New real-world data presented this week at the HIV Drug Therapy Glasgow 2026 congress (November 8 to 11) suggest that, for most people, the twice-yearly HIV prevention shot is going well outside of clinical trials. But for the small group who stopped early, one factor stood out: injection-site reactions, such as pain and lumps under the skin, that were bothersome enough to make them call or message their clinic.

The shot is lenacapavir, sold in the United States as Yeztugo for HIV pre-exposure prophylaxis (PrEP). It is given under the skin every six months. Here is what the new findings show, how they fit with earlier real-world studies, and what it may mean if you are dating, on PrEP, or thinking about it.

What the Chicago study found

The poster (abstract P014) comes from clinicians at Howard Brown Health and the University of Chicago and is published in the HIV Glasgow 2026 abstract supplement of the Journal of the International AIDS Society. The team looked back at the health records of everyone who started lenacapavir PrEP at Howard Brown Health through June 15, 2026. According to the abstract:

• 310 people started lenacapavir PrEP, and 52 of them (17.4%) had completed their second injection visit by the end of the study period.
• 48 people (15.5%) had never used PrEP before. Compared with people switching from another PrEP method, first-time users were more likely to be cisgender women or nonbinary.
• 33 people (10.7%) had an injection-site reaction that led them to contact the clinic by phone, patient portal message or office visit. Most of these (24, or 72.7%) followed injections in the abdomen.
• 15 people (4.8%) stopped lenacapavir PrEP during follow-up. The only factor the researchers found linked to stopping was having an injection-site reaction that needed clinical contact.

The authors noted that 4.8% is still uncommon, but higher than the discontinuation rates reported in the PURPOSE 1 (0.2%) and PURPOSE 2 (1.2%) trials that led to the drug's approval. They concluded that "optimizing the injection experience" through patient-centred counselling and proactive management of injection-site reactions may be among the most impactful ways to help people stay on the shot.

It matches a larger multicenter study

The Glasgow poster echoes a larger study from many of the same researchers, published in Clinical Infectious Diseases. That study followed 501 people who started lenacapavir PrEP at 17 U.S. clinical programs between June 18 and December 31, 2025. It reported that:

• The median wait from prescription to first injection was 27 days. Needing a prior authorization from insurance added about 11.6 days.
• Injection-site reactions that prompted clinical contact happened in 72 people (14.4%), most often because of pain (43.1% of those reactions) or nodules (36.1%).
• Early stopping after the first injection was uncommon: 18 of 501 people (3.6%). All 18 had received the injection in the abdomen (5.3% of abdominal injections compared with 0% of thigh injections).
• Abdominal injection was also linked to higher odds of a reaction that needed clinical contact compared with thigh injection.

The researchers called injection-site selection a possibly "modifiable strategy" to improve tolerability. The U.S. prescribing information lists the abdomen as the injection area, with the thigh as an alternative. These were observational studies, so they show links, not proof of cause, and follow-up was short.

What people on the shot say

A third, smaller report, a research letter in the journal AIDS (2026, volume 40, issue 12), surveyed people at four U.S. community PrEP programs shortly after their first lenacapavir injection. Of 96 people who started the shot, 58 answered. Most (82.8%) chose it because they wanted to dose less often, and 79.3% said they were more satisfied with it than with their previous PrEP. At the same time, 77.5% reported at least one injection-site reaction, most often pain, swelling or nodules, and seven people (12.1%) said they did not plan to continue.

When asked what might make them stop, persistent nodules and pain were the most common answers. The authors wrote that several respondents described persistent nodules as cosmetically bothersome or as affecting intimacy. That detail matters for anyone dating: a lump you can feel can raise questions from a partner, even when it is an expected side effect. In the same survey, some people taking erectile dysfunction medicines (PDE-5 inhibitors) said they noticed a change in how those medicines worked after starting lenacapavir, which is one more reason to tell your clinician about every medicine you take.

