What is the recommended post-exposure prophylaxis (PEP) regimen for Human Immunodeficiency Virus (HIV) after anal sex?

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Last updated: June 10, 2025View editorial policy

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From the Guidelines

The recommended post-exposure prophylaxis (PEP) regimen for HIV after anal sex is a 28-day course of three antiretroviral medications, typically consisting of tenofovir disoproxil fumarate (TDF) 300mg plus emtricitabine (FTC) 200mg once daily, combined with either dolutegravir 50mg once daily or raltegravir 400mg twice daily, as recommended by the 2016 guidelines of the International Antiviral Society-USA panel 1. This regimen should be initiated as soon as possible, ideally within 72 hours of exposure, as effectiveness decreases with delayed administration. The complete 28-day course must be taken without interruption to maximize effectiveness. Before starting PEP, baseline HIV testing should be performed to confirm the exposed person is HIV-negative, using a combination antibody/antigen test, as suggested by the guidelines 1. Additional testing for other sexually transmitted infections is also recommended, including pregnancy testing for women of childbearing potential, and hepatitis B and C serologies. Follow-up HIV testing should occur at 4-6 weeks and 3 months after exposure, with the option of shorter serologic follow-up if using a fourth-generation assay 1. Side effects may include nausea, fatigue, and headache, which are generally manageable and temporary. PEP works by preventing HIV from establishing infection in the body by inhibiting viral replication at multiple stages. The three-drug regimen provides comprehensive protection by targeting different phases of the HIV life cycle, with tenofovir and emtricitabine blocking reverse transcription while dolutegravir or raltegravir prevents viral DNA integration into host cells. Key considerations for PEP include:

  • Initiating treatment as soon as possible after exposure
  • Completing the full 28-day course
  • Baseline and follow-up HIV testing
  • Testing for other sexually transmitted infections
  • Managing side effects and providing support for adherence. It is also important to note that persons who repeatedly seek PEP should be considered for Pre-Exposure Prophylaxis (PrEP), as daily PrEP may be more protective than repeated episodes of PEP 1.

From the Research

Post-Exposure Prophylaxis (PEP) Regimens for HIV

  • The recommended PEP regimen for HIV after anal sex is not explicitly stated in the provided studies, but it can be inferred that integrase strand transfer inhibitors (INSTIs) combined with a tenofovir and lamivudine or emtricitabine backbone are effective in preventing HIV acquisition 2.
  • Studies have shown that INSTIs, such as dolutegravir, raltegravir, elvitegravir, bictegravir, and cabotegravir, have a high genetic barrier to resistance and are well-tolerated 3, 4.
  • The use of INSTIs in PEP regimens has been associated with high rates of virologic suppression and favorable tolerability 3, 4.
  • However, the presence of certain transmitted drug resistance mutations (TDRMs) may increase the risk of virological failure in patients treated with INSTI-based regimens 5.

Awareness and Utilization of PEP

  • Awareness of PEP is low among men who engage in condomless anal sex with men, but interest in using PEP is high once the method is described to them 6.
  • Despite the availability of effective PEP regimens, PEP remains underutilized globally, and interventions are needed to increase provider and community awareness of PEP 2.

INSTIs in PEP Regimens

  • INSTIs, such as dolutegravir and bictegravir, are preferred for treatment-naïve individuals due to their high genetic barrier to resistance, limited drug-drug interactions, and excellent rates of virologic suppression 3.
  • Cabotegravir, a long-acting INSTI, has been approved for pre-exposure prophylaxis and may be helpful for individuals who have difficulty taking daily oral medications 3.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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