HIV Prophylaxis Following Non-Occupational Exposure Including Sexual Assault

Free Online CME: Antiretroviral Chemoprophylaxis

Updated May 2010 — Currently Under Revision

What’s New — May 2010 Update

Updated: Section VIII: Non-Occupational Exposures to Hepatitis B and C

I. INTRODUCTION

January 2008

The New York State Department of Health AIDS Institute (NYSDOH AI) has published guidelines that address HIV post-exposure prophylaxis (PEP) following occupational exposure¹ and sexual assault. The purpose of this chapter is to provide recommendations and guidelines for prescribing PEP following non-occupational exposure to HIV including sexual assault. These guidelines will address PEP for significant risk exposures following sexual and needle-sharing activities, needlesticks outside of occupational settings, and trauma, including human bites. Updated guidelines for PEP following sexual assault are also included.

ARV prophylaxis following occupational exposures has been a standard of care for healthcare workers since the 1980s. Prophylaxis following sexual assault has also been recommended in New York State since 1997. Prophylaxis following sexual exposures and other blood exposures, including injection drug use, has been extensively considered and debated. Practice guidelines and policy recommendations for non-occupational HIV prophylaxis must consider the limitations of current scientific knowledge and the lack of definitive evidence concerning efficacy to support such recommendations. Although there are no studies that directly demonstrate the efficacy of non-occupational PEP (nPEP), several data sources support its biologic plausibility, including animal studies of prophylaxis following exposure to simian immunodeficiency virus (SIV) and HIV-2, efficacy data from mother-to-child transmission studies, and case-controlled studies of occupational exposure.^2-4 Several studies also support the feasibility of nPEP.^5-7

Within the category of sexual exposure, sexual assault merits special focus. Although infrequent, cases of HIV transmission following sexual assault have been described.^8,9 As with occupational exposure, exposure occurs at a single point in time and is unlikely to recur. Because of the special considerations regarding evaluation of the risk of HIV exposure as well as counseling and support for sexual assault survivors, PEP in the setting of sexual assault is addressed separately in this chapter (see Section III: PEP for Sexual Assault Survivors).

Developing guidelines for HIV exposures outside of the healthcare 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 ARV therapy, and the potential public health impact of such guidelines. 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.^10,11

Although the most effective way to prevent HIV transmission is to protect against exposure, nPEP offers the possibility of preventing HIV transmission when possible exposure to HIV has occurred. It is likely to be most effective when treatment of high-risk exposures is combined with a strong educational component that emphasizes prevention of future exposures.

The rationale supporting provision of nPEP with respect to the risk of transmission follows a similar logic to that of occupational exposure. Model-based data have indicated probabilities of infection of 0.5% to 3% per episode of receptive anal intercourse^12,13 and 0.1% to 0.2% per episode of receptive vaginal intercourse.^13,14 The estimated risk for insertive anal and insertive vaginal intercourse, or for oral sex with ejaculation, is lower. The estimated risk of an intravenous needle-sharing exposure is 0.67%.¹⁵ The estimated risk from occupational exposure following percutaneous injury is 0.3%.⁵

Therefore, the per-episode estimated transmission risk for HIV following sexual and injection drug exposures is, in some cases, higher than that for occupational exposure.

In 1998, the Centers for Disease Control and Prevention (CDC) published a commentary on the use of nPEP, which reviewed considerations involved in offering such therapy but did not either recommend or discourage its use.¹⁶ Massachusetts and Rhode Island have issued guidelines and procedures for the administration of nPEP, and California has issued guidelines for PEP following sexual assault.^17-19 Several countries have official policies regarding nPEP. A number of observational studies have been designed to assess the feasibility and potential efficacy of nPEP programs, including the national HIV Post-Exposure Prophylaxis Registry, which collects information on the use of ARV therapy in non-occupational HIV exposures. Initial published reports from San Francisco, Boston, and Brazil have demonstrated the feasibility of such programs in high-risk populations.^6-8

Because there are no randomized, placebo-controlled experimental clinical trials on which to definitively base recommendations, the following NYSDOH guidelines are based on 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.

To develop these guidelines for nPEP, the group of clinicians and scientists serving on 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 discussions 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.

The Committee addressed the following questions:

Under what circumstances would individuals at risk for HIV infection benefit from nPEP?
What settings and program service components allow for the most effective delivery of nPEP?
What is the appropriate timing for initiation of nPEP? Is there a time after which prophylaxis would not be indicated or advisable?
Which drugs should be used for nPEP?
For how long should nPEP be continued?
What constitutes appropriate monitoring and follow-up?
What are the cost considerations?

There are many factors to consider when deciding whether to implement nPEP. Figure 1 is meant to serve as a general guide. The sections that follow the figure provide more detail regarding the specific factors that are weighed in decision-making.

Figure 1: PEP Following Non-Occupational Exposure Including Sexual Assault

^a See Tables 2 and 3.
^b Decisions should be individualized, weighing the likelihood of transmission against the potential benefits and risks of treatment.
^c In cases of sexual assault, the decision to initiate PEP is based on whether a significant exposure has occurred during the assault rather than on the risk behavior of the alleged assailant.
^d If the source is known to be HIV infected, information about his/her CD4 count, viral load, ARV medication history, and history of ARV drug resistance should be obtained when possible to assist in selection of a PEP regimen.²¹
^e The two regimens listed are essentially the same regimen because lamivudine and emtricitabine are interchangeable. The zidovudine + Truvada option has been added to increase access to the recommended PEP regimen and allow faster initiation of PEP, when indicated, based on the institution’s availability of medications.
^f If a sexual assault survivor is too distraught to engage in a discussion about the drug regimen or make a decision about whether to initiate treatment at the initial assessment, the clinician should offer a first dose of medication and make arrangements for a follow-up appointment within 24 hours to further discuss the indications for PEP.
^g See Appendix A for dosing recommendations in patients with renal impairment.

II. PEP FOLLOWING NON-OCCUPATIONAL EXPOSURES (nPEP)

January 2008

This section addresses 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 Section III: PEP for Sexual Assault Survivors. 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.

A. Assessment to Determine Whether nPEP Is Indicated

RECOMMENDATIONS:

Whenever possible, risk assessment and initiation of nPEP should occur in clinical settings where HIV prevention counseling services, as well as HIV clinical expertise, are available or are easily accessed by referral.

Patients who present for nPEP should be evaluated as soon as possible in order to initiate therapy, if indicated, within recommended time frames (see Section IV: Timing of Initiation of PEP for All Non-Occupational Exposures).

When deciding whether to recommend the initiation of nPEP, the clinician should assess and carefully weigh the following factors (see Table 1):

the behavioral factors and circumstances that led to HIV exposure
the patient’s risk of HIV acquisition based on the type of exposure
the possibility that the source is HIV-infected

The clinician should provide risk-reduction counseling and primary prevention counseling whenever someone is assessed for nPEP, regardless of whether PEP is initiated.

Non-occupational PEP should not be prescribed when there is negligible or low risk of HIV transmission (see Table 2).

Non-occupational PEP should not be used as a pre-exposure prophylactic measure to prevent HIV transmission in a woman wishing to become pregnant with an HIV-infected male partner, or as prophylaxis for any person who plans to engage in high-risk behavior.

Clinicians should provide supportive counseling and make referrals for counseling for patients for whom nPEP is not prescribed.

