HIV Prophylaxis in Sexual Assault

Guidelines for use of HIV postexposure prophylaxis (PEP) regimens in at-risk patients from either occupational (oPEP) or non-occupational (nPEP) exoisyres have been issued by the Centers for Disease Control and Prevention (CDC),[1]  the Unites States Public Health Service,[2] and The World Health Organization.[3]  Guidelines pertaining to non-occupational exposures (including but not limited to sexual assault, high-risk consensual sexual encounters, and injection drug use) are reviewed and summarized below. For information regarding occupational exposures, see HIV Postexposure Prophylaxis, Occupational.

Updates to this article are as follows:

• Adoption of CDC interim guidance for increased doses of ceftriaxone for the treatment of gonorrhea ^[4]
• Addition of dolutegravir and boosted darunavir into treatment algorithm
• Integration of data regarding treatment as prevention (U=U) 
• Update of use of integrase-inhibitors in individuals of childbearing potential

Exposure types

HIV nPEP is indicated in all HIV-negative patients after significant exposure to a substantial-risk bodily fluid, as detailed below. PEP with antiretrovirals in patients who are already HIV-positive is not recommended, although considerations for other treatments (eg, other infections, trauma, legal issues, undesired pregnancy) remain unchanged when the exposed patient is already HIV-positive. If rapid (< 1 hour) determination of the exposed patient’s HIV status cannot be obtained, it is prudent to proceed under the assumption that they are HIV-negative. Oral HIV tests are not recommended for use during this evaluation owing to a lack of sensitivity.

Significant exposure

Contact with a substantial-risk fluid to vagina, rectum, eye, mouth, non-intact skin (including dermatitis), or percutaneously is considered a significant exposure.

If the source patient is known or found to be HIV-negative and not at a significant risk for acute HIV illness (ie, current intravenous drug use or frequent high-risk sexual contacts), PEP can often be discontinued after testing, but should not be delayed while awaiting test results. If the source’s HIV status is unavailable, a determination of risk must be based on the source’s known risk for acute or chronic HIV infection.

Substantial-risk fluids

Substantial-risk fluids are as follows:

• Blood
• Semen
• Vaginal secretions
• Rectal secretions
• Breast milk
• Any fluid visibly contaminated with blood

Negligible-risk fluids

Negligible-risk fluids (if not visibly blood) are as follows:

• Urine
• Tears
• Saliva
• Nasal secretions
• Sweat

HIV PEP timing

Consideration for initiation of PEP is a medical emergency and should begin as soon as possible after exposure. PEP is recommended only in patients who present to care 72 hours or sooner since the last exposure, as the window to prevent HIV integration into host cells is limited.[1, 2, 3]  Persons with repeated exposures can be considered for treatment from their last known exposure. The decision to treat those exposed more than 72 hours prior to presentation should be made in conjunction with expert medical advice as treatment is not generally advisable in these situations. Recommendations for testing, STI treatments, and other supportive care remain unchanged for patients who present outside this window.

According to the World Health Organization (WHO), PEP is contraindicated if the exposed person is already HIV-positive due to a previous exposure, if the patient is chronically exposed to HIV, if the exposure does not pose a risk for transmission, or if the exposure occurred more than 72 hours previously.[3]

Because nPEP carries a risk for adverse effects and toxicities, it should be used for only infrequent exposures. Persons who engage in behaviors that result in frequent recurrent exposures that would require sequential or near-continuous courses of antiretroviral medications (eg, multiple sex partners who rarely use condoms or injection-drug users who often share injection equipment) should not receive nPEP. In these instances, exposed persons should instead be provided with intensive risk-reduction interventions.[5] In addition, HIV pre-exposure prophylaxis (PrEP) should be discussed to prevent future infection.

Initial testing is focused on determining the exposed patient’s pre-existing burden of illness (HIV, hepatitis B, hepatitis C), as well as acquired infections (gonorrhea, chlamydia, syphilis, if applicable), obtaining pregnancy status (if applicable), and preparing for safe administration of nPEP therapy.

HIV testing, as follows:

• Ag/Ab combination (alternative, Ab only) upon presentation and then at 4-6 weeks and 3 months
• Testing at 6 months indicated if patient recently infected with hepatitis C

Hepatitis B testing, as follows:

• Hepatitis B surface antigen (HBsAg) upon presentation and then at 6 months, if susceptible
• Hepatitis B surface antibody (HBsAb) upon presentation and then at 6 months, if susceptible
• Hepatitis B core antibody (HBcAb) upon presentation and then at 6 months, if susceptible

Hepatitis C testing: Surface antibody upon presentation and then at 6 months, if susceptible

Other tests, if applicable, as follows:

• Syphilis serology upon presentation and then at 4-6 weeks and 6 months
• Gonorrhea (nucleic acid amplification) from all exposed sites (genital, pharyngeal, anal)
• Chlamydia (nucleic acid amplification) from all exposed sites (genital, pharyngeal, anal)

Baseline laboratory tests for nPEP medications, as follows:

• Urine human chorionic gonadotropin (HCG), if applicable, upon presentation and then at 4-6 weeks
• Complete blood cell (CBC) count
• Aspartate transaminase (AST) and alanine transaminase (ALT)

Source testing should include HIV Ab/Ag (and quantitative polymerase chain reaction [PCR], if applicable), hepatitis B, hepatitis C, and STI screening as above.

