How Do I Prescribe PEP?

PEP is short for post-exposure prophylaxis. It is the use of antiretroviral medication to prevent HIV infection in an HIV-negative person who has had a specific high-risk exposure to HIV. Such an exposure typically occurs through sex or sharing syringes (or other injection equipment) with someone who has or might have HIV. Nonoccupational post-exposure prophylaxis (nPEP) is a term used to specify that the exposure was not work related.

Algorithm for Evaluation and Treatment of Possible Nonoccupational HIV Exposures

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Exposure to HIV is a medical emergency because HIV establishes infection very quickly, often within 24 to 36 hours after exposure.^1-3 Evaluate patients rapidly for PEP when care is sought ≤72 hours after a potential exposure. Determine HIV status in patients being considered for PEP using rapid combined antigen/antibody or antibody blood tests.

If rapid HIV blood test results are unavailable, and PEP is indicated, administer the first dose of PEP immediately. PEP can be stopped later if the person is found to have HIV or if the source of the exposure is determined not to have HIV.⁴

PEP is not recommended when care is sought >72 hours after exposure.

Consider initiating PEP in people whose vagina, rectum, eye, mouth or other mucous membrane, nonintact skin, or perforated skin (e.g., needle stick) came into contact with body fluids from a person with HIV within 72 hours before they sought care. If the exposure source’s HIV status is unknown, make a case-by-case determination.

People who have frequent, recurrent exposures to HIV through sex or injection drug use should be considered for intensive risk-reduction interventions and PrEP. If the most recent recurring exposure was within the 72-hour window before evaluation, PEP may be indicated, and the patient can be prescribed pre-exposure prophylaxis (PrEP) after taking PEP medication for 28 days.

Emergency medicine physicians are among the most frequent prescribers of PEP, given the need for immediate treatment after exposure. If you work in an ambulatory care practice, ensure that your patients who are HIV negative and report HIV risk factors are aware of PEP and know how to access it after-hours.

If you are inexperienced with prescribing or managing patients on antiretroviral medication, or if information from the exposure source indicates the possibility of antiretroviral resistance, consult with an infectious disease or other HIV care specialist before prescribing PEP to determine the correct regimen—but only do this if these specialists are immediately available.

Similarly, consulting with specialists who have experience using antiretroviral drugs is also advisable when considering prescribing PEP for certain people, such as pregnant people, children, and people with kidney disease. However, if such consultation is not available, initiate PEP promptly and, if necessary, revise after consultation is obtained.

Prescribe all people offered PEP a 28-day course of a three-drug antiretroviral regimen.* For PEP to be effective, patients must take their PEP medication as prescribed. To support this, select regimens that minimize side effects, the number of doses per day, and the number of pills per dose.

Alternative regimens may be used in cases of potential HIV resistance, toxicity risks, preference, or constraints on the availability of particular medications. In those cases, seek consultation with other providers knowledgeable in using antiretroviral medications for similar patients (e.g., children, pregnant people, people with comorbid conditions).

Be aware that abacavir sulfate should not be prescribed in any PEP regimen because the prompt initiation of PEP does not allow for genetic testing for the HLA-B*5701 allele, which is associated with a hypersensitivity syndrome that can be fatal.

The current preferred regimen is generally safe and well tolerated.^5,6 Patients usually experience only mild side effects on the preferred PEP regimen. Most importantly, PEP is only taken for 28 days. In almost all cases, the benefits of HIV prevention outweigh any other risks posed by the medication. In a meta-analysis of 24 PEP-related studies, including 23 cohort studies and one randomized clinical trial, nausea, vomiting, diarrhea, and fatigue were the most commonly reported side effects.⁷

The current preferred regimen is generally safe and well tolerated.^5,6 Patients usually experience only mild side effects on the preferred PEP regimen. Most importantly, PEP is only taken for 28 days. In almost all cases, the benefits of HIV prevention outweigh any other risks posed by the medication. In a meta-analysis of 24 PEP-related studies, including 23 cohort studies and one randomized clinical trial, nausea, vomiting, diarrhea, and fatigue were the most commonly reported side effects.⁷

Patients who use PrEP. People who are already using PrEP typically do not need PEP if they experience a potential HIV exposure while taking their PrEP medication as prescribed. If they may not have taken their PrEP medication as prescribed, review CDC’s recommended antiretroviral management options.

