Comparative Effectiveness of Daily Oral and Long-acting Injectable Prep: A Critical Review of Clinical Evidence and Public Health Implications.

The Human Immunodeficiency Virus (HIV) is the cause of Acquired Immunodeficiency Syndrome (AIDS). Preexposure Prophylaxis (PrEP) antiretroviral drugs to prevent HIV-1 infection are currently available in many countries. In Brazil, the recommended and approved regimen for PrEP is a daily Fixed-Dose Combination (FDC) tablet of Tenofovir Disoproxil Fumarate (TDF) with Emtricitabine (FTC) (300/200 mg), marketed as Truvada®. However, adherence to daily oral pill regimens remains one of the greatest challenges for the successful use of PrEP. Therefore, a Long-Acting Injectable (LAI) PrEP regimen, such as Cabotegravir (CAB), could significantly improve adherence to prophylaxis. The aim of this study was to compare the use of PrEP with TDF+FTC and the long-acting injectable cabotegravir, as well as to examine the mechanisms of action of the drugs involved in PrEP. In fact, the results confirmed the safety and efficacy of the use of CAB as an LAI PrEP. In June 2025, the FDA approved the use of LEN for PrEP, and it is expected that other regulatory agencies will follow suit by the end of the year. Emerging strategies under development include annual LEN formulations, the use of broadly Neutralizing Antibodies (bNAbs), and the Dapivirine Vaginal Ring (DPV), which has demonstrated greater convenience and improved adherence among pregnant women compared to oral PrEP. Additionally, digital monitoring tools are being explored, although their effectiveness relies on the implementation of equitable health policies. Thus, integrated prevention models that combine biomedical innovations with community-based interventions emerge as essential to expanding the reach and impact of PrEP.