PEP for Non-Occupational Exposure to HIV (nPEP)

PEP for Non-Occupational Exposure to HIV (nPEP)

Introduction

Medical Care Criteria Committee, updated May 2018

UPDATE
  • Tenofovir (TDF) + emtricitabine (FTC) plus either raltegravir (RAL) or dolutegravir (DTG) [see safety statement below] is now the Medical Care Criteria Committee’s preferred initial nPEP regimen because of its excellent tolerability, proven potency in established HIV infection, and ease of administration.
    • Lamivudine (3TC) may be substituted for FTC
  • Zidovudine (ZDV; AZT) is no longer recommended in the preferred PEP regimen because it is believed to have no clear advantage in efficacy over tenofovir while having significantly higher rates of treatment-limiting side effects.
  • Plasma HIV RNA testing of the source person is recommended in addition to HIV serologic screening in the following settings; nPEP should be initiated and continued in these situations until results of the plasma HIV RNA assay are available:
    • If the source person’s HIV screening result is negative but there has been a risk for HIV exposure in the previous 6 weeks
    • If the source person’s HIV screening result is positive but the confirmatory antibody-differentiation assay is nonreactive or indeterminate
  • Figure 1 lists steps for evaluating and managing non-occupational exposures.
  • The Committee continues to recommend the following from the July 2013 Update:
    • Baseline STI testing for sexual exposures that do not occur as a result of sexual assault. STI management recommendations, including prophylactic treatment, differ for cases of sexual assault. See PEP for Victims of Sexual Assault.
    • Regardless of whether the exposed person accepts or declines PEP treatment, if the post-exposure evaluation determines that nPEP is indicated, repeat HIV testing at 4 weeks and 12 weeks should be obtained. A negative HIV test result at 12 weeks post-exposure reasonably excludes HIV infection related to the exposure; routine testing at 6 months post-exposure is no longer recommended.
    • Pre-exposure prophylaxis (PrEP) after completion of the 28-day nPEP regimen for persons who present with repeated high-risk behavior or for repeat courses of nPEP.

*Lamivudine (3TC) may be substituted for emtricitabine (FTC).

Dolutegravir (DTG) Safety Statement, May 2018

On May 18, 2018, the FDA and the DHHS Antiretroviral Guidelines Panels issued statements in response to preliminary results from a study that reported increased risk of neural tube defects in babies born to mothers taking DTG-based ARV drug regimens at the time of conception [AIDSinfo 2018; FDA 2018].

Until more data become available, DTG-containing regimens should be avoided in any HIV-exposed individual who is or could become pregnant and is not using effective contraception. If there are no alternatives to DTG for individuals of child-bearing potential, then clinicians should strongly advise the use of effective contraception and should obtain a pregnancy test before initiating treatment.

For more information, see: DHHS Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States

 

Purpose

The purpose of this chapter is to provide recommendations and guidelines for prescribing PEP following non-occupational exposure to HIV (nPEP). These guidelines will address nPEP for significant risk exposures following sexual and needle-sharing activities, needlesticks outside of occupational settings, and trauma, including human bites. Within the category of sexual exposure, sexual assault merits special focus.

KEY POINT
  • Because of the special considerations regarding evaluation, counseling, and support for sexual assault victims, PEP in the setting of sexual assault is addressed separately (see NYSDOH AI PEP for Victims of Sexual Assault Guideline). PEP regimens for sexual assault are the same as PEP regimens for other types of non-occupational and occupational exposures.

For guidelines that address HIV PEP following occupational exposure, see NYSDOH AI PEP for Occupational Exposure to HIV (oPEP) Guideline.

Although the most effective way to prevent HIV transmission is to protect against exposure, nPEP offers the possibility of preventing HIV transmission when potential exposure to HIV has already occurred. Situations that may prompt a request for nPEP include condom slippage, breakage, or lapse in use by serodiscordant partners; unsafe needle-sharing; or other episodic exposure to blood. Treatment of high-risk exposures should be combined with a strong educational component that emphasizes prevention of future exposures [Golub et al. 2008].

The appendix, Estimated Per-Act Probability of Acquiring HIV, shows the risk of HIV transmission for various types of exposure to a known HIV-infected source as well as factors that may increase transmission risk. HIV transmission most frequently occurs during sexual or drug-using exposures; however, there are many factors that can influence transmission risk. Due to the presence of high HIV viral load levels, the probability of transmission when the source person is in the acute and early stage of HIV infection (first 6 months) has been shown to be 8- to almost 12-fold higher than exposures that take place after the viral set point [Wawer et al. 2005; Pilcher et al. 2004]. The presence of sexually transmitted infections (STIs) in either the source or exposed person also increases risk [ACHSP 1998; CDC 2010; Johnson and Lewis 2008]. Conversely, transmission risk has been shown to be significantly decreased in source persons who are receiving effective antiretroviral therapy (ART) [Cohen et al. 2011]. The Centers for Disease Control and Prevention (CDC) is reviewing the most recent data and constructing mathematical models to update transmission risk.

Evidence base: Practice guidelines and policy recommendations for nPEP must consider the lack of definitive evidence concerning efficacy to support them. Because randomized, placebo-controlled experimental clinical trials on nPEP have not been conducted and are not feasible to design to generate conclusive data, these guidelines are based on existing published studies and best-practice evidence and constitute the considered opinion of the group of expert clinicians in the field of adult HIV medicine who comprise the Medical Care Criteria Committee.

Although there are no studies that directly demonstrate the efficacy of nPEP, there are data to support its biologic plausibility, including animal studies of prophylaxis following exposure to simian immunodeficiency virus (SIV) and HIV-2 [Otten et al. 2000; Smith et al. 2000; Van Rompay 2000], efficacy data from mother-to-child transmission studies [Connor et al. 1994], and a case-control study of occupational exposure [CDC 1995]. A number of observational studies have been designed to assess the feasibility and potential efficacy of nPEP programs. Initial published reports from San Francisco, Boston, and Brazil have demonstrated the feasibility of such programs in high-risk populations [Kahn et al. 2001; Schechter et al. 2004; Kwong et al. 2000]. Cost-effectiveness analyses have suggested that nPEP is cost-effective in high-risk exposures such as receptive anal sex with an HIV-infected partner or a partner of unknown HIV status [Pinkerton et al. 2004; Herida et al. 2006]. However, a 2008 survey of emergency departments in New York State showed that implementation of these guidelines in New York State is not optimal [Ende et al. 2008].

Developing guidelines for HIV exposures outside of the occupational setting raises a multitude of issues beyond the questions of biologic rationale and transmission risk. Issues include cost of care, payment for medications, feasibility of implementation of guidelines, individual adherence to nPEP, the risks and benefits of prophylactic ART, and the potential public health impact of such guidelines. To develop these guidelines for nPEP, the Medical Care Criteria Committee reviewed the medical literature as well as existing recommendations and guidelines from government and community sources. They also considered specific concerns related to the process of implementing nPEP. Throughout the deliberations of the Committee, a conscious effort was made to weigh both the medical and psychological benefits and risks of medical intervention in the context of a potential HIV exposure.

References

ACHSP. HIV prevention through early detection and treatment of other sexually transmitted diseases—United States. Recommendations of the Advisory Committee for HIV and STD Prevention. MMWR Recomm Rep 1998;47(RR-12);1-24. [PubMed]

AIDSinfo. Statement on Potential Safety Signal in Infants Born to Women Taking Dolutegravir from the HHS Antiretroviral Guideline Panels. 2018 May 18. https://aidsinfo.nih.gov/news/2094/statement-on-potential-safety-signal-in-infants-born-to-women-taking-dolutegravir [accessed 2018 May 23]

CDC. Case-control study of HIV seroconversion in health-care workers after percutaneous exposure to HIV-infected blood: France, United Kingdom, and United States, January 1988-August 1994. MMWR Morb Mortal Wkly Rep 1995;44(50):929-933. [PubMed]

CDC. Sexually Transmitted Diseases Treatment Guidelines 2010. http://cdc.gov/std/treatment

Cohen MS, Chen YQ, McCauley M, et al. HPTN 052 Study Team. Prevention of HIV-infection with early antiretroviral therapy. N Engl J Med 2011;365:493-505. [PubMed]

Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatrics AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med 1994;331:1173-1180. [PubMed]

Ende AR, Hein L, Sottolano DL, et al. Nonoccupational postexposure prophylaxis for exposure to HIV in New York State emergency departments. AIDS Patient Care STDs 2008;22:797-802. [PubMed]

U.S. Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA to evaluate potential risk of neural tube birth defects with HIV medicine dolutegravir (Juluca, Tivicay, Triumeq). 2018 May 18. https://www.fda.gov/Drugs/DrugSafety/ucm608112.htm [accessed 2018 May 23]

Golub SA, Rosenthal L, Cohen DE, et al. Determinants of high-risk sexual behavior during Post-exposure prophylaxis to prevent HIV infection. AIDS Behav 2008;12:852-859. [PubMed]

Herida M, Larsen C, Lot F, et al. Cost-effectiveness of HIV post-exposure prophylaxis in France. AIDS 2006;20:1753-1761 [PubMed]

Johnson LF, Lewis DA. The effect of genital tract infections on HIV-1 shedding in the genital tract: A systematic review and meta-analysis. Sex Transm Dis 2008;35:946-959. [PubMed]

Kahn JO, Martin JN, Roland ME, et al. Feasibility of postexposure prophylaxis (PEP) against human immunodeficiency virus infection after sexual or injection drug use exposure: The San Francisco PEP Study. J Infect Dis 2001;183:707-714. [PubMed]

Kwong J, Mayer K, Peterson N, et al. Non-occupational post-exposure prophylaxis (PEP) at a Boston Community Health Center. XIII International AIDS Conference; 2000; Durban, South Africa.

Otten RA, Smith DK, Adams DR, et al. Efficacy of postexposure prophylaxis after intravaginal exposure of pig-tailed macaques to a human-derived retrovirus (human immunodeficiency virus type 2). J Virol 2000;74:9771-9775. [PubMed]

Pilcher CD, Tien HC, Eron JJ Jr, et al. Brief but efficient: Acute HIV infection and the sexual transmission of HIV. J Infect Dis 2004;189:1785-1792. [PubMed]

Pinkerton SD, Martin JN, Roland ME, et al. Cost-effectiveness of postexposure prophylaxis after sexual or injection-drug exposure to human immunodeficiency virus. Arch Intern Med 2004;164:46-54. [PubMed]

Schechter M, do Lago RF, Mendelsohn AB, et al. Behavioral impact, acceptability, and HIV incidence among homosexual men with access to postexposure chemoprophylaxis for HIV. J Acquir Immune Defic Syndr 2004;35:519-525. [PubMed]

Smith MS, Foresman L, Lopez GJ, et al. Lasting effects of transient postinoculation tenofovir [9-R-(2-Phosphonomethoxypropyl)adenine] treatment on SHIV (KU2) infection of rhesus macaques. Virology 2000;277:306-315. [PubMed]

Van Rompay KK, Miller MD, Marthas ML, et al. Prophylactic and therapeutic benefits of short-term 9-[2-(R)-(phosphonomethoxy) propyl]adenine (PMPA) administration to newborn macaques following oral inoculation with simian immunodeficiency virus with reduced susceptibility to PMPA. J Virol 2000;74:1767-1774. [PubMed]

Wawer MJ, Gray RH, Sewankambo NK, et al. Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis 2005;191:1403-1409. [PubMed]

Initial Assessment

Medical Care Criteria Committee, October 2014

RECOMMENDATIONS
Assessing the Exposure
  • Risk assessment and initiation of nPEP should occur in clinical settings that can provide the following: (A3)
    • Assessment of HIV risk following exposure
    • HIV and STI testing and treatment
    • Prevention and risk-reduction counseling
    • Clinicians with expertise in the use of ART
    • Timely access to care and initiation of nPEP
  • If all of these services are not available, clinicians should assess the exposure and initiate nPEP when indicated according to the criteria and recommendations in these guidelines. The patient should then be referred for follow-up care to a clinician who has experience in the use of antiretroviral agents and who can provide ongoing prevention counseling.
  • Treating clinicians who do not have access to experienced HIV clinicians should call the Clinical Education Initiative CEI PEP Line at 1-866-637-2342 to review the case. When using the PEP Line, providers from New York State should identify themselves as practicing in the State.
  • Patients who present for nPEP should be evaluated as soon as possible in order to initiate therapy, if indicated, within recommended time frames. (A2)
  • Wound and skin exposure sites should be washed with soap and water. Needlestick injuries should not be squeezed. (A2)
  • When an HIV exposure occurs, the events and the subsequent interventions should be clearly documented in order to facilitate determination of the effectiveness of nPEP. (A2)
Is nPEP Indicated?
  • When deciding whether to recommend the initiation of nPEP, the clinician should assess the patient’s risk of HIV acquisition based on the type of exposure (see text). (A3)
  • Non-occupational PEP should not be prescribed when there is negligible or low risk of HIV transmission (see text). (A3)
  • Non-occupational PEP should not be routinely dismissed solely on the basis of repeated risk behavior or repeat presentation for nPEP. (A3) Persons who present with repeated high-risk behavior or for repeat courses of nPEP should be the focus of intensified education and prevention interventions.
  • After completion of the 28-day nPEP regimen, the patient should be evaluated to determine whether initiation of pre-exposure prophylaxis (PrEP) is warranted and feasible. (A2)
HIV Exposure Through Bites
  • When bite wounds result in blood exposure, nPEP should be considered for the person(s) who was exposed to blood; this could be the person bitten, the biter, or both (A2) (see text). PEP should not be initiated when the integrity of the skin is not disrupted.
  • Clinicians should wash bite wounds with soap and water and should not squeeze the wound. (A2)
HIV Status of the Source Person
  • Source person is unavailable or unwilling to undergo HIV testing: When assessment of the exposure determines that nPEP is indicated, but the source is anonymous, unavailable, or unwilling to undergo HIV testing, nPEP should be initiated and the 28-day course should be completed. (A2)                 
  • Source person is known to be HIV-infected: If the source of contact is known to be HIV-infected, information about his/her viral load, antiretroviral medication history, and history of antiretroviral drug resistance should be obtained when possible to assist in the selection of an nPEP regimen; however, administration of the first dose of nPEP should not be delayed while awaiting this information. (A2)                  
  • Source person’s HIV status is unknown and source is available for testing: When the source person is available and consents to HIV testing, clinicians should obtain the most expeditious HIV test available (ideally with a turnaround time <1 hour), using either an FDA-approved HIV rapid test or an FDA-approved laboratory-based screening test. [A 4th-generation antigen/antibody combination assay is recommended; see the CDC’s Recommended Laboratory HIV Testing Algorithm for Serum or Plasma Specimens]. (A1)
    • If the test results are not immediately available, the initiation of nPEP should not be delayed pending the test result.
  • Plasma HIV RNA testing of the source person is recommended in addition to HIV serologic screening in the following settings:
    • If the source person’s HIV screening test result is negative but there may have been exposure to HIV in the previous 6 weeks (B3)
    • If the source person’s screening result is positive but the confirmatory antibody-differentiation assay is nonreactive or indeterminate (A1)
  • When plasma HIV RNA testing is indicated, nPEP should be continued until results of the plasma HIV RNA assay are available. If the result is positive, the 28-day regimen should be completed; if the result is negative, PEP should be discontinued. (B3)
  • The source person should also be evaluated for hepatitis B and hepatitis C. (A1)
Baseline HIV Testing for Patients Who Present with Risk Exposure  
  • Clinicians should perform baseline HIV testing of the exposed person within 3 days of the exposure. (A3) Testing must be performed in full compliance with New York State Public Health Law. Exposed persons who decline baseline HIV testing should not receive nPEP. (A3)
  • nPEP should be started without waiting for the results of the exposed person’s baseline HIV test. (A2) If the initial test result is positive, nPEP should be continued until the positive result is repeated with a confirmatory assay. Decisions regarding continuation of ART should be based on current treatment guidelines.
Testing for STIs Other Than HIV
  • For patients who are sexually exposed in non-assault situations, clinicians should perform STI testing at baseline and should treat as indicated. Testing should include the following:
    • Nucleic acid amplification testing (NAAT) to screen for gonorrhea and chlamydia, based on site of exposure (A2)
    • Serologic screening for syphilis [clinicians should be familiar with their laboratory’s syphilis screening protocol and should ensure that the same test is used when monitoring serology. (A3)
  • Clinicians should counsel patients about the risk of acquiring other STIs and symptoms that may occur; patients should be instructed to call their healthcare provider if symptoms occur. (A2)
  • For men who have sex with men who present with sexual exposures, clinicians should assess for the need to vaccinate against meningococcal disease according to current New York State Department of Health recommendations. (A2)
Pregnancy Testing
  • Clinicians should obtain baseline pregnancy testing for exposed individuals who could become pregnant. (A2) Emergency contraception should be discussed and offered to anyone who could become pregnant as a result of the exposure. (A2)

