Guidelines for use of HIV postexposure prophylaxis (PEP) regimens in at-risk patients from either occupational (oPEP) or non-occupational (nPEP) exoisyres have been issued by the Centers for Disease Control and Prevention (CDC),[1] the Unites States Public Health Service,[2] and The World Health Organization.[3] Guidelines pertaining to non-occupational exposures (including but not limited to sexual assault, high-risk consensual sexual encounters, and injection drug use) are reviewed and summarized below. For information regarding occupational exposures, see HIV Postexposure Prophylaxis, Occupational.
Updates to this article are as follows:
HIV nPEP is indicated in all HIV-negative patients after significant exposure to a substantial-risk bodily fluid, as detailed below. PEP with antiretrovirals in patients who are already HIV-positive is not recommended, although considerations for other treatments (eg, other infections, trauma, legal issues, undesired pregnancy) remain unchanged when the exposed patient is already HIV-positive. If rapid (< 1 hour) determination of the exposed patient’s HIV status cannot be obtained, it is prudent to proceed under the assumption that they are HIV-negative. Oral HIV tests are not recommended for use during this evaluation owing to a lack of sensitivity.
Significant exposure
Contact with a substantial-risk fluid to vagina, rectum, eye, mouth, non-intact skin (including dermatitis), or percutaneously is considered a significant exposure.
If the source patient is known or found to be HIV-negative and not at a significant risk for acute HIV illness (ie, current intravenous drug use or frequent high-risk sexual contacts), PEP can often be discontinued after testing, but should not be delayed while awaiting test results. If the source’s HIV status is unavailable, a determination of risk must be based on the source’s known risk for acute or chronic HIV infection.
Substantial-risk fluids
Substantial-risk fluids are as follows:
Negligible-risk fluids
Negligible-risk fluids (if not visibly blood) are as follows:
Consideration for initiation of PEP is a medical emergency and should begin as soon as possible after exposure. PEP is recommended only in patients who present to care 72 hours or sooner since the last exposure, as the window to prevent HIV integration into host cells is limited.[1, 2, 3] Persons with repeated exposures can be considered for treatment from their last known exposure. The decision to treat those exposed more than 72 hours prior to presentation should be made in conjunction with expert medical advice as treatment is not generally advisable in these situations. Recommendations for testing, STI treatments, and other supportive care remain unchanged for patients who present outside this window.
According to the World Health Organization (WHO), PEP is contraindicated if the exposed person is already HIV-positive due to a previous exposure, if the patient is chronically exposed to HIV, if the exposure does not pose a risk for transmission, or if the exposure occurred more than 72 hours previously.[3]
Because nPEP carries a risk for adverse effects and toxicities, it should be used for only infrequent exposures. Persons who engage in behaviors that result in frequent recurrent exposures that would require sequential or near-continuous courses of antiretroviral medications (eg, multiple sex partners who rarely use condoms or injection-drug users who often share injection equipment) should not receive nPEP. In these instances, exposed persons should instead be provided with intensive risk-reduction interventions.[5] In addition, HIV pre-exposure prophylaxis (PrEP) should be discussed to prevent future infection.
Initial testing is focused on determining the exposed patient’s pre-existing burden of illness (HIV, hepatitis B, hepatitis C), as well as acquired infections (gonorrhea, chlamydia, syphilis, if applicable), obtaining pregnancy status (if applicable), and preparing for safe administration of nPEP therapy.
HIV testing, as follows:
Hepatitis B testing, as follows:
Hepatitis C testing: Surface antibody upon presentation and then at 6 months, if susceptible
Other tests, if applicable, as follows:
Baseline laboratory tests for nPEP medications, as follows:
Source testing should include HIV Ab/Ag (and quantitative polymerase chain reaction [PCR], if applicable), hepatitis B, hepatitis C, and STI screening as above.
