STAYING FIT & HEALTHY WHILE AGING WITH HIV

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Lecture Agenda:

  • Weight Gain in the New HIV Era- Review of Studies
  • Preventing Heart Disease
  • Reducing Visceral Fat
  • Healthy Nutrition Tips
  • Exercise Tips
  • Weight Loss Medications
  • Hormone Balance
  • Sleep- The Pillar of Health
  • Resources

Weight Gain in HIV: Then and Now

  • 1996- 2006: Weight gain was characterized by accumulation in the visceral and cervical area (lipohypertrophy) in the boosted protease plus thymidine nucleoside era (Crixivan, Kaletra, AZT, Zerit) along with fat loss under the skin (lipoatrophy). Lipoatrophy decreased after Zerit and AZT were no longer recommended in the U.S. in 2004.
  • ARV-related mitochondrial toxicity plus insulin resistance were factors identified in body changes along with inflammatory cytokines. Some genetic factors were also identified but not investigated in detail.
  • The term “lipodystrophy”” was later changed to “return-to-health” syndrome as strong immune reconstitution was identified as a major factor.
  • The only treatment approved for the treatment of increased abdominal fat is Egrifta SR
  • We hoped that integrase inhibitors would not cause weight gain since they are not associated with mitochondrial toxicity or insulin resistance. They were later found to cause greater weight gain than protease inhibitors in naïve patients and those switching to integrase inhibitors.  This trend is most pronounced in women, blacks, and persons ≥ 60 yrs. of age
  • We have learned that all ARVs can cause weight gain and that patient-related factors that may worsen their effect.  Fortunately, disfiguring lipodystrophy is rare in patients not exposed to AZT, Zerit and older ARVs.  However, many long-term survivors are still dealing with these body changes.

Weight gain after switch is influenced by initial ARV regimen

  • Greater weight gain was seen after switch to integrase- based (INST) regimen from NNRTI vs. PI regimens
  • Among those switched from NNRTI- to integrase-based ART, annualized weight gain was greatest for females, non-whites older PWH, and those switched to dolutegravir (DTG) (Tivicay)
  • Increases in BMI in YPHIV receiving INSTIs
  • NA-ACCORD Study: Weight Gain Among 24,001 ART-Naive Patients Initiating Treatment
  • ADVANCE STUDY: Mean Weight Change by Sex and ARV
  • Greater weight increase with dolutegravir (DTG) vs efavirenz (EFV), with TAF vs tenofovir (TDF); plateau in weight gain after  Wk 48 observed in men but not in women

Same patterns observed for percentage change in weight and change in BMI category over time

Visceral Fat (VAT) increases in PLWH initiating INSTIs

In a sub-analysis of the ADVANCE trial, TAF/FTC+DTG led to greater rises in VAT from baseline to Week 96 vs either comparator (P < 0.001)

How might regimens containing Integrase Inhibitors (INSTIs) or TAF cause weight gain?

 

INSTIs:

  • Interaction with genes associated with obesity
  • Induction of adipogenesis, lipogenesis, oxidative stress, fibrosis and insulin resistance, directly impacting adipocytes and adipose tissue
  • Improved GI tolerability and lack of secondary-effects of cobicistat in INSTIs not requiring boosting
  • Reduction in inflammatory biomarkers, and potentially catabolic processes, compared to NNRTI-based regimens
  • Potency and correlation with lower energy expenditure
  • Proposed Predictors and Mechanisms

TAF

  • TDF may exert a mild weight suppressive effect absent in TAF
  • Increases LDL cholesterol unlike TDF
  • TAF may amplify (or TDF may mitigate) the weight-gain effect of DT

Effects of Obesity

  • Diabetes
  • Heart Disease
  • Colon, Gastric, Breast, Pancreatic Cancer
  • Osteoarthritis
  • Sleep Apnea
  • Hypertension
  • Stroke
  • Dyslipidemia
  • Infertility

Where are People Trying to Lose Weight Going for Help?

  • Americans spend over 60 billion dollars a year on weight loss efforts
  • Prepackaged foods
  • Supplements
  • Weight loss clinics
  • Nutritionists
  • Personal Trainers
  • Pharmaceuticals
  • Surgery

Metabolic Syndrome

  • Risk Factors for Coronary Heart Disease (CHD)
    (National Cholesterol Education Program, JAMA, May 2001))
  • LDL >130
  • Cigarette smoking
  • Hypertension (blood pressure >140/90 or on BP meds)
  • HDL< 40
  • Family history of early CHD (male <55y.o., female <65y.o.)
  • Diabetes

How To Minimize Cardiovascular Disease

  • Do not smoke!
  • Exercise and avoid a diet rich in sugar/simple carbs
  • Lose weight if you are overweight
  • Manage stress. Relax!
  • Manage blood pressure
  • Decrease triglycerides with Omega 3 fatty acids (cold water fish oils)
  • Improve HDL with Niacin 300-500 mg 3 x day. Start with lower dose to minimize “flushing” and take an aspirin 20 min before (Niaspan is the prescription grade)
  • Consume Soluble Fiber (oats, etc)
  • If everything else fails, use prescription lipid lowering agents (statins, fibrates, etc)
  • A baby aspirin a day (81 mg)
  • Talk to your doctor about lipid friendly HIV meds

Potential Interventions for Decreasing Abdominal Fat (visceral adipose tissue-VAT)

