Gilead’s injectable HIV prevention drug Yeztugo (lenacapavir) received FDA approval as the first twice-yearly PrEP medication, showing near-complete protection in large clinical trials across diverse populations. Pricing concerns persist for low-income countries. Concurrently, Merck initiated Phase 3 trials for an oral once-monthly PrEP candidate MK-8527, including trials supported by the Gates Foundation in sub-Saharan Africa. These advancements mark significant progress toward extended-duration HIV prevention agents expanding the PrEP arsenal globally.