Individual state laws on source testing have substantial variability, and legal ramifications should be known for each jurisdiction (see http://www.cdc.gov/hiv/policies/law/states/)

Postexposure prophylaxis for non-occupational HIV exposures remains controversial. Comparatively, HIV PEP following occupational exposures has been shown to reduce risk of transmission by around 80%.[6]  It is unclear whether PEP is effective in preventing seroconversion after non-occupational exposure to HIV. Justification of the efficacy, timing, and duration of nPEP has been extrapolated from 4 lines of evidence, as follows:

• Animal studies ^{[7, 8, 9]}
• Human studies of prophylaxis to prevent vertical transmission of HIV ^{[10, 11, 12, 13, 14]}
• Prophylaxis after needlestick injury ( occupational postexposure prophylaxis) ^[15]
• Feasibility and observational studies of nPEP ^{[16, 17, 18, 19]}

PEP is not 100% effective. PEP failures are more likely to be associated with zidovudine monotherapy,[16, 20, 21] infections with HIV strains that are resistant to the antiretroviral medications,[22] and ongoing exposures to HIV.[19, 22, 23, 24, 23] In patients who seroconvert despite nPEP, resistance testing should be strongly considered to guide early and subsequent treatment decisions.

Despite this, outcomes are typically good, as per-act risk of HIV acquisition remains low. For reference, a needlestick from an HIV-infected source leads to seroconversion in only 1 of 435 percutaneously exposed healthcare workers, and a single act of receptive penile-vaginal intercourse leads to infection in 1 of 125 instances.[1]  Receptive anal intercourse remains a higher risk, at 1 of 73 instances.[1]  Studies have shown that the odds of seroconversion were 0.04% for female-to-male transmission and 0.08% for male-to-female transmission per penile-vaginal sexual act in higer resource settings and demonstrated a transmission rate of 0.38% and 0.30% for female-to-male and male-to-female transmission, respectively, in resouce-poor settings.[25]  

Extensive scientific progress has been made in understanding factors effecting the risk of disease transmission, one of those findings is that viral load is a key determinant of transmission risk.[4]  If the source patient is known to have HIV infection but is virologically controlled on medication, the risk for sexual transmission has been shown to be negligible.[26, 27]  Following the results of HPTN 052,[4] multiple large studies[28, 26] have confirmed these findings and established that Undetectable = Untransmittable (U=U), and subsequently led to a national education campaign regarding the success of treatment as prophylaxis against HIV transmission.

CDC recommendations state that all persons evaluated for possible HIV PEP should be evaluated for other exposures and conditions. These include bacterial STIs, traumatic injuries, hepatitis B and hepatitis C infection, and/or pregnancy. The following guidelines are based upon CDC guidelines[29] and interim updates,[30] and should be administered regardless of initial patient testing and whether HIV PEP is administered or not afterfollowing sexual assault.

Gonorrhea, as follows:

• Ceftriaxone 500 mg IM (or 1 gram for patients over 300lbs), once PLUS
• Doxycycline 100 mg orally, twice daily, for 7 days (prefered) OR
• Azithromycin 1 gram orally, once (alternative in pregnancy or if adherence to doxycycline regimen is uncertain) 

Chlamydia, as follows:

• Azithromycin 1 gram orally, once OR
• Doxycycline 100 mg orally, twice daily, for 7 days

Trichomoniasis (females only), as follows:

• Metronidazole 2 grams orally, once OR
• Tinidazole 2 grams orally, once

Human papillomavirus (HPV) infection, as follows:

• In males aged 9-21 years and females aged 9-26 years, initiate HPV vaccine series (upon presentation and at 1-2 months and 4-6 months)
• For those 45 years or younger, the FDA has approved use of HPV vaccination, although the CDC guidelines have not yet included this. ^[31]

Treatment to be administered after bodily fluid exposures (including, but not limited to, sexual encounters) is discussed below.

Hepatitis B, as follows:

• If patient immunized and documented vaccine responder: No action
• If patient immunized without documented vaccine response: Booster hepatitis B vaccine dose once
• If patient non-immunized: Hepatitis B vaccine series (upon presentation and then at 1-2 months and 4-6 months) and hepatitis B immune globulin given once

Hepatitis C: PEP not currently recommended

The CDC recommends that all persons who report behaviors or situations that place them at risk for frequently recurring HIV exposures (eg, injection drug use, sex without condoms) or who report receipt of one or more courses of nPEP in the preceding year should be provided risk-reduction counseling and intervention services, including consideration of preexposure prophylaxis (PrEP).

Patients who require HIV PEP may often benefit from PrEP, and the evaluation and discussion of preemptive therapy should occur at some point during the initial visit or follow-up appointments. As indications and modalities for PrEP are likely to continue to change, see Preexposure HIV Prophylaxis for a full discussion.