When possible, assessment for and initiation of nPEP should occur in a setting that can provide the following:

Assessment of HIV risk
HIV and STD testing and treatment
Prevention and risk-reduction counseling
Clinicians with expertise in the use of ARV therapy
Timely access to care and initiation of nPEP

Clinicians should assess risk, discuss potential risks and benefits of nPEP, provide risk-reduction counseling and education, and provide follow-up care. If patients present with risk exposures at sites that do not offer these services, the clinician should initiate nPEP based on these guidelines, then seek phone consultation with an HIV-experienced provider to review the case. The patient should then be referred to a clinician who has experience in the use of ARV agents and who can provide ongoing prevention counseling for follow-up care. The National Clinicians’ Consultation Center PEP line at 1-888-HIV-4911 (1-888-448-4911) is available for telephone consultation. Patients who present for nPEP should be evaluated as soon as possible by a provider who can perform the assessment outlined in Table 1. In areas where referral is not possible, telephone consultation should be used as part of co-management.

Table 1: Elements of Assessment to Determine Whether nPEP Is Indicated

Risk Behavior:

Did exposure to potentially HIV-infected blood or body fluid occur?
Was the exposure an isolated or episodic event, or result of habitual behavior?

Degree of Transmission Risk Based on Type of Exposure:

What was the route of exposure?
Are factors present that are known to further increase transmission risk?

Exposure Source:

Is the source known to be HIV infected?*
If HIV status of the source is unknown, what is the likelihood of the source being HIV infected (see Table 4)?

* If the source is known to be HIV infected, information about his/her CD4 count, viral load, ARV medication history, and history of ARV drug resistance should be obtained when possible to assist in selection of a PEP regimen.

The use of nPEP carries both significant costs and potential risk of toxicity from medications. As a result, it should only be used when the risks of taking nPEP are outweighed by the potential benefits. Non-occupational PEP is not indicated for perceived exposures that are of negligible or low-risk (see Table 2). Prophylaxis during pregnancy attempts by serodiscordant partners is not recommended because other methods of assisted reproduction are presumed to be safer and are preferable for those who can access them. The NYSDOH is currently developing guidelines for assisted reproduction technology in HIV-infected women, which will be posted to www.hivguidelines.org upon completion.

1. Assessing Risk Behavior

Assessment should include a determination of whether the risk is an isolated event, episodic event, or habitual risk behavior. Non-occupational PEP is recommended in situations in which there is an isolated exposure (sexual, needle, or trauma), a lapse in previous risk-reduction practices, or when patients have expressed interest in behavioral change. 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.

Non-occupational PEP should not be routinely dismissed solely on the basis of repeated risk behavior or repeat presentation for nPEP. Persons who present with repeated high-risk behavior or for repeat courses of nPEP should be the focus of intensified education and prevention interventions. Intent to change behavior should be assessed, and an individualized risk-reduction plan should be developed. Clinicians providing nPEP in the case of repeated high-risk behaviors, despite behavioral intervention, should consider potential medication toxicity, adherence, potential resistance, and cost considerations when determining whether repeat courses of nPEP should be offered. The cost and potential toxicity would outweigh the benefit of nPEP for use in patients who plan to continue to engage in high-risk behaviors and who rely on nPEP as the sole intervention for HIV prevention.

2. Degree of Transmission Risk Based on Type of Exposure

Determining the degree of risk of HIV transmission is an important factor in guiding the patient and clinician in making a decision concerning nPEP. Table 2 lists types of exposures that do not warrant nPEP and those that should prompt consideration of nPEP.

Table 2: Consideration of nPEP According to the Type of Risk Exposure*
Types of Exposures That Do Not Warrant nPEP	Types of Exposures That Should Prompt Consideration of nPEP
Kissing Oral-to-oral contact without mucosal damage (mouth-to-mouth resuscitation) Human bites not involving blood Exposure to needles or sharps not in contact with an HIV-infected or at-risk person Mutual masturbation without skin breakdown Oral-anal contact Receptive penile-oral contact without ejaculation Insertive penile-oral contact Oral-vaginal contact without blood exposure	Unprotected receptive and insertive vaginal or anal intercourse with a source that is HIV-infected or at risk for HIV infection Unprotected receptive penile-oral contact with ejaculation with a source that is HIV-infected or at risk for HIV infection Oral-vaginal contact with blood exposure Needle sharing with a source known to be HIV-infected or at risk for HIV infection Injuries with exposure to blood from a source known to be HIV-infected or at risk for HIV infection (including needlesticks, human bites, accidents)
*Table 3 provides risk calculations for specific risk behaviors; Table 4 defines who is considered at high risk for HIV infection.

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 Table 3). For more information, refer to Prevention with Positives: Integrating HIV Prevention into HIV Primary Care.

Table 3: Estimated Risk of HIV Transmission Following Different Types of Exposures^a
Type of Exposure	Estimated Risk	Reference
Needle-sharing exposure to an infected source	0.67% (1 in 150)	Ref. 15
Receptive anal intercourse with an infected source	0.5% (1 in 200) to 3.0% (6 in 200)	Refs. 12,13
Receptive vaginal intercourse with an infected source	0.1% (1 in 1000) to 0.2% (2 in 1000)	Refs. 13,14
Insertive anal intercourse with an infected source	0.065% (1 in 1500)	Refs. 13,14
Insertive vaginal intercourse with an infected source	0.05% (1 in 2000)	Refs. 13,14
Oral sex with ejaculation with an infected source	Conflicting data—however, risk is considered to be low^b	Refs. 20,21
^a These risk estimates depend on many factors, including source viral load, presence of STDs, and presence of ejaculate. ^b It is prudent to recommend nPEP for receptive oral sex with ejaculation, although discussion about the conflicting data should occur.

Risk evaluation should also assess whether factors known to further increase the risk of transmission of HIV infection are present, including trauma at the site of exposure, the presence of genital ulcer disease and/or other STDs, and high plasma viral load in the HIV-infected partner/source. Other factors that may enhance transmission include cervical ectopy and lack of circumcision.

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 in the non-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. 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 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. 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.^22,23

A bite wound that results in blood exposure should prompt consideration of nPEP. When a human bite occurs, it is possible for either the person bitten or the biter or both to have incurred blood exposure. Use of nPEP in this setting potentially would be indicated only when there is significant exposure to deep, bloody wounds. Blood exposure could occur in the following scenarios involving bites:

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)

A bite is not considered a risk exposure to either party when the integrity of the skin is not disrupted.

3. Considering the HIV Status of the Exposure Source

If the source of contact is known to be HIV infected, information about his/her CD4 count, viral load, ARV medication history, and history of ARV drug resistance should be obtained when possible to assist in the selection of an nPEP regimen. If the source is anonymous, or the contact’s HIV status is not known, the source’s potential risk of having HIV infection should be assessed (see Table 4). Regional information regarding HIV prevalence also should be considered.²⁴

Table 4: Sources That May Be at Increased Risk for HIV Infection
Sources with a history of multiple sexual partners Sources with a sexually transmitted disease, particularly ulcerative diseases Sources who are men who have sex with men Sources with a history of needle-sharing behavior Sources with a history of trading sex for money or drugs

B. Baseline Testing for Patients Who Present With Risk Exposures

RECOMMENDATIONS:

The clinician should perform baseline HIV testing of the exposed person. Initiation of nPEP should not be delayed pending HIV test results. Where available, rapid testing should be used.

The clinician should perform an assessment for other sexually transmitted diseases, such as chlamydia, gonorrhea, and syphilis, and should provide STD prophylaxis in sexually exposed patients.

The clinician should obtain baseline pregnancy testing for exposed women. Emergency contraception should be offered to and discussed with women at risk of pregnancy from the exposure.