  • Diet- Lower carb?- No data available in HIV
  • Exercise- cardiovascular and resistance training- Some pilot data with good results
  • Weight reduction.
  • Anti-diabetic drug Metformin (Glucophage)- conflicting and inconclusive data
  • Human Growth Hormone Releasing Hormone- Egrifta SR

Benefits of Exercise and Dietary Changes in the Metabolic Syndrome

A 6-month randomized trial in HIV-infected subjects with NCEP-defined metabolic syndrome receiving lifestyle modification (n=16) or observation (n=18)

Metformin Patients Lost Weight and Had Decreased Waist Circumference

Metabolic Effects of Metformin and Exercise in Treated HIV(+) Patients

Pre-Diabetes Common in HIV+ People

Nutritional Considerations

Reduce fried foods and hydrogenated oils

Eat omega-3 fish oil-rich foods- salmon, tuna, sardines or flax seed oil (alternative)

  Use monounsaturated fats: olive oil

Minimize sugar, fructose (sweets, sodas, foods with high fructose corn syrup )

Eat adequate amounts (0.7-1 gm/lb./day) of protein (fish, eggs, cottage cheese, lean meats, chicken, whey, nuts, etc.)

More Nutritional Considerations

Do not skip breakfast (keep an eye on sugar and refined flower products!)

Try to eat  several smaller meals or snacks instead of 2-3 large ones

Eat more almonds, walnuts, pecans and  pistachios (good cholesterol lowering fats)

Eat fruits and vegetables of all colors ( varied  antioxidant profile)

Minimize caffeine after 2 pm

Spend most of your money at the perimeter of the grocery store

Grocery Shopping List

  • Almonds and other nuts
  • Beans and other legumes
  • Spinach and other green leafy vegetables
  • Low fat dairy, yogurt
  • Whey protein
  • Oatmeal
  • Eggs
  • Lean meats, salmon, tuna, etc
  • Peanut, almond , cashew butters
  • Olive oil and avocados
  • Raspberries and all berries. Fruits (avoid fruit juices)
  • Flaxseed , pumpkin and sunflower seeds
  • Sweet potatoes
  • Green tea

Aerobic (Cardiovascular) Exercise

  • Start with a brisk walk every day . Aim at 5,000-10,000 steps per day (Get an App)
  • Concentrate in low impact or no impact exercises (e.g. Elliptical Trainers)
  • Do what you enjoy (bicycling, roller skating, etc.)
  • Good for burning fat, triglycerides, blood sugar, and to improve blood pressure.
  • 20 – 30 minutes 3-4 times a week is enough for many people
  • Cardiovascular exercise can help decrease blood pressure, LDL cholesterol, and weight.  It can also help to increase HDL, mood, and bone density. It has also shown to decrease dementia risk.

Progressive Resistance  Exercise (PRE)

  • Increases strength, bone density and firmness.
  • Lift maximum weight or use machines for muscular failure (exhaustion) at 8-12 repetitions
  • One-hour sessions 3 times a week
  • Three sets per body part
  • If no access to a gym, start with crunches, pushups, and squats at home
  • For more details, visit exrx.net

Weight Loss Medications

  • Phentermine (Adipex)
  • Diethylproption (Tenuate)
  • Phendimetrazine (Bontril)
  • Lorcaserin (Belviq)
  • Phentermine/Topiramate (Qsymia) (Discontinued in Feb 2020)
  • Naltrexone/Bupropion (Contrave)

Who Can Get Weight Loss Medications Prescribed?

 The US Food and Drug Administration (FDA) has approved weight loss drugs for long-term use in obese (body mass index [BMI] ≥30) or overweight (BMI≥27) individuals with at least 1 weight-associated co-morbidity (type 2 diabetes, hypertension, hyperlipidemia).

Body mass index is calculated as weight in kilograms divided by height in meters squared. 

Appetite Suppressant Side Effects

  • Increase in blood pressure
  • Increase in heart rate
  • Dry mouth
  • Constipation
  • Insomnia
  • Erectile dysfunction
  • All are self-limited
  •  

Weight Loss Medications- Prescribing Requirements

  • BMI > 28
  • Cardiovascular Exam
  • EKG
  • Patients aged 40+
  • History of cardiac abnormalities
  • History of atherosclerosis

Weight Loss Medication Contraindications

  • Uncontrolled hypertension
  • Renal disease
  • Coronary artery disease

Signs and Symptoms of Testosterone Deficiency in Women

  • Decreased lean body mass
  • Increased body fat
  • Thinning or loss of hair
  • Osteopenia or Osteoporosis

Thyroid Medications

  • T4 only medications (synthetic)-Levothroid, Levoxyl, Synthroid, Unithroid
  • T3 only medications (synthetic)- Liothyronine, Cytomel
  • T4/T3 combo medications (synthetic)- Liotrix, Euthroid, Thyrolar, Compounded Products
  • Desiccated Thyroid (Armour) and Compounded Desiccated Thyroid


Sleep Changes in Aging

  • Sleep during the night changes with increasing age:
  • Less deep sleep and more lighter sleep
  • More difficulty maintaining sleep due to  arousals and awakenings
  • Sleep is less efficient and more fragmented
  • The internal biological clock shifts to earlier bed and wake times
  • Older persons experience a higher prevalence of medical conditions and take more medications that interrupt sleep and are associated with sleep
  • Older persons experience a higher prevalence of sleep disorders

 Effect of Sleep on Hormones

  • Cerebral Blood Flow Spikes
  • Melatonin increases
  • Cortisol increases before waking up
  • Growth Hormone Increases
  • Thyroid Hormones Increase
  • Testosterone Increases