This section provides guidance for assessing non-occupational exposures that occur from blood and body fluid exposures, including sexual and needle-sharing activities unrelated to sexual assault. (Special considerations for PEP following sexual assault are covered in PEP for Victims of Sexual Assault). Situations that may prompt a request for nPEP include condom slippage, breakage, or lapse in use by serodiscordant partners; unsafe needle-sharing; or other exposure to blood or body fluids.

For persons presenting with wounds or needlestick injuries, the site should be washed with soap and water, avoiding irritation of the skin. The wound should not be “milked” or squeezed. Squeezing the wound may promote hyperemia and inflammation at the wound site, potentially increasing systemic exposure to HIV if present in the contaminating fluid.

Evaluation of the Exposure: Is nPEP Indicated?

The use of nPEP involves both significant costs and potential risk of toxicity from medications. As a result, it should only be used when the potential benefits of taking nPEP outweigh its risks. Non-occupational PEP is not indicated for perceived exposures that are of negligible or low-risk (see below).

Click to enlarge

Determining the degree of risk of HIV transmission is an important factor in guiding the patient and clinician in making a decision concerning nPEP. Types of exposures that should prompt consideration of nPEP and those that do not warrant nPEP are listed below. Figure 1 lists steps for evaluating and managing non-occupational exposures. There may be factors which complicate assessment of the exposure. Clinicians who do not have access to experienced HIV clinicians should call the Clinical Education Initiative CEI PEP Line at 1-866-637-2342. When using the PEP Line, providers from New York State should identify themselves as practicing in the State.

Types of exposures for which nPEP should be recommended (higher-risk exposures):

  • Receptive and insertive vaginal or anal intercourse with a source known to be HIV-infected or HIV status is unknown
  • Needle sharing with a source known to be HIV-infected or HIV status is unknown.
  • Injuries with exposure to blood or other potentially infected fluids from a source known to be HIV-infected or HIV status is unknown (including needlesticks with a hollow-bore needle, human bites, accidents)

Lower-risk exposures that require case-by-case evaluation for nPEP (lower-risk exposures: assess for factors that increase risk before recommending initiation of nPEP):

  • Oral-vaginal contact (receptive and insertive)
  • Oral-anal contact (receptive and insertive)
  • Receptive penile-oral contact with or without ejaculation
  • Insertive penile-oral contact with or without ejaculation
  • Factors that increase risk:
    • Source person is known to be HIV-infected with high viral load
    • An oral mucosa that is not intact (e.g., oral lesions, gingivitis, wounds)
    • Blood exposure — it is important to note that blood exposure can be minimal and therefore not recognized by the exposed person. If the exposed person reports frank blood exposure, PEP would be indicated
    • Presence of genital ulcer disease or other STIs

Types of exposures that do not warrant nPEP (no risk):

  • Kissing: There is no risk associated with close-mouthed kissing. There is a remote risk associated with open-mouthed kissing if there are sores or bleeding gums and blood is exchanged [Kaplan and Heimer 1992]. 
  • Oral-to-oral contact without mucosal damage (mouth-to-mouth resuscitation)
  • Human bites not involving blood
  • Exposure to solid-bore needles or sharps not in recent contact with blood: Examples of solid-bore needles include tattoo needles and lancets used by diabetics to measure blood-sugar levels.
  • Mutual masturbation without skin breakdown or blood exposure

The appendix, Estimated Per-Act Probability of Acquiring HIV, provides risk calculations for specific risk behaviors.

HIV exposure through sexual and drug-using activities: The clinician should have a frank discussion with the patient regarding sexual activities, needle-sharing, and other drug-using activities that have a potential for exposure to blood and body fluids (see above and the appendix). The behaviors that confer the highest risk are needle-sharing and receptive anal intercourse with an infected source [CDC 1997; Varghese et al. 2002; DeGruttola et al. 1989]. 

Clinicians should also discuss factors that influence HIV transmission risk, including trauma at the site of exposure, the presence of genital ulcer disease and/or other STIs [CDC 2010; LeGoff et al. 2007], and high plasma viral load in the HIV-infected source person [Tovanabutra et al. 2002; Patterson et al. 2002]. Other factors that may enhance transmission include cervical ectopy and lack of male circumcision [Patterson et al. 2002; Bailey et al. 2007; Gray et al. 2007]. Factors that may decrease transmission risk include exposure to a source person who is receiving effective ART and condom use [Weller and Davis 2002]. Correct condom use is highly effective in preventing transmission of HIV; however, during the post-exposure evaluation, it often is not possible to reliably ascertain whether condoms were used correctly or whether breakage, slippage, or spillage occurred.

HIV exposure through needlestick injuries: Another route of exposure that prompts requests for nPEP is needlestick injuries in the non-healthcare setting. Factors associated with risk from needlestick injuries outside of the healthcare setting include the potential source of the needle, type of needle, presence of blood, and skin penetration.

People who incur needlestick injuries from discarded needles are often concerned about potential HIV exposure. Consideration of potential risk from discarded needles should include the prevalence of HIV in the community or facility where the exposure occurred and the surrounding prevalence of injection drug use. However, the risk of HIV transmission through exposure to dried blood found on syringes is extremely low [Zamora et al. 1998]. Discarded needles should not be tested for HIV because of low yield and the risk of injury to personnel involved in testing. Vaccination to prevent tetanus and administration of hepatitis B immunoglobulin and vaccine may be indicated for needlestick injuries resulting in puncture wounds.

HIV exposure through bites: An estimated 250,000 human bites occur annually in the United States in a variety of settings [AAP 1997]. Although possible, HIV transmission following bites is thought to be extremely rare. While there have been many reported instances of bites, there have been few cases of HIV transmission as a result of a human bite exposure. The few documented cases of possible HIV transmission following bites were in adults exposed to blood-tinged saliva [Pretty et al. 1999; Vidmar et al. 1996].

A bite wound that results in blood exposure should prompt consideration of nPEP. When a human bite occurs, it is possible for both the person bitten and the biter to incur blood exposure (see below). Use of nPEP in this setting potentially would be indicated when there is significant exposure to deep, bloody wounds. A bite is not considered a risk exposure to either party when the integrity of the skin is not disrupted.

Scenarios in which bites may result in blood exposure:

  • Blood exposure to the biter: when the biter inflicts a wound that breaks the skin, and blood from the bitten person enters the biter’s mouth
  • Blood exposure to the bitten person: when the biter has blood in his/her mouth (e.g., from bleeding gums or lesions) and inflicts a wound that breaks the skin of the person bitten
  • Blood exposure to both parties: when there is a break in the skin of the person who was bitten and the biter had blood in his/her mouth (e.g., from bleeding gums or lesions)

HIV Status of the Source Person

In most cases of non-occupational exposures, the source person is not available for testing. The HIV status of the source person should not be the main focus at the initial presentation, but rather determination of whether the exposure warrants nPEP and, when indicated, prompt initiation of nPEP. Following are the possible scenarios regarding availability of the source person and how each may affect decision-making.

When the source person is available and consents to HIV testing, HIV testing using rapid technology is strongly recommended as soon as possible in order to aid in decision-making regarding nPEP. Results from rapid testing are usually available within 60 minutes. Laboratory-based screening tests may be used if results can be available within an hour. If the test results are not immediately available, the initiation of nPEP should not be delayed pending the test result.

The most sensitive screening tests available should be used to allow for detection of early or acute HIV infection. The CDC recommends screening with an FDA-approved 4th-generation antigen/antibody combination immunoassay, followed by confirmation with an FDA-approved HIV-1/HIV-2 antibody-differentiation assay (see the CDC’s Recommended Laboratory HIV Testing Algorithm for Serum or Plasma Specimens). Source persons who are in the “window period” prior to seroconversion may not be identified. When the source person’s screening test result is negative and the clinician has ascertained that the source person could have been exposed to HIV in the previous 6 weeks or when the source person’s screening result is positive but the confirmatory antibody-differentiation assay is nonreactive or indeterminate, then a plasma HIV RNA assay should be obtained to determine the source person’s HIV status. In these situations, nPEP should be initiated and continued until results of the plasma HIV RNA assay are available.

Baseline Testing for Patients Who Present With Risk Exposures

HIV testing: Baseline HIV testing of the exposed person identifies individuals who were already infected with HIV at the time of presentation. This allows decisions to be made regarding the initiation of ART to treat established HIV infection rather than nPEP to prevent it. However, the nPEP regimen should not be discontinued until the positive result is repeated with a confirmatory assay.

KEY POINT
  • A negative baseline HIV test only demonstrates that the exposed person was not previously infected with HIV before the exposure occurred; the baseline HIV test cannot determine whether the exposed person was infected as a result of the exposure for which he/she is presenting.

Sexually transmitted infections other than HIV: Risk behaviors leading to HIV infection also put the patient at risk for other STIs. Patients who present for nPEP should be evaluated for other STIs after a sexual exposure.

Baseline testing for STIs generally cannot detect STIs that were acquired as a result of the exposure, but may detect infections prior to the exposure leading to HIV PEP. Presentation for nPEP provides an opportunity to screen and treat individuals at risk for STIs. High rates of concomitant STIs at the time of presentation for nPEP have been found in men who have sex with men [Hamlyn et al. 2006; Jamani et al. 2013]. Routine empiric treatment for STIs is not recommended for sexual exposures that are not related to sexual assault. Patients should be educated about STI symptoms and instructed to call their healthcare provider if symptoms occur. Follow-up STI testing should be considered at 2 weeks post-exposure to definitively exclude STI acquisition from the exposure.

Management of exposure to other STIs differs for cases of sexual assault. See PEP for Victims of Sexual Assault.

Pregnancy testing: Emergency contraception for individuals of child-bearing age should be initiated within 72 hours of the sexual exposure to be effective; optimally, pregnancy prophylaxis should be initiated within 12 hours of the exposure. The following websites offer more information about the use of emergency contraception:

References

AAP. Hepatitis B. 1997 Red Book: Report of the Committee on Infectious Diseases; 24th edition. American Academy of Pediatrics, Elk Grove Village; 1997:247-260.