Risk behaviors leading to HIV infection also put the patient at risk for other STDs. Patients who present for nPEP should receive baseline HIV counseling and testing as well as evaluation and prophylaxis for other STDs after a sexual exposure. Rapid HIV testing is the preferred method of HIV testing in this situation because it can immediately identify patients who were already infected with HIV at the time of presentation in order to avoid unnecessary risks from inappropriate initiation of nPEP. When rapid testing is not available, nPEP should be started without waiting for the results of the HIV test, otherwise the 36-hour window of effectiveness for nPEP would be lost. A negative antibody test only demonstrates that the patient was not previously infected with HIV; therefore, nPEP would still be initiated when indicated. Emergency contraception for female patients 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:

C. Deciding to Recommend nPEP

RECOMMENDATIONS:

The clinician should initiate nPEP ideally within 2 hours and generally no later than 36 hours following exposure when an isolated exposure (sexual, needle, or trauma) has occurred or when risk-reduction practices fail.

The clinician should discuss the following issues with the patient and should document that they were discussed before initiating a regimen:

the potential benefit, unproven efficacy, and potential toxicity of nPEP
the need for adherence
the need to initiate/resume risk-reduction and preventive behaviors
signs and symptoms of primary HIV infection
the need for clinical and laboratory monitoring and follow-up

The patient should agree to follow-up monitoring and initiation of interventions to reduce risk, if applicable, before the clinician initiates nPEP. All components of this discussion should be documented so that events leading to infection can be clearly identified and the efficacy of nPEP can be assessed.

ARV 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 Section VI: Monitoring Following Non-Occupational Exposure Including Sexual Assault).

Sexual assault survivors can access reimbursement through the Crime Victims Board; however, reimbursement for other types of nPEP is not generally available for the uninsured, and private insurers may refuse to reimburse for it. This challenging issue should be discussed during counseling before nPEP is initiated. Strategies should be sought to address this reality.

D. Behavioral Intervention and Risk-Reduction Counseling

RECOMMENDATIONS:

Behavioral intervention for risk reduction should occur regardless of whether nPEP is initiated or not.

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.

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.

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. For more information, refer to Prevention with Positives: Integrating HIV Prevention into HIV Primary Care.

III. PEP FOR SEXUAL ASSAULT SURVIVORS

January 2008

RECOMMENDATION:

Survivors of sexual assault should be treated in an emergency department or equivalent healthcare setting where all appropriate medical resources are available as needed.

A. Assessment to Determine Whether nPEP Is Indicated Following Sexual Assault

RECOMMENDATIONS:

When deciding whether to recommend the initiation of nPEP following sexual assault, the clinician should assess and carefully weigh the following factors:

whether or not a significant exposure has occurred during the assault
knowledge of the HIV status of the alleged assailant
whether the survivor is ready and willing to complete the nPEP regimen

The clinician’s decision to recommend nPEP should not be influenced by the geographic location of the assault.

Although the seroprevalence of HIV in different New York communities may vary, the HIV status of an individual who has been accused of perpetrating a sexual assault remains unknown until that individual has been tested. It is also important to consider that HIV prevalence in sexual assailants may be higher than that in the general population.²⁴ In the acute setting of sexual assault, the decision to recommend prophylaxis should not be based on the geographic location of the assault but rather on the nature of the exposure during the assault, the readiness of the survivor to initiate and adhere to the prophylactic regimen, and the HIV status of the alleged assailant, if known.

1. Degree of Risk Based on Type of Exposure

RECOMMENDATIONS:

Clinicians should recommend HIV nPEP to survivors when significant exposure may have occurred, as defined by direct contact of the vagina, anus, or mouth with the semen or blood of the alleged assailant, with or without physical injury, tissue damage, or presence of blood at the site of the assault.

Non-occupational PEP should also be offered in cases when broken skin or mucous membranes of the survivor have been in contact with blood or semen of the alleged assailant. Similarly, nPEP should be offered in cases of bites that result in visible blood.

Genital trauma is present in the majority of sexual assault survivors, with anal trauma present in just over half. Absence of visible trauma does not indicate that an assault did not occur; microabrasions are common and the appearance of manifestations may be delayed. Oral trauma may also occur during sexual assault with potential exposure to blood or semen from the alleged assailant, which would carry a potential risk for HIV exposure. Bites or trauma may be inflicted during an assault and are indications for prophylaxis if there is contact with blood or semen from the alleged assailant.

2. Considering the HIV Status of the Alleged Assailant

RECOMMENDATIONS:

Unless the identity and HIV status of the alleged assailant has been clearly established to assist with the decision-making, nPEP should be promptly initiated when a significant risk exposure has occurred.

Even when the alleged assailant is known to be HIV infected, the decision to recommend nPEP should be based on the nature of the exposure and the survivor’s ability to complete the regimen.

If prophylaxis has been initiated and the alleged assailant is found to be HIV antibody negative, then nPEP should be discontinued.

As of November 1, 2007, New York State Criminal Procedure Law § 210.16 requires testing of criminal defendants, indicted for certain felony sex offenses, for human immunodeficiency virus (HIV), upon the request of the victim. For guidance on defendant testing, please visit NYS Court-Ordered HIV Testing of Defendants.

In most instances, the HIV status of the alleged assailant will not be known and cannot be available in sufficient time to influence the decision to initiate nPEP. If the HIV status of the alleged assailant is established and confirmed, ideally through the use of rapid testing, that knowledge should be used in decisions to initiate or continue nPEP, as well as to assist in choosing the PEP regimen if viral resistance data are available. Testing of the source should be pursued in accordance with New York State Public Health Law and Regulations.

It is not possible to know whether an alleged assailant has HIV infection solely on the basis of risk behaviors. Categorical judgments should not be made on the basis of perceived risk. The decision to offer prophylaxis should be based on whether significant exposure has occurred during the assault rather than on the risk behavior of the alleged assailant.

When the survivor knows the alleged assailant personally, assumptions about HIV status or risk should have limited influence on the decision to initiate prophylaxis. Familiarity with the alleged assailant may influence the survivor’s perception of risk, which will influence his/her decision to initiate nPEP. Because HIV risk behaviors and status may be hidden from close friends and family, decisions based on familiarity with the alleged assailant should be made cautiously.

If the alleged assailant has not been confirmed to be HIV antibody negative, then the decision to initiate nPEP should be based on the nature of the exposure and the survivor’s ability to complete the treatment. If the alleged assailant has been confirmed to be HIV antibody positive, HIV-specific information about the source, including a treatment history, should be obtained because it may influence the recommended nPEP regimen. Consultation with a provider with experience with ARV therapy is especially recommended when the source person is known to harbor drug-resistant HIV because an alternate nPEP regimen may be more effective. However, initiation of the first dose of nPEP should not be delayed while awaiting this information.

B. Recommending nPEP for Sexual Assault Survivors

RECOMMENDATIONS:

Non-occupational PEP should be initiated as soon as possible after exposure. Non-occupational PEP is unlikely to be effective more than 36 hours post-exposure (see Section IV: Timing of Initiation of PEP).

In New York State, hospitals providing treatment to victims of sexual assault must have seven-day starter packs of medication available on-site for rapid initiation of nPEP following sexual assault. Arrangements should be made to ensure that the patient receives a continued supply of medication and an appointment is made with a clinician experienced in HIV PEP.

The recommendation for nPEP should be communicated simply and clearly to the patient, considering his/her emotional state and ability to comprehend the nature of ARV treatment.

If a sexual assault survivor is too distraught to engage in a discussion about the drug regimen or make a decision about whether to initiate treatment at the initial assessment, the clinician should offer a first dose of medication and make arrangements for a follow-up appointment within 24 hours to further discuss the indications for nPEP.

