Dr. Christian Marsolais reports

THERATECHNOLOGIES IDWEEK PRESENTATIONS HIGHLIGHT THE IMPACT OF EXCESS VISCERAL ABDOMINAL FAT (EVAF) ON CARDIOVASCULAR DISEASE (CVD) RISK IN PEOPLE WITH HIV

Theratechnologies Inc. today released data from two poster presentations, focusing on the association between excess visceral abdominal fat (EVAF) and cardiovascular disease (CVD) risk in people with HIV (PWH), and on the use of tesamorelin to reduce such risk.

In a poster presentation at IDWeek 2024 in Los Angeles, Calif., investigators from the Visceral Adiposity Measurement and Observations Study (VAMOS) reported that EVAF is one of several risk factors that contribute to heightened CVD risk in PWH who are on modern anti-retroviral therapy (ART) regimens. In a separate poster presentation, researchers demonstrated that the EVAF-lowering properties of tesamorelin, a growth hormone-releasing factor (GHRF), enable a reduction in CVD risk in PWH.

"The two studies presented at IDWeek 2024 suggest that excess visceral abdominal fat is an overlooked risk factor for cardiovascular disease in people with HIV, and that use of tesamorelin for visceral abdominal fat reduction may contribute to lowering cardiovascular disease risk," said Christian Marsolais, PhD, senior vice-president and chief medical officer of Theratechnologies. "We hope greater awareness of EVAF, and of strategies to address this risk factor, lead to improved outcomes in people with HIV being treated with ART medicines."

VAMOS data

VAMOS, a cross-sectional, multicentre observational study, is the first trial designed to improve the understanding of the impact of EVAF on CVD, steatotic liver disease, insulin resistance and other metabolic parameters in PWH who are on modern ART regimens. The investigators examined the impact of EVAF (defined as visceral fat surface area greater than equals 130 square centimetres by CT scan) on traditional CVD risk factors and overall cardiovascular (CV) risk in 170 participants with HIV. The prevalence of EVAF in the study was 58 per cent, and the mean visceral fat area was 148 square cm. Among participants with EVAF, values for the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR; p less than or equal to 0.0001) and triglyceride: high-density lipoprotein (TG:HDL) ratios (p equals 0.0013) were higher than in those without EVAF. Investigators noted a positive correlation between EVAF and HOMA-IR (rho equals 0.43, p less than or equal to 0.0001) and TG:HDL ratios (rho equals 0.33, p less than or equal to 0.0001).

Importantly, greater EVAF was associated with a higher 10-year atherosclerotic cardiovascular disease (ASCVD) risk (p less than or equal to 0.0001). The investigators also found that increasing visceral fat surface area was inversely associated with growth hormone (GH) levels (rho equals negative 0.17, p equals 0.03), and that participants with EVAF had lower GH levels overall (p equals 0.05).

"Excess visceral abdominal fat, or EVAF, is the key characteristic of central adiposity, a condition that is still prevalent in today's population of people living with HIV, even among those who were never exposed to earlier anti-retroviral agents," commented VAMOS investigator, John Koethe, MD, associate professor of medicine at Vanderbilt University. "As the quantity of visceral fat rises, 10-year ASCVD risk scores increase, as well as traditional risk factors including insulin resistance and lipid levels. Together, these factors contribute to the heightened risk of cardiovascular disease we see in people with HIV, which is a particular concern among aging individuals. Additionally, the relationship we observed between EVAF and decreased growth hormone levels appears to support a focus on the growth hormone axis to impact EVAF."

Tesamorelin CV risk data

Researchers examined data from two phase 3 randomized studies to assess the impact of tesamorelin-induced reduction of EVAF on CVD outcomes in 543 PWH. They calculated 10-year ASCVD risk scores for participants at baseline and at 26 weeks of tesamorelin treatment. The percentages of participants on lipid-lowering therapies, antihypertensive treatment or diabetes medications were 44 per cent, 37 per cent and 18 per cent, respectively.

Although most participants had low CVD risk at baseline, 44 per cent had borderline to high CVD risk. Participants on tesamorelin tended toward a modest reduction in 10-year ASCVD risk scores, with an estimated change of negative 0.4 per cent (95-per-cent confidence interval [CI] negative 0.89 per cent, 0.05 per cent). The reduction in CVD risk was relatively larger among subjects with higher CVD risk at baseline (p equals 0.038 for the overall trend among all participants). These reductions in ASCVD risk scores were driven primarily by reductions in total cholesterol, independent of lipid-lowering therapies.

"Our analysis provides evidence that tesamorelin may contribute to a reduction in forecasted cardiovascular disease risk in persons with HIV, particularly among individuals at the highest baseline risk," stated investigator Lindsay Fourman, MD, Massachusetts General Hospital and Harvard Medical School. "Given the high prevalence of obesity and central adiposity in this population, a strategy that selectively reduces excess visceral abdominal fat may be particularly effective in CVD risk management."

IDWeek 2024, taking place Oct. 16 to Oct. 19, is the joint annual meeting of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, the Pediatric Infectious Diseases Society and the Society of Infectious Diseases Pharmacists.

About Theratechnologies Inc.

Theratechnologies is a biopharmaceutical company focused on the development and commercialization of innovative therapies addressing unmet medical needs.

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