Bailey RC, Moses S, Parker CB, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: A randomised controlled trial. Lancet 2007;369:643-656. [PubMed]

CDC. Sexually Transmitted Diseases Treatment Guidelines 2010. http://cdc.gov/std/treatment

CDC. Transmission of HIV possibly associated with exposure of mucous membrane to contaminated blood. MMWR Morb Mortal Wkly Rep 1997;46(27):620-623. [PubMed]

DeGruttola V, Seage GR 3rd, Mayer KH, et al. Infectiousness of HIV between male homosexual partners. J Clin Epidemiol 1989;42:849-856. [PubMed]

Gray RH, Kigozi G, Serwadda D, et al. Male circumcision for HIV prevention in men in Rakai, Uganda: A randomised trial. Lancet 2007;369:657-666. [PubMed]

Hamlyn E, McAllister J, Winston A, et al. Is screening for sexually transmitted infections in men who have sex with men who receive non-occupational HIV post-exposure prophylaxis worthwhile? Sex Transm Infect 2006;82:21-23. [PubMed]

Jamani S, Gulholm T, Poynten IM, et al. Timing and frequency of chlamydia and gonorrhea testing in a cross-sectional study of HIV postexposure prophylaxis recipients. Sex Transm Infect 2013;May 29:ePub ahead of print. [PubMed]

Kaplan EH, Heimer R. A model-based estimate of HIV infectivity via needle sharing. J Acquir Immune Defic Syndr 1992;5:1116-1118. [PubMed]

LeGoff J, Weiss HA, Gresenguet G, et al. Cervicovaginal HIV-1 and herpes simplex virus type 2 shedding during genital ulcer disease episodes. AIDS 2007;21:1569-1578. [PubMed]

Patterson BK, Landay A, Siegel JN, et al. Susceptibility to human immunodeficiency virus-1 infection of human foreskin and cervical tissue grown in explant culture. Am J Pathol 2002;161:867-873. [PubMed]

Pretty IA, Anderson GS, Sweet DJ. Human bites and the risk of human immunodeficiency virus transmission. Am J Forensic Med Pathol 1999;20:232-239. [PubMed]

Tovanabutra S, Robison V, Wongtrakul J, et al. Male viral load and heterosexual transmission of HIV-1 subtype E in Northern Thailand. J Acquir Immune Defic Syndr 2002;29:275-283. [PubMed]

Varghese B, Maher JE, Peterman TA, et al. Reducing the risk of sexual HIV transmission: Quantifying the per-act risk for HIV on the basis of choice of partner, sex act, and condom use. Sex Transm Dis 2002;29:38-43. [PubMed]

Vidmar L, Poljak M, Tomazic J, et al. Transmission of HIV-1 by human bite. Lancet 1996;347:1762. [PubMed]

Weller S, Davis K. Condom effectiveness in reducing heterosexual HIV transmission. Cochrane Database Syst Rev 2002;1:CD003255. [PubMed]

Zamora AB, Rivera MO, García-Algar Ó, et al. Detection of infectious human immunodeficiency type 1 virus in discarded syringes of intravenous drug users. Pediatr Infect Dis J 1998;17:655-657. [PubMed]

Appendix: Estimated Per-Act Probability of Acquiring HIV

October 2014

Risk per 10,000 exposures of acquiring HIV from a known HIV-infected source by exposure act and factors that may increase risk. Modified from the Centers for Disease Control and Prevention, HIV Risk Transmission Fact Sheet. July 2012. 

Parenteral Exposure

  • Blood transfusion: 9,000 [Donegan et al. 1990; Kaplan and Heimer 1992; Bell 1997]
  • Needle-sharing during injection drug use: 67
  • Percutaneous (needlestick): 30

Factors associated with increased risk of HIV transmission from needle-sharing/needlestick injuries:

  • Source person is known to be HIV-infected and is not receiving ART or has incomplete viral suppression; the risk of transmission increases with higher HIV viral load levels in the source person [Quinn et al. 2000; Tovanabutra et al. 2002]
  • Hollow-bore needle
  • Deep skin penetration
  • Presence of blood on needle; however, risk through exposure to dried blood on discarded needles is extremely low [Zamora et al. 1998]

Sexual Exposure

  • Receptive anal intercourse: 50 [Varghese et al. 2002; European Study Group 1992]
  • Receptive penile-vaginal intercourse: 10 [Varghese et al. 2002; European Study Group 1992; Leynaert et al. 1998]
  • Insertive anal intercourse: 6.5 [Varghese et al. 2002; European Study Group 1992]
  • Insertive penile-vaginal intercourse: 5 [Varghese et al. 2002; European Study Group 1992]
  • Receptive oral intercourse: Low [Varghese et al. 2002; Page-Shafer et al. 2002]
  • Insertive oral intercourse: Low [Varghese et al. 2002]
  • HIV transmission through oral sex has been documented, but rare. Accurate estimates of risk are not available. It is prudent to recommend nPEP for receptive oral sex with ejaculation, although discussion about the low risk should occur.

Factors associated with increased risk of transmission from sexual exposure:

  • Source person is known to be HIV-infected and is not receiving ART or has incomplete viral suppression; the risk of transmission increases with higher HIV viral load levels in the source person [Quinn et al. 2000; Tovanabutra et al. 2002], most notably during acute HIV infection when the probability of transmission has been shown to be 8- to almost 12-fold higher than exposures that take place after the viral set point [Wawer et al. 2005; Pilcher et al. 2004]
  • Lack of use of barrier protection, such as male or female condoms
  • Presence of genital ulcer disease or other STIs [CDC 2010; LeGoff et al. 2007]
  • Trauma at the site of exposure
  • Blood exposure — it is important to note that blood exposure can be minimal and therefore not recognized by the exposed person. If the exposed person reports frank blood exposure, PEP would be indicated
  • Lack of male circumcision [Bailey et al. 2007; Gray et al. 2007]
  • Cervical ectopy [Patterson et al. 2002]
  • Oral mucosa is not intact (e.g., oral lesions, gingivitis, wounds)–for oral sex exposure

Other Types of Exposure 

HIV transmission through these exposure routes is technically possible but extremely unlikely and cases are not well documented.

  • Biting: Negligible [Pretty et al. 1999]
  • Spitting: Negligible
  • Throwing bodily fluids (including semen or saliva): Negligible
  • Sharing sex toys: Negligible

Factors associated with increased risk of transmission from otherwise negligible-risk exposures:

  • Source person is known to be HIV-infected with high HIV viral load [Quinn et al. 2000; Tovanabutra et al. 2002]
  • Activity involved exposure to blood
References

Bailey RC, Moses S, Parker CB, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: A randomised controlled trial. Lancet 2007;369:643-656. [PubMed]

Bell DM. Occupational risk of human immunodeficiency virus infection in healthcare workers: An overview. Am J Med 1997;102:9-15. [PubMed]

CDC. Sexually Transmitted Diseases Treatment Guidelines 2010. http://cdc.gov/std/treatment

Donegan E, Stuart M, Niland JC, et al. Infection with human immunodeficiency virus type 1 (HIV-1) among recipients of antibody-positive blood donations. Ann Intern Med 1990;113:733-739. [PubMed]

European Study Group on Heterosexual Transmission of HIV. Comparison of female to male and male to female transmission of HIV in 563 stable couples. BMJ 1992;304:809-813. [PubMed]

Gray RH, Kigozi G, Serwadda D, et al. Male circumcision for HIV prevention in men in Rakai, Uganda: A randomised trial. Lancet 2007;369:657-666. [PubMed]

Kaplan EH, Heimer R. A model-based estimate of HIV infectivity via needle sharing. J Acquir Immune Defic Syndr 1992;5:1116-1118. [PubMed]

LeGoff J, Weiss HA, Gresenguet G, et al. Cervicovaginal HIV-1 and herpes simplex virus type 2 shedding during genital ulcer disease episodes. AIDS  2007;21:1569-1578. [PubMed]

Leynaert B, Downs AM, de Vincenzi I, et al. Heterosexual transmission of HIV: Variability of infectivity throughout the course of infection. Am J Epidemiol 1998;148:88-96. [PubMed]

Page-Shafer K, Shiboski CH, Osmond DH, et al. Risk of HIV infection attributable to oral sex among men who have sex with men and in the population of men who have sex with men. AIDS 2002;16:2350-2352. [PubMed]

Patterson BK, Landay A, Siegel JN, et al. Susceptibility to human immunodeficiency virus-1 infection of human foreskin and cervical tissue grown in explant culture. Am J Pathol 2002;161:867-873. [PubMed]

Pilcher CD, Tien HC, Eron JJ, et al. Brief but efficient: Acute HIV infection and the sexual transmission of HIV. J Infect Dis 2004;189:1785-1792. [PubMed]

Pretty IA, Anderson GS, Sweet DJ. Human bites and the risk of human immunodeficiency virus transmission. Am J Forensic Med Pathol 1999;20:232-239. [PubMed]

Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med 2000;342:921-929. [PubMed]

Tovanabutra S, Robison V, Wongtrakul J, et al. Male viral load and heterosexual transmission of HIV-1 subtype E in Northern Thailand. J Acquir Immune Defic Syndr 2002;29:275-283. [PubMed]

Varghese B, Maher JE, Peterman TA, et al. Reducing the risk of sexual HIV transmission: Quantifying the per-act risk for HIV on the basis of choice of partner, sex act, and condom use. Sex Transm Dis 2002;29:38-43. [PubMed]

Wawer MJ, Gray RH, Sewankambo NK, et al. Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis 2005;191:1403-1409. [PubMed]

Zamora AB, Rivera MO, García-Algar Ó, et al. Detection of infectious human immunodeficiency type 1 virus in discarded syringes of intravenous drug users. Pediatr Infect Dis J 1998;17:655-657. [PubMed]

Behavioral Intervention and Risk-Reduction Counseling

Medical Care Criteria Committee, December 2014

RECOMMENDATIONS
Risk Reduction and Prevention
  • The clinician or a member of the HIV care team should provide risk-reduction counseling and primary prevention counseling whenever someone is assessed for nPEP, regardless of whether PEP is initiated. (A2)
  • Clinicians should assess for emotional, psychological, and social factors that can contribute to risk behavior, such as depression, history of sexual abuse, and drug and alcohol use. (A2)
  • Clinicians should refer patients to mental health and/or substance use programs when indicated and should consider the need for intensive risk-reduction counseling services. (A2)
  • Persons who present with repeated high-risk behavior or for repeat courses of nPEP should be the focus of intensified education and prevention interventions and, after completion of the 28-day nPEP regimen, initiation of pre-exposure prophylaxis (PrEP) should be considered. (A2)

Non-occupational PEP should not be routinely dismissed solely on the basis of repeated risk behavior or repeat presentation for nPEP. Rather, presentation of persons with repeated high-risk behavior or for repeat courses of nPEP should be viewed as an opportunity for intensification of education and prevention planning in a high-risk individual. Intent to change behavior should be assessed, and an individualized risk-reduction plan should be developed. After completion of the 28-day nPEP regimen, initiation of pre-exposure prophylaxis (PrEP) should be considered [USPHS 2014a, 2014b]. See NYSDOH AI PrEP to Prevent HIV Acquisition Guideline.

References

U.S. Public Health Service (USPHS). Preexposure Prophylaxis for HIV Prevention in the United States – 2014a. A Clinical Practice Guideline. Centers for Disease Control and Prevention; Atlanta, GA. www.cdc.gov/hiv/pdf/PrEPguidelines2014.pdf

U.S. Public Health Service (USPHS). Preexposure Prophylaxis for HIV Prevention in the United States – 2014b. Clinical Providers’ Supplement. Centers for Disease Control and Prevention; Atlanta, GA. www.cdc.gov/hiv/pdf/guidelines/PrEPProviderSupplement2014.pdf

Timing of Initiation

Medical Care Criteria Committee, October 2014

RECOMMENDATIONS
When to Start nPEP
  • When a potential non-occupational exposure to HIV occurs, every effort should be made to initiate PEP as soon as possible, ideally within 2 hours. (A2)
  • Decisions regarding initiation of nPEP beyond 36 hours post exposure should be made on a case-by-case basis with the realization of diminished efficacy when timing of initiation is prolonged. (A3)

Data from animal models of PEP have shown that effective antiretroviral treatment is most likely to prevent infection when initiated within 24 to 36 hours of exposure [Otten et al. 2000; Smith et al. 2000; Van Rompay et al. 2000; Black 1997; Van Rompay et al. 1998; Tsai et al. 1998]. HIV virions can traverse epithelial barriers in just hours, and many antiretroviral medications require an intracellular activation step that delays the onset of antiviral activity. Therefore, every effort should be made to initiate nPEP as soon as possible following an exposure and ideally within 2 hours. An absolute elapsed time after which nPEP should not be given cannot be stated with certainty.

Decisions regarding initiation of nPEP beyond 36 hours post exposure should be made by the clinician in conjunction with the patient with the realization of diminished efficacy when timing of initiation is prolonged. Some individuals who are victims of sexual assault or who have higher-risk exposures, such as unprotected anal receptive intercourse with a known HIV-infected partner, may wish to initiate nPEP, even though they may present for treatment more than 36 hours following the exposure. These decisions need to be individualized based on the type of exposure, the patient’s desire to initiate nPEP, and the amount of time that has elapsed.

Once a decision has been made that nPEP is indicated, patients should be encouraged to initiate the regimen immediately. After the first dose is administered, telephone or in-person consultation with an experienced HIV care provider is recommended. Expert advice may be obtained from the Clinical Education Initiative CEI PEP Line at 1-866-637-2342. When using the PEP Line, providers from New York State should identify themselves as practicing in the State.

References

Black RJ. Animal studies of prophylaxis. Am J Med 1997;102:39-44. [PubMed]

Otten RA, Smith DK, Adams DR, et al. Efficacy of postexposure prophylaxis after intravaginal exposure of pig-tailed macaques to a human-derived retrovirus (human immunodeficiency virus type 2). J Virol 2000;74:9771-9775. [PubMed]

Smith MS, Foresman L, Lopez GJ, et al. Lasting effects of transient postinoculation tenofovir [9-R-(2-Phosphonomethoxypropyl)adenine] treatment on SHIV (KU2) infection of rhesus macaques. Virology 2000;277:306-315. [PubMed]

Tsai CC, Emau P, Follis KE, et al. Effectiveness of postinoculation (R)-9-(2-phosphonylmethoxypropyl) adenine treatment for prevention of persistent simian immunodeficiency virus SIVmne infection depends critically on timing of initiation and duration of treatment. J Virol 1998;72:4265-4273. [PubMed]

Van Rompay KK, Miller MD, Marthas ML, et al. Prophylactic and therapeutic benefits of short-term 9-[2-(R)-(phosphonomethoxy) propyl]adenine (PMPA) administration to newborn macaques following oral inoculation with simian immunodeficiency virus with reduced susceptibility to PMPA. J Virol 2000;74:1767-1774. [PubMed]

Van Rompay KK, Berardi CJ, Aguirre NL, et al. Two doses of PMPA protect newborn macaques against oral simian immunodeficiency virus infection. AIDS 1998;12:F79-F83. [PubMed]

Counseling and Education Before Initiating PEP

Medical Care Criteria Committee, October 2014

RECOMMENDATION
Pre-nPEP Initiation Counseling
  • The clinician should discuss the following issues with the patient and should document that they were discussed before initiating a regimen (A3):
    • Potential benefit, unproven efficacy, and potential toxicity of nPEP
    • Duration of nPEP regimen
    • Importance of adherence to the treatment regimen to prevent nPEP failure or the development of drug resistance should infection occur
    • Need to reduce risk and prevent exposure to others
    • Clinical and laboratory monitoring and follow-up schedule
    • Signs and symptoms of acute HIV infection
    • How a full supply of medication will be obtained

Antiretroviral medications have the potential to cause significant side effects and toxicity. The patient should be made aware of these possibilities and weigh them against the potential but unproven benefit of nPEP. Non-occupational PEP is presumed to be more effective when patients strictly adhere to the prescribed regimen. Follow-up visits will need to occur on a regular basis to assess for adherence, drug tolerance, and medication toxicity (see Follow-Up and Sequential HIV Testing). Supports to facilitate adherence with the treatment regimen should be evaluated and provided to the extent possible.