If a sexual assault survivor decides to initiate treatment, a follow-up visit should be scheduled within 24 hours to review the decision, evaluate initial drug tolerability, reinforce the need for adherence to the regimen, and arrange for follow-up care. In New York State, hospitals providing treatment to victims of sexual assault must provide or arrange for an appointment for medical follow-up related to nPEP and other care as appropriate. See the Voluntary HIV Provider Directory.

The discussion regarding initiation of nPEP should include the following:

The potential to prevent HIV infection
Possible side effects of the nPEP regimen
Duration of nPEP and the monitoring schedule
Importance of adherence to the treatment regimen to prevent nPEP failure or the development of drug resistance should infection occur

Because evidence indicates the need to begin prophylaxis within hours after an exposure, the clinician is in the position of deciding how strongly to advise the survivor to initiate the regimen. This requires the clinician to balance the survivor’s readiness with the knowledge that the most efficacious intervention should occur promptly. If a patient is too distraught to engage in discussion, he/she should be encouraged to take a single dose of nPEP, and then revisit the issue the following day. The risk of taking one dose is likely to be minimal, and the efficacy that would be lost if delayed a whole day may be salvaged. However, if the victim decides to defer making a decision at the time of the initial intervention, then the follow-up visit to consider nPEP should occur within 24 hours of the exposure to ensure that nPEP is started within 36 hours of exposure. This follow-up visit also offers clinicians a chance to re-evaluate the decision to initiate nPEP. If the survivor is pregnant, a full discussion of the benefits and risks of prophylaxis for both maternal and fetal health should occur (see Section VII: Non-Occupational PEP for the Pregnant Patient).

Various payment methods for nPEP are available for survivors of sexual assault, including Medicaid, Medicare, or Crime Victims Compensation. Third-party reimbursement may cover nPEP, depending on the plan’s prescription drug policy, if the individual has prescription drug coverage. In cases where the medication-dispensing facility does not receive reimbursement for these services, such expenses may be included in their annual Institutional Cost Report as part of indigent care costs. Timely initiation of medication is crucial to the success of nPEP, and hospitals providing treatment to victims of sexual assault are required to have seven-day starter packs available onsite.

The Crime Victim’s Board (CVB) has developed special procedures to ensure availability of nPEP for sexual assault victims. CVB will contact the prescription provider to attempt to facilitate availability of needed drugs, if requested to do so, and will directly reimburse pharmacy providers. Documentation of a visit to a medical facility that provides a forensic physical examination satisfies the CVB reporting requirement, thereby providing access to compensation for people who may be either unwilling or unable to report the crime to the police.

For Crime Victims Compensation, claim forms can usually be obtained from hospital emergency departments and can also be downloaded from the Crime Victims Board website at www.cvb.state.ny.us. Survivors of sexual assault may also contact a Rape Crisis Center or Victims Services Agency in their county or region for assistance in filing claims with CVB, particularly when emergency assistance is needed. Many of these agencies have 24-hour hotlines. For more information about accessing Crime Victims Compensation, and for a list of victims services agencies and other resources, consult the CVB website at www.cvb.state.ny.us.

C. The Role of the Rape Crisis Counselor and Sexual Assault Examiner

RECOMMENDATIONS:

The rape crisis counselor should be an active participant in the discussion regarding HIV nPEP.

The plan for follow-up care should be discussed with the rape crisis counselor or an outreach worker who will be working with the survivor following the survivor’s departure from the emergency department or equivalent healthcare setting.

The rape crisis counselor is often a volunteer from the community whose primary role is to provide comfort, assistance, and information to the survivor. The counselor is neither an employee of the healthcare facility nor a representative of the Department of Health. The active role that a counselor plays in the decision-making process to initiate nPEP and to facilitate ongoing care and monitoring depends solely on the decision of the survivor to accept such involvement. To the extent possible, the treating clinician and the rape crisis counselor should coordinate care to encourage medical follow-up and adherence to nPEP. Through this effort, the rape crisis counselor may become the crucial link between the survivor and the provider, clarifying communication and facilitating follow-up care for the survivor. When the survivor does not have a primary care provider or has difficulty arranging access to a provider with experience with HIV PEP, this link becomes especially important. Support from the counselor will increase the likelihood that the individual will adhere to the nPEP regimen and that medical problems will be addressed expeditiously when they arise.

If the rape crisis counselor is part of the multidisciplinary healthcare team as determined by the clinician, then the counselor may provide additional support to the survivor in the test counseling process (see Section D: HIV Testing of the Survivor). If the counselor is not part of the treatment team, permission to communicate HIV-related information to him/her will need to be obtained in writing from the survivor. Specific permission does not need to be obtained to discuss the general benefits and risks of ARV therapy or the decision to initiate nPEP.

The sexual assault forensic examiner (SAFE) also plays a critical role in management of care following sexual assault. Sexual assault forensic examiners are specially trained in areas such as forensic techniques (e.g., screening for the presence of “date rape” drugs) and health care of sexual assault survivors (e.g., emergency contraception, treatment for possible exposure to STIs). See Appendix C for more information about the SAFE programs in New York State.

D. HIV Testing of the Survivor

RECOMMENDATIONS:

Clinicians should obtain blood for baseline HIV serologic testing when recommending initiation of nPEP. Prophylaxis, when indicated, should be started without waiting for the results of this test.

Refusal to undergo baseline testing should not preclude initiation of nPEP.

Because a negative antibody test only demonstrates that the patient was not previously infected with HIV, nPEP is still indicated when a risk exposure has occurred. When rapid testing is not available, nPEP should be started without waiting for the results of the HIV test, otherwise the 36-hour window of effectiveness for nPEP would be lost. Rapid testing allows for preliminary identification of previously HIV-infected patients within 30 minutes, so that unnecessary risks from inappropriate initiation of nPEP can be avoided. Possible complications of initiating nPEP without baseline HIV testing in the context of sexual assault include the inability to subsequently establish that the assault resulted in HIV transmission, if the survivor later tests positive for HIV.

If the survivor prefers not to undergo HIV testing in the emergency department setting, a referral should be arranged to obtain HIV testing the next day. If excess blood is remaining from blood specimens obtained in the emergency room for other reasons, it may be used for later HIV testing only if informed consent has been obtained.

The emergency department provider should obtain the HIV test; however, with agreement of all parties, this responsibility may be transferred to the treating clinician or primary care provider. If the survivor is being treated with nPEP, this responsibility should be coordinated with the treating clinician, who may need to discuss long-term treatment options with the survivor should he/she seroconvert. If the survivor is not under the care of a primary care physician or HIV provider, the emergency department provider who has obtained the test is responsible for communicating the result in person to the survivor.

IV. TIMING OF INITIATION OF PEP FOR ALL NON-OCCUPATIONAL EXPOSURES

January 2008

RECOMMENDATION:

Non-occupational PEP should be offered as soon as possible after exposure and initiated ideally within 2 hours and generally no later than 36 hours following exposure. Non-occupational PEP is unlikely to be effective more than 36 hours post-exposure.

Animal models of nPEP have shown that effective ARV treatment is most likely to prevent infection when initiated within 24 hours of experimental simian immunodeficiency virus (SIV) exposure. It is unknown whether initiation of nPEP beyond this point confers protection. With the exception of nevirapine, which is immediately active intracellularly, the currently recommended nPEP drugs require an intracellular activation step that delays the onset of antiviral activity. Thus, clinicians should begin nPEP as soon as possible following an exposure that carries a risk of HIV transmission, and generally no later than 36 hours, although 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 potential for success when timing of initiation is prolonged. Some individuals who have survived sexual assault or who have higher risk exposures (i.e., 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. If the clinician strongly suspects that HIV transmission is likely to have occurred, consultation with a provider with experience with HIV PEP is strongly advised.