If HIV nPEP is offered, the following information should be discussed with the patient:

• The low risk of HIV infection following a single sexual encounter
• The theoretical but unproven benefit and known toxicities of antiretrovirals
• The importance of close follow-up
• The importance of adherence to recommended dosing to prevent selection of resistant viruses
• The necessity of early initiation of PEP to optimize potential benefits (ie, as soon as possible and up to 72 hours after the assault)
• Cost of the medication regimen

Patients should be informed that various payment methods for nPEP are available for survivors of sexual assault, including Medicaid, Medicare, or Crime Victims Compensation. Third-party reimbursement may cover nPEP, depending on the plan’s prescription drug policy, if the individual has prescription drug coverage. In cases where the medication-dispensing facility does not receive reimbursement for these services, such expenses may be included in their annual Institutional Cost Report as part of indigent care costs.

The Crime Victim’s Board (CVB) has developed special procedures to ensure availability of nPEP for sexual assault victims. Victims of sexual assault may also contact a Rape Crisis Center or Victims Services Agency in their county or region for assistance in filing claims with the CVB, particularly when emergency assistance is needed. Many of these agencies have 24-hour hotlines. For more information about accessing Crime Victims Compensation and for a list of Victims Services Agencies and other resources, consult the CVB website.

For more details on sexual assault in general, see Sexual Assault. For child sexual abuse, see the article Child Sexual Abuse.

Additional resources for HIV/sexual assault include the following:

CDC / National Prevention Information Network

Patient informational handouts and discharge instructions available:

Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HIV and Recommendations for Postexposure Prophylaxis

National HIV/AIDS Hotline

American Social Health Association                                                                                                                                                                              PO Box 13827                                                                                                                                                                                                            Research Triangle Park, NC 27709                                                                                                                                                                              (800) 342 - AIDS                                                                                                                                                                                                          (800) 344 - SIDA (Spanish)                                                                                                                                                                                        (800) 243 - 7889 (TDD)

They provide HIV/AIDS information 24 hours a day, 7 days a week and will send free written information. They also make referrals to any organization/agency that provides information, including legal services, counseling, and therapies.

National Center for Victims of Crime                                                                                                                                                                            2000 M Street NW, Suite 480                                                                                                                                                                          Washington, DC 20036                                                                                                                                                                                            Phone: (202) 467-8700                                                                                                                                                                                                Fax: (202) 467-8701

National Sexual Violence Resource Center                                                                                                                                                                  123 North Enola Drive                                                                                                                                                                                                Enola, Pennsylvania 17025                                                                                                                                                                                          877-739-3895 (toll-free)                                                                                                                                                                                                717-909-0710(phone)                                                                                                                                                                                                    717-909-0714 (fax)                                                                                                                                                                                                            717-909-0715 (TTY)

Rape, Abuse, and Incest National Network (RAINN) National Sexual Assault Hotline                                                                                                2000 L Street, NW, Suite 40                                                                                                                                                                            Washington, DC 20036                                                                                                                                                                                              (202) 544-1034                                                                                                                                                                                                            (800) 656-HOPE (4613)                                                                                                                                                                               info@rainn.org

National Native American AIDS Prevention Center                                                                                                                                                    2100 Lakeshore, Suite A                                                                                                                                                                                                    Oakland, CA 94606                                                                                                                                                                                                    (800) 283 - AIDS                                                                                                                                                                                                    

National Association of People with AIDS (NAPWA)                                                                                                                                                  1413 K Street, NW                                                                                                                                                                                             Washington, DC 20005                                                                                                                                                                                               (202) 898 - 0414                                                                                                                                                                                                        (202) 789 - 2222 (FAX: AIDS information facts on demand)

NAPWA is a nonprofit organization that provides information services, educational resources, national advocacy, and technical assistance for community-based organizations.

Assistance with PEP-related decisions can be obtained by contacting the following:

• National Clinician Consultation Center
• HIV Antiretroviral Pregnancy Registry; Address: Research Park, 1011 Ashes Drive, Wilmington, NC 28405. Telephone: 800-258-4263; Fax: 800-800-1052; E-mail: registry@nc.crl.com
• FDA (for reporting unusual or severe toxicity to antiretroviral agents); Telephone: 800-332-1088; Address: MedWatch, HF-2, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857
• CDC (for reporting HIV infections in HCP and failures of PEP) at telephone 800-893-0485
• HIV/AIDS Treatment Information Service

In New York State: For referrals to HIV specialists, call the AIDS Institute’s Office of the Medical Director: (212) 417-4536 (M-F, 8am-5pm); all other hours, call the HIV/AIDS Hotline: 1-866-881-2809. For NYSDOH protocol for management of sexual assault victims, call the NYSDOH Rape Crisis Program: (518) 474-3664 and/or visit the NYSDOH HIV Guidelines Website.

 

Patients evaluated for PEP should be educated about the symptoms of acute HIV seroconversion (notably fever, sore throat, lymphadenopathy, and/or diffuse rash