Sexual assault victims can access reimbursement for PEP through the New York State Office of Victim Services; however, private insurers may refuse to reimburse for other types of nPEP. Strategies should be actively sought to provide medication for those who cannot obtain it. Once treatment is initiated, the initiating provider should assume responsibility for ensuring that the patient has access to a full supply of medication to complete the 28-day course of nPEP. For payment options, see NYSDOH Payment Options for Adults and Adolescents for Post Exposure Prophylaxis Following Sexual Assault and Payment Options for Adults and Adolescents For Post Exposure Prophylaxis for all other Non-Occupational Exposures. For more information on accessing reimbursement through the Office of Victim Services, see PEP for Victims of Sexual Assault.

ART Regimens for nPEP

Medical Care Criteria Committee, updated May 2018

RECOMMENDATIONS
What to Start
  • The preferred PEP regimen is tenofovir + emtricitabine (lamivudine may be substituted for emtricitabine) plus either raltegravir or dolutegravir [see DTG safety statement]. See text for dosing and Antiretroviral Agents Recommended for PEP for links to descriptions of each drug). (A2)
    • The first dose should be given as soon as possible after exposure, ideally within 2 hours.
    • The recommended duration of PEP is 28 days. (A2)
  • Starter packs with a 3- to 5-day supply of medication should be available on-site for rapid initiation of treatment, and arrangements should be made for continuation of treatment. (A3)
  • If the source person is known to be HIV-infected and information is immediately available regarding past and present ART experience, current level of viral suppression, or resistance profile, the treating clinician, in consultation with a clinician experienced in managing PEP, should individualize the PEP regimen to maximize potential effectiveness against the exposed HIV strain (A2). Initiation of the first dose and continuation of PEP should never be delayed while awaiting this information (A2). If indicated, the regimen can be changed when more information becomes available.
  • The text lists recommended alternative PEP regimens that should be used in the setting of potential HIV resistance, toxicity risks, clinician preference, or constraints on the availability of particular agents (A2).
  • Clinicians should switch exposed persons to an alternative regimen if the initial or subsequent PEP regimen is not well tolerated (A2) (see Antiretroviral Agents Recommended for PEP for links to potential adverse events).
  • Treating clinicians should consult with a clinician experienced in managing PEP when alternative agents are prescribed or if there is doubt as to whether PEP should be continued after the first dose. (A2)
  • The prescribing clinician should ensure that the exposed person has access to the full 28-day recommended course of antiretroviral medications (A3) and is appropriately monitored for toxicities during the treatment.
  • Treating clinicians who do not have access to experienced HIV clinicians should call the Clinical Education Initiative CEI PEP Line at 1-866-637-2342. When using the PEP Line, providers from New York State should identify themselves as practicing in the State.
Duration of nPEP Regimen
  • The recommended duration of nPEP is 28 days.
  • If the exposed person’s baseline test shows evidence of HIV infection acquired before the exposure and initiation of nPEP, decisions regarding continuation of ART should be based on current treatment guidelines (A1). However, the nPEP regimen should not be discontinued until the positive result is repeated with a confirmatory assay. (A1)
  • If the exposed person’s week 4 post-exposure HIV test results are indeterminate or the exposed person has symptoms suggestive of acute HIV infection, clinicians should continue ART beyond 28 days until a definitive diagnosis is established. (A2)
  • When the source person is confirmed to be HIV-negative, clinicians should discontinue the nPEP regimen before completion. (A1)
Preferred Alternative nPEP Regimen
  • The preferred alternative PEP regimen is tenofovir + emtricitabine (lamivudine may be substituted for emtricitabine) plus ritonavir-boosted darunavir, atazanavir, or fosamprenavir (A2) (see text).
  • Clinicians should carefully assess for potential drug interactions between these agents and other medications (including prescription medications and over-the-counter drugs, such as proton pump inhibitors and H2-blockers) that the patient may be taking. (A1) See Antiretroviral Agents Recommended for PEP for links to information regarding dosing, adverse effects, and drug interactions.
  • Clinicians should consult a clinician experienced in managing nPEP when using alternative PEP regimens (A2). If consultation cannot be immediately obtained, the first dose of the regimen should be given rather than delaying initiation, with consultation occurring as soon as possible thereafter (A2). Clinicians who do not have access to experienced HIV clinicians should call the Clinical Education Initiative CEI PEP Line at 1-866-637-2342. When using the PEP Line, providers from New York State should identify themselves as practicing in the State.
Other Alternative Regimens
  • Clinicians who continue to prescribe zidovudine for PEP should recognize and inform patients that the drug has significant side effects and that better-tolerated agents are available (see Antiretroviral Agents Recommended for PEP for links to side effects associated with alternative PEP agents).
Dolutegravir (DTG) Safety Statement, May 2018

On May 18, 2018, the FDA and the DHHS Antiretroviral Guidelines Panels issued statements in response to preliminary results from a study that reported increased risk of neural tube defects in babies born to mothers taking DTG-based ARV drug regimens at the time of conception [AIDSinfo 2018; FDA 2018].

Until more data become available, DTG-containing regimens should be avoided in any HIV-exposed individual who is or could become pregnant and is not using effective contraception. If there are no alternatives to DTG for individuals of child-bearing potential, then clinicians should strongly advise the use of effective contraception and should obtain a pregnancy test before initiating treatment.

For more information, see: DHHS Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States

Post-Exposure Prophylaxis Regimens for Non-Occupational Exposures to HIV 

Table 1: Preferred and Alternative Antiretroviral Regimens for nPEP

RECOMMENDED Regimen
Note: All are oral medications

Notes

Tenofovir disoproxil fumarate (TDF) 300 mg* daily plus emtricitabine (FTC) 200 mg daily plus raltegravir (RAL) 400 mg twice daily or dolutegravir (DTV) 50 mg daily [see DTG safety statement, above]

  • When the source is known to be HIV-infected, past and current ART experience, viral load data, and genotypic or phenotypic resistance data (if available) may indicate the use of an alternative PEP regimen. Consult with a clinician experienced in managing PEP.
  • Renal insufficiency: The dosing of TDF and FTC/lamivudine (3TC) should be adjusted in patients with baseline creatinine clearance <50 mL/min (see Antiretroviral Agents Recommended for PEP for links to dosing recommendations).
  • TDF should be used with caution in exposed persons with renal insufficiency or who are taking concomitant nephrotoxic medications.
  • Fixed-dose combinations should not be used in patients who need dose adjustment due to renal failure.
  • 3TC 300 mg PO daily may be substituted for FTC. However, a fixed-dose combination (Truvada) is available when TDF is used with FTC.
  • RAL or DTV: See Antiretroviral Agents Recommended for PEP for links to drug-drug interactions, dosing adjustments, and contraindications associated with raltegravir and dolutegravir.
Preferred Alternative Regimen
Note: All are oral medications
Notes

Tenofovir disoproxil fumarate (TDF) 300 mg PO daily plus emtricitabine (FTC) 200 mg daily plus darunavir (DRV) 800 mg daily, or atazanavir (ATV) 300 mg daily, or fosamprenavir (FPV) 1400 mg daily and ritonavir (RTV) 100 mg daily 

Other Alternative Regimens Notes
  • Tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC) + zidovudine (ZDV)
  • Tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC) + lopinavir/ritonavir (LPV/r)
  • Zidovudine (ZDV) + lamivudine (3TC) + one of the following ritonavir (RTV)-boosted protease inhibitors: darunavir (DRV), atazanavir (ATV), fosamprenavir (FPV), or lopinavir (LPV)
  • See Antiretroviral Agents Recommended for PEP for links to full dosing information for alternative ARV agents that may be used in the PEP regimen.
  • Dosing interval of ZDV should be adjusted in patients with baseline creatinine clearance <15 mL/min. The dosing interval of 3TC, FTC, and TDF should be adjusted in patients with baseline creatinine clearance <50 mL/min. Fixed-dose combinations should not be used in patients who need dose adjustment due to renal failure.
  • 3TC 300 mg*daily may be substituted for FTC. However, a fixed-dose combination (Truvada) is available when TDF is used with FTC.
  • FTC 200 mg* daily may be substituted for 3TC. However, a fixed-dose combination (Combivir) is available when ZDV is used with 3TC.

Rationale: This Committee now recommends tenofovir + emtricitabine (lamivudine may be substituted for emtricitabine) plus either raltegravir or dolutegravir as the preferred initial PEP regimen because of its excellent tolerability, proven potency in established HIV infection, and ease of administration.

The recommended regimen has a favorable side effect profile, fewer potential drug-drug interactions, and an expected efficacy similar to PEP regimens containing zidovudine or protease inhibitors. Studies have shown increased rates of adherence and regimen completion when tenofovir + either emtricitabine or lamivudine have been used as components of the PEP regimen [Tosini et al. 2010; Mayer et al. 2008]. Limited data show similar improved tolerability with tenofovir + emtricitabine plus raltegravir [Mayer et al. 2012; Annandale et al. 2012; McAllister et al. 2017]. Additionally, tenofovir + emtricitabine has been highly successful in recent studies of pre-exposure prophylaxis [Grant et al. 2010; Baeten and Celum 2011; Thigpen et al. 2011].

This Committee no longer recommends that zidovudine must be included in PEP regimens because it is believed to have no clear advantage in expected efficacy over tenofovir while having significantly higher rates of treatment-limiting side effects. As experience with PEP continues to accumulate, it has become increasingly clear that tolerability is one of the most important factors in selecting a PEP regimen, especially when the source person is not available for testing and the patient will need to complete the full 28-day course.

Unlike protease inhibitors, which block HIV replication in steps after integration with cellular DNA, all drugs in the recommended regimen (tenofovir, emtricitabine, and raltegravir or dolutegravir) act before viral integration with cellular DNA, providing a theoretical advantage in preventing establishment of HIV infection.

Use of a three-drug PEP regimen: Once a decision has been made that a significant risk exposure has occurred and that PEP is warranted, this Committee recommends a three-drug regimen as the preferred option.

Duration: The recommended 28-day treatment duration is based on limited animal data and expert opinion [Tsai et al. 1998]. If the source person is confirmed to be HIV-negative, the PEP regimen should be discontinued before completion.

If at any time acute HIV infection is suspected, consultation with a clinician experienced in managing acute HIV infection should occur immediately (also see Diagnosis and Management of Acute HIV Guideline). Clinicians who do not have access to experienced HIV clinicians can call the New York State Clinician Education Initiative CEI PEP Line at 1-866-637-2342 (24 hours/7 days per week). When using the PEP Line, providers from New York State should identify themselves as practicing in the State.

Preferred alternative nPEP regimen: The preferred alternatives to the recommended regimen are acceptable options when the preferred regimen is not available. They are expected to be less well tolerated than the preferred regimen of tenofovir + emtricitabine plus either raltegravir or dolutegravir, but significantly better tolerated than regimens containing zidovudine or lopinavir/ritonavir. Effectiveness of the preferred alternative regimens is expected to be equivalent to other alternative regimens (see Other Alternative PEP Regimens, below); however, effectiveness will differ if the source person’s HIV strain is resistant to one or more of the agents.

The potential for drug interactions in patients receiving protease inhibitors is increased due to the extensive cytochrome P450 interactions. For example, proton pump inhibitors may adversely affect the absorption of atazanavir. Clinicians should assess for potential interactions before prescribing a PEP regimen.

RESOURCES: DRUG-DRUG INTERACTIONS

Other alternative regimens: Other alternative PEP regimens are listed above and may be acceptable in certain situations. For patients who are paying out of pocket, cost is a factor to weigh in selecting a regimen. VeryWell publishes the average wholesale price of HIV drugs

Use of lopinavir/ritonavir has greater potential for drug interactions and side effects than raltegravir, dolutegravir, or the preferred protease inhibitors (darunavir, atazanavir, or fosamprenavir; with each protease inhibitor taken with ritonavir 100 mg daily), with little added efficacy benefit expected. Recent studies have demonstrated decreasing protease inhibitor resistance among HIV strains [Pacquet et al. 2011], suggesting that there may be diminishing benefit to choosing lopinavir/ritonavir for its activity against resistant HIV strains. The other recommended ritonavir-boosted protease inhibitor regimens listed above also have excellent activity against protease inhibitor-resistant strains and are better tolerated than lopinavir/ritonavir.

This Committee recommends a three-drug regimen because of the greater likelihood of enhanced effectiveness; however, use of a two-drug regimen would be preferred to discontinuing the regimen completely if tolerability is a concern. An early case-control study of occupational exposure demonstrated an 81% reduction in seroconversion with the use of zidovudine monotherapy alone [Cardo et al. 1997], suggesting that treatment with any active antiretroviral agent is beneficial in reducing risk.

Antiretroviral Drugs to Avoid as PEP Components

Antiretroviral drugs that are generally not recommended as components of PEP are listed below. Consultation with a clinician experienced in managing PEP is recommended before using any of the antiretroviral drugs listed below (see nPEP for HIV-Exposed Women Who Are Pregnant or Breastfeeding for drugs to avoid in exposed persons who are pregnant or breastfeeding). If efavirenz is used in individuals who are or could become pregnant, a pregnancy test should be obtained before initiation and the patient should be counseled about the use of effective contraception while taking efavirenz.

  • Efavirenz
    • Poor adherence anticipated due to CNS side effects, which are common
    • CNS side effects may impair work after the initial and subsequent doses
    • EFV should be avoided in first 6 weeks of pregnancy and in individuals who are or could become pregnant who are not using effective contraception
    • Substantial EFV resistance in community HIV isolates
  • Nevirapine: Contraindicated for use in PEP due to potential for severe hepatotoxicity [CDC 2001]
  • Abacavir: Potential for hypersensitivity reactions
  • Stavudine, didanosine: Possibility of toxicities
  • Nelfinavir, indinavir: Poorly tolerated
  • CCR5 co-receptor antagonists: Lack of activity against potential CXCR4 tropic virus

Consultation with a clinician experienced in HIV PEP management is recommended before using agents for which there are limited data, such as rilpivirine and etravirine.

