This study offers a critical reexamination of the criminalization of HIV transmission and raises a fundamental question: in the modern era—marked by effective strategies such as pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP)—can strict penal policies still be justified? Our central claim is that these scientific developments, particularly the principle of undetectable equals untransmittable (U=U), have destabilized the traditional foundations of criminal responsibility and rendered the proof of mental elements such as intent and recklessness increasingly problematic. For instance, in cases like Neill in Australia, the court overturned the defendant’s conviction based on an undetectable viral load, illustrating that contemporary medical science no longer aligns with outdated criminal law concepts. Ultimately, we conclude that criminalization is not only ineffective but also contrary to justice and conducive to social stigma. Therefore, the future of penal policy should rest upon the pillars of science, prevention, and human dignity.