06.11.21 | Practical Aspects of Dealing with Weight Gain in People with HIV

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Practical Aspects of Dealing with Weight Gain in
People with HIV (PWH)
Daniel Lee, MD
Clinical Professor of Medicine
UC San Diego School of Medicine/UC San Diego Health –
UCSD Owen Clinic
June 11th, 2021

ACTHIV 2021: A State-of-the-Science Conference for Frontline Health Professionals

Learning Objectives
Upon completion of this presentation, learners should be better able to:
• Identify risk factors that may contribute to weight gain
• Offer nonpharmacologic options for managing weight gain
• Determine which pharmacologic options are appropriate for managing
weight gain

Faculty Disclosure
Commercial Interest Nature of Relevant Financial Relationship
Name of Company
Employee, Grants/Research Support recipient, Board Member,
Advisor or Review Panel member, Consultant, Independent Contractor,
Stock Shareholder (excluding mutual funds), Speakers’ Bureau, Honorarium
recipient, Royalty recipient, Holder of Intellectual Property Rights, or Other
1. Theratechnologies Consultant, Advisory Board Member, Speakers’ Bureau
2. Janssen Consultant
3. ViiV Advisory Board Member, Speakers’ Bureau
4. Gilead Sciences Advisory Board Member
Off-Label Disclosure
The following off-label/investigational uses will be discussed in this presentation:
• Growth hormone-releasing factor (GHRF) for weight loss

Audience Response Question #1
As an HIV care provider, you are planning to start the same antiretroviral
(ARV) regimen of your choice on three ARV-naïve PWH
– PWH #1 – 34-year-old male with HIV for 5 years, CD4 = 280, VL = 145,000
– PWH #2 – 65-year-old female with HIV for 1 year, CD4 = 365, VL = 28,000
– PWH #3 – 52-year-old male w/PJP pneumonia and recent diagnosis of HIV last week,
CD4 = 25, VL >750,000
Which patient do you expect to gain the most weight within the first year
after starting ARVs?
1. PWH #1
2. PWH #2
3. PWH #3

Factors Contributing to Weight Changes in HIV
• HIV-related factors
– Lower CD4, higher VL
– Chronic Inflammation – increased proinflammatory cytokines
– Microbial Translocation – effects on gut absorption
– Likely many other unknown off-target effects on metabolism?
1. Crum-Cianflone N, et al. PLoS ONE 2010;5:e10106.
2. Bakal et al. J Antimicrob Chemother. 2018 Aug 1;73(8):2177-2185.
3. Tate el al. Antivir Ther. 2012;17(7):1281-9.
4. Bhagwat et al. Open Forum Infect Dis. 2018 Nov 16;5(11).
5. Lakey et al. AIDS Res Hum Retroviruses. 2013;29(3):435-40.
6. Yuh et al. Clin Infect Dis. 2015 Jun; 60(12):1852-9.
7. Achhra et al. HIV Med. 2016 Apr;17(4):255-68.
8. McCormick et al. Front Immunol. 2014 Nov 13;5:507.
9. Bares et al. J Womens Health (Larchmt). 2018 Sep;27(9):1162-1169.
10. Sax P, et al. CID 2020; 71:1379-89.

Factors Contributing to Weight Changes in HIV (2)
• Antiretroviral Therapy-related factors
– Altered lipid trafficking
– Abnormal adipose tissue distribution
– Medications
• Integrase strand transfer inhibitors (INSTIs)?
• Tenofovir alefenamide (TAF)?
– “Return to Health” phenomenon
9. Sax P, et al. CID 2020; 71:1379-89.
10. Menard et al. AIDS. 2017 Jun 19;31(10):1499-1500.

Adapted from Riddler et al. JAMA 2003;289:2978-82.
“Return to Health” Phenomenon Not Only Applies
to Lipids, But Likely Also Applies to Weight Gain
0
50
100
150
200
250
0 2 4 6 8 10 12 14
Years
Weight
Preseroconversion Pre-HAART HAART
Weight
(lbs)

Weight Gain During ART: Return to Health vs.
Obesity Trajectory
• Untreated HIV associated with weight
loss/wasting
• Following ART initiation, weight gain
is common, but need to distinguish
weight gain due to:
– “Return to health”: desirable weight gain
related to restoration of body nutrient stores
– Clinically undesirable weight gain that leads
to complications of overweight or obesity
• Gains in abdominal fat, weight, and BMI
after ART may increase long-term risk for
diabetes, CVD, other complications
Kumar S, et al. Front Endocrinol. 2018;9:705.

