nPEP: A Provider’s Guide

A quick reference guide and resources for providers on prescribing and managing nonoccupational post-exposure prophylaxis (nPEP) for prevention of HIV.

by Rachel K. Scott, MD, MPH and Hannah Sinks, BS

published 03/18/22

Nonoccupational post-exposure prophylaxis (nPEP) is FDA approved for HIV-negative individuals not on pre-exposure prophylaxis (PrEP) or those taking PrEP sporadically who seek care within 72 hours of a potential nonoccupational HIV exposure. nPEP is taken after exposure and is highly effective at preventing HIV if taken within 72 hours, up to 99% reported efficacy. The sooner nPEP is taken, the more effective it is at preventing HIV infection. An individual’s risk of HIV acquisition from nonoccupational exposure varies depending on the site and type of exposure. There is increased risk of HIV acquisition with exposure of the vagina, penis, rectum, eye, mouth or other mucous membrane, non-intact skin, or percutaneous contact with blood, semen, vaginal or rectal secretions, breast milk, or any body fluid visibly containing blood. The risk is lower if contact is with urine, nasal secretions, saliva, sweat, or tears.

nPEP is intended for emergency situations and is not intended to be used in place of other HIV prevention methods that are beyond the scope of this Provider’s Guide such as condom use, harm-reduction strategies for people who inject drugs, PrEP, and antiretroviral therapy (ART) for people with HIV, commonly referred to as “treatment as prevention” (TasP) or “undetectable equals untransmittable” (U=U). “For more on PrEP, check out the Provider’s Guide from Bedsider Providers.

nPEP Regimens

nPEP is a three-drug regimen taken for 28 days. Decisions about which regimen to use are based on age and renal function:

Adults and adolescents ≥ 13 years (including pregnant people):

  • Preferred regimen: Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC, brand name Truvada) 300 mg/200 mg once daily plus either dolutegravir (DTG, brand name Tivicay) 50 mg once daily or raltegravir (RAL, brand name Isentress) 400 mg twice daily.
  • Alternative regimen: TDF/FTC 300/200 mg once daily and darunavir (DRV, brand name Prezista)/ritonavir (RTV, brand name Norvir) 800 mg/100 mg once daily.

Decreased renal function (eCrCl < 60 ml/min):

  • Preferred regimen: zidovudine/lamivudine (ZDV/3TC, brand name Combivir) plus either DTG 50 mg once daily or RAL 400 mg twice daily.
  • Alternative regimen: ZDV/3TC plus DRV/RTV 800 mg/100 mg once daily.

Children less than 13 years:

There are multiple regimens available depending on age. Please refer to the Centers for Disease Control and Prevention (CDC) Updated Guidelines for Antiretroviral Postexposure Prophylaxis for details.

Prescribing, Initial Labs, & Follow-Up

Before initiating nPEP, patients should be screened for HIV infection with a rapid combined Ag/Ab or antibody test. If rapid testing is not available, nPEP should be started without delay and can be stopped later if test results indicate HIV-positive status. Blood tests for Hepatitis B and Hepatitis C should be collected at presentation. Liver (AST/ALT) and kidney (creatinine) function should also be evaluated for those prescribed nPEP with TDF/FTC. Patients requesting nPEP for sexual exposure should receive a blood test for syphilis in addition to testing for gonorrhea and chlamydia at all anatomic sites of exposure. For people who can get pregnant, consider pregnancy testing and offer emergency contraception without delay.

Follow-up labs include screening for HIV at four to six weeks and three months after exposure, syphilis at four to six weeks and three to six months, and Hepatitis B and C serology at six months if susceptible at baseline. Patients prescribed TDF/FTC-containing regimens should also receive creatinine and ALT/AST tests four to six weeks after nPEP initiation.

Counseling Tips for nPEP

  • Side effects: The most common side effects are nausea, GI upset, and fatigue.
  • Daily dosing: nPEP is most effective when taken daily for the entire 28-day course. Missed doses increase the risk of HIV acquisition, and in the setting of nPEP, there is a risk of developing a drug-resistant strain.
  • Transition to PrEP: PrEP should be offered to anyone who seeks nPEP more than once and is at ongoing risk of HIV acquisition. PrEP can be started at the end of a 28-day nPEP course after confirming HIV-negative status.
  • Only HIV: nPEP protects against HIV but not against other STIs.

Paying for nPEP

Patients may qualify for free or low-cost nPEP, depending on the reason for prescription. For those in need of financial assistance, there are medication assistance programs available for providers to apply to, including Gilead’s Advancing Access Form and NASTAD’s Patient Assistance Tool.

Bottom Line

nPEP is a safe and effective tool for HIV prevention after suspected nonoccupational exposure. For patients who repeatedly utilize nPEP or continue to be at risk of HIV acquisition, providers should discuss and offer PrEP.

Rachel Scott is an OB/GYN at MedStar Washington Hospital Center and MedStar Health Research Institute. Both her clinical work and research focus on improving health and healthcare for women with HIV and HIV prevention for women. When not hard at work, she enjoys yoga, cooking, and spending time with her husband, kiddo, and pups.
Hannah Sinks is a fourth-year medical student at Georgetown University. She will start her residency in Obstetrics and Gynecology at Zucker SOM-Northwell NS/LIJ in June 2022. She is passionate about health equity and family planning. Outside of work, she enjoys baking, hiking, and watching true crime shows.
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