWHA to: Decreased virologic/immunologic response Worse adherence to ART Increased rates of non AIDS-defining malignancies (lung,

head/neck) Low BMD Significantly more CAD, myocardial infarctions

Mdodo et al Ann Intern Med. 2015Sigel et al AIDS 2012Stead et al Cochrane Reviews 2012Rasmussen CID 2015

Smoking in HIV-infected individuals: 16 less years of life?

Helleberg CID 2013

A 35-year-old HIV patient had a median life expectancy of 62.6 years (95% CI, 59.9–64.6) for smokers and 78.4 years (95% CI, 70.8–84.0) for nonsmokers.

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Quitting smoking could result in an increase of 4-6 years of life expectancy

Reddy et al JID 1 Nov 2016

Relative gains in life expectancy for different interventions

Reddy et al JID 1 Nov 2016

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How would you advise him with smoking cessation?

Pick a quit date and:

A) Advise him to quit cold turkey

B) Advise him to cut back slowly

0A B

How would you help him with smoking cessation?

A) Counsel + Nicotine patch/lozenge

B) Counsel + E-cigarettes

C) Counsel + Bupropion SR (Wellbutrin)

D) Counsel + Varenicline

0A B C D

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USPSTF Guidance: Updated 2015

http://www.uspreventiveservicestaskforce.org/

RCT of abrupt vs gradual smoking in 2 weeks before quitting Used NRT before and after quit date

Outcome: prolonged validated abstinence 4 wks after quit date

Abstinent, n (%)

Time after quitting

Gradual cessation (n=342)

Abrupt cessation (n=355)

RR (95% CI)

4 wks 134 (39.2) 174 (49) 0.80 (0.66-0.93)

6 wks 100 (29.2) 130 (36.6) 0.80 (0.62-0.95)

6 months 53 (15.5) 78 (22.0) 0.71 (0.46-0.91)

Lindson-Hawley et al Annals of Internal Med 2016

Cochrane meta-analysis of pharmacologic interventions for smoking cessation: 2013

Cahill et al Cochrane Library 2013

0.5 1.0 1.5 2.0 2.5

Posterior Median Odds

Better Efficacy

Bupropion vs NRT

Varenicline vs NRT

Varenicline vs Bupropion

Varenicline vs Combo NRT

Is varenicline safe?

Thomas et al BMJ 2015

Meta analysis of 39 RCTs (>10000 patients)

-- No increased risk of suicide or attempted suicide, suicidal ideation, depression, or death in varenicline users compared with placebo users -- Varenicline was associated with an increased risk of sleep disorders, insomnia, andabnormal dreams

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What about in patients with psychiatric co-morbidities?

Anthenelli et al Lancet 2016

Large RCT of safety and efficacy of varenicline vs buproprion vs nicotine patch vs placebo

8144 patients 4116 to psychiatric cohort

4028 to non-psychiatric cohort

What about in patients with psychiatric co-morbidities?

Anthenelli et al Lancet 2016

-4 -2 0 2 4

Absolute Risk Difference in primary neuropsychiatric endpoint

Favors varenicline

Varenicline vs Placebo

Varenicline vs NRT

Varenicline vs Bupropion

Non-psychiatric cohortPsychiatric cohort

Favors comparator

No significant difference in primary composite neuropsychiatric endpoint No difference in secondary endpoints including

suicadality

What about in patients with psychiatric co-morbidities?

Anthenelli et al Lancet 2016

Varenicline more effective than bupropion and nicotine replacement in non-psychiatric and psychiatric populations

0.5 1.0 1.5 2.0 2.5

Odds Ratio

Better Efficacy

Bupropion vs NRT

Varenicline vs NRT

Varenicline vs Bupropion

Non-psychiatric cohortPsychiatric cohort

Can varenicline be used in patients not ready to quit?

Ebbert et al JAMA 2015

RCT of 1510 patients not ready to quit in next month -- Randomized to varenicline or

placebo for 24 weeks

-- Clinically significant reductions in abstinencerates at end of treatmentand at 1 year

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Pharmacist-led interventions in HIV clinics

Cropsey et al JAIDS 2015: Randomized trial of algorithm-based pharmacotherapy of tobacco vsstandard of care in HIV clinics Research staff with no specific prior training in

tobacco cessation administered questionnaire and assessed patient’s readiness to quit

If patient ready, algorithmic approach of medications (varenicline if no kidney impairment or history of suicide; then wellbutrin; then NRT)

Results: more quit attempts, greater smoking reduction, more cessation readiness

What about E-cigarettes? Would you recommend vaping to patients to consider quitting smoking?

Yes

No

0A B

Vaping – what controversy?

USPSTF statement on E-cigarettes: September 2015

We conclude that available data on the use of ENDS (electronic nicotine delivery systems) for smoking cessation are quite limited and suggest no benefit among smokers intending to quit.”

“the evidence on the use of ENDS for tobacco smoking cessation … is insufficient, and the balance of benefits and harms cannot be determined.

“the lack of well-designed, randomized, controlled trials (RCTs) on ENDS that report smoking abstinence or adverse events as a critical gap in the evidence.”