Individual state laws on source testing have substantial variability, and legal ramifications should be known for each jurisdiction (see http://www.cdc.gov/hiv/policies/law/states/)
Postexposure prophylaxis for non-occupational HIV exposures remains controversial. Comparatively, HIV PEP following occupational exposures has been shown to reduce risk of transmission by around 80%.[6] It is unclear whether PEP is effective in preventing seroconversion after non-occupational exposure to HIV. Justification of the efficacy, timing, and duration of nPEP has been extrapolated from 4 lines of evidence, as follows:
PEP is not 100% effective. PEP failures are more likely to be associated with zidovudine monotherapy,[16, 20, 21] infections with HIV strains that are resistant to the antiretroviral medications,[22] and ongoing exposures to HIV.[19, 22, 23, 24, 23] In patients who seroconvert despite nPEP, resistance testing should be strongly considered to guide early and subsequent treatment decisions.
Despite this, outcomes are typically good, as per-act risk of HIV acquisition remains low. For reference, a needlestick from an HIV-infected source leads to seroconversion in only 1 of 435 percutaneously exposed healthcare workers, and a single act of receptive penile-vaginal intercourse leads to infection in 1 of 125 instances.[1] Receptive anal intercourse remains a higher risk, at 1 of 73 instances.[1] Studies have shown that the odds of seroconversion were 0.04% for female-to-male transmission and 0.08% for male-to-female transmission per penile-vaginal sexual act in higer resource settings and demonstrated a transmission rate of 0.38% and 0.30% for female-to-male and male-to-female transmission, respectively, in resouce-poor settings.[25]
Extensive scientific progress has been made in understanding factors effecting the risk of disease transmission, one of those findings is that viral load is a key determinant of transmission risk.[4] If the source patient is known to have HIV infection but is virologically controlled on medication, the risk for sexual transmission has been shown to be negligible.[26, 27] Following the results of HPTN 052,[4] multiple large studies[28, 26] have confirmed these findings and established that Undetectable = Untransmittable (U=U), and subsequently led to a national education campaign regarding the success of treatment as prophylaxis against HIV transmission.
CDC recommendations state that all persons evaluated for possible HIV PEP should be evaluated for other exposures and conditions. These include bacterial STIs, traumatic injuries, hepatitis B and hepatitis C infection, and/or pregnancy. The following guidelines are based upon CDC guidelines[29] and interim updates,[30] and should be administered regardless of initial patient testing and whether HIV PEP is administered or not afterfollowing sexual assault.
Gonorrhea, as follows:
Chlamydia, as follows:
Trichomoniasis (females only), as follows:
Human papillomavirus (HPV) infection, as follows:
Treatment to be administered after bodily fluid exposures (including, but not limited to, sexual encounters) is discussed below.
Hepatitis B, as follows:
Hepatitis C: PEP not currently recommended
The CDC recommends that all persons who report behaviors or situations that place them at risk for frequently recurring HIV exposures (eg, injection drug use, sex without condoms) or who report receipt of one or more courses of nPEP in the preceding year should be provided risk-reduction counseling and intervention services, including consideration of preexposure prophylaxis (PrEP).
Patients who require HIV PEP may often benefit from PrEP, and the evaluation and discussion of preemptive therapy should occur at some point during the initial visit or follow-up appointments. As indications and modalities for PrEP are likely to continue to change, see Preexposure HIV Prophylaxis for a full discussion.
If HIV nPEP is offered, the following information should be discussed with the patient:
Patients should be informed that various payment methods for nPEP are available for survivors of sexual assault, including Medicaid, Medicare, or Crime Victims Compensation. Third-party reimbursement may cover nPEP, depending on the plan’s prescription drug policy, if the individual has prescription drug coverage. In cases where the medication-dispensing facility does not receive reimbursement for these services, such expenses may be included in their annual Institutional Cost Report as part of indigent care costs.
The Crime Victim’s Board (CVB) has developed special procedures to ensure availability of nPEP for sexual assault victims. Victims of sexual assault may also contact a Rape Crisis Center or Victims Services Agency in their county or region for assistance in filing claims with the CVB, particularly when emergency assistance is needed. Many of these agencies have 24-hour hotlines. For more information about accessing Crime Victims Compensation and for a list of Victims Services Agencies and other resources, consult the CVB website.