References

AIDSinfo. Statement on Potential Safety Signal in Infants Born to Women Taking Dolutegravir from the HHS Antiretroviral Guideline Panels. 2018 May 18. https://aidsinfo.nih.gov/news/2094/statement-on-potential-safety-signal-in-infants-born-to-women-taking-dolutegravir [accessed 2018 May 23]

Annandale D, Richardson C, Fisher M, et al. Raltegravir-based post-exposure prophylaxis (PEP): A safe, well-tolerated alternative regimen. J Int AIDS Soc 2012;15(Suppl 4):18165. Available at: http://www.jiasociety.org/index.php/jias/article/view/18165

Baeten J, Celum C. Antiretroviral pre-exposure prophylaxis for HIV-1 prevention among heterosexual African men and women: The Partners PrEP study. HIV-1-infected adults. Abstract MOAX0106. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 2011 Jul 17-20; Rome, Italy. https://f1000.com/prime/12630956

Cardo DM, Culver DH, Ciesielski CA, et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure: Centers for Disease Control and Prevention Needlestick Surveillance Group. N Engl J Med 1997;337:1485-1490. [PubMed]

CDC. Serious adverse events attributed to nevirapine regimens for postexposure prophylaxis after HIV exposures — Worldwide, 1997-2000. MMWR Morb Mortal Wkly Rep 2001;49:1153-1156. [PubMed]

U.S. Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA to evaluate potential risk of neural tube birth defects with HIV medicine dolutegravir (Juluca, Tivicay, Triumeq). 2018 May 18. https://www.fda.gov/Drugs/DrugSafety/ucm608112.htm [accessed 2018 May 23]

Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010;363:2587-2599. [PubMed]

Mayer KH, Mimiaga MJ, Cohen D, et al. Tenofovir DF plus lamivudine or emtricitabine for nonoccupational postexposure prophylaxis (nPEP) in a Boston Community Health Center. J Acquir Immune Defic Syndr 2008;47:494-499. [PubMed]

Mayer KH, Mimiaga MJ, Gelman M, et al. Raltegravir, tenofovir DF, and emtricitabine for postexposure prophylaxis to prevent the sexual transmission of HIV: Safety, tolerability, and adherence. J Acquir Immune Defic Syndr 2012;59:354-359. [PubMed]

McAllister JW, Towns JM, McNulty A, et al. Dolutegravir with tenofovir disoproxil fumarate-emtricitabine as HIV postexposure prophylaxis in gay and bisexual men. AIDS 2017;31(9):1291-1295. [PubMed]

Paquet AC, Evans M, Petropoulos C, et al. Significant reductions in the prevalence of protease inhibitor and 3-class resistance: Recent trends in a large HIV-1 protease/reverse transcriptase database. Abstract H2-800. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy; 2011 Sep 17-20; Chicago, IL. http://www.natap.org/2011/ICAAC/ICAAC_68.htm

Thigpen MC, Kebaabetswe PM, Smith DK, et al. Daily oral antiretroviral use for the prevention of HIV infection in heterosexually active young adults in Botswana: Results from the TDF2 study. HIV-1-infected adults. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 2011 Jul 17-20; Rome, Italy. http://www.abstract-archive.org/Abstract/Share/10082

Tosini W, Muller P, Prazuck T, et al. Tolerability of HIV postexposure prophylaxis with tenofovir/emtricitabine and lopinavir/ritonavir tablet formulation. AIDS 2010;24:2375-2380. [PubMed]

Tsai CC, Emau P, Follis KE, et al. Effectiveness of postinoculation (R)-9-(2-phosphonylmethoxypropyl) adenine treatment for prevention of persistent simian immunodeficiency virus SIVmne infection depends critically on timing of initiation and duration of treatment. J Virol 1998;72:4265-4273. [PubMed]

Follow-Up and Sequential HIV Testing

Medical Care Criteria Committee, October 2014

RECOMMENDATIONS
Follow-Up
  • All patients receiving PEP should be re-evaluated within 3 days of the exposure to further clarify the nature of the exposure, review available source person data, evaluate adherence, and monitor toxicities associated with the PEP regimen. (A3)
  • The exposed person should be evaluated weekly while receiving PEP to assess treatment adherence, side effects of treatment, interval physical complaints, and emotional status. (A3) Longitudinal care of the exposed person during PEP treatment and the follow-up period should be provided by or in consultation with a clinician experienced in managing nPEP. Emergency Departments and urgent care centers should establish linkages with local HIV providers to facilitate easy referral of patients for follow-up care. Providers who do not have access to a clinician experienced in PEP should use the Clinical Education Initiative CEI PEP Line at 1-866-637-2342 for phone consultation. When using the PEP Line, providers from New York State should identify themselves as practicing in the State.
  • Clinicians should provide risk-reduction counseling to exposed persons to prevent secondary transmission during the 12-week follow-up period. HIV-exposed individuals should be advised to:
    • use condoms to prevent potential sexual transmission (A1)
    • avoid pregnancy and breastfeeding (A1)
    • avoid needle-sharing (A1)
    • refrain from donating blood, plasma, organs, tissue, or semen (A1)
Sequential HIV Testing
  • Sequential confidential HIV testing should be obtained at baseline, week 4, and week 12 post-exposure:
    • HIV testing at 6 months post-exposure is no longer recommended
    • HIV testing of the exposed person at 4 weeks and 12 weeks should be performed with laboratory-based HIV tests rather than point-of-care HIV tests (a 4th-generation HIV antigen/antibody combination test is the recommended serologic screening test).
    • If the post-exposure evaluation determined that PEP was indicated, but the exposed person declines PEP, serial testing should still be obtained (see Table 2. Recommended Monitoring after Initiation of nPEP)
  • If at any time the HIV test result is positive, an FDA-approved confirmatory assay must be performed to confirm the diagnosis of HIV infection (see the CDC’s Recommended Laboratory HIV Testing Algorithm for Serum or Plasma Specimens).
  • If the exposed person presents with signs or symptoms of acute HIV seroconversion, an HIV serologic screening test should be used in conjunction with a plasma HIV RNA assay to diagnose acute HIV infection. (A2) A 4th-generation HIV antigen/antibody combination test is the recommended serologic screening test (see the CDC’s Recommended Laboratory HIV Testing Algorithm for Serum or Plasma Specimens). Immediate consultation with a clinician experienced in managing ART should be sought for optimal treatment options.

During the PEP treatment period, other blood tests may be indicated to monitor for side effects of treatment. The timing and specific testing indicated varies based on the PEP regimen used (see Table 2, below).

KEY POINT
Post-exposure care involves simultaneous attention to multiple issues: the emotional state of the exposed person, adherence to the PEP regimen, monitoring for potential adverse effects, and sequential HIV testing to determine infection status.

Clinicians should be aware of the resources within the community that offer medical and supportive counseling/adherence services needed following non-occupational exposure.

Table 2: Recommended Monitoring after Initiation of nPEP
  Baseline Week 1 Week 2 Week 3 Week 4 Week 12
Clinic visit X or phone call or phone
call
or phone call X  
Pregnancy test X          

Serum liver enzymes, BUN, creatinine, CBC [a]

X   X   X  
HIV test [b] X       X X
STI screening [c] X   consider      
  1. For post-exposure management of HBV and HCV, see Non-Occupational Exposure to HBV and HCVCBC should be obtained for all exposed persons at baseline; follow-up CBC is only for those receiving ZDV

  2. Recommended even if nPEP is declined

  3. For exposures not related to sexual assault: GC/CT NAAT (based on site of exposure) and RPR; recommended even if nPEP is declined. See PEP for Victims of Sexual Assault if exposure is related to assault.

Adherence to the PEP regimen: Follow-up care is necessary for patients receiving PEP to monitor for adverse effects of the PEP regimen and to maximize adherence to the prescribed regimen. Adherence to a 28-day PEP regimen has historically been modest (40-60%) [Parkin et al. 2000; Day et al. 2006; Lunding et al. 2010], although newer studies using tenofovir + either lamivudine or emtricitabine as components for PEP regimens show increased rates of adherence [Tosini et al. 2010; Mayer et al. 2008]. Limited data show similar improved tolerability with tenofovir + emtricitabine plus raltegravir [Mayer et al. 2012; Annandale et al. 2012; McAllister et al. 2017].

If the recommended regimen is not well tolerated, an early switch to an alternative regimen is encouraged to improve adherence. Again, consultation with a clinician experienced in managing PEP should occur when switching to an alternative regimen due to tolerability or resistance.

Sequential HIV Testing

When individuals are potentially exposed to HIV, longitudinal medical follow-up is necessary regardless of whether PEP is initiated or completed, in order to test sequentially for HIV infection.

HIV seroconversion will generally occur within 2 to 4 weeks if HIV infection develops after an exposure. HIV testing at baseline, 4 weeks, and 12 weeks is recommended after significant exposures, regardless of whether the individual accepts or declines PEP treatment. Point-of-care HIV tests are slightly less sensitive than laboratory-based HIV tests; therefore, exposed persons should be tested with laboratory-based HIV tests whenever possible. A 4th-generation HIV antigen/antibody combination test is the recommended serologic screening test.

HIV testing at 6 months after exposure is no longer recommended. Late seroconversion (i.e., after 3 months) has been rarely reported and has not been described since 1990 [Ridzon et al. 1997; Ciesielski and Metler 1997]. It is unclear if these rare events were related to the original or subsequent exposures. The Medical Care Criteria Committee believes that the benefit of routinely testing all exposed persons for HIV at 6 months is outweighed by the negative consequences of routinely extending post-exposure HIV follow-up testing to 6 months because of the infrequency of late seroconversion, the increased sensitivity of standard HIV tests to detect early infection and seroconversion, and the added anxiety and significant consequences of an additional 3 months of precautions and testing for exposed individuals.

Patients acutely infected with HIV will often experience at least some symptoms of the acute retroviral syndrome. Fever and flu- or mono-like symptoms are common in acute HIV infection but are nonspecific. Rash, mucocutaneous ulcers, oropharyngeal candidiasis, and meningismus are more specific. Symptoms may also include fatigue or malaise, joint pain, headache, loss of appetite, night sweats, myalgias, lymphadenopathy, oral and/or genital ulcers, nausea or diarrhea, or pharyngitis. Acute HIV infection is often not recognized in the primary care setting because of the similarity of the symptom complex with that of the flu or other common illnesses. When infection occurs and a 3rd-generation ELISA antibody test is used, it will generally be positive within 3 weeks of the onset of symptoms and is virtually always positive within 3 months following exposure. However, the CDC now recommends 4th-generation antibody/antigen combination immunoassays for initial HIV screening. These tests can simultaneously detect both HIV-1/HIV-2 antibodies and HIV-1 p24 antigens and will generally be positive within 14-15 days of infection. Western blot, which may yield an indeterminate result during the early stages of seroconversion, is no longer recommended as the confirmatory test. Instead, HIV screening should be confirmed with an FDA-approved HIV-1/HIV-2 antibody-differentiation assay. When acute HIV infection is suspected based on the clinical scenario or when there is a discrepancy between screening and confirmatory serologic testing, plasma HIV RNA assay should be obtained to diagnose HIV infection. (AII) For information regarding interpretation of HIV tests, see the CDC’s Recommended Laboratory HIV Testing Algorithm for Serum or Plasma Specimens.

See the following resources for more information:

References

Annandale D, Richardson C, Fisher M, et al. Raltegravir-based post-exposure prophylaxis (PEP): A safe, well-tolerated alternative regimen. J Int AIDS Soc 2012;15(Suppl 4):18165. [link]

Ciesielski CA, Metler RP. Duration of time between exposure and seroconversion in healthcare workers with occupationally acquired infection with human immunodeficiency virus. Am J Med 1997;102(Suppl 5B):115-116. [PubMed]

Day S, Mears A, Bond K, et al. Post-exposure HIV prophylaxis following sexual exposure: A retrospective audit against recent draft BASHH guidance. Sex Trasm Infect 2006;82:236-237. [PubMed]

Lunding S, Katzenstein TL, Kronborg G, et al. The Danish PEP registry: Experience with the use of postexposure prophylaxis (PEP) following sexual exposure to HIV from 1998 to 2006. Sex Transm Dis 2010;37:49-52. [PubMed]

Mayer KH, Mimiaga MJ, Cohen D, et al. Tenofovir DF plus lamivudine or emtricitabine for nonoccupational postexposure prophylaxis (nPEP) in a Boston Community Health Center. J Acquir Immune Defic Syndr 2008;47:494-499. [PubMed]

Mayer KH, Mimiaga MJ, Gelman M, et al. Raltegravir, tenofovir DF, and emtricitabine for postexposure prophylaxis to prevent the sexual transmission of HIV: Safety, tolerability, and adherence. J Acquir Immune Defic Syndr 2012;59:354-359. [PubMed]

McAllister JW, Towns JM, McNulty A, et al. Dolutegravir with tenofovir disoproxil fumarate-emtricitabine as HIV postexposure prophylaxis in gay and bisexual men. AIDS 2017;31(9):1291-1295. [PubMed]

Parkin JM, Murphy M, Anderson J, et al. Tolerability and side effects of post-exposure prophylaxis for HIV infection. Lancet 2000;355:722-723. [PubMed]

Ridzon R, Gallagher K, Ciesielski C, et al. Simultaneous transmission of human immunodeficiency virus and hepatitis C virus from a needle-stick injury. N Engl J Med 1997;336:919-922. [PubMed]

Tosini W, Muller P, Prazuck T, et al. Tolerability of HIV postexposure prophylaxis with tenofovir/emtricitabine and lopinavir/ritonavir tablet formulation. AIDS 2010;24:2375-2380. [PubMed]

nPEP for HIV-Exposed Women Who Are Pregnant or Breastfeeding

Medical Care Criteria Committee, updated May 2018

RECOMMENDATIONS
nPEP for Patients Who are Pregnant
  • Based on increasing clinical experience with ART, nPEP is indicated at any time during pregnancy when a significant exposure has occurred, despite possible risk to the individual and the fetus. (A2) Expert consultation should be sought. When non-occupational exposure to HIV occurs, every effort should be made to initiate PEP as soon as possible, and ideally within 2 hours. 
  • The preferred PEP regimen for pregnant individuals is tenofovir disoproxil fumarate + emtricitabine (lamivudine may be substituted for emtricitabine) plus raltegravir (see Antiretroviral Agents Recommended for PEP for dosing information). The recommended duration of PEP is 28 days. (AII)
  • Before administering nPEP to a pregnant individual, the clinician should discuss the potential benefits and risks to the individual and to the fetus. (A3)
  • Pregnant individuals presenting for nPEP as a result of risky behavior should be the focus of intensified education and prevention interventions. (A2) After completion of the 28-day nPEP regimen, initiation of pre-exposure prophylaxis (PrEP) should be considered. (A1)
nPEP for Patients Who are Breastfeeding
  • Clinicians should advise individuals who may have been exposed to HIV through non-occupational exposure to avoid breastfeeding for 3 months after the exposure [Parkin et al. 2000]. (A2) If HIV infection is definitively excluded in the source person at any time prior to 3 months post-exposure, breastfeeding can be resumed. (A1)

PEP for HIV-Exposed Women Who Are Pregnant

Dolutegravir (DTG) Safety Statement, May 2018

On May 18, 2018, the FDA and the DHHS Antiretroviral Guidelines Panels issued statements in response to preliminary results from a study that reported increased risk of neural tube defects in babies born to mothers taking DTG-based ARV drug regimens at the time of conception [AIDSinfo 2018; FDA 2018].