Patnode et al Ann Int Med 2015

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UCSF Metaanalysis: E-cigarettes associated with less quit attempts

Kalkhoran et al Lancet Resp Med 2016

Key Recommendations• Smoking if the biggest avoidable

cause of death in the UK• Provision of nicotine without harmful

components of tobacco smoke can prevent most of the harm from smoking

• Hazard to health arising from long-term vapor inhalation from e-cigarettes is unlikely to exceed 5% harm from smoking tobacco

• In the interests of public health it is important to promote the use of e-cigarettes, NRT, and other nicotine products as a substitute for smoking

British Royal College of Physicians: Vaping as harm reduction: April 2016

C.C.

Cured his HCV with ledipasvir/sofosbuvir

Declined bupropion and varenicline due to black box warnings

Decided to use e-cigarettes – Quit regular cigarettes, but continues to vape

Case 2: S.B.

48 y.o man from Fiji Diagnosed with pulmonary TB at diagnosis in 2009

GFR of 45 at dx

Started on RIPE + EFZ + ABC/3TC

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Case 2: S.B.

PMH No prior medical

problems

Social history: Undocumented

From Fiji

Gets $177/month GA

Family history Father with heart attack in

60s

Vitals: Height 5’8”, Weight: 172

lbs

BP 132/68

Labs CD4 50, VL 65000

HbA1C: 5.6

Case 2: S.B.

Excellent response to DOT RIPE + ART CD4 rise to >200, VL quickly suppressed

Housed through TB clinic

But… after DOT ended

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What ART would you switch to now? (K103N, M184V, GFR 45)

A) DRV/r + TAF/FTC

B) DRV/r + ETR + 3TC

C) DRV/r + RAL + 3TC

D) DRV/r + DTG + 3TC

E) DTG/3TC

F) Something else

0A B C D E F

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Sometimes getting ‘healthy’ has its consequences

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Sometimes getting ‘healthy’ has its consequences

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Metformin

Lantus+Metformin

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Lost insurance

Case 2: S.B.

Activity

Walks daily

Uses gym (YMCA) a few times per week

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What about activity? DHHS guidelines for activity (2008)

For “substantial” health benefits: 150 minutes (2 hours and 30 minutes) per week

of moderate intensity aerobic exercise (i.e. brisk walking, general gardening, “doubles” tennis) OR

75 minutes (1 hour and 15 minutes) per week of vigorous-intensity aerobic exercise (jogging/running, swimming laps, hiking uphill, aerobic dancing) , or equivalent combination of moderate and vigorous activity

All adults should moderate or high intensity muscle training 2 or more times per week

How many of you in this room exercise this much?

“Substantial health benefits:” 2 hours 30 minutes of moderate-intensity, or 1 hour 15 minutes of vigorous intensity exercise + strength training at least 2 times per week

A) Yes

B) No

0A B

What about shorter periods of exercise?

25 sedentary men randomized to 12 weeks of exercise 3 times per week:- Current activity- 50 minute bicycle

(moderate intensity, MICT)- Sprint interval training (SIT)

(2 minute bike warm-up then 20 sec “sprint”, repeated 3 total times (10 minutes total))

Gillen et al PLoS One 2016

Peak oxygen intake

Insulin sensitivity

Would you recommend a Fitbit™ or other activity tracker?

A) YesB) No

0A B

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Randomized trial of 471 participants, 77% women aged 18-35, 30% non-white Standard intervention: Self monitoring of diet/exercise

Enhanced: Wearable device to monitor diet/exercise

Results: Standard intervention had Greater weight loss (2.4 kg) over 24 months

Conclusion: Devices that monitor/provide feedback on physical activity may not offer an advantage over standard behavioral weight loss approaches.

Jakicic et al JAMA 2016

Back to case 1: C.C.

Early this year – partner of 30 years passed away from pancreatic CA Significant grief, anxiety from this loss Began drinking heavily

Feels like his quality of life was poor to begin with but has only gotten worse since the death of his partner

Van der Kolk et al. Clin Infect Dis. 2010;50:255-263

Poor health-related quality of life associated with reduced survival in HIV patients

Smoking cessation and HRQoL

Taylor et al BMJ 2014: Smoking cessation associated with reduced depression, anxiety, stress, and QOL.

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Case 1: C.C.

Began walking daily for up to 3-4 hours (from Tenderloin to ocean and back)

Started talking to me about meditation and asking me if I have suggestions on “decalcifying his pineal gland”.

Evidence for meditation?

JAMA Intern Med. 2014;174(3):357-368.

Meditation: Positive impact on anxiety, depression, pain, and mental health-related quality of life.

What about meditation?

Mindfullness on 60 minutes

UCSF offers Mindfulness-based stress reduction program

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Summary: Life expectancy and wellness in HIV

Mind the (life expectancy) gap! HIV in 2016 Gap narrowing but persists Smoking, Late ART initiation, ETOH/drugs, other co-

morbid conditions (hepatitis, obesity)

For smoking cessation Abrupt quitting may be more successful than gradual

quitting

Varenicline is safe and effective in patients with psychiatric conditions

Evidence gap remains on e-cigarettes

Summary: Life expectancy and wellness in HIV

Exercise May not need so much activity: Consider short interval training

Exercise trackers not quite ready for primetime

Mind the (quality of life) gap! Anxiety, depression, social isolation drive this gap

Consider mindfulness/meditation as an approach to improve this

Thanks! Extra Slides