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
- Increase in total limb fat ~400-500 g/year (in the first two years)
- Risk of toxicity from new drug, see Adverse Effects of ARVs & Drug Classes
- 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
- 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
- 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): 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 |
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Contributing factors |
Older age |
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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: |
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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 |
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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 |