GLP-1 Use in HIV, Innovations in STI Treatment Take Center Stage

Laughs rang out from around the packed auditorium as Jeanne Marrazzo, MD, MPH, CEO of the Infectious Diseases Society of America, declared syphilis to be “my favorite infection, depending on where I am and who I’m talking to,” on the second morning of the Conference on Retroviruses and Opportunistic Infections (CROI) 2026. The levity kept the talks grounded, as experts began the day with important lectures on how glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may play a part in HIV care and the status of sexually transmitted infections (STIs) in an era where control has started to wane.

Are GLP-1s Worth the Hype for HIV?

Todd T. Brown, MD, PhD, a clinical investigator at Johns Hopkins Medicine, started the day expressing excitement that endocrinology had finally “hit the big time here at CROI.”

“With the exception of antiretroviral therapy, I can’t think of another class of medications where there has been so much buzz…. Even if you’re not taking these medications, even if you’re not prescribing these medications, buzz about these medications really is everywhere,” said Brown.

GLP-1, he said, has effects on insulin secretion and inhibits glaucochroites. With each injection, the medication helps the beta cell to increase insulin release in the pancreas and works with alpha cells to suppress glucose production. GLP-1 RAs are showing efficacy in a variety of areas, most notably in treating diabetes and obesity but also in cardiovascular areas, chemical dependency, and nonalcoholic fatty liver disease, among other areas.¹

Brown highlighted how, along with GLP-1 RAs’ efficacy in diabetes, they have significant positive effects on obesity and its related conditions as well. “All of these drugs, after approval, go through a large cardiovascular outcomes trial, and most of them have shown significant decreases in cardiovascular events,” explained Brown.

Adverse events are being reported in these trials, including nausea, vomiting, and diarrhea, which necessitates that these medications are first given at a low dose and then increased over time. Other areas of research for GLP-1 RAs are in aging, reproductive health, and the treatment of substance use disorders.

When it comes to HIV specifically, said Brown, chronic inflammation is being looked into as a potential target of GLP-1 RAs. “They have very significant effects on markers of systemic inflammation like CRP [C-reactive protein], with about a 50% reduction in CRP, which happens even before people lose weight. And looking at the decrease in weight in glucose, it really only accounts for somewhere between 20% and 60% of the reduction. So, there must be some additional effects, and the mechanisms are varied,” Brown said.

Understanding the future of GLP-1 RAs in HIV care requires research into how people with HIV respond to the use of these drugs, whether they can truly help attenuate inflammation, and whether comorbid conditions that are common in HIV, such as cardiovascular disease and prediabetes, can be adequately treated with GLP-1 RAs.

“Is our exuberance regarding GLP-1 RAs rational or irrational? I’d say it’s rational,” Brown concluded. “This class of medications has really transformed the way that we treat multiple diseases, and we really are just at the beginning of this transformation.”

STI Incidence Has Climbed, but New Treatments Offer Hope

Marrazzo took the stage to warm applause from the audience as she focused on the increased incidence of STIs around the world, even as progress toward HIV control is seeing some improvement. Cases of gonorrhea, syphilis, and congenital syphilis have increased by 37%, 155%, and 696% since 2015, whereas cases of chlamydia have only decreased by 1%. However, Marazzo noted that there has been a slope downward in the past couple of years, which should give a glimmer of hope.

When it comes to syphilis, 31% of all primary and secondary cases were in men who have sex with men, but prevalence in women is starting to creep up, with 29% of new cases in 2024. This trend is also being seen in Europe as well.

The diagnosis and management of syphilis is a prominent challenge in being able to treat the virus. “We’ve been using the same diagnostic approach since well before I was born, in fact since before many of you were born in this audience, and that’s saying a lot,” joked Mazzarro to laughter from the room. “I love you all, you know that, but we are getting long in the tooth.”

Doctors cannot distinguish treatment failure from reinfection, which is a big challenge. Some cases, said Mazzarro, may not be diagnosed for 6 months until a biopsy is performed. If sexual history is not provided, it can lead to misdiagnosis for these patients. A vaccine is also difficult because the virus is a complicated organism that makes it hard to pin down. Patients with primary syphilis and early latent syphilis have shown success with 1 dose of penicillin G rather than 3 doses, which should encourage smart uses of the treatment.

Mazzarro also highlighted doxycycline prophylaxis (DoxyPEP) as a promising medication to prevent STIs. Early data from San Francisco² have shown that DoxyPEP was able to reduce the incidence of chlamydia and syphilis among men who have sex with men and transgender women. With some currently ongoing studies showing a decrease in syphilis incidence when using DoxyPEP, the preventive method can also help women who have sex with men who have sex with men.

Durable immunity through vaccines is the goal, which makes DoxyPEP a medium-term solution for syphilis, said Mazzarro. She acknowledged that everyone wants a magic pill that can help women avoid contracting viruses that spread more commonly in men.

“No pill, in my opinion, can provide the freedom and power that most cisgender men have had to pursue the sex that they want… Cisgender women do not have that privilege; do not have, in general, that power. So until we consider this power imbalance, I really think the potential for any intervention is going to be difficult,” she concluded to applause.

References

1. Allen K, Lovoy P, Bulloch MN. Five unexpected new uses for GLP-1 receptor agonists. Pharmacy Times. 2024;13(3):26-30.
2. Sankaran M, Glidden DV, Kohn RP, et al. Doxycycline postexposure prophylaxis and sexually transmitted infection trends. JAMA Intern Med. 2025;185(3):266-272. doi:10.1001/jamainternmed.2024.7178