Transition From Oral to Long-Acting Injectable Preexposure Prophylaxis: Comparative Levels of Cabotegravir, Tenofovir, and Emtricitabine in Plasma and Seminal Fluids

Background: Although oral preexposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) is highly effective for individuals whose sexual activities place them at high risk for HIV infection, it is limited by adherence. Long-acting injectable cabotegravir (CAB-LAI) offers an alternative, but limited data are available on its distribution in seminal fluid (SF), a key vector for sexual HIV transmission. In this study, the pharmacokinetics of antiretrovirals in the blood plasma (BP) and SF of HIV-negative men who have sex with men during the transition to CAB-LAI were characterized. Methods: Forty-four men who have sex with men initiated on CAB-LAI at San Raffaele Hospital (January–May 2025) were enrolled. At baseline (T0), 23 of the participants were on daily TDF/FTC, 18 were on event-driven TDF/FTC, and 3 were PrEP naïve. Oral PrEP users continued TDF/FTC for 7 days after the first injection. BP and SF samples were collected at 0 (T0), 7 (T1), 30 (T2), and 90 (T3) days after injection. The drug levels were quantified using liquid chromatography-tandem mass spectrometry. HIV testing was performed longitudinally. Results: At T0, the median TDF levels were 31 ng/mL in BP and 152 ng/mL in SF, whereas the median FTC levels were 79 ng/mL in BP and 676 ng/mL in SF. At T1, both drugs remained detectable in fewer participants, with consistently higher levels in SF. By T2, both drugs had largely decreased in level, with isolated detectable cases, and neither drug was measurable at T3. The median BP CAB concentration was 1844 ng/mL at T1, with 80% of the men exceeding the protective 664 ng/mL threshold. This proportion remained high at T2 (77.3%) and T3 (60.6%). By contrast, the SF CAB concentrations were approximately 100-fold lower. Conclusions: Most participants achieved BP-protective CAB levels within 1 week, confirming sustained efficacy. However, CAB was often below the detection limit in SF.