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Lipodystrophy and Obesity

Lipoatrophy

Prevention

  • Avoid d4T and ZDV or pre-emptively switch. No evidence of benefit by switching other antiretrovirals
  • Avoid excessive weight loss due to diet and exercise
  • In ART-naïve persons, limb fat usually increases with initiation of ART not containing d4T or ZDV, reflecting “return-to-health” type of response

Management

  • Modification of ART: Switch away from d4T or ZDV
  • Surgical intervention
    • Offered for cosmetic relief of (facial) lipoatrophy
    • Autologous fat (whenever possible) or resorbable facial filler (if autologous fat not available) should be preferred against nonresorbable filler

Lipohypertrophy(i)

Prevention

  • No proven strategy
  • No contemporary ART has been specifically associated with increased visceral adiposity
  • An excess of visceral fat has been reported in people with HIV compared with non-HIV persons for the same BMI (even in the absence of obesity)
  • Weight reduction or avoidance of weight gain may decrease visceral fat
  • Avoid corticosteroids with RTV or COBI-boosted drugs as it may cause Cushing syndrome or adrenal insufficiency, see Drug-Drug Interactions between Corticosteroids and ARVs

Management

  • Diet and exercise may reduce visceral adiposity
    – No prospective trials in persons with HIV to indicate degree of diet and/ or exercise needed to reduce visceral fat
  • Pharmacological interventions to treat lipohypertrophy have not been proven to provide long-term effects
  • Surgical therapy can be considered for localised lipomas/buffalo humps
    – Duration of effect variable

  1. Lipohypertrophy may occur as localised lipomas in the subcutaneous region or as increased visceral adiposity, both intra-abdominally and/or in the epicardium. Lipohypertrophy may occur without obesity. 
    Increased visceral adiposity is defined by waist circumference: 
    - for men: ≥ 94 cm (≥ 90 cm for Asian men) is high, and > 102 cm is very high 
    - for women: ≥ 80 cm is high and > 88 cm is very high

 

Weight Gain and Obesity 

  Weight Gain Obesity Comments
Definition It is a physiological phenomenon associated with aging.
Body weight of an average European adult is estimated to increase by 0.3 - 0.5 kg per year.
An increase > 5% of weight may be considered to define weight gain potentially associated with insulin resistance

BMI-based definitions (WHO):
Overweight: BMI 25 to < 30 kg/m2
Class I obesity: BMI 30 to < 35 kg/m2
Class II obesity: BMI 35 to < 40 kg/m2
Class III obesity: BMI ≥ 40 kg/m2

For Asian populations, overweight is defined as BMI 23 to 27.5 kg/m2 and obesity ≥ 27.5 kg/m2

 Weight gain and obesity represent a continuum associated with negative health outcomes
Consequences Increased risk of DM, hypertension, dyslipidemia and CVD Body image disturbance
Increased risk of DM, hypertension, CVD, some cancers, obstructive sleep apnoea, cholecystitis, erectile dysfunction, metabolic dysfunction-associated steatotic liver disease, osteoarthritis, depression and neurocognitive impairment		  
Contributing factors

Older age
Sedentary lifestyle
Altered sleep pattern
Intake of excess or poor-quality calories (e.g., saturated fats, processed sugars)
Excess alcohol consumption
Some medications (e.g., psychotropic drugs, steroids, anti-diabetic drugs)
Endocrine disorders (e.g., GH deficiency, hypothyroidism, Cushing’s syndrome, hypogonadism)

  
Impact of ART Initiation of ART increases weight as part of a return-to-health phenomenon
INSTI and TAF may induce greater weight gain than other ARVs
Switching from INSTI and/or TAF may have a small weight loss effect in overweight/obese people with HIV		 See Adverse effects of ARVs and drug classes
Aim of intervention

Emphasise the importance of behaviour goals rather than weight loss goals
An objective of 5 - 10% weight loss may have benefits on:
• ↑ 5% HDL cholesterol
• ↓ 5 mmHg systolic and diastolic BP in hypertension
• ↓ 0.5% (decrease 2.55 mmol/mol) HbA1c in DM
• Improving sleep apnoea

  
Management Motivation to change:
Discuss support systems (e.g. family, friends), motivating factors, and barriers to change
Discuss benefits of making changes
Set realistic and achievable lifestyle changes		  
Lifestyle recommendations Consider behavioral intervention (motivational interviewing, stimulus control or cognitive restructuring) along with self-monitoring; intensify behavioral intervention if several unsuccessful weight loss attempts See Lifestyle Interventions
General principles Treat underlying or associated conditions
There are several drugs specifically recommended for those with a BMI ≥ 30 kg/m2 or ≥ 25 kg/m2 and weight-related complications (DM, hypertension) (e.g. orlistat, phentermine/topiramate, lorcaserin, naltrexone/bupropion, liraglutide, semaglutide). These drugs should be prescribed by an endocrinologist or obesity expert. All of them may have adverse effects and drug-drug interactions with ART

Consider TDM (therapeutic drug monitoring) in PWH with obesity.
Obesity alone doesn’t ↑ risk of virological failure with long-acting CAB/RPV; other factors are required
Bariatric surgery   Medical devices or endoscopic procedures (e.g intragastric balloon, aspiration therapy, endoscopic sleeve gastroplasty) or bariatric surgery should be considered in persons with a BMI ≥ 40 kg/m2 or ≥ 35 kg/m2 with obesity-related co-morbidities refractory to serious attempts at lifestyle changes and should be coordinated through an established, specialist-led obesity programme Bariatric surgery may impact ARVs absorption*.
Consider therapeutic drug monitoring and drug dose adjustment post-bariatric surgery

 * www.hiv-druginteractions.org/prescribing_resources/hiv-guidance-gastric-surgery