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Cardiometabolic Considerations

CE / CME

Individualizing ART With Cardiometabolic Considerations

Nurses: 0.75 Nursing contact hour

Pharmacists: 0.75 contact hour (0.075 CEUs)

Physicians: maximum of 0.75 AMA PRA Category 1 Credit™

Released: July 10, 2024

Expiration: July 09, 2025

Grace A McComsey
Grace A McComsey, MD
CME/CE Information

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Now we return to our case for a follow-up visit 2 years later. She is still on the same dolutegravir plus TAF/FTC regimen and is tolerating it well. Her viral load is undetectable and her CD4 cell count is maintained at >500 cells/mm3.

This is the good scenario that we see mostly in clinic now. However, there are a few items she would like to discuss. Her weight has increased by 5% from baseline and she talks to you about semaglutide, which she saw on a TV commercial. She would like to shed the weight.

She also heard about CV risk from a male friend living with HIV. She wonders if she needs to be concerned about CV risk as a woman or if she is protected. Our electronic medical record system calculated her CVD risk score or her chance of having a major CV event in the next 10 years to be 4%.

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Cardiometabolic Complications of ART-Associated Weight Gain

Why should we even care about weight gain? Isn't it just cosmetic? What if this woman was happy that she gained some weight? Is that something that we should worry about?

First, I want to make the point that weight gain is not just a cosmetic issue. We should consider the cardiometabolic consequences of weight gain, in particular the diabetes and CV risks.8,9  For example, studies show that people who gain 5% or more in the first 6 months of ART have an increased risk of diabetes.10

I think the data with cardiovascular disease (CVD) associated with the weight gain is lagging behind because a longer follow-up is needed to be able to see long-term clinical outcomes such as CVD. Nonetheless, diabetes risk increases with the weight gain after ART and so it is more than just a cosmetic issue.

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Effects of Semaglutide on Adipose Tissue in HIV-Associated Lipohypertrophy

How should we address the women’s question about semaglutide? Do we have any data on this glucagon-like peptide-1 (GLP-1) receptor agonist (RA) in HIV?

In this recently presented study, we assessed the effects of semaglutide on adipose tissue in HIV-associated lipohypertrophy.11 It is a randomized controlled trial—the first such study in people living with HIV—in 108 people with an undetectable viral load, on a stable regimen, who had a BMI of at least 25 and lipohypertrophy. Participants had increased abdominal circumference, an indirect marker of increased visceral fat in the abdomen that causes a lot of cardiometabolic consequences. These patients with controlled HIV were randomized to receive either semaglutide or placebo.

The study was designed with a lead-in phase to allow people to adjust to the medication because they may initially have nausea and vomiting. We slowly escalated the dose from 0.25 mg once/week for 4 weeks, to 0.5 mg once/week for another 4 weeks, before they started on 1 mg/week for 24 weeks. All doses were administered in the clinic as subcutaneous injections. This is one study where adherence was totally accounted for.11

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Changes in Weight, BMI, Total Fat, and Total Lean Mass

We found that even after a short term of 32 weeks of semaglutide administration, there were significant differences in weight, BMI, total fat, and total lean mass. There were changes in visceral fat as well as in subcutaneous adipose tissue.11

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Semaglutide vs Placebo: Changes in Weight, BMI, Total Fat, and Total Lean Mass

When I presented this data, I warned about 2 things that we should keep in mind that are specific to HIV.

First, we saw a decrease in total lean mass.11 This is not something that we want to see in our patients. Our patients with HIV have sarcopenia and they lose muscle mass compared with people having the same demographics but who do not have HIV. Therefore, seeing lean mass decrease may be concerning and something to watch in future longer studies with GLP-1 RAs.

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Effects of Semaglutide on Adipose Tissue in HIV-Associated Lipohypertrophy: Other Findings and Concerns

The second thing to keep in mind is the limb fat or peripheral fat. In the past, when we used the older antiretroviral drugs such as stavudine and zidovudine, we saw a lot of a complication called lipoatrophy, which many older people living with HIV still have. When we give this population semaglutide, we are happy about shrinking visceral abdominal fat, but we must also worry about worsening the lipoatrophy in the legs and the arms due to peripheral fat loss.

For this reason, lipoatrophy and muscle loss are 2 things that we must closely watch in people living with HIV. More studies with GLP-1 RAs are needed to evaluate these outcomes long-term and to determine whether these medications are good to give our patients.11

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ACTG A5371/SLIM LIVER Study: Semaglutide for MASLD in People Living With HIV

Semaglutide was also evaluated for treatment of metabolic dysfunction–associated steatotic liver disease (MASLD) in the ACTG A5371/SLIM LIVER Study in 51 people living with HIV on suppressive ART.

This was a single-arm, open label study with no control and no placebo. Study participants had waist circumferences of ≥94 cm (females) or ≥95 cm (males). They had no diabetes but had prediabetes or insulin resistance, and fatty liver as defined by ≥5% intrahepatic triglycerides on MRI-PDFF.

Participants were given semaglutide 0.25 mg for 2 weeks, then 0.5 mg for 2 weeks, and then 1 mg weekly for 20 weeks.12 Overall, this study was shorter in duration than our study.

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ACTG A5371/SLIM LIVER Study: Participant Characteristics and Primary Outcome

Nonetheless, the findings were impressive for a single-arm short study. More than 30% of participants had a reduction in their intrahepatic triglyceride. Total resolution of MASLD, defined as a reduction in intrahepatic triglyceride to less than 5%, occurred in 29%.12 Therefore, semaglutide seemed to be a good strategy to reduce both visceral and hepatic fat.

As I mentioned earlier, further studies are needed to assess safety, muscle wasting, and peripheral fat—as well as longer term effects and the durability of the effect—but semaglutide is a therapy that we can now offer to select patients.

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