Until more data become available, DTG-containing regimens should be avoided in any HIV-exposed individual who is or could become pregnant and is not using effective contraception. If there are no alternatives to DTG for individuals of child-bearing potential, then clinicians should strongly advise the use of effective contraception and should obtain a pregnancy test before initiating treatment.

For more information, see: DHHS Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States

With the exception of dolutegravir, the agents listed below are not recommended for use in PEP regimens and are not likely to be used; however, clinicians should be aware that these agents should not be prescribed in pregnant individuals. Initiation of PEP at any time during pregnancy requires a careful discussion of the risks and benefits.

HIV drugs to avoid during pregnancy: 

  • Dolutegravir: Teratogenicity; preliminary reports of increased risk of neural tube defects
  • Efavirenz: Teratogenicity
  • Combination of stavudine and didanosine: Mitochondrial toxicity
  • Nevirapine: Hepatotoxicity
  • Unboosted IDV in the 2nd or 3rd trimester: Substantially lower antepartum indinavir plasma concentrations; risk for nephrolithiasis
KEY POINT
In addition to the risk of seroconversion for the exposed person, the high viral load levels associated with the acute retroviral syndrome markedly increase the risk of transmission to the fetus or breastfeeding infant.

Although birth defects and adverse effects on human fetuses have generally not been associated with the antiretroviral agents that are currently available, exposure of a fetus to antiretroviral agents during pregnancy carries a theoretical risk of embryotoxicity.

HIV-Exposed Women Who Are Breastfeeding

Initiation of PEP in exposed individuals who are breastfeeding requires careful discussion. Both HIV and antiretroviral drugs may be found in breast milk; therefore, breastfeeding should be avoided for 3 months after the exposure to prevent HIV transmission and potential drug toxicities [Committee on Pediatric AIDS 2013]. Clinicians should discuss the risks and benefits with the patient. The infant’s pediatrician should be informed of any potential exposure to HIV or antiretroviral medications.

References

AIDSinfo. Statement on Potential Safety Signal in Infants Born to Women Taking Dolutegravir from the HHS Antiretroviral Guideline Panels. 2018 May 18. https://aidsinfo.nih.gov/news/2094/statement-on-potential-safety-signal-in-infants-born-to-women-taking-dolutegravir [accessed 2018 May 23]

Committee on Pediatric AIDS. Infant feeding and transmission of human immunodeficiency virus in the United States. Pediatrics 2013;131;391-396. [PubMed]

U.S. Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA to evaluate potential risk of neural tube birth defects with HIV medicine dolutegravir (Juluca, Tivicay, Triumeq). 2018 May 18. https://www.fda.gov/Drugs/DrugSafety/ucm608112.htm [accessed 2018 May 23]

Resources for Consultation

October 2014

Persons who have responsibility for providing nPEP may need expert advice and consultation, as well as assistance in helping their clients obtain medication.

The following resources are the preferred initial contacts for expert consultation:

  • The Clinical Education Initiative CEI PEP Line at 1-866-637-2342. When using the PEP Line, providers from New York State should identify themselves as practicing in the State.

For providers in New York State:

  • For further education of health providers or for consultation regarding setting up PEP services, contact the HIV/HCV Center of Excellence.
  • To obtain the NYSDOH protocol for sexual assault victims, call the NYSDOH Rape Crisis Program at 1-518-474-2664.

For information about rape crisis services, see PEP for Victims of Sexual Assault.

Non-Occupational Exposure to HBV

Medical Care Criteria Committee, October 2014

RECOMMENDATIONS
Non-Occupational Exposure to HBV 
  • When a non-occupational exposure occurs, and the source is available, the source should be evaluated for both hepatitis B and hepatitis C. (A2)
  • The hepatitis B vaccine series should be initiated in non-HBV-immune persons who sustain a blood or body fluid exposure. (A1) Decision-making should not be delayed while testing for anti-HBs. If antibody response is unknown, follow recommendations for “antibody response unknown” below.
  • Administration of prophylactic hepatitis B immune globulin (HBIG) and the initiation of the hepatitis B vaccine series injected at different sites is recommended when the non-HBV-immune person sustains a blood or body fluid exposure to a source person with known acute or active HBV. (A1)
    • Both HBIG and the first dose of the hepatitis B vaccine series should be ideally administered within 24 hours of exposure (A2); HBIG should not be given later than 14 days post-exposure. The three-dose HBV vaccine series is given at 0, 1 to 2 months, and 6 months. Hepatitis B antibodies should be obtained 1 to 2 months after completion of the third dose of the vaccine.
  • Needlestick injuries and wounds should be washed with soap and water and should not be squeezed. Mucous membranes should be flushed with water. (A3)

Initiation of the hepatitis B virus (HBV) vaccine series within 12 to 24 hours of an exposure has been demonstrated to be 70% to 90% effective in preventing HBV infection. The combination of vaccine and HBIG achieves a similar level of efficacy. Among known non-responders to vaccination, one dose of HBIG is 70% to 90% effective in preventing HBV when administered within 7 days of percutaneous HBV exposure [Weinbaum et al. 2003], and multiple doses have been shown to be 75% to 95% effective [Beasley et al. 1983]. The maximum effective interval for prophylaxis is likely within 14 days for sexual exposure [Szmuness et al. 1980; Redeker et al. 1975; Papaevangelou et al. 1988; Roumeliotou-Karayannis et al. 1986; Perrillo et al. 1984]. Pregnant women can safely receive both the HBV vaccination and HBIG.

When considering nPEP for HBV exposures, both the source’s HBsAg status and the exposed person’s vaccination status should be considered (see below).

KEY POINT
Determination of antibody response of previously vaccinated exposed persons should be based on information available at presentation. It is not recommended that decision-making be delayed while testing for anti-HBs. If antibody response is unknown, follow recommendations for “antibody response unknown” below.

Both HBIG and the first dose of the hepatitis B vaccine should be ideally administered within 24 hours of exposure; HBIG should not be given later than 14 days post-exposure. The three-dose HBV vaccine series is given at 0, 1 to 2 months, and 6 months. Hepatitis B antibodies should be obtained 1 to 2 months after completion of the third dose of the vaccine.

Even if the risk of exposure to HBV is not deemed significant, HBV vaccination should still be advised for all non-HBV-immune persons (see the HBV-HIV Coinfection Guideline for more information). Household, sex, and needle-sharing contacts of HBsAg-positive individuals should be identified and vaccinated according to the guidelines for patients exposed to known HBsAg-positive individuals.

Recommended Post-Exposure Prophylaxis 

Scenario 1: Exposed patient is unvaccinated/non-immune

If source patient is:                    

  • HBsAg positive: HBIG x 1; initiate HBV vaccine series in exposed patient
    • HBIG dose is 0.06 mL/kg intramuscularly
  • HBsAg negative: Initiate HBV vaccine series in exposed patient
  • Unknown or not available for testing: Initiate HBV vaccine series in exposed patient

Scenario 2: Exposed patient is previously vaccinated and a known responder

If source patient is:          

  • HBsAg positive: No treatment for exposed patient
  • HBsAg negative: No treatment for exposed patient
  • Unknown or not available for testing: No treatment
  • Comments:
    • Exposed patient was vaccinated with full three-dose series; “known responder” is based on information available at presentation.
    • Responder is defined as person with previously documented adequate levels of serum antibody to HBsAg (serum anti-HBs >10mIU/mL); non-responder is a person with previously documented inadequate response to vaccination (serum anti HBs <10mIU/mL).
    • It is not recommended that decision-making be delayed while testing for anti-HBs at presentation.

Scenario 3: Exposed patient is previously vaccinated and a known non-responder

If source patient is:          

  • HBsAg positive: HBIG x 1 and initiate revaccination orHBIG x 2 in exposed patient
    • HBIG dose is 0.06 mL/kg intramuscularly
  • HBsAg negative: No treatment for exposed patient
  • Unknown or not available for testing: No treatment unless source is known to be high-risk source; if high-risk source, then treat as if source were HBsAg positive
  • Comments:
    • Patient was vaccinated with full three-dose series; “known non-responder” is based on information available at presentation.
    • Responder is defined as person with previously documented adequate levels of serum antibody to HBsAg (serum anti-HBs >10mIU/mL); non-responder is a person with previously documented inadequate response to vaccination (serum anti HBs <10mIU/mL).
    • It is not recommended that decision-making be delayed while testing for anti-HBs at presentation.
    • The option of giving one dose of HBIG and re-initiating the vaccine series is preferred for non-responders who have not completed a second three-dose vaccine series.
    • For persons who previously completed a second vaccine series but failed to respond, two doses of HBIG are preferred
    • High-risk is defined as sources who engage in needle-sharing or high-risk sexual behaviors, and those born in geographic areas with HBsAg prevalence of >2% [Weinbaum et al. 2008].

Scenario 4: Exposed patient is previously vaccinated, with unknown antibody response

If source patient is:

  • HBsAg positive: Administer single vaccine booster dose to exposed patient
  • HBsAg negative: No treatment for exposed patient
  • Unknown or not available for testing: No treatment for exposed patients unless the source is known to be high-risk; if high-risk source, then treat as if source were HBsAg
  • Comments:
    • Exposed patient was vaccinated with full three-dose series.
    • High-risk is defined as sources who engage in needle-sharing or high-risk sexual behaviors, and those born in geographic areas with HBsAg prevalence of >2% [Weinbaum et al. 2008].

Scenario 5: Exposed patient is still undergoing vaccination

If source patient is:

  • HBsAg positive: Administer HBIG x 1; complete series to exposed patient
  • HBsAg negative: Administer HBIG x 1; complete series to exposed patient
  • Unknown or not available for testing: Administer HBIG x 1; complete series to exposed patient
  • Comments: HBIG dose is 0.06 mL/kg intramuscularly

Abbreviation key: hepatitis B surface antigen (HBsAG); hepatitis B immune globulin (HBIG); antibody to hepatitis B surface antigen (anti-HBs)

References

Beasley RP, Hwang L-Y, Stevens CE, et al. Efficacy of hepatitis B immune globulin for prevention of perinatal transmission of the hepatitis B virus carrier state: Final report of a randomized double-blind, placebo-controlled trial. Hepatology 1983;3:135-141. [PubMed]

Papaevangelou G, Roumeliotou-Karayannis A, Richardson SC, et al. Postexposure immunoprophylaxis of spouses of patients with acute viral hepatitis B. In: Zuckerman AJ, ed. Viral Hepatitis and Liver Disease. New York, NY: Alan R. Liss, Inc.; 1988:992-994.

Perrillo RP, Campbell CR, Strang S, et al. Immune globulin and hepatitis B immune globulin. Prophylactic measures for intimate contacts exposed to acute type B hepatitis. Arch Intern Med 1984;144:81-85. [PubMed]

Redeker AG, Mosley JW, Gocke DJ, et al. Hepatitis B immune globulin as a prophylactic measure for spouses exposed to acute type B hepatitis. N Engl J Med 1975;293:1055-1059. [PubMed]

Roumeliotou-Karayannis A, Dandolos E, Richardson SC, et al. Immunogenicity of a reduced dose of recombinant hepatitis B vaccine. Vaccine 1986;4:93-94. [PubMed]

Szmuness W, Stevens CE, Harley EJ, et al. Hepatitis B vaccine: Demonstration of efficacy in a controlled clinical trial in a high-risk population in the United States. N Engl J Med 1980;303:833-841. [PubMed]

Weinbaum C, Lyerla R, Margolis HS. Prevention and control of infections with hepatitis viruses in correctional settings: Centers for Disease Control and Prevention. MMWR Recomm Rep 2003;52(RR-1):1-33. www.cdc.gov/mmwr/preview/mmwrhtml/rr5201a1.htm

Weinbaum CM, Williams I, Mast EE, et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep 2008;57(RR-08):1-20. www.cdc.gov/mmwr/preview/mmwrhtml/rr5708a1.htm