For more details on sexual assault in general, see Sexual Assault. For child sexual abuse, see the article Child Sexual Abuse.
Additional resources for HIV/sexual assault include the following:
CDC / National Prevention Information Network
Patient informational handouts and discharge instructions available:
Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HIV and Recommendations for Postexposure Prophylaxis
National HIV/AIDS Hotline
American Social Health Association PO Box 13827 Research Triangle Park, NC 27709 (800) 342 - AIDS (800) 344 - SIDA (Spanish) (800) 243 - 7889 (TDD)
They provide HIV/AIDS information 24 hours a day, 7 days a week and will send free written information. They also make referrals to any organization/agency that provides information, including legal services, counseling, and therapies.
National Center for Victims of Crime 2000 M Street NW, Suite 480 Washington, DC 20036 Phone: (202) 467-8700 Fax: (202) 467-8701
National Sexual Violence Resource Center 123 North Enola Drive Enola, Pennsylvania 17025 877-739-3895 (toll-free) 717-909-0710(phone) 717-909-0714 (fax) 717-909-0715 (TTY)
Rape, Abuse, and Incest National Network (RAINN) National Sexual Assault Hotline 2000 L Street, NW, Suite 40 Washington, DC 20036 (202) 544-1034 (800) 656-HOPE (4613) info@rainn.org
National Native American AIDS Prevention Center 2100 Lakeshore, Suite A Oakland, CA 94606 (800) 283 - AIDS
National Association of People with AIDS (NAPWA) 1413 K Street, NW Washington, DC 20005 (202) 898 - 0414 (202) 789 - 2222 (FAX: AIDS information facts on demand)
NAPWA is a nonprofit organization that provides information services, educational resources, national advocacy, and technical assistance for community-based organizations.
Assistance with PEP-related decisions can be obtained by contacting the following:
In New York State: For referrals to HIV specialists, call the AIDS Institute’s Office of the Medical Director: (212) 417-4536 (M-F, 8am-5pm); all other hours, call the HIV/AIDS Hotline: 1-866-881-2809. For NYSDOH protocol for management of sexual assault victims, call the NYSDOH Rape Crisis Program: (518) 474-3664 and/or visit the NYSDOH HIV Guidelines Website.
Patients evaluated for PEP should be educated about the symptoms of acute HIV seroconversion (notably fever, sore throat, lymphadenopathy, and/or diffuse rash)[32] and instructed to seek medical care if they develop. Follow-up with a primary care provider or infectious disease physician should occur at 4-6 weeks, 3 months, and 6 months regardless of whether PEP was initiated in order to screen for medication side effects, to evaluate for symptoms of seroconversion, and to test for development of infections. If initiated, PEP adherence should be stressed, as overall adherence rates are around 60% but are commonly reported to be below 30%, often due to medication side effects such as nausea.[33]
Patients who are pregnant or become pregnant should be advised on the risk of HIV-transmission with breast feeding.
All patients should be advised to abstain from sexual encounters or stricly adhere to condom usage for all encounters (including oral sex) until 3 month follow up, as risk of secondary HIV transmission is highest during the acute phase of illness.
Although the exact drug regimens for HIV PEP have changed in recent years, consensus remains that the preferred regimen is a 3-drug regimen given over a 28-day course.[1] Anyone prescribed PEP should be given the full 28-day course. On occasion, a 30-day supply will be dispensed due to the cost of adjusting manufacterer-supplied bottles, but no added benefits have been shown for continuation of the treatment course beyond 28 days.
