Lipodystrophy and Obesity:

Lipodystrophy

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

 

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 HIV vs. non-HIV non-obese persons for the same BMI
  • 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;
    • Limited data, but not consistently associated with improvement in insulin sensitivity and blood lipids
    • No prospective trials in PLWH to indicate degree of diet and/or exercise needed to maintain reduction in visceral fat
  • Pharmacological interventions to treat lipohypertrophy have not been proven to provide long-term effects and may introduce new complications
  • Growth hormone (not approved for this indication in Europe)
           •   Decreases visceral adipose tissue
    • May worsen insulin resistance
  • Tesamorelin (not approved in Europe; approved for this indication by FDA(ii)
  • Metformin (not approved for this indication in Europe) 
    • Decreases visceral adipose tissue in insulin resistant persons
    • May worsen subcutaneous lipoatrophy
  • 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:
    1. for men: ≥ 94 cm (≥ 90 cm for Asian men) is high, and > 102 cm is very high
    2. for women: ≥ 80 cm is high and > 88 cm is very high
  2. Tesamorelin (growth hormone releasing factor) was shown to reduce visceral adipose tissue volume but this effect was lost on discontinuation.

 

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 Definition is lacking.
An increase > 5% of weight is often used, as opposed to the magnitude of weight loss recommended in lifestyle interventions as initial treatment of cardiometabolic conditions

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 apnea, cholecystitis, erectile dysfunction, non-alcoholic fatty 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 in PWH increases weight as part of a return-to-health phenomenon
INSTI and TAF may induce greater weight gain than other ARVs		 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). 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 obese PLWH. ↑ risk of virological failure with long acting CAB/RPV in obese PLWH
Bariatric surgery   Medical devices or endoscopic procedures (e.g intragastric balloon, aspiration therapy, endoscopic sleeve gstrroplasty) or bariatric surgery should be considered in persons with a BMI ≥ 40 kg/m2 or ≥ 35 kg/m2 with obesityrelated co-morbidities refractory to serious attempts at lifestyle changes and should be coordinated through an established, specialistled obesity programme Consider therapeutic drug monitoring and drug dose adjustment post-bariatric surgery