Why this is news for people dating with HIV or on PrEP

• The shot is reaching new people. In the Chicago program, about one in six people starting lenacapavir had never taken PrEP before, including more cisgender women and nonbinary people. Wider PrEP use protects more partners.
• Side effects, not effectiveness, drove early stops. These studies were not designed to measure how well the shot prevents HIV. They show that comfort with the injection may decide whether people stay on it.
• Lumps are expected, and you can talk about them. Our explainer on how long PrEP shot lumps last covers what the label and CDC say about nodules, including how long they can last.
• Stopping has its own considerations. The prescribing information says lenacapavir can stay in the body for a long time after the last shot, which is why any change to your PrEP plan should be made with a clinician rather than by simply skipping an injection.

Questions to bring to your clinician

• Where will my injections go, and is the thigh an option for me?
• What can I do before and after the injection to manage pain or swelling?
• Which reactions should make me call the clinic, and how do I reach you?
• If the shot is not working for me, what other PrEP options do I have, and how do I switch safely?
• Could any of my other medicines, including erectile dysfunction medicines, interact with lenacapavir?

Keep the bigger picture in view

Twice-yearly PrEP is only one option. Daily pills, the every-two-months cabotegravir shot, condoms and U=U (undetectable equals untransmittable) all play a part, and our guide to layering protection with condoms, antivirals and PrEP explains how they fit together. PrEP also does not protect against other STIs, as we explain in what PrEP and DoxyPEP do not protect against. For an earlier look at how many people stay on the shot compared with daily pills, see our report on the PURPOSE 5 persistence data.

If you are in a mixed-status relationship, our guide to serodiscordant couples covers how partners combine treatment and prevention. And when you meet someone new, follow our first meetup safety checklist: meet in public, tell a friend your plans, and take conversations about sex and protection at a pace that feels right for both of you.

Frequently asked questions

Did these studies show the PrEP shot stopped working?

No. These studies looked at starting the shot, side effects and whether people continued. They did not measure how well it prevents HIV. In the approval trials described in the prescribing information, HIV infections on lenacapavir were rare.

How many people stopped the PrEP shot early in real-world care?

In the Chicago study presented at HIV Glasgow 2026, 15 of 310 people (4.8%) stopped. In the 17-site U.S. study, 18 of 501 (3.6%) stopped after their first injection. Both rates were higher than in the PURPOSE trials but still uncommon.

Are lumps from the PrEP shot dangerous?

Nodules are a known, common reaction listed in the prescribing information, and they can last for months. Tell your clinician about any reaction, especially one that is very painful, red, warm, open or getting worse.

Should I ask for the shot in my thigh?

The label lists the thigh as an alternative injection area, and these observational studies linked abdominal injections with more reported problems. Whether it is right for you is a decision to make with your clinician.

The bottom line

Early real-world data suggest the twice-yearly PrEP shot is working for most people who start it, and it is reaching some people who never used PrEP before. For the few who stop early, injection-site reactions are the main reason, which gives clinics and patients something concrete to work on. If you want to meet people who understand life with HIV and prevention choices, explore HIV dating on MeetPositives.

Sources

• Cherabie J, Schafer T, Crone A, Hazra A. "Injection-Site Reactions Drive Early Discontinuation of Lenacapavir for HIV PrEP in Real-World Clinical Practice." Abstract P014, HIV Glasgow 2026. Journal of the International AIDS Society 2026;29(Suppl 6):e70211.
• Hazra A, et al. "Real-World Implementation Outcomes of Lenacapavir for HIV Preexposure Prophylaxis: Early Findings From a Multicenter United States Cohort." Clinical Infectious Diseases, 2026.
• Hazra A, et al. "Early patient-reported outcomes and planned persistence with lenacapavir for HIV preexposure prophylaxis in routine clinical care." AIDS 2026;40(12):1912-1914.
• Yeztugo (lenacapavir) U.S. prescribing information, DailyMed, revised August 2026.

This article is for general information only and is not medical advice. It does not create a doctor-patient relationship. Talk with a licensed health care provider about your own situation. This article does not recommend or promote any product.