Highlights
- Long-acting injectable PrEP options promise to enhance adherence and reduce daily pill burden.
- Expanding accessibility through innovative strategies is essential for increasing PrEP uptake globally.
Summary and Overview of PrEP
Pre-exposure prophylaxis (PrEP) involves antiretroviral medication use by HIV-negative individuals at high risk to prevent HIV infection. Since FDA approval of oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC, Truvada) in 2012, PrEP has become vital in HIV prevention. Alternative oral formulations and long-acting injectables like cabotegravir (CAB-LA) and lenacapavir (LEN-SQ) have expanded options, improving adherence and convenience. These long-acting agents require careful HIV testing to avoid drug resistance.
Despite multiple effective PrEP options, global uptake remains low—1.6 million users in 2021 versus a 10 million target by 2025—due to barriers like stigma, healthcare disparities, and regulatory challenges. Research is focused on increasing accessibility through telehealth, pharmacy-based delivery, and multipurpose prevention technologies combining HIV prevention with contraception. Coordinated global efforts are essential to scale up PrEP and reduce new HIV infections.
Recent Advances and Dosing Regimens
FDA-approved PrEP medications include oral TDF/FTC and tenofovir alafenamide/emtricitabine (TAF/FTC), plus injectable cabotegravir (every two months) and lenacapavir (twice yearly). Oral generics have improved access, while injectables address adherence challenges but require strict HIV-negative testing before administration. Side effects are generally mild, with injection site pain common for cabotegravir.
PrEP dosing options include daily oral use, on-demand regimens (e.g., IPERGAY trial showed 86% risk reduction), and long-acting injectables. Target populations are those at substantial HIV risk, such as men who have sex with men, people who inject drugs, and certain heterosexual groups in high-prevalence areas. Innovative delivery models like mobile programs, same-day initiation, and telehealth support improved uptake and persistence.
Safety, Efficacy, and Clinical Outcomes
PrEP is generally safe with manageable side effects. Oral regimens (TDF/FTC and TAF/FTC) provide substantial protection; TAF/FTC is noninferior to TDF/FTC in key populations. Long-acting injectables have demonstrated high efficacy—lenacapavir showed 100% protection in large trials involving African women. The dapivirine vaginal ring offers an effective alternative for women.
Clinical guidelines recommend daily oral PrEP for those at substantial risk, though adherence remains a challenge. Injectable PrEP requires regular HIV testing to prevent resistance. Strategies to improve adherence and clarify optimal dosing continue to evolve.
Population Impact and Barriers to Access
By 2024, about 40.8 million people lived with HIV globally, with 1.5 million new infections in 2021. U.S. PrEP users increased by 17% between 2023 and 2024, correlating with declines in new HIV diagnoses. However, stigma, discrimination, limited awareness, and insurance barriers limit equitable access, especially for marginalized groups. Frequent clinic visits and monitoring requirements pose additional adherence challenges.
Facilitators and Implementation Strategies
Effective interventions include mobile and telehealth PrEP programs, same-day initiation, reduced in-person visits, at-home HIV testing, and 90-day prescriptions. Provider education improves risk identification and PrEP provision. Technology and peer support enhance uptake among youth. Adherence counseling tailored to individual risk patterns promotes prevention-effective use.
Pharmacy-based PrEP services increase convenience and access. Telemedicine and online pharmacies support privacy and broader reach. Policy support, including insurance mandates, is crucial for affordability and expanded access.
Future Directions and Challenges
Long-acting injectables like lenacapavir and cabotegravir represent key future advances, supported by WHO-endorsed rapid HIV testing approaches. Research into multipurpose prevention technologies and improved dosing regimens continues. Regulatory developments show active drug approvals, though challenges remain in trial timelines and access equity.
Adherence issues and stigma persist as major barriers. Coordinated efforts among governments, healthcare providers, civil society, and manufacturers are essential to overcome these challenges, ensuring equitable PrEP access and maximizing its public health impact in reducing HIV incidence worldwide.
The content is provided by Harper Eastwood, Scopewires