• Patient/Host-related factors
– Older age → slower metabolism → weight gain
– Diet: food preferences, food insecurity, access to healthy foods (food deserts)
– Energy Balance: Calories consumed = calories expended
– Physical Activity: regularity of exercise, opportunities for physical activity, safety and walkability of
community
– Basal Metabolic Rate (BMR) – minimum number of calories needed to keep the body functioning at rest
– Resting Energy Expenditure (REE) – number of calories that your body burns at rest
» Related most directly to amount of fat-free (lean) mass
– Genetics: race/ethnicity, gender, family history
10. Sax P, et al. CID 2020; 71:1379-89.

• Patient/Host-related factors
– Other Comorbidities: thyroid abnormalities, dyslipidemia, diabetes, infections, malignancies
– Concurrent Medications: psychiatric medications, corticosteroids, medications affecting
testosterone/estrogen balance
– Habits: smoking, alcohol, other illicit substances
– Consequences of use vs. cessation
– Adipocytokine production and growth hormone (GH) secretion
– Leptin deficiency, decreased adiponectin levels, decreased GH levels
7. Sax P, et al. CID 2020; 71:1379-89.

PWH #3 is a 52-year-old male w/PJP pneumonia and recent diagnosis of HIV last week,
CD4 = 25, VL >750,000. He was seen by you in clinic and was started on a single-tablet
regimen of Bictegravir/TAF/FTC. His CD4 improves to 150 and his VL is <20 after 3 months.
However, his weight rises from 150 lbs to 180 lbs and he is concerned about obesity. He
cites that his normal weight is 170 lbs.
What do you advise at this time?
1. Improve diet and increase physical activity
2. Improve diet, increase physical activity, and behavioral therapy
3. Improve diet, increase physical activity, behavioral therapy, and pharmacologic therapy

WHAT OPTIONS EXIST FOR MANAGING
WEIGHT GAIN?

Benefits of Weight Loss
• Decreased risk of diabetes
– Average weight losses of 2.5 to 5.5 kg at 2 or more years, achieved with lifestyle treatment, reduces
the risk for developing type 2 diabetes by 30-60%
– Weight loss of 5 to 10 percent is associated with HbA1c reductions of 0.6 to 1.0 percent and reduced
need for diabetes medications
• Decreased lipids
– There is a dose-response relationship between the amount of weight loss achieved by lifestyle
intervention and the improvement in lipid profile. The level of weight loss needed to observe these
improvements varies by lipid.
• With a 3 kg weight loss, may see triglycerides↓ of at least 15 mg/dL
• With a 5-8 kg weight loss, may see LDL-C↓ of ~5 mg/dL and HDL-C↑ of 2 to 3 mg/dL
• Decreased blood pressure
– There is a dose-response relationship between the amount of weight loss achieved by lifestyle
intervention and the lowering of blood pressure.
• With a 5% weight loss, may see ↓ in systolic and diastolic blood pressure of ~3 and 2 mmHg
NIH. Managing Overweight and Obesity in Adults – Systematic Evidence Review from the Obesity Expert Panel, 2013.

Steps to Treating Overweight and Obesity
1. Measure height and weight
– To determine body mass index (BMI)
2. Measure waist circumference (WC)
– Men with WC > 40 in or Women with WC > 35 in are at higher risk
for diabetes, dyslipidemia, hypertension, and cardiovascular disease due to excess abdominal fat
3. Assess comorbidities
– Ask about hypertension, dyslipidemia, cardiovascular disease, sleep apnea, smoking status
4. Should your patient be treated?
– Consider a combination of diet modification, increased physical activity, and behavioral therapy
5. Is the patient ready and motivated?
– Reasons and motivation for weight loss?
– Previous attempts at weight loss?
– Support from others?
– Attitudes towards diet/exercise?
– Barriers to change?
Adapted from NHLBI Obesity Education Initiative. Practical Guide to the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults, October 2000

Dietary Recommendations
• Caloric intake should be reduced by 500 to 1,000 calories per day from current level
– This will produce a recommended weight loss of 1-2 pounds per week
• Diet should be low in calories, but it should not be too low (<800 kcal/day)
• In general,
– Women should consider a diet containing 1,000 to 1,200 kcal/day
– Men should consider a diet containing 1,200 to 1,600 kcal/day
• Long-term changes in food choices are more likely to be successful when
– Individual food preferences are taken into account
– Education about food composition, labeling, preparation, and portion size
• Although dietary fat is a rich source of calories, reducing dietary fat without
reducing calories will not produce weight loss
• Encourage referral to a registered dietician (RD)
NHLBI Obesity Education Initiative. Practical Guide to the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults, October 2000.

