by Manuel Maidorn,Max Planck Society

Minimal susceptible-infectious-treated-susceptible model for CT transmission among high-risk MSM, influenced by HIV risk perception and PrEP uptake. Credit:Proceedings of the National Academy of Sciences(2025). DOI: 10.1073/pnas.2524944122

For several years, pre-exposure prophylaxis against HIV (PrEP) has been a major success in preventing new cases. However, individuals on PrEP typically engage in riskier sexual behavior and thus are more susceptible to acquiring other sexually transmitted infections (STIs).

To counteract this, people on PrEP have to regularly take mandatory tests for STIs such as chlamydia and gonorrhea. Surveillance evidence shows an increase in people infected with such STIs after initiating PrEP.

Now, a new modeling study provides a counterintuitive explanation revealing a testing paradox: even when the observed cases increase, the true numbers of STIs can decrease. The findings arepublishedin the journalProceedings of the National Academy of Sciences.

The researchers based their approach on a classical mathematical epidemiological model in which a person can be either susceptible to the disease, infected, or removed from the pool after recovery.

"A key point of the model is that it distinguishes between symptomatic and asymptomatic infections, allowing us to implement differential testing," explains Laura Mueller, one of the researchers leading the project.

"Regular testing for STIs can thus reveal a higher number of active infections, so we see more cases when we actually have fewer," Mueller continues.

Notably, theparadoxis even more likely to occur if the test frequency is increased, highlighting the benefit of testing.

The study demonstrates thatfrequent screeningfor STIs, as recommended in German PrEP programs, is a highly effective public health intervention. Their study shows that frequent screening can successfully reduce the spread of bacterial STIs, effectively counteracting potential changes in sexual behavior upon protection against HIV. Consequently, increasing reported numbers of people with STIs after HIV prophylaxis may be a paradoxical signal of its success, identifying previously hidden infections.

"Our research highlights thatHIV pre-exposure prophylaxisprograms can be a powerful and dual-benefit tool, but we need to be careful when evaluating them," concludes Seba Contreras, principal investigator of the project.

"As a rise in reported cases can also be a sign of success, surveillance data have to be interpreted carefully when taking public health decisions," he concludes.

The findings of the study can be useful for developing policies to monitor the progression and containment of sexually transmitted infections.

More information Laura Müller et al, Testing paradox may explain increased observed prevalence of bacterial STIs among MSM on HIV PrEP: A modeling study, Proceedings of the National Academy of Sciences (2025). DOI: 10.1073/pnas.2524944122 Journal information: Proceedings of the National Academy of Sciences

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