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Tesamorelin Improves Fat Quality Independent of Changes in Fat Quantity
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Download the PDF here
Reported by Jules Levin
CROI 2018 - March 4-7, Boston, Massachusetts
JE Lake1, KM Erlandson2, S Adrian2, A Sanyal3, A Scherzinger2, MP Dubé4, T Stanley5, S Grinspoon5, JC Mamputu6, C Marsolais6, TT Brown3 and GA McComsey7
1University of Texas Health Science Center, Houston, TX USA; 2University of Colorado, Aurora, CO; 3Johns Hopkins University, Baltimore, MD;
4University of Southern California, Los Angeles, CA; 5Harvard Medical School, Boston, MA; 6Theratechnologies, Montreal, Canada; 7Case Western Reserve University, Cleveland, OH
Abstract abstract:
Fat quality may contribute to metabolic disease and inflammation as much or differently than fat quantity. HIV-infected (HIV+) adults have multiple risk factors for fat dysfunction, including HIV and antiretroviral therapy (ART). Both visceral (VAT) and subcutaneous (SAT) fat quality can be measured on computed tomography (CT) by measuring fat density (greater density=smaller, better quality adipocytes). Tesamorelin, a growth hormone-releasing hormone analogue, reduces VAT quantity in some HIV+ adults with central adiposity, but its effect on fat density is unknown.
Participants were selected from two completed, randomized (2:1) trials of tesamorelin vs placebo for the treatment of central adiposity in HIV+ adults. Included participants had a clinical response to tesamorelin (defined as a VAT area decrease ≥8%, ≈70% of tesamorelin-treated participants) or were randomized to placebo. Week 0 and 26 abdominal (L4-5) CT scans were re-analyzed for VAT and SAT density (in Hounsfield Units, HU) by a central lab blinded to treatment arm. Paired t tests and linear regression models assessed 26-week, between-group differences in fat density changes.
Participants (193 responders, 148 placebo) were mostly male (87%) and Caucasian (83%). Arms were similar (p>0.10) at baseline in regards to sex, race/ethnicity, age, adiposity, concomitant medications, CD4+ T-cell count, HIV-1 RNA, ART, and time since HIV diagnosis. Baseline mean VAT and SAT HU were -91 and -94 in the tesamorelin arm, and -91 and -95 in the placebo arm (SAT p=0.29, VAT p=0.80). Over 26 weeks (Fig.), mean (SD) VAT density increased 6.2 (8.7) HU in the tesamorelin arm vs 0.3 (4.2) HU for placebo (p<0.0001). The effect was attenuated but persisted after controlling for baseline VAT HU and area, and VAT area change (2.3 HU, 95% CI [4.5, 7.3], p=0.001). Mean (SD) SAT density increased 4.0 (8.7) HU in the tesamorelin arm vs 0.3 (4.8) HU for placebo (p<0.0001), with no significant attenuation of effect after controlling for baseline SAT HU and area, and SAT area change (3.5 HU, 95% CI [2.3, 4.7], p<0.001).
In HIV+ adults with central adiposity who responded to tesamorelin, VAT and SAT density increased independent of changes in fat quantity. These findings suggest that tesamorelin improves VAT and SAT quality in HIV+ adults in addition to reducing VAT quantity. Additional studies will determine whether these changes in fat density are associated with improvements in cardiometabolic and inflammatory parameters.
References
1N Engl J Med. 2007 Dec 6;357(23):2359-70.
2Clin Infect Dis. 2012 Jun;54(11):1642-51.
3Dietary and Hormonal Factors Involved in Healthy or Unhealthy Visceral Adipose Tissue Expansion, Adiposity - Epidemiology and Treatment Modalities. DOI: 10.5772/65927.
4J Gerontol A Biol Sci Med Sci 2014;69:109-17.
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