Physical Activity Recommendations
• Physical activity has direct and indirect benefits
– Increases energy expenditure
– Plays an integral role in weight maintenance
– Reduces risk of heart disease more than that achieved by weight loss alone
– May help reduce body fat and prevent the decrease in muscle mass often found during weight
loss
• Physical activity should be generally increased slowly, with care taken to avoid injury
• A wide variety of activities and/or household chores, including walking, dancing,
gardening, and team or individual sports, may help satisfy this goal
• All adults should set a long-term goal to accumulate at least 30 minutes or more of
moderate-intensity physical activity on most, and preferably all, days of the week

American Heart Association Recommendations for
Physical Activity in Adults
• Recommendations are based on the Physical Activity Guidelines for Americans, 2nd
edition
– Get at least 150 minutes per week of moderate-intensity aerobic activity or 75 minutes per week
of vigorous aerobic activity, or a combination of both, preferably spread throughout the week
– Add moderate- to high-intensity muscle-strengthening activity (such as resistance or weights) on
at least 2 days per week
– Spend less time sitting. Even light-intensity activity can offset some of the risks of being
sedentary
– Gain even more benefits by being active at least 300 minutes (5 hours) per week
– Increase amount and intensity gradually over time
https://www.heart.org/en/healthy-living/fitness/fitness-basics/aha-recs-for-physical-activity-in-adults
https://health.gov/sites/default/files/2019-09/Physical_Activity_Guidelines_2nd_edition.pdf

American Heart Association Recommendations for
Physical Activity in Adults
https://www.heart.org/en/healthy-
living/fitness/fitness-basics/aha-recs-for-
physical-activity-in-adults
https://health.gov/sites/default/files/2019-
09/Physical_Activity_Guidelines_2nd_edi
tion.pdf
150 minutes per
week
75 minutes per
week

Behavioral Therapy Recommendations
• Behavioral therapy is a useful adjunct to planned adjustments in food intake and
physical activity
– May be employed to promote adoption of diet and activity adjustments
• Specific behavioral strategies include
– Self-monitoring
– Stress management
– Stimulus control
– Problem-solving
– Contingency management
– Cognitive restructuring
– Social support

Pharmacotherapy for Weight Loss
• Pharmacotherapy, approved by the FDA for long-term treatment, can be a helpful
adjunct for the treatment of obesity in some patients
– May be helpful for eligible high-risk patients
– These drugs should only be used in the context of a comprehensive treatment program that
includes diet, physical activity changes, and behavioral therapy
– If lifestyle changes do not promote weight loss after 6 months, pharmacotherapy should be
considered
• Pharmacotherapy is limited to those who have a BMI ≥ 30, or those who have a BMI
≥ 27 if concomitant obesity-related risk factors or diseases exist
• Currently, there are 5 FDA approved agents for long-term use in weight loss
– Orlistat, Lorcaserin (withdrawn from market in 2/2020 due to increased incidence of cancers),
Phentermine-Topiramate, Naltrexone-Bupropion, Liraglutide
• Consider referral to a weight management clinic
https://www.niddk.nih.gov/health-information/weight-management/prescription-medications-treat-overweight-obesity

Surgical Intervention for Weight Loss
• Bariatric surgery is an option for patients with extreme obesity
– Must have clinically severe obesity (BMI ≥ 40) or a BMI ≥ 35 with serious comorbid
conditions
– Types of bariatric surgery
• Biliopancreatic diversion with duodenal switch (BPD/DS)
• Gastric bypass (Roux-en-Y)
• Sleeve gastrectomy
– Can provide medically significant sustained weight loss for more than 5 years in most
patients
– There are risks associated with surgery, but it is not yet known whether these risks are
greater in the long term than those of any other form of treatment
– Will require monitoring for complications and lifestyle adjustments throughout their
lives
https://www.niddk.nih.gov/health-information/weight-management/prescription-medications-treat-overweight-obesity

cites that his normal weight is 170 lbs. After 3 more months, his weight increases to 200
lbs despite working on his diet, improving exercise, and counseling.
Which of the following interventions would you suggest? (Choose 1 best answer)
1. Weight loss medication (e.g., Orlistat, Phentermine-Topiramate, Naltrexone-Bupropion, Liraglutide)
2. Growth-hormone releasing-factor (tesamorelin)
3. Weight management clinic referral
4. Continuation of current management
5. Consider switching antiretroviral therapy