Patients who were exposed to HIV >73 hours prior. PEP is not recommended for people whose exposure occurred 73 hours or more before they sought treatment because PEP is unlikely to be effective after this time.

Patients whose risk of getting HIV is very low. PEP is not recommended for people who were exposed to non-blood-contaminated secretions, such as urine, saliva, sweat, tears, or nasal secretions, as their risk of getting HIV is very low.

CDC’s Updated PEP Guidelines recommend the following baseline screening: 

• HIV rapid test at baseline
  If the baseline rapid test indicates the patient has HIV, do not initiate PEP. If rapid HIV baseline testing is not available, start PEP immediately. Oral HIV tests are not recommended for use among patients being evaluated for PEP.
• Pregnancy test
  Perform a pregnancy test if the patient could become pregnant, is not using highly effective contraception (e.g., intrauterine devices or other long-acting reversible contraceptives, oral contraceptives, or properly used condoms), and has vaginal exposure to semen.
• Serum liver enzyme test
• Blood urea nitrogen/creatinine test
• Sexually transmitted infection screening
  For patients being evaluated for PEP because of a sexual encounter, test for chlamydia and gonorrhea at each site of potential exposure using nucleic acid amplification tests and do a blood test for syphilis.
• Hepatitis B (HBV) test
  Including HBV surface antigen, surface antibody, and core antibody
• Hepatitis C (HCV) antibody test

Administer PEP if indicated, even before you receive all testing results. There are few absolute contraindications to the recommended PEP regimen. All medications in this regimen have minimal drug-drug interactions. In almost all cases, you should prescribe the first dose of a PEP regimen before obtaining further consultation.

PEP was first attempted for HIV prevention in the 1980s among health care workers who experienced occupational exposures. This type of PEP is now called oPEP, to differentiate it from PEP used after exposures that were not related to work, or nPEP. At that time, only AZT (zidovudine) was available.

Anecdotal evidence of success began to accumulate, leading to the first formal study of PEP effectiveness, a case-control study of occupational exposures. This study demonstrated an 81% reduction in HIV infection in those who received AZT alone compared with those who did not receive any treatment.⁸ PEP was proposed for nonoccupational exposures more recently.

The additional evidence supporting PEP includes:

• Its biologic plausibility (based on animal studies).^1,2
• The efficacy of antiretrovirals given post-partum in reducing mother-to-child transmission.³
• Observational studies (such as data from existing PEP programs).^4,9

Studies of specific populations

In many states, PEP is covered by insurance, including Medicaid. If your patient is not covered under insurance, you can help them access assistance programs run by various manufacturers.

Assist your patients to pay for PEP by:

• Applying for assistance with the medication co-pay if the patient is insured; or
• Applying for complete coverage of the medication if the patient does not have insurance or needs financial assistance. Note that the paperwork must be signed and submitted by a licensed clinical provider.

The Partnership for Prescription Assistance can also help qualified patients get the prescriptions they need at a very low cost.

Be sure to stay in touch with your patients on PEP, by either telephone or clinic visits, for the entire duration of PEP. This helps to both support patients taking their PEP medication as prescribed and facilitate follow-up HIV testing at 30 and 90 days. Additionally, for people who get both HCV and HIV at the same time, it might take longer for HIV tests to detect HIV infection. Click on the diagram to the right to access the recommended schedule of laboratory evaluations for people who were exposed to HIV and prescribed PEP.

Counsel patients on PEP to take steps to reduce the risk of transmitting HIV during the 12-week follow-up period. These steps include using condoms consistently, avoiding pregnancy or breast/chestfeeding, not sharing needles, and not donating blood, plasma, organs, tissue, or sperm.

CDC’s Updated Guidelines for Antiretroviral Postexposure Prophylaxis After Sexual, Injection Drug Use, or Other Nonoccupational Exposure to HIV—United States, 2016⁴ provides guidance for how to prescribe antiretroviral medications for PEP, as well as evidence about the effectiveness of PEP from animal studies and human observational studies.

The Updated PEP Guidelines also include considerations and resources for specific groups, such as pregnant patients, victims of sexual assault (including children), and patients without health insurance, as well as a suggested procedure for transitioning patients between PEP and HIV PrEP as appropriate.⁴