Once a decision has been made that nPEP is indicated, patients should be encouraged to initiate the regimen immediately. Supports to facilitate adherence with the treatment regimen should be evaluated and provided to the extent possible.²⁵

V. RECOMMENDED nPEP REGIMENS

January 2008

RECOMMENDATIONS:

Clinicians should initiate three-drug ARV therapy for significant exposures to HIV. The preferred nPEP regimen is shown in Table 5. Alternative agents may be used in the setting of drug intolerance or toxicity (see Table 5 and Appendix A).

Starter packs of medication should be available on-site for rapid initiation of treatment, and arrangements should be made for continuation of treatment.

When the source is known to be HIV infected and information regarding previous ARV therapy, current level of viral suppression, or genotypic/phenotypic resistance profile is available, the clinician, in consultation with a provider with experience with HIV PEP, should individualize the regimen to more effectively suppress viral replication.

The nPEP regimen should be continued for 4 weeks.

Table 5: HIV PEP Regimen Following Non-Occupational Exposure^a,b,c

Zidovudine^d 300 mg PO bid + Lamivudine 150 mg PO bid (or Combivir 1 PO bid)

Plus

Tenofovir 300 mg PO qd

Zidovudine^d 300 mg PO bid

Plus

Emtricitabine 200 mg PO qd + Tenofovir 300 mg PO qd (or Truvada 1 PO qd)

Notes:
^a When the source is known to be HIV-infected, past and current ARV therapy experience, viral load data, and genotypic or phenotypic resistance data (if available) may indicate the use of an alternative PEP regimen. Consult a provider with experience with ARV therapy.
^b NNRTIs should be considered only when 1) the patient cannot tolerate either tenofovir or a protease inhibitor alternative, or 2) the patient has been exposed to a source with known drug-resistant HIV that is sensitive to NNRTIs. Use of efavirenz should only be considered in men and in women not capable of bearing children because of associations with teratogenicity in animal studies and in anecdotal reports in humans. Initial central nervous system toxicity, often seen with efavirenz, may affect one’s ability to work. Nevirapine is not recommended for women with CD4 counts >250 cells/mm³ or men with CD4 counts >400 cells/mm³ and should only be used when NRTIs or PIs are not an option and no other hepatic risk (e.g., hepatitis) is present. If nevirapine is used, it is essential that the 14-day lead-in period be strictly followed. Serum liver enzymes should be obtained at baseline, at dose escalation, and 2 weeks after dose escalation.
^c The dosing interval of lamivudine, emtricitabine, and tenofovir should be adjusted in patients with baseline creatinine clearance <50 mL/min. Because Combivir and Truvada are fixed-dose combinations, clinicians should consider using the individual components (i.e., Combivir = zidovudine + lamivudine; Truvada = emtricitabine + tenofovir) dose adjusted for creatinine clearance (see Appendix A for dosing recommendations in patients with renal impairment). If the combination pills are used in this setting, clinicians should monitor for renal toxicity.
^d If the patient is intolerant to zidovudine, stavudine 40 mg PO bid may be substituted (if patient is <60 kg, 30 mg PO bid should be given). Dosing interval of zidovudine should be adjusted in patients with baseline creatinine clearance <15 mL/min (see Appendix A for dosing recommendations in patients with renal impairment).

Once a decision has been made that a significant risk exposure has occurred and that nPEP is warranted, three-drug combination therapy should be offered unless contraindications exist. This recommendation is identical to NYSDOH guidelines for prophylaxis following occupational exposure. Some occupational and non-occupational PEP programs have used a two-drug regimen due to adherence and cost issues; however, this Committee recommends that all PEP regimens contain a minimum of three ARV agents, which will more likely decrease viral burden. The Committee chose tenofovir as the third agent because it achieves high intracellular levels and has been effective in trials of PEP in primates. The combination of two NRTIs plus tenofovir has high failure rates for treatment of established HIV infection and is only recommended for PEP where the goal is prevention of infection and not treatment.

Timely initiation of medication is crucial to the success of PEP. Starter packs of medication should be available on-site for rapid initiation of treatment, and arrangements should be made for continuation of treatment.

Current guidelines for prophylaxis following occupational exposure recommend treatment for 4 weeks. These same recommendations should apply to PEP following non-occupational exposure. Continuation of treatment beyond 4 weeks will depend on results of HIV serologic testing.

If the patient’s baseline HIV test shows evidence of HIV infection acquired before starting nPEP, then the decision to continue ARV therapy should be based on accepted treatment guidelines and resistance test results, taking into account the patient’s CD4 status and willingness to continue therapy. In the case of an indeterminate test and in the setting of symptoms suggestive of primary HIV infection, the clinician should continue ARV treatment until a definitive diagnosis is established. A provider with experience with ARV therapy should be consulted.

As experience with nPEP continues to accumulate, it has become increasingly clear that the reasons for non-adherence to nPEP are multifactorial. Factors affecting adherence include ARV drug intolerance, regimen complexity, fear, anxiety, expense, frustration, and beliefs that the regimen will not work. Although there are no clinical trial data (other than that with zidovudine), based on post-exposure animal data using tenofovir and its excellent tolerability and simplicity,²⁶ the Committee now recommends the simpler standard nPEP regimen of zidovudine, lamivudine, and tenofovir. Substitutions for tenofovir include the PIs nelfinavir and lopinavir/ritonavir (co-formulated as Kaletra). If these cannot be used, an NNRTI may be considered. In the setting of renal insufficiency, tenofovir and lamivudine may require dose reduction or may be contraindicated (see Appendix A). The package insert for these agents should be consulted.

Reports of nevirapine-induced hepatotoxicity among people receiving PEP have led to the recommendation that nevirapine be considered as an alternative component of the nPEP regimen only when NRTIs and PIs are not an option.²⁷ Use of efavirenz in an nPEP regimen should only be considered in men and in women not capable of bearing children because it has been associated with teratogenicity in animal studies and in humans anecdotally.

VI. MONITORING FOLLOWING NON-OCCUPATIONAL EXPOSURE INCLUDING SEXUAL ASSAULT

January 2008

RECOMMENDATIONS:

Clinicians should closely monitor people receiving nPEP to detect ARV-induced toxicities.

Because of the complexity and potential adverse effects of the nPEP regimens, longitudinal care of the exposed patient should be provided either directly by or in consultation with a provider with experience with HIV PEP.

Sequential confidential HIV testing should be obtained at baseline, 1, 3, and 6 months post-exposure even if nPEP is declined (see Table 6). In New York State, if the test result is positive, a Western blot assay must be performed to confirm the diagnosis of HIV infection.

Any acute febrile illness post-exposure accompanied by one or more of the following—rash, lymphadenopathy, myalgias, sore throat—suggests the possibility of acute HIV seroconversion and requires urgent evaluation. If the patient presents with signs or symptoms of acute HIV seroconversion, immediate consultation with a provider with experience with HIV PEP should be sought for optimal diagnostic testing and treatment options.

Table 6: Monitoring Recommendations After Initiation of PEP Regimens Following Non-Occupational Exposure
	Clinic Visit	CBC with Differential	Serum Liver Enzymes	HIV Antibody*
Baseline	X	X	X	X
Week 1	X
Week 2	X	X	X
Week 3	X
Month 1	X	X	X	X
Month 3				X
Month 6				X
*Recommended even if PEP is declined.

Post-exposure care involves simultaneous attention to multiple issues: the emotional state of the exposed patient, adherence to the nPEP regimen, monitoring for potential adverse effects, and sequential HIV testing to exclude acquisition of infection.