Practical Tips for Evaluating Weight in the Clinic
• History
– Review the evolution of the weight gain
– Ask what their normal weight and waist size was prior to HIV infection
– Ask when the patient believes that they became HIV-infected (not the date of HIV diagnosis)
– Review medical history for other comorbidities that may contribute to weight gain
– Review medications to look for possible contributors to weight gain
– Ask if other family members are obese or not
Expert Opinion: Lee, D.

Practical Tips for Evaluating Weight in the Clinic (2)
• Physical Exam
– Try to obtain a gowned weight to get an accurate weight (using the same scale to reduce
variability)*
– Obtain waist and hip circumference (including waist-to-hip ratio) using a tape measurement (if
available)*
– Evaluate for the presence of abdominal lipohypertrophy (lipodystrophy)
• Feel the abdomen and do a “pinch” test to determine how much subcutaneous fat is present in relation
to the entire size of the abdomen.
– If there is a lot of subcutaneous fat that can be pinched, then this may be a sign of obesity
– If not much subcutaneous fat can be pinched, the rest is likely visceral fat and perhaps, this is a sign of
lipohypertrophy
• Determine where the majority of the fat is on abdominal exam (in relation to umbilicus)
– If there is more fat in the lower abdomen (below the umbilicus), this is more likely obesity
– If there is more fat in the upper abdomen (above the umbilicus), this may be lipohypertrophy
* If multidisciplinary team is available, gowned weight and circumference measurements may be performed by nursing staff or registered dietician

• Labs
– Check fasting glucose to look for evidence of insulin resistance, prediabetes, or diabetes
• May consider checking a1c, fasting insulin level, oral glucose tolerance testing (OGTT)
– Check fasting lipids to look for presence of dyslipidemia
– Check thyroid function tests to rule out hypothyroidism
– Check testosterone levels to rule out hypogonadism

• Recommended interventions
– Diet, exercise, and behavioral therapy is recommended for everyone with weight issues*
– Pharmacologic therapies – optional and the choice depends on what you think is driving the
cause of the weight gain**
• If there is evidence of abdominal lipohypertrophy (lipodystrophy) with increased visceral adiposity, may
consider growth-hormone releasing-factor (tesamorelin), as this is indicated for this condition
– However, growth-hormone releasing-factor is weight neutral and not indicated for weight loss
• If there is evidence of insulin resistance or prediabetes, may favor using liraglutide, which has the
benefit of improving insulin sensitivity and weight loss
• If there is no evidence of lipodystrophy or insulin resistance, may consider use of other FDA-approved
weight loss medications taking into account patient preference and side effect profile
• May consider referral to weight management clinic if uncomfortable in managing these issues
– Switching antiretroviral therapy (removal of INSTI or TAF) for weight gain is not recommended as
it is unclear to have benefit at this current time due to the absence of clinical studies/data
* If multidisciplinary team is available, diet/exercise counseling may be performed by registered dietician, behavioral therapy may be performed by therapists/psychiatrists
** If multidisciplinary team is available, discussion of pharmacological therapies may be performed by clinical pharmacists

cites that his normal weight is 170 lbs. After 3 more months, his weight increases to 200
lbs despite working on his diet, improving exercise, and counseling.
Which of the following interventions would you suggest?
1. Weight loss medication (e.g., Orlistat, Phentermine-Topiramate, Naltrexone-Bupropion, Liraglutide)
2. Growth-hormone releasing-factor (tesamorelin)
3. Weight management clinic referral
4. Continuation of current management
5. Consider switching antiretroviral therapy

Key Takeaways for the HIV Care Team
• Weight gain has become a common medical issue for PWH, especially as
PWH live longer
• There are many risk factors that contribute to weight gain including host-
related, HIV-related, and antiretroviral therapy (and other medication) -
related factors
• In regards to initial weight management, a combination of diet
modification, increased physical activity, and behavioral therapy is key
– Pharmacotherapy may be used if no response to initial weight management and
should be targeted toward underlying contributors to weight gain
– Surgical interventions are reserved for extreme obesity and usually after lack of
response to pharmacotherapy

06.11.21 | Practical Aspects of Dealing with Weight Gain in People with HIV

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