Tesamorelin for HIV-Associated Lipodystrophy: Focus on Subcutaneous Fat
Tesamorelin is specifically indicated for reducing excess abdominal visceral fat in HIV-infected patients with lipodystrophy but does not significantly affect subcutaneous fat and is not appropriate for treating subcutaneous fat loss (lipoatrophy). 1
Mechanism and Indication
Tesamorelin (Egrifta SV) is a synthetic analogue of human growth hormone-releasing hormone that stimulates the synthesis and release of endogenous growth hormone. It is FDA-approved specifically for the reduction of excess abdominal visceral adipose tissue (VAT) in HIV-infected adult patients with lipodystrophy 1, 2.
Key Points About Tesamorelin's Effects on Fat Distribution:
- Visceral vs. Subcutaneous Fat:
Clinical Evidence and Efficacy
In two 26-week phase 3 clinical trials:
- Tesamorelin reduced visceral adipose tissue by approximately 24 cm² (-15.4%) compared to placebo 3
- No significant changes were observed in abdominal subcutaneous adipose tissue (-2 cm² vs. 2 cm², p=0.08) 3
- Effects on visceral fat were maintained for up to 52 weeks in patients who continued treatment 3
- Discontinuation resulted in reaccumulation of visceral fat 4, 5
Treatment Considerations
Patient Selection
Patients most likely to benefit from tesamorelin include those with:
- HIV-associated lipodystrophy with excess abdominal fat
- Metabolic syndrome (particularly by NCEP definition)
- Elevated triglyceride levels (>1.7 mmol/L)
- White race 6
Administration
- Recommended dose: 1.4 mg (0.35 mL of reconstituted solution) injected subcutaneously once daily 1
- Injection site: Abdomen (rotate injection sites to minimize reactions) 1
Limitations
- Not indicated for weight loss management (weight neutral effect)
- Not indicated for treating subcutaneous fat loss (lipoatrophy)
- Long-term cardiovascular safety not established 1
- Effects reverse upon discontinuation 4, 5
Safety and Adverse Effects
Common adverse reactions include:
- Injection site reactions (17% vs. 6% with placebo)
- Arthralgia (13% vs. 11%)
- Peripheral edema (6% vs. 2%)
- Hyperglycemia (increased risk of developing diabetes, hazard ratio 3.3) 1
Contraindications
- Active malignancy
- Disruption of hypothalamic-pituitary axis
- Hypersensitivity to tesamorelin
- Pregnancy 1
Historical Context
HIV lipodystrophy is a complex condition characterized by fat maldistribution (both lipoatrophy and fat accumulation), often accompanied by metabolic abnormalities. Prior to tesamorelin, no clearly effective therapy for fat accumulation in HIV lipodystrophy was established 7. Discontinuation of antiretroviral medications or class switching generally did not result in substantial benefit for most patients 7.
Conclusion
For HIV patients with lipodystrophy characterized by excess abdominal fat, tesamorelin effectively reduces visceral adipose tissue but has minimal impact on subcutaneous adipose tissue. It should be considered specifically for patients troubled by increased abdominal visceral fat, not for those primarily concerned with subcutaneous fat loss.