Approximately 50% of patients in whom nPEP is initiated do not complete therapy due to side effects or non-adherence. When a patient is potentially exposed to HIV, longitudinal medical follow-up of the patient is necessary regardless of whether nPEP is initiated and/or completed, in order to test sequentially for HIV infection. Follow-up is necessary for patients receiving nPEP to monitor for adverse effects of the nPEP regimen and maximize adherence to the prescribed regimen.

When infection occurs, the ELISA will generally be positive within 3 weeks of the onset of symptoms and is virtually always positive within 3 months following exposure. The confirmatory Western blot may yield an indeterminate result during the early stages of seroconversion. Subsequent testing should be performed to confirm definite seroconversion.

Approximately 50% of patients acutely infected with HIV will experience at least some symptoms of the acute retroviral syndrome. Symptoms may include pharyngitis, morbilliform rash, thrush, lymphadenopathy, and hepatosplenomegaly. 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 acute HIV seroconversion is strongly suspected based on the clinical scenario, a plasma HIV RNA assay should be used in conjunction with an HIV-1 antibody test to diagnose acute or primary HIV infection. See Diagnostic, Monitoring, and Resistance Laboratory Tests for HIV for further information on HIV testing, and Diagnosis and Management of Acute HIV Infection for further information on management of acute HIV infection.

VII. NON-OCCUPATIONAL PEP FOR THE PREGNANT PATIENT

January 2008

RECOMMENDATIONS:

Before administering nPEP to a pregnant woman, the clinician should discuss the potential benefits and risks to her and to the fetus. Drugs to avoid during pregnancy are listed in Table 7.

Based on increasing clinical experience with HAART, nPEP is indicated at any time during pregnancy when a significant exposure has occurred, despite possible risk to the woman and the fetus. Expert consultation should be sought. When nPEP is indicated, it should be initiated within 36 hours of exposure.

Clinicians should not prescribe efavirenz for pregnant women because it has been associated with teratogenicity in monkeys.

Clinicians should not prescribe the combination of didanosine and stavudine due to an increased risk of mitochondrial toxicity in pregnant women.

Unboosted indinavir should not be used in pregnant women in the second or third trimester due to a substantial decrease in antepartum indinavir plasma concentrations.

Clinicians should advise women who may have been exposed to HIV to avoid breastfeeding for 6 months after the exposure.

Table 7: PEP Drugs to Avoid During Pregnancy
Drug(s) to Avoid	Toxicity
Efavirenz	Teratogenicity
Combination of stavudine and didanosine	Mitochondrial toxicity
Unboosted IDV in the 2nd or 3rd trimester	Substantially lower antepartum indinavir plasma concentrations

Initiation of nPEP at any time during pregnancy requires a careful discussion of the risks and benefits of this therapy. In addition to the risk of seroconversion for the patient, there is a high risk of transmission to the fetus or breastfeeding infant, should the pregnant patient develop the acute retroviral syndrome. Although birth defects and adverse effects on human fetuses have generally not been associated with the currently available ARV agents, exposure of a fetus to ARV agents during pregnancy carries a theoretical risk of teratogenicity.

The recommendation to initiate nPEP in the breastfeeding patient presents several concerns. Both HIV and ARV drugs may be found in breast milk. As such, breastfeeding should be avoided for 6 months after the exposure to prevent HIV transmission and potential drug toxicities. Because HIV infection is most often diagnosed within 3 months of exposure, some women may prefer to breastfeed between 3 to 6 months following exposure. Clinicians should discuss the risks and benefits with the patient. The infant’s pediatrician should be informed of any potential exposure to HIV or ARV medications.

For additional information, refer to NYSDOH guidelines on Management of the HIV-Infected Pregnant Woman.

VIII. NON-OCCUPATIONAL PEP FOR HEPATITIS B AND C

Updated May 2010 — Currently Under Revision

RECOMMENDATION:

When a non-occupational exposure occurs, and the source is available, the source should be evaluated for both hepatitis B and hepatitis C. (AII)

A. Hepatitis B Virus Post-Exposure Management

RECOMMENDATIONS:

The hepatitis B vaccine series should be initiated in non-HBV-immune persons who sustain a blood or body fluid exposure. (AI)

Administration of prophylactic hepatitis B immune globulin (HBIG) and the initiation of the hepatitis B vaccine series 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 (see Table 8). (AI) Both HBIG and the first dose of the hepatitis B vaccine series should be ideally administered within 24 hours of exposure (AII); 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.

Needlestick injuries and wounds should be washed with soap and water and should not be squeezed. Mucous membranes should be flushed with water. (AIII)

Initiation of the 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,²⁸ and multiple doses have been shown to be 75% to 95% effective.²⁹ The maximum effective interval for prophylaxis is likely within 14 days for sexual exposure. ^30-34 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 Table 8). 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” in Table 8.

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 month, and 6 months. Hepatitis B antibodies should be obtained 1 to 2 months after completion of the third dose of the vaccine; however, levels may be falsely elevated if the exposed person received HBIG within the past 3 to 4 months.

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 Hepatitis B Virus guidelines 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.

Table 8: Recommended Post-Exposure Prophylaxis for Hepatitis B Virus
Vaccination and/or antibody response status of exposed patient^a	Treatment when source is:
	HBsAg positive	HBsAg negative	Source unknown or not available for testing
Unvaccinated/ non-immune	HBIG^b x1; initiate HB vaccine series	Initiate HB vaccine series	Initiate HB vaccine series
Previously vaccinated,^c known responder^d	No treatment	No treatment	No treatment
Previously vaccinated,^c known non-responder^d	HBIG^b x1 and initiate revaccination^e or HBIG^b x2	No treatment	No treatment unless known high-risk source; if high-risk source, ^f then treat as if source were HBsAg positive
Previously vaccinated,^c antibody response unknown	Single vaccine booster dose	No treatment	No treatment unless known high-risk source; if high-risk source,^f then treat as if source were HBsAg positive
If still undergoing vaccination	HBIG^b x1; complete series	Complete series	Complete series
HBsAg, hepatitis B surface antigen; HBIG, hepatitis B immune globulin; anti-HBs, antibody to hepatitis B surface antigen. ^a Persons who have previously been infected with HBV are immune to re-infection and do not require PEP. ^b Dose 0.06 mL/kg intramuscularly. ^c Vaccinated with full three-dose series. ^d 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. ^e 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. ^f 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%.³⁵

B. Hepatitis C Virus Post-Exposure Management

RECOMMENDATIONS:

Clinicians should consider concurrent exposure to HCV when individuals present with an HIV exposure. (AII)

Neither immunoglobulin nor antiviral agents are recommended for HCV post-exposure prophylaxis.

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. (AII)

Currently, no effective prophylaxis for HCV has been identified. Immunoglobulin and antiviral agents are not recommended for HCV post-exposure prophylaxis (PEP). However, if an individual becomes acutely infected with hepatitis C and is diagnosed at that time, immediate referral to a provider experienced in the treatment of hepatitis C is recommended. Recent data suggest that early treatment of acute hepatitis C with interferon is highly effective, perhaps as high as 95%.³⁰

1. Baseline Management

RECOMMENDATIONS:

Following an exposure to blood or body fluid, the clinician should assess the risk for exposure to HCV. (AII) Wounds should be washed with soap and water, and should not be squeezed. (AII) Mucous membranes should be flushed with water.

Once the clinician has determined that exposure to blood or body fluid has occured, the following baseline tests should be obtained (see Table 9 for follow-up according to baseline results):

Source Patient:

HCV antibody test (e.g., EIA/ELISA), and if positive, HCV RNA test or RIBA

Exposed Person:

Liver panel including liver enzymes
HCV antibody, and if positive, HCV RNA test

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. According to the most recent Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis (2001), either HCV RNA or RIBA may be used as the confirmatory test. However, most clinicians currently obtain HCV RNA testing, instead of RIBA, to confirm a positive antibody screening result. When the source person tests positive by either RIBA or HCV RNA test, the exposed person should be managed as if the source has chronic HCV.

