Back Back
GLP-1 RAs for People Living With HIV
The Ongoing Weight Debate: Using GLP-1 Receptor Agonists to Address Weight Gain in People Living With HIV

Released: November 08, 2023

Darcy Wooten
Darcy Wooten, MD, MS
Activity Information

Activity

Progress
1
Course Completed
Key Takeaways
  • Most studies show that switching ART regimens does not ameliorate weight gain, except for the CHARACTERISE study, which reported that women who switched from DTG + FTC/TAF to TDF/3TC/DTG lost weight.
  • GLP-1 RA therapy is effective for weight loss in people living with HIV, although the accompanying loss of lean muscle mass raises concerns, particularly among aging people living with HIV and those experiencing frailty.

People living with HIV continue to live longer, in large part because of continued developments and improvements in antiretroviral therapy (ART). Simultaneously, a substantial number of people living with HIV experience weight gain after starting ART and certain medications. Of note, dolutegravir (DTG) and bictegravir (BIC) have been associated with substantial weight gain in some studies. Additionally, tenofovir alafenamide (TAF) has been associated with more weight gain than tenofovir disoproxil fumarate (TDF). Data from some studies suggest that worse metabolic outcomes, such as cardiovascular disease and diabetes, may be associated with this weight gain.

ART Switch Studies to Address Weight Gain
Several studies have been conducted to determine whether switching ART regimens can address weight gain once it has occurred (Table). Unfortunately, the vast majority of switch studies have not demonstrated improvement in weight outcomes. The one exception comes from the CHARACTERISE study, which showed that women who switched from DTG + emtricitabine (FTC)/TAF lost weight when they were switched to TDF/lamivudine (3TC)/DTG. While we are awaiting results from the DO IT trial, which is comparing weight and metabolic outcomes among patients who are switched from an integrase strand transfer inhibitor (INSTI)‒containing regimen to a doravirine (DOR)‒containing regimen, alternative strategies are acutely needed to help patients manage weight gain.

GLP-1 RAs for Weight Management
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are incretin-based therapies for diabetes and weight management that improve glycemic control and can lead to substantial weight loss. Two studies at IDWeek 2023 evaluated the impact of GLP-1 RAs on weight and other metabolic outcomes in people living with HIV.

In a retrospective cohort study, Nguyen and colleagues showed that patients receiving a GLP-1 RA for an average of 15 months experienced a mean weight loss of 5.4 kg. Patients with a higher baseline weight and those receiving a GLP-1 RA for a longer duration achieved significantly more weight loss in the multivariable analysis.

McComsey and colleagues presented the first randomized, controlled trial of the GLP-1 RA semaglutide compared with placebo in people living with HIV. Not surprisingly, patients receiving semaglutide had significantly more weight loss and a greater decrease in visceral fat compared with placebo. Of interest, those who took semaglutide also had significantly more lean muscle mass loss and a greater decrease in subcutaneous fat. This raises concerns about the impact of muscle loss with semaglutide, particularly among aging patients and those experiencing frailty. The loss of subcutaneous fat also raises concerns about the development or worsening of lipoatrophy.

Additional prospective studies are underway to better understand the risks and benefits of GLP-1 RAs in people living with HIV, including the SWIFT trial, which will compare the impact of semaglutide vs semaglutide coupled with lifestyle modifications on weight and metabolic outcomes.

In summary, there are limited pharmacologic options to manage weight and weight gain among people living with HIV. The available options with supporting data (switch from a TAF-based to TDF-based regimen, use of GLP-1 RAs) are not without potential adverse events. While we await additional data to better understand these strategies, healthcare professionals can take a patient-centered approach and individualize treatment with patients by reviewing the risks and benefits and prioritizing what is most important to the patient in front of them.

Table. Summary of Stable Switch Studies and Impact on Weight in People Living With HIV

Your Thoughts?
Are you recommending GLP1-RAs to manage weight for people living with HIV on ART? See more studies from IDWeek and EACS 2023, and get involved by posting a comment below.