Non-Occupational Exposure to HCV

Medical Care Criteria Committee, October 2014

RECOMMENDATIONS
Non-Occupational Exposure to HCV
  • Clinicians should consider concurrent exposure to HCV when individuals present with an HIV exposure. (A2)
  • Neither immunoglobulin nor antiviral agents are recommended for HCV post-exposure prophylaxis. (A2)
  • When HCV infection is identified, the exposed person should be referred for medical management to a gastroenterologist or other clinician with experience in treating HCV. (A2)
Baseline Management
  • Following an exposure to blood or body fluid, the clinician should assess the risk for exposure to HCV. (A2) Wounds should be washed with soap and water, and should not be squeezed. (A2) Mucous membranes should be flushed with water.
  • Once the clinician has determined that exposure to blood or body fluid has occurred, the following baseline tests should be obtained (A2) (see text for follow-up according to baseline results):
    • Exposed Person:
      • HCV antibody, and if positive, HCV RNA test
      • Liver panel including liver enzymes
    • Source Patient:
      • HCV antibody test (e.g., EIA/ELISA), and if positive, HCV RNA test
  • Clinicians should educate exposed persons about the natural history of HCV infection and should counsel exposed persons about the following:
    • Avoidance of alcohol and, if possible, medications that may be toxic to the liver
    • Risk of transmission related to:
      • Blood-to-blood contact, including sharing personal care items that may have come in contact with another person’s blood, such as razors or toothbrushes; occupational needlestick injuries; and sharing needles, syringes, or other equipment to inject drugs
      • Sexual activity
      • Donating blood, plasma, organs, tissue, or semen
      • Perinatal transmission
    • Hepatitis C virus is not spread via food or water and is not transmitted by:
      • Sharing eating utensils
      • Hugging, kissing, or holding hands
      • Coughing or sneezing
      • Breastfeeding: HCV is not transmitted by breastfeeding; however, clinicians should advise women who may have been exposed to HIV to avoid breastfeeding for 3 months after the exposure. 
Post-Exposure Follow-Up
  • If the source is known to be positive for HCV antibody and/or HCV RNA, the follow-up schedule for the exposed person should be as follows (A2):
    • Week 4: HCV RNA and liver panel
    • Week 12: HCV RNA and liver panel
    • Week 24: Liver panel and HCV antibody
  • If at any time the serum ALT level is elevated, the clinician should repeat HCV RNA testing to confirm acute HCV infection. (A3)
  • At any time that exposed persons test positive for HCV RNA, the clinician should refer for medical management and possible treatment by a clinician with experience in treating HCV. (A3)

Currently, no effective prophylaxis for hepatitis C virus (HCV) infection has been identified. Immunoglobulin and antiviral agents are not recommended for HCV post-exposure prophylaxis. However, if an individual becomes acutely infected with HCV and is diagnosed at that time, immediate referral to a specialist experienced in the treatment of HCV is strongly recommended. Data suggest that early treatment of acute HCV with interferon for 24 weeks is highly effective, perhaps as high as 98% [Jaeckel et al. 2001]. However, the best regimen or duration of therapy is unknown, and no data currently exist for treating acute infection with newer direct-acting HCV antiviral therapy.

Observation for a period of 8 to 12 weeks post-infection is reasonable to assess for possible spontaneous resolution of acute HCV [Ghany et al. 2009]. Whether standard interferon, pegylated-interferon with or without ribavirin, or treatment with direct-acting antiviral agents is used will depend on the individual scenario, as there have been no randomized, controlled trials to guide this decision.

Baseline management: If the source patient is tested with an EIA/ELISA and found to be positive, then follow-up testing is necessary to confirm the source person’s status. HCV RNA may be used as the confirmatory test. When the source person tests positive with an HCV RNA test, the exposed person should be managed as if the source has chronic HCV.

Clinical scenario and follow-up are described in Table 3, below (see below for interpretation of test results).

Table 3: Management of HCV Exposure According to Baseline Test Results
Test Result Management 
Source is HCV-antibody negative
  • No further testing or follow-up is necessary for source or the exposed person
  • If at any time the serum ALT level is elevated in the exposed person, the clinician should test for HCV RNA to assess for acute HCV infection.
Source is unavailable or refuses testing
  • Follow-up exposed person HCV antibody at 3 and 6 months 
  • If at any time the serum ALT level is elevated in the exposed person, the clinician should test for HCV RNA to assess for acute HCV infection.
Source is HCV-antibody positive and HCV RNA negative
  • Manage the exposed person as if the source has chronic hepatitis C
  • A single negative HCV RNA result does not exclude active infection.
Source is positive for both HCV antibody and HCV RNA and exposed person is HCV-antibody negative
  • Counsel and manage as follows: 
    • Source: Counsel and manage as chronic hepatitis C regardless of status of exposed person
    • Exposed person: Follow up as outlined below in Post-Exposure Follow-Up for HCV 
Exposed person tests positive for both HCV antibody and HCV RNA
  • Counsel and manage as chronic hepatitis C (refer to Interpretation of Test Results, below).

Factors that may increase the risk of sexual transmission include sex with multiple partners, history of STIs, including HIV, or any other practice that might disrupt mucous membranes. The potential need for mental health counseling should be anticipated and offered as needed.

Post-Exposure Follow-Up for HCV

For persons exposed to a hepatitis C-infected source, regular follow-up with HCV RNA testing is recommended in addition to HCV antibody testing, because HCV RNA testing can identify acute infection within 2 weeks of exposure, whereas accuracy of the antibody test can be delayed up to several months after acute infection (i.e., “window period”). Seroconversion with the ELISA antibody test occurs in 50% of patients who are infected within 9 weeks of exposure, in 80% of patients within 15 weeks of exposure, and in at least 97% of patients within 6 months of exposure [CDC 2001]. The ELISA test is highly sensitive but relatively nonspecific, resulting in a low positive predictive value in low-prevalence populations. Positive HCV ELISA antibody test results require confirmation by a quantitative viral load assay, such as HCV PCR.

Interpretation of Test Results

Interpretation of results of tests for hepatitis C virus infection is described below, with recommended further actions.

Table 4: Interpretation of Results of Tests for HCV Infection and Further Action*

HCV Test Result Interpretation Recommended Further Action

HCV antibody nonreactive

No HCV antibody detected
  • Sample can be reported as nonreactive for HCV antibody. No further action required.
  • If recent HCV exposure in person tested is suspected, test for HCV RNA. 
  • If HCV RNA testing is not feasible and person tested is not immunocompromised, perform follow-up testing for HCV antibody to demonstrate seroconversion.
  • If the person tested is immunocompromised, consider testing for HCV RNA.

HCV antibody reactive

Presumptive HCV infection: A repeatedly reactive result is consistent with current HCV infection, or past HCV infection that has resolved, or biologic false positivity for HCV antibody.

  • Test for HCV RNA to identify current infection.

HCV antibody reactive and HCV RNA detected

Current HCV infection
  • Provide person tested with appropriate counseling and link person tested to medical care and treatment.
  • It is recommended before initiating antiviral therapy to retest for HCV RNA in a subsequent blood sample to confirm HCV RNA positivity.

HCV antibody reactive and HCV RNA not detected

No current HCV infection
  • No further action required in most cases.
  • If distinction between true positivity and biologic false positivity for HCV antibody is desired, and if sample is repeatedly reactive in the initial test, test with another HCV antibody assay.
  • If the person tested is suspected of having HCV exposure within the past 6 months, or has clinical evidence of HCV disease, or if there is concern regarding the handling or storage of the test specimen, then follow up with HCV RNA testing and appropriate counseling.
*Reproduced from Centers for Disease Control and Prevention (CDC). Testing for HCV infection: An update of guidance for clinicians and laboratorians. MMWR Morb Mortal Wkly Rep 2013;62:362-365
References

Centers for Disease Control and Prevention (CDC). Recommendations for preventing transmission of infections among chronic hemodialysis patients. MMWR Recomm Rep 2001;50(RR-5):1-43. www.cdc.gov/mmwr/preview/mmwrhtml/rr5005a1.htm

Ghany MG, Strader DB, Thomas, DL, et al. Diagnosis, management, and treatment of hepatitis C: An update. Hepatology 2009;49:1335-1374. [PubMed]

Jaeckel E, Cornberg M, Wedemeyer H, et al. Treatment of acute hepatitis C with interferon alfa-2b. N Engl J Med 2001;345:1452-1457. [PubMed]

All Recommendations

Medical Care Criteria Committee, October 2014

Dolutegravir (DTG) Safety Statement, May 2018

On May 18, 2018, the FDA and the DHHS Antiretroviral Guidelines Panels issued statements in response to preliminary results from a study that reported increased risk of neural tube defects in babies born to mothers taking DTG-based ARV drug regimens at the time of conception [AIDSinfo 2018; FDA 2018].

Until more data become available, DTG-containing regimens should be avoided in any HIV-exposed individual who is or could become pregnant and is not using effective contraception. If there are no alternatives to DTG for individuals of child-bearing potential, then clinicians should strongly advise the use of effective contraception and should obtain a pregnancy test before initiating treatment.

For more information, see: DHHS Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States