Table 9: Hepatitis C Post-Exposure Management According to Baseline Test Results
Clinical Scenario	Follow-Up^a
Source is HCV-antibody negative	No further testing or follow-up is necessary for source or the exposed person^b
Source is unavailable or refuses testing	Exposed person: Follow-up HCV antibody at 3 and 6 months^b
Source is HCV-antibody positive and HCV RNA negative	Manage the exposed person as if the source has chronic hepatitis C (see Section VIII. B. 2: Post-Exposure Follow-Up)^c
Source is positive for both HCV antibody and HCV RNA and Exposed person is HCV-antibody negative	Source: Counsel and manage as chronic hepatitis C regardless of status of exposed person Exposed person: Follow up as outlined in Section VIII. B. 2: Post-Exposure Follow-Up
Exposed person tests positive for both HCV antibody and HCV RNA	Counsel and manage as chronic hepatitis C
^a Refer to Appendix D for information about HCV tests and how to interpret results. ^b 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. ^c A Single negative HCV RNA result does not exclude active infection.

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 6 months after the exposure.

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.

2. Post-Exposure Follow-Up for HCV

RECOMMENDATIONS:

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 (AII) :

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. (AIII)

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. (AIII)

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 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.³⁶ 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.

IX. RESOURCES FOR CONSULTATION

May 2010

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 National Clinicians’ Consultation Center PEP line at 1-888-HIV-4911 (1-888-448-4911).

For providers in New York State:

For further education of health providers or for consultation regarding setting up PEP services, contact: CEI PEP, Testing and Diagnosis Center
To obtain the NYSDOH protocol for sexual assault victims, call the NYSDOH Rape Crisis Program at 518-473-6919.

For information about rape crisis services, see Appendix B.

REFERENCES

1. New York State Department of Health AIDS Institute. HIV Prophylaxis Following Occupational Exposure. NYSDOH AI;2004. Available at: www.hivguidelines.org.

2. 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.

3. 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.

4. Centers for Disease Control and Prevention. 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;44:929-933. Available at: www.cdc.gov/mmwr/pdf/wk/mm4450.pdf

5. 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.

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

7. Schechter M, Lago RF, Ismerio R, et al. Acceptability, behavioral impact, and possible efficacy of post-sexual-exposure chemoprophylaxis (PEP) for HIV. 9th Conference on Retroviruses and Opportunistic Infections; Seattle, Washington; February 24-28, 2002.

8. Murphy S, Kitchen V, Harris JR, et al. Rape and subsequent seroconversion to HIV. BMJ 1989;299:718.

9. Myles JE, Hirozawa A, Katz MH, et al. Postexposure prophylaxis for HIV after sexual assault. JAMA 2000;284:1516-1518.

10. Pinkerton FD, Martin JN, Roland ME, et al. Cost-effectiveness of post-exposure prophylaxis after sexual or injection-drug exposure to HIV. Arch Intern Med 2004;164:46-54.

11. Hamers FF, Lot F, Larsen C, et al. Cost-effectiveness of prophylaxis following non-occupational exposure to HIV infection in France. In: Program and Abstracts of the 8th Conference on Retroviruses and Opportunistic Infections; Chicago, Illinois; February 4-8, 2001.

12. DeGruttola V, Seage GR III, Mayer KH, et al. Infectiousness of HIV between male homosexual partners. J Clinical Epidemiol 1989;42:849-856.

13. 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.

14. European Study Group. Comparison of female to male and male to female transmission of HIV in 563 stable couples. BMJ 1992;304:809-813.

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

16. Centers for Disease Control and Prevention. Management of possible sexual, injecting-drug-use, or other nonoccupational exposure to HIV, including considerations related to antiretroviral therapy. MMWR Morb Mortal Wkly Rep 1998;47(RR17):1-14. Available at: www.cdc.gov/mmwr/pdf/rr/rr4717.pdf

17. Koh HK, DeMaria A, Mcguire JF. Massachusetts Clinical Advisory. Massachusetts; 2001.

18. Non-Occupational HIV PEP Task Force, Brown University AIDS Program and the Rhode Island Department of Health. Non-occupational human immunodeficiency virus postexposure prophylaxis guidelines for Rhode Island healthcare practitioners. August 1, 2002.

19. Myles JE, Bamberger J, and the California HIV PEP after Sexual Assault Task Force. Offering HIV Prophylaxis Following Sexual Assault: Recommendations for the State of California. San Francisco, CA: Housing and Urban Health of the San Francisco Department of Public Health and the California State Office of AIDS;2001. Available at: http://www.dhs.ca.gov

20. Dillon B, Hecht FM, Swanson M, et al. Primary HIV infections associated with oral transmission. In: Program and Abstracts of the 7th Conference on Retroviruses and Opportunistic Infections; San Francisco, California. January 30-February 2, 2000.

21. Page-Shafer K, Shiboski CH, Dennis H, 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.

22. Vidmar L, Poljack M, Tomazic J, et al. Transmission of HIV-1 by human bite. Lancet 1996;347:1762-1763.

23. Pretty I, Anderson G, Sweet D. Human bites and the risk of human immunodeficiency virus transmission. Am J Forensic Med Pathol 1999;20:232-239.

24. Rich JD, Macalino G, Merchant RC, et al. HIV seroprevalence of adult males incarcerated for a sexual offense in Rhode Island, 1994-1999. JAMA 2002;288:164-165.

25. New York State Department of Health AIDS Institute. Promoting Adherence to HIV Antiretroviral Therapy: Best Practices from New York State. Albany, NYSDOH; 2001. Available at: http://www.hivguidelines.org

26. Tsai CC, Emau P, Sun JC, et al. Post-exposure chemoprophylaxis (PECP) against SIV infection of macaques as a model for protection from HIV infection. J Med Primatol 2000;29:248-258.

27. Centers for Disease Control and Prevention. 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. Available at: www.cdc.gov/mmwr/pdf/wk/mm4951.pdf

28. 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):1-36. Available at: www.cdc.gov/mmwr/preview/mmwrhtml/rr5201a1.htm

29. 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;3:135-41.

30. 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]

31. 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]

32. 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.

33. 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]

34. 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]

35. 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. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5708a1.htm

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

APPENDIX A: ANTIRETROVIRAL DRUGS

The tables that follow include antiretroviral agents recommended for PEP (zidovudine, lamivudine, tenofovir) as well as alternative antiretroviral drugs because the recommended regimen may require alteration based on factors such as prior use of antiretroviral therapy in the person who is the source of the exposure. For information on all antiretroviral medications, see Antiretroviral Therapy. The following tables indicate dosage, toxicity, and dose adjustment recommendations for a 4-week course of prophylaxis. Because there are toxicity and dose adjustment considerations for all of these medications when used for chronic treatment, other references should also be consulted. The tables also include letters that reference FDA pregnancy categories as described below.

Alternative PEP Medication: Stavudine (d4T)

Alternative PEP Medication: Efavirenz (EFV)

Alternative PEP Medication: Nevirapine (NVP)

Alternative PEP Medication: Nelfinavir (NFV)

Alternative PEP Medication: Indinavir (IDV)

Alternative PEP Medication: Lopinavir/ritonavir (LPV/r)

FDA Pregnancy Categories

A Adequate and well-controlled studies of pregnant women fail to demonstrate a risk to the fetus during the first trimester of pregnancy (and there is no evidence of risk during later trimesters).