The FDA announced in May 2018 that it was investigating correlations between dolutegravir use in early pregnancy and neural tube defects. Although such a correlation had not been shown definitively, guidance was issued at that time that women who were pregnant or of childebearing potential avoid dolutegravir and bictegravir while further evaluation was performed. Studies indicated that the increased rate of neural tube deficits seen in a cohort of HIV-infected individuals in Botswana[34] was not seen in the United States.[35] Further, Raltegravir has a well-established safety profile for this use and remains a primary treatment option.[36] In February of 2021, the Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission recommended the use of dolutegravir as a prefered agent both for women who are pregnant, and those attempting to get pregnant. This was based on the lack of neural tube defect in later cohorts, as well as the known benefits of dolutegrvir which include therapeutic efficacy, tolerance, and ease of administration with once daily dosing.[37]
Patients older than 13 years with normal renal function (CrCl ≥60 mL/min), including pregnant individuals
The preferred 3-drug regimen is as follows:
OR
Caution: Coadministration of raltegravir or dolutegravir with antacids or cations (iron, calcium, or magnesium) can reduce drug absorption and therefore efficacy of PEP.
An alternative regimen is as follows:
Patients older than 13 years with chronic kidney disease (CrCl < 60 mL/min)
The preferred 3-drug regimen is as follows:
Caution: Coadministration of raltegravir or dolutegravir with antacids or cations (iron, calcium, or magnesium) can reduce drug absorption and therefore efficacy of PEP.
An alternative regimen is as follows:
PEP is especially important in pregnant women and should not be avoided because of known or possible pregnancy.
Note that tenofovir alafenamide (TAF), a newer formulation of tenofovir, has not been specifically studied for HIV PEP and is not currently recommended for this indication. A TAF-containing co-formulation with emtricitabine (Descovy) is FDA-approved for the treatment of HIV infection in combination with other active agents, but its ultimate role in HIV PEP remains undefined at the time of this writing.
Children aged 2-12 years
Each drug dosed to age and weight
Preferred 3-drug regimen: Tenofovir DF AND emtricitabine AND raltegravir
Alternative regimens are as follows:
Children aged 3-12 years: Tenofovir DF AND emtricitabine AND darunavir/ritonavir (darunavir is approved in children aged 3 years or older)
Children aged 4 week to < 2 years
Preferred 3-drug regimen: Zidovudine AND lamivudine with raltegravir or lopinavir/ritonavir
Alternative regimen: Zidovudine AND emtricitabine with raltegravir or lopinavir/ritonavir
Children aged birth to 27 days
Consult a pediatric HIV specialist.
Overview
What are the guidelines on HIV prophylaxis following sexual assault?
When is HIV postexposure prophylaxis (PEP) indicated?
How is a significant exposure to HIV defined?
What are the substantial risk fluids of HIV exposure?
What are the negligible risk fluids of HIV exposure?
When is HIV postexposure prophylaxis (PEP) administered following a sexual assault?
What are contraindications for HIV postexposure prophylaxis (PEP)?
What is the focus of the initial lab tests prior to HIV postexposure prophylaxis (PEP)?
When is HIV testing performed following a sexual assault?
What is the role of hepatitis B testing in the workup of HIV postexposure prophylaxis (PEP)?
Which STIs tests should be performed in the workup of HIV postexposure prophylaxis (PEP)?
What are the baseline lab tests for HIV postexposure prophylaxis (PEP) medications?
What source testing is performed in the workup of HIV postexposure prophylaxis (PEP)?
What is the efficacy of HIV postexposure prophylaxis (PEP)?
What are the CDC guidelines for the evaluation of STIs following sexual assault?
Which medications are administered to prevent STIs following a sexual assault?
What are the CDC recommendations for preexposure HIV prophylaxis (PrEP)?
Periprocedural Care
Where are additional resources for HIV postexposure prophylaxis (PEP) and sexual assault found?
Where can assistance with HIV postexposure prophylaxis (PEP)-related decisions be obtained?
Medications
What are HIV postexposure prophylaxis (PEP) regimens for children aged 4 week to < 2 years?
What are the HIV postexposure prophylaxis (PEP) regimens?
What are the HIV postexposure prophylaxis (PEP) regimens during pregnancy?
What are the HIV postexposure prophylaxis (PEP) regimens for children aged 2-12 years?
What are the HIV postexposure prophylaxis (PEP) regimens for children aged birth to 27 days?