ALL RECOMMENDATIONS: PEP FOR NON-OCCUPATIONAL EXPOSURE (nPEP) TO HIV GUIDELINE
Assessing the Exposure
  • Risk assessment and initiation of nPEP should occur in clinical settings that can provide the following: (A3)
    • Assessment of HIV risk following exposure
    • HIV and STI testing and treatment
    • Prevention and risk-reduction counseling
    • Clinicians with expertise in the use of ART
    • Timely access to care and initiation of nPEP
  • If all of these services are not available, clinicians should assess the exposure and initiate nPEP when indicated according to the criteria and recommendations in these guidelines. The patient should then be referred for follow-up care to a clinician who has experience in the use of antiretroviral agents and who can provide ongoing prevention counseling.
  • Treating clinicians who do not have access to experienced HIV clinicians should call the Clinical Education Initiative CEI PEP Line at 1-866-637-2342 to review the case. When using the PEP Line, providers from New York State should identify themselves as practicing in the State.
  • Patients who present for nPEP should be evaluated as soon as possible in order to initiate therapy, if indicated, within recommended time frames. (A2)
  • Wound and skin exposure sites should be washed with soap and water. Needlestick injuries should not be squeezed. (A2)
  • When an HIV exposure occurs, the events and the subsequent interventions should be clearly documented in order to facilitate determination of the effectiveness of nPEP. (A2)
Is nPEP Indicated?
  • When deciding whether to recommend the initiation of nPEP, the clinician should assess the patient’s risk of HIV acquisition based on the type of exposure (see text). (A3)
  • Non-occupational PEP should not be prescribed when there is negligible or low risk of HIV transmission (see text). (A3)
  • Non-occupational PEP should not be routinely dismissed solely on the basis of repeated risk behavior or repeat presentation for nPEP. (A3) Persons who present with repeated high-risk behavior or for repeat courses of nPEP should be the focus of intensified education and prevention interventions.
  • After completion of the 28-day nPEP regimen, the patient should be evaluated to determine whether initiation of pre-exposure prophylaxis (PrEP) is warranted and feasible. (A2)
HIV Exposure Through Bites
  • When bite wounds result in blood exposure, nPEP should be considered for the person(s) who was exposed to blood; this could be the person bitten, the biter, or both (A2) (see text). PEP should not be initiated when the integrity of the skin is not disrupted.
  • Clinicians should wash bite wounds with soap and water and should not squeeze the wound. (A2)
HIV Status of the Source Person
  • Source person is unavailable or unwilling to undergo HIV testing: When assessment of the exposure determines that nPEP is indicated, but the source is anonymous, unavailable, or unwilling to undergo HIV testing, nPEP should be initiated and the 28-day course should be completed. (A2)                 
  • Source person is known to be HIV-infected: If the source of contact is known to be HIV-infected, information about his/her viral load, antiretroviral medication history, and history of antiretroviral drug resistance should be obtained when possible to assist in the selection of an nPEP regimen; however, administration of the first dose of nPEP should not be delayed while awaiting this information. (A2)                  
  • Source person’s HIV status is unknown and source is available for testing: When the source person is available and consents to HIV testing, clinicians should obtain the most expeditious HIV test available (ideally with a turnaround time <1 hour), using either an FDA-approved HIV rapid test or an FDA-approved laboratory-based screening test. [A 4th-generation antigen/antibody combination assay is recommended; see the CDC’s Recommended Laboratory HIV Testing Algorithm for Serum or Plasma Specimens]. (A1)
    • If the test results are not immediately available, the initiation of nPEP should not be delayed pending the test result.
  • Plasma HIV RNA testing of the source person is recommended in addition to HIV serologic screening in the following settings:
    • If the source person’s HIV screening test result is negative but there may have been exposure to HIV in the previous 6 weeks (B3)
    • If the source person’s screening result is positive but the confirmatory antibody-differentiation assay is nonreactive or indeterminate (A1)
  • When plasma HIV RNA testing is indicated, nPEP should be continued until results of the plasma HIV RNA assay are available. If the result is positive, the 28-day regimen should be completed; if the result is negative, PEP should be discontinued. (B3)
  • The source person should also be evaluated for hepatitis B and hepatitis C. (A1)
Baseline HIV Testing for Patients Who Present with Risk Exposure  
  • Clinicians should perform baseline HIV testing of the exposed person within 3 days of the exposure. (A3) Testing must be performed in full compliance with New York State Public Health Law. Exposed persons who decline baseline HIV testing should not receive nPEP. (A3)
  • nPEP should be started without waiting for the results of the exposed person’s baseline HIV test. (A2) If the initial test result is positive, nPEP should be continued until the positive result is repeated with a confirmatory assay. Decisions regarding continuation of ART should be based on current treatment guidelines.
Testing for STIs Other Than HIV
  • For patients who are sexually exposed in non-assault situations, clinicians should perform STI testing at baseline and should treat as indicated. Testing should include the following:
    • Nucleic acid amplification testing (NAAT) to screen for gonorrhea and chlamydia, based on site of exposure (A2)
    • Serologic screening for syphilis [clinicians should be familiar with their laboratory’s syphilis screening protocol and should ensure that the same test is used when monitoring serology. (A3)
  • Clinicians should counsel patients about the risk of acquiring other STIs and symptoms that may occur; patients should be instructed to call their healthcare provider if symptoms occur. (A2)
  • For men who have sex with men who present with sexual exposures, clinicians should assess for the need to vaccinate against meningococcal disease according to current New York State Department of Health recommendations. (A2)
Pregnancy Testing
  • Clinicians should obtain baseline pregnancy testing for exposed individuals who could become pregnant. (A2) Emergency contraception should be discussed and offered to anyone who could become pregnant as a result of the exposure. (A2)
Risk Reduction and Prevention
  • The clinician or a member of the HIV care team should provide risk-reduction counseling and primary prevention counseling whenever someone is assessed for nPEP, regardless of whether PEP is initiated. (A2)
  • Clinicians should assess for emotional, psychological, and social factors that can contribute to risk behavior, such as depression, history of sexual abuse, and drug and alcohol use. (A2)
  • Clinicians should refer patients to mental health and/or substance use programs when indicated and should consider the need for intensive risk-reduction counseling services. (A2)
  • Persons who present with repeated high-risk behavior or for repeat courses of nPEP should be the focus of intensified education and prevention interventions and, after completion of the 28-day nPEP regimen, initiation of pre-exposure prophylaxis (PrEP) should be considered. (A2)
When to Start nPEP
  • When a potential non-occupational exposure to HIV occurs, every effort should be made to initiate PEP as soon as possible, ideally within 2 hours. (A2)
  • Decisions regarding initiation of nPEP beyond 36 hours post exposure should be made on a case-by-case basis with the realization of diminished efficacy when timing of initiation is prolonged. (A3)
Pre-nPEP Initiation Counseling
  • The clinician should discuss the following issues with the patient and should document that they were discussed before initiating a regimen (A3):
    • Potential benefit, unproven efficacy, and potential toxicity of nPEP
    • Duration of nPEP regimen
    • Importance of adherence to the treatment regimen to prevent nPEP failure or the development of drug resistance should infection occur
    • Need to reduce risk and prevent exposure to others
    • Clinical and laboratory monitoring and follow-up schedule
    • Signs and symptoms of acute HIV infection
    • How a full supply of medication will be obtained
What to Start
  • The preferred PEP regimen is tenofovir + emtricitabine (lamivudine may be substituted for emtricitabine) plus either raltegravir or dolutegravir [see DTG safety statement]. See text for dosing and Antiretroviral Agents Recommended for PEP for links to descriptions of each drug). (A2)
    • The first dose should be given as soon as possible after exposure, ideally within 2 hours.
    • The recommended duration of PEP is 28 days. (A2)
  • Starter packs with a 3- to 5-day supply of medication should be available on-site for rapid initiation of treatment, and arrangements should be made for continuation of treatment. (A3)
  • If the source person is known to be HIV-infected and information is immediately available regarding past and present ART experience, current level of viral suppression, or resistance profile, the treating clinician, in consultation with a clinician experienced in managing PEP, should individualize the PEP regimen to maximize potential effectiveness against the exposed HIV strain (A2). Initiation of the first dose and continuation of PEP should never be delayed while awaiting this information (A2). If indicated, the regimen can be changed when more information becomes available.
  • The text lists recommended alternative PEP regimens that should be used in the setting of potential HIV resistance, toxicity risks, clinician preference, or constraints on the availability of particular agents (A2).
  • Clinicians should switch exposed persons to an alternative regimen if the initial or subsequent PEP regimen is not well tolerated (A2) (see Antiretroviral Agents Recommended for PEP for links to potential adverse events).
  • Treating clinicians should consult with a clinician experienced in managing PEP when alternative agents are prescribed or if there is doubt as to whether PEP should be continued after the first dose. (A2)
  • The prescribing clinician should ensure that the exposed person has access to the full 28-day recommended course of antiretroviral medications (A3) and is appropriately monitored for toxicities during the treatment.
  • Treating clinicians who do not have access to experienced HIV clinicians should call the Clinical Education Initiative CEI PEP Line at 1-866-637-2342. When using the PEP Line, providers from New York State should identify themselves as practicing in the State.
Duration of nPEP Regimen
  • The recommended duration of nPEP is 28 days.
  • If the exposed person’s baseline test shows evidence of HIV infection acquired before the exposure and initiation of nPEP, decisions regarding continuation of ART should be based on current treatment guidelines (A1). However, the nPEP regimen should not be discontinued until the positive result is repeated with a confirmatory assay. (A1)
  • If the exposed person’s week 4 post-exposure HIV test results are indeterminate or the exposed person has symptoms suggestive of acute HIV infection, clinicians should continue ART beyond 28 days until a definitive diagnosis is established. (A2)
  • When the source person is confirmed to be HIV-negative, clinicians should discontinue the nPEP regimen before completion. (A1)
Preferred Alternative nPEP Regimen
  • The preferred alternative PEP regimen is tenofovir + emtricitabine (lamivudine may be substituted for emtricitabine) plus ritonavir-boosted darunavir, atazanavir, or fosamprenavir (A2) (see text).
  • Clinicians should carefully assess for potential drug interactions between these agents and other medications (including prescription medications and over-the-counter drugs, such as proton pump inhibitors and H2-blockers) that the patient may be taking. (A1) See Antiretroviral Agents Recommended for PEP for links to information regarding dosing, adverse effects, and drug interactions.
  • Clinicians should consult a clinician experienced in managing nPEP when using alternative PEP regimens (A2). If consultation cannot be immediately obtained, the first dose of the regimen should be given rather than delaying initiation, with consultation occurring as soon as possible thereafter (A2). Clinicians who do not have access to experienced HIV clinicians should call the Clinical Education Initiative CEI PEP Line at 1-866-637-2342. When using the PEP Line, providers from New York State should identify themselves as practicing in the State.
Other Alternative Regimens
  • Clinicians who continue to prescribe zidovudine for PEP should recognize and inform patients that the drug has significant side effects and that better-tolerated agents are available (see Antiretroviral Agents Recommended for PEP for links to side effects associated with alternative PEP agents).
Follow-Up
  • All patients receiving PEP should be re-evaluated within 3 days of the exposure to further clarify the nature of the exposure, review available source person data, evaluate adherence, and monitor toxicities associated with the PEP regimen. (A3)
  • The exposed person should be evaluated weekly while receiving PEP to assess treatment adherence, side effects of treatment, interval physical complaints, and emotional status. (A3) Longitudinal care of the exposed person during PEP treatment and the follow-up period should be provided by or in consultation with a clinician experienced in managing nPEP. Emergency Departments and urgent care centers should establish linkages with local HIV providers to facilitate easy referral of patients for follow-up care. Providers who do not have access to a clinician experienced in PEP should use the Clinical Education Initiative CEI PEP Line at 1-866-637-2342 for phone consultation. When using the PEP Line, providers from New York State should identify themselves as practicing in the State.
  • Clinicians should provide risk-reduction counseling to exposed persons to prevent secondary transmission during the 12-week follow-up period. HIV-exposed individuals should be advised to:
    • use condoms to prevent potential sexual transmission (A1)
    • avoid pregnancy and breastfeeding (A1)
    • avoid needle-sharing (A1)
    • refrain from donating blood, plasma, organs, tissue, or semen (A1)
Sequential HIV Testing
  • Sequential confidential HIV testing should be obtained at baseline, week 4, and week 12 post-exposure:
    • HIV testing at 6 months post-exposure is no longer recommended
    • HIV testing of the exposed person at 4 weeks and 12 weeks should be performed with laboratory-based HIV tests rather than point-of-care HIV tests (a 4th-generation HIV antigen/antibody combination test is the recommended serologic screening test).
    • If the post-exposure evaluation determined that PEP was indicated, but the exposed person declines PEP, serial testing should still be obtained (see Table 2. Recommended Monitoring after Initiation of nPEP)
  • If at any time the HIV test result is positive, an FDA-approved confirmatory assay must be performed to confirm the diagnosis of HIV infection (see the CDC’s Recommended Laboratory HIV Testing Algorithm for Serum or Plasma Specimens).
  • If the exposed person presents with signs or symptoms of acute HIV seroconversion, an HIV serologic screening test should be used in conjunction with a plasma HIV RNA assay to diagnose acute HIV infection. (A2) A 4th-generation HIV antigen/antibody combination test is the recommended serologic screening test (see the CDC’s Recommended Laboratory HIV Testing Algorithm for Serum or Plasma Specimens). Immediate consultation with a clinician experienced in managing ART should be sought for optimal treatment options.
nPEP for Patients Who are Pregnant
  • Based on increasing clinical experience with ART, nPEP is indicated at any time during pregnancy when a significant exposure has occurred, despite possible risk to the individual and the fetus. (A2) Expert consultation should be sought. When non-occupational exposure to HIV occurs, every effort should be made to initiate PEP as soon as possible, and ideally within 2 hours. 
  • The preferred PEP regimen for pregnant individuals is tenofovir disoproxil fumarate + emtricitabine (lamivudine may be substituted for emtricitabine) plus raltegravir (see Antiretroviral Agents Recommended for PEP for dosing information). The recommended duration of PEP is 28 days. (AII)
  • Before administering nPEP to a pregnant individual, the clinician should discuss the potential benefits and risks to the individual and to the fetus. (A3)
  • Pregnant individuals presenting for nPEP as a result of risky behavior should be the focus of intensified education and prevention interventions. (A2) After completion of the 28-day nPEP regimen, initiation of pre-exposure prophylaxis (PrEP) should be considered. (A1)
nPEP for Patients Who are Breastfeeding
  • Clinicians should advise individuals who may have been exposed to HIV through non-occupational exposure to avoid breastfeeding for 3 months after the exposure [Parkin et al. 2000]. (A2) If HIV infection is definitively excluded in the source person at any time prior to 3 months post-exposure, breastfeeding can be resumed. (A1)
Non-Occupational Exposure to HBV 
  • When a non-occupational exposure occurs, and the source is available, the source should be evaluated for both hepatitis B and hepatitis C. (A2)
  • The hepatitis B vaccine series should be initiated in non-HBV-immune persons who sustain a blood or body fluid exposure. (A1) Decision-making should not be delayed while testing for anti-HBs. If antibody response is unknown, follow recommendations for “antibody response unknown” below.
  • Administration of prophylactic hepatitis B immune globulin (HBIG) and the initiation of the hepatitis B vaccine series injected at different sites is recommended when the non-HBV-immune person sustains a blood or body fluid exposure to a source person with known acute or active HBV. (A1)
    • Both HBIG and the first dose of the hepatitis B vaccine series should be ideally administered within 24 hours of exposure (A2); HBIG should not be given later than 14 days post-exposure. The three-dose HBV vaccine series is given at 0, 1 to 2 months, and 6 months. Hepatitis B antibodies should be obtained 1 to 2 months after completion of the third dose of the vaccine.
  • Needlestick injuries and wounds should be washed with soap and water and should not be squeezed. Mucous membranes should be flushed with water. (A3)
Non-Occupational Exposure to HCV
  • Clinicians should consider concurrent exposure to HCV when individuals present with an HIV exposure. (A2)
  • Neither immunoglobulin nor antiviral agents are recommended for HCV post-exposure prophylaxis. (A2)
  • When HCV infection is identified, the exposed person should be referred for medical management to a gastroenterologist or other clinician with experience in treating HCV. (A2)
Baseline Management
  • Following an exposure to blood or body fluid, the clinician should assess the risk for exposure to HCV. (A2) Wounds should be washed with soap and water, and should not be squeezed. (A2) Mucous membranes should be flushed with water.
  • Once the clinician has determined that exposure to blood or body fluid has occurred, the following baseline tests should be obtained (A2) (see text for follow-up according to baseline results):
    • Exposed Person:
      • HCV antibody, and if positive, HCV RNA test
      • Liver panel including liver enzymes
    • Source Patient:
      • HCV antibody test (e.g., EIA/ELISA), and if positive, HCV RNA test
  • Clinicians should educate exposed persons about the natural history of HCV infection and should counsel exposed persons about the following:
    • Avoidance of alcohol and, if possible, medications that may be toxic to the liver
    • Risk of transmission related to:
      • Blood-to-blood contact, including sharing personal care items that may have come in contact with another person’s blood, such as razors or toothbrushes; occupational needlestick injuries; and sharing needles, syringes, or other equipment to inject drugs
      • Sexual activity
      • Donating blood, plasma, organs, tissue, or semen
      • Perinatal transmission
    • Hepatitis C virus is not spread via food or water and is not transmitted by:
      • Sharing eating utensils
      • Hugging, kissing, or holding hands
      • Coughing or sneezing
      • Breastfeeding: HCV is not transmitted by breastfeeding; however, clinicians should advise women who may have been exposed to HIV to avoid breastfeeding for 3 months after the exposure. 
Post-Exposure Follow-Up
  • If the source is known to be positive for HCV antibody and/or HCV RNA, the follow-up schedule for the exposed person should be as follows (A2):
    • Week 4: HCV RNA and liver panel
    • Week 12: HCV RNA and liver panel
    • Week 24: Liver panel and HCV antibody
  • If at any time the serum ALT level is elevated, the clinician should repeat HCV RNA testing to confirm acute HCV infection. (A3)
  • At any time that exposed persons test positive for HCV RNA, the clinician should refer for medical management and possible treatment by a clinician with experience in treating HCV. (A3)

Updates to this Guideline

May 2018

Language regarding potential increased risk of neural tube defects with dolutegravir (DTG)-based ART regimens was added throughout the guideline (for clarity, some changes in blue):

  1. Introduction: Tenofovir + emtricitabine* plus either raltegravir or dolutegravir [see DTG saftey statement below] is now the Medical Care Criteria Committee’s preferred initial nPEP regimen because of its excellent tolerability, proven potency in established HIV infection, and ease of administration.
    Dolutegravir (DTG) Safety Statement, May 2018

    On May 18, 2018, the FDA and the DHHS Antiretroviral Guidelines Panels issued statements in response to preliminary results from a study that reported increased risk of neural tube defects in babies born to mothers taking DTG-based ARV drug regimens at the time of conception [AIDSinfo 2018; FDA 2018].

    Until more data become available, DTG-containing regimens should be avoided in any HIV-exposed individual who is or could become pregnant and is not using effective contraception. If there are no alternatives to DTG for individuals of child-bearing potential, then clinicians should strongly advise the use of effective contraception and should obtain a pregnancy test before initiating treatment.

    For more information, see: DHHS Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States

  2. ART Regimens for nPEP: Added the DTG saftey statement noted above.
  3. nPEP for HIV-Exposed Women Who are Pregnant or Breastfeeding: Added the DTG safety statement noted above. 
  4. Updated recommendation: The preferred PEP regimen for pregnant individuals is tenofovir disoproxil fumarate + emtricitabine (lamivudine may be substituted for emtricitabine) plus raltegravir (see Antiretroviral Agents Recommended for PEP for dosing information). The recommended duration of PEP is 28 days. (A2)
  5. Updated text: With the exception of dolutegravir, the agents listed below are not recommended for use in PEP regimens and are not likely to be used; however, clinicians should be aware that these agents should not be prescribed in pregnant individuals.
  6. Updated text: Added dolutegravir to the list of drugs to avoid during pregnancy: Dolutegravir: Teratogenicity; preliminary reports of increased risk of neural tube defects