B Animal reproduction studies fail to demonstrate a risk to the fetus and adequate and well-controlled studies of pregnant women have not been conducted.

C Safety in human pregnancy has not been determined, animal studies are either positive for fetal risk or have not been conducted, and the drug should not be used unless the potential benefit outweighs the potential risk to the fetus.

D Positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experiences, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks.

X Studies in animals or reports of adverse reactions have indicated that the risk associated with the use of the drug for pregnant women clearly outweighs any possible benefit.

APPENDIX B: RAPE CRISIS PROGRAM

RAPE CRISIS PROGRAM

The Rape Crisis Program is the only New York State agency-sponsored program that focuses on sexual assault prevention and treatment for survivors of sexual assault. Located within the Bureau of Women’s Health, the Rape Crisis Program’s mission is to support activities to prevent sexual assault and to ensure that services are available, accessible, and appropriate for sexual assault survivors.

The Rape Crisis Program is committed to improving New York State’s response to sexual assault survivors through advocacy, policy development, and coordination and oversight of a statewide network of rape crisis service providers. Technical assistance on sexual assault issues is provided within the NYSDOH, with other State agencies, healthcare facilities, and professional organizations.

The Rape Crisis Program is available at: www.health.ny.gov/community/adults/women/violence/rape_crisis/

The Rape Crisis Providers Report is available at: www.health.ny.gov/community/adults/women/violence/rape_crisis/rape_crisis_provider_report.htm

APPENDIX C: SEXUAL ASSAULT FORENSIC EXAMINER (SAFE) PROGRAM

SEXUAL ASSAULT FORENSIC EXAMINER (SAFE) PROGRAM

The Sexual Assault Forensic Examiner (SAFE) program is a collaborative effort in which the Rape Crisis Center works with healthcare providers, law enforcement, and the prosecutor’s office to provide a team approach to meet the needs of the sexual assault survivor. There are three general objectives for sexual assault forensic examiner programs:

To provide the survivor of sexual violence with victim-centered, sensitive care and treatment.
To ensure quality evidence collection by a trained healthcare practitioner.
To provide expert testimony when needed.

Sexual assault forensic examiners are on-call for survivors of sexual assault. They have special education in the following areas:

forensic interviewing techniques;
cultural sensitivity;
elderly, male, and child victims;
health care of sexual assault survivors (e.g., emergency contraception, treatment for possible exposure to sexually transmitted diseases, and coordination of follow-up services); and
forensic techniques (e.g., use of the colposcope, forensic photography, screening for the presence of “date rape drugs”).

Together, with the sexual assault victim advocate, this team approach provides comprehensive and holistic health care.

To find out about the availability of sexual assault forensic examiner care in your community, contact your local Rape Crisis Center or Victims Services Agency.

More information about sexual assault forensic examiner programs in New York State is available at: www.health.ny.gov/professionals/safe/, or contact:

New York State Coalition Against Sexual Assault (NYSCASA)
28 Essex Street
Albany, New York 12206
Phone: (518) 482-4222
Fax: (518) 482-4248
Email: info@nyscasa.org
Joe Farrell, Director of Training: (518) 482-4222, ext. 310
Email: jfarrell@nyscasa.org

APPENDIX D: REPORTING RESULTS OF TESTING FOR ANTIBODY TO HEPATITIS C VIRUS

Appendix D: Recommendations for Reporting Results of Testing for Antibody to Hepatitis C Virus (Anti-HCV) by Type of Reflex Supplemental Testing Performed
Anti-HCV screening test results	Supplemental test results	Interpretation	Comments
Screening-test-negative^*	Not applicable	Anti-HCV-negative	Not infected with HCV, unless recent infection is suspected or other evidence exists to indicate HCV infection
Screening-test-positive^* with high signal-to-cut- off (s/co) ratio	Not done	Anti-HCV-positive	Probably indicates past or present HCV infection; supplemental serologic testing not performed. Samples with high s/co ratios usually (≥95%) confirm positive, but <5 of every 100 might represent false-positives; more specific testing can be requested, if indicated
Screening-test-positive	Recombinant immunoblot assay (RIBA^®)-positive	Anti-HCV-positive	Indicates past or present HCV infection
Screening-test-positive	RIBA-negative	Anti-HCV-negative	Not infected with HCV, unless recent infection is suspected or other evidence exists to indicate HCV infection
Screening-test-positive	RIBA- indeterminate	Anti-HCV- indeterminate	HCV antibody and infection status cannot be determined; another sample should be collected for repeat anti-HCV testing (>1 month) or for HCV RNA testing
Screening-test-positive	Nucleic acid test (NAT)-positive	Anti-HCV-positive, HCV RNA-positive	Indicates active HCV infection
Screening-test-positive	NAT-negative, RIBA-positive	Anti-HCV-negative, HCV RNA-positive	The presence of anti-HCV indicates past or present HCV infection; a single negative HCV RNA result does not rule out active infection
Screening-test-positive	NAT-negative, RIBA-negative	Anti-HCV-negative, HCV RNA-negative	Not infected with HCV
Screening-test-positive	NAT-negative, RIBA- indeterminate	Anti-HCV- indeterminate, HCV RNA-negative	Screening test anti-HCV result probably a false-positive, which indicates no HCV infection
From Centers for Disease Control and Prevention. Guidelines for Laboratory Testing and result Reporting of antibody to Hepatitis C Virus. MMWR Recomm rep 2003;52(RR03):1-16. ^* Screening immunoassay test results interpreted as negative or positive on the basis of criteria provided by the manufacturer.

I. INTRODUCTION
II. PEP FOLLOWING NON-OCCUPATIONAL EXPOSURES (nPEP)
A. Assessment to Determine Whether nPEP Is Indicated
1. Assessing Risk Behavior
2. Degree of Transmission Risk Based on Type of Exposure
3. Considering the HIV Status of the Exposure Source
B. Baseline Testing for Patients Who Present With Risk Exposures
C. Deciding to Recommend nPEP
D. Behavioral Intervention and Risk-Reduction Counseling
III. PEP FOR SEXUAL ASSAULT SURVIVORS
A. Assessment to Determine Whether nPEP Is Indicated Following Sexual Assault
1. Degree of Risk Based on Type of Exposure
2. Considering the HIV Status of the Alleged Assailant
B. Recommending nPEP for Sexual Assault Survivors
C. The Role of the Rape Crisis Counselor and Sexual Assault Examiner
D. HIV Testing of the Survivor
IV. TIMING OF INITIATION OF PEP FOR ALL NON-OCCUPATIONAL EXPOSURES
V. RECOMMENDED nPEP REGIMENS
VI. MONITORING FOLLOWING NON-OCCUPATIONAL EXPOSURE INCLUDING SEXUAL ASSAULT
VII. NON-OCCUPATIONAL PEP FOR THE PREGNANT PATIENT
VIII. NON-OCCUPATIONAL PEP FOR HEPATITIS B AND C
A. Hepatitis B Virus Post-Exposure Management
B. Hepatitis C Virus Post-Exposure Management
1. Baseline Management
2. Post-Exposure Follow-Up for HCV
IX. RESOURCES FOR CONSULTATION
REFERENCES
APPENDIX A: ANTIRETROVIRAL DRUGS
APPENDIX B: RAPE CRISIS PROGRAM
APPENDIX C: SEXUAL ASSAULT FORENSIC EXAMINER (SAFE) PROGRAM
APPENDIX D: REPORTING RESULTS OF TESTING FOR ANTIBODY TO HEPATITIS C VIRUS

T
A
B
L
E

O
F

C
O
N
T
E
N
T
S