Post-exposure prophylaxis-in-pocket (PIP) was associated with healthcare savings and improved quality of life outcomes compared to pre-exposure prophylaxis (PrEP), based on data presented at Conference on Retroviruses and Opportunistic Infections (CROI) 2026 Annual Meeting.

Although daily PrEP is effective for HIV prevention, treatment gaps remain for individuals reluctant to start PrEP, or those whose infrequent exposures (defined as one to four per year) make them less than ideal candidates for PrEP, wrote Mia E. Sapin, MS, an epidemiologist at the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada, now with the Nova Scotia Health Authority, and colleagues.

PIP offers an alternative strategy in the form of a 28-day course of HIV medication for low-risk individuals to keep at home and initiate if needed. PIP is now endorsed by the World Health Organization and allows individuals to start treatment themselves within 72 hours of exposure, eliminating the need for an emergency department or clinic visit. However, real-world data comparing PIP to standard PrEP are lacking, the researchers noted.

In a matched control study, the researchers compared PIP and PrEP in terms of sexually transmitted infections (STIs), healthcare costs, and quality of life. The study population included 32 PIP users prospectively recruited from hospitals and health clinics who were matched with up to two daily PrEP users with similar age and HIV risk who were enrolled in the Ontario PrEP Cohort Study (61 individuals).

The researchers assessed HIV risk using an adapted HIV Incidence Risk Index for Men who have Sex with Men (HIRI-MSM) score. The median age of the participants was 40 years, and the median HIRI-MSM score was 10 in the PIP group and 11 in the PrEP group.

Over a median follow-up of 15 months (12-28 months), 22% of PIP users and 38% of PrEP users developed STIs; no HIV seroconversion occurred in either group. In terms of healthcare costs, PIP use was associated with an annual savings of up to $1488 per person (95% CI, $1137-$1747). In addition, the researchers assessed psychological outcomes based on changes in HIV-related anxiety and sexual satisfaction in PIP vs PrEP users. The difference was not significant (P = .66), but PIP participants showed a slight tendency toward better psychological outcomes, with 32% and 29% (PIP vs PrEP) moving to a higher outcome category based on proportional odds models.

Added Value in Cost and Effectiveness

“Daily PrEP is highly effective, but not everyone has frequent HIV exposures,” said Jason E. Zucker, MD, assistant professor of medicine at Columbia University Irving Medical Center, New York City. “PIP offers a postexposure option for individuals with intermittent risk, but real-world data comparing PIP with daily PrEP have been limited, and the current study evaluated effectiveness, STI outcomes, psychological impact, and costs in routine practice,” said Zucker, who was not involved in the study.

However, it is important to note that the current study did not include 2-1-1 on-demand PrEP, he said.

The current study found no HIV seroconversions in either group, reinforcing the effectiveness of both PrEP and PIP, said Zucker. The study was not randomized, so confounding is possible, he noted. Other limitations include the modest sample size and self-reporting of outcomes, he added.

However, the results were reassuring overall, with a takeaway that HIV prevention should be individualized, Zucker told Medscape Medical News. “For patients with infrequent exposures, PIP may be a reasonable and potentially less costly alternative to daily PrEP,” he said. However, STI screening remains essential regardless of strategy, he emphasized.

“Future studies should directly compare daily PrEP, 2-1-1 PrEP, and PIP, with larger samples and longer follow-up,” he said.

This study received no outside funding. The researchers disclosed no financial conflicts of interest. Zucker disclosed having no financial conflicts of interest.