Body Composition and Adipose Tissue in HIV

HIV lipodystrophy is increasingly recognized as a common and clinically significant long-term sequelae of HIV treatment. In the HIV lipodystrophy lipohypertrophy phenotype, visceral adipose tissue (VAT) is increased and this is associated with reduced growth hormone (GH) secretion. Mounting evidence also links this phenotype with dyslipidemia, insulin resistance, subclinical atherosclerosis and cardiovascular (CV) disease in patients with HIV disease. The etiology of HIV lipodystrophy (HIVLD) with central adiposity is unclear, but this phenotype is increasingly common with newer, less lipotoxic combination anti-retroviral therapy (cART) use. VAT and hepatic lipid accumulation, are important health concerns for HIVLD patients. This body composition pattern may contribute to the increased cardiovascular risk that has been demonstrated in patients with HIV lipodystrophy. Patients with HIVLD and central adiposity have been shown to have reduced GH secretion. Thus, a medication has been developed to augment GH secretion. This medication is tesamorelin. GH supplementation in other clinical settings has been shown to reduce visceral adiposity and may reduce hepatic lipid content.

• Tesamorelin (Drug), also known as Egrifta: Patients will be treated with tesamorelin 2 mg by subcutaneous injection daily

Primary outcomes

• Hepatic Lipid Content [Baseline]: Hepatic lipid content (percent) will be measured by abdominal magnetic resonance imaging (MRI).

Secondary outcomes

• Visceral Adipose Tissue (VAT) Mass [Baseline]: Visceral adipose tissue mass (kilograms) will be measured by abdominal MRI.
• Change in Relative Gene Expression of CD68 Gene [Baseline and 12 months]: Relative gene expression of CD68 gene in adipose tissue
• Change in Relative Gene Expression on TNF-alpha Gene [Baseline and 12 months]: Relative gene expression of tumor necrosis factor (TNF)-alpha gene in adipose tissue
• Change in Resting Energy Expenditure (REE) [Baseline and 12 months]: Resting metabolic rate measured by indirect calorimetry

Sex: All, ages: 18 Years to 68 Years

Inclusion Criteria:

* HIV-infected subjects with HIV lipodystrophy (HIVLD)
* Abdominal fat accumulation defined as: Waist Circumference (WC) 102 cm for men, 88 cm for women, except in subjects of East/South Asian ethnicity in whom this will be defined by WC 90 cm for men and 80 cm for women.
* Weight stable for 8 weeks prior to enrollment,
* CD4 count >100 cells/mm3
* HIV RNA load <1000 copies/mL
* Fasting plasma glucose <120 mg/dL
* Stable combination anti-retroviral therapy (cART) of any regimen for ≥ 8 weeks prior to study enrollment

Exclusion Criteria:

* Diabetes mellitus requiring medication
* History of any malignancy
* Abnormal renal or liver function
* Pregnancy or women of childbearing age who are not using an acceptable means of contraception
* History disorder of the hypothalamic-pituitary axis due to hypophysectomy, hypopituitarism or pituitary tumor/surgery
* Head irradiation or head trauma or adrenal insufficiency
* Systemic glucocorticoid use
* Known hypersensitivity to tesamorelin and/or mannitol

Participant flow

Outcome results

• Hepatic Lipid Content (Primary), Number, percent of liver volume: Tesamorelin 7
• Visceral Adipose Tissue (VAT) Mass (Secondary), Number, kilograms: Tesamorelin 6.7
• Change in Relative Gene Expression of CD68 Gene (Secondary)
• Change in Relative Gene Expression on TNF-alpha Gene (Secondary)
• Change in Resting Energy Expenditure (REE) (Secondary)

Adverse events

Time frame: Baseline visit (1 day)

• Study Protocol and Statistical Analysis Plan (PDF, 2021-11-10)

• Pamela U. Freda, MD, Principal investigator, Columbia University

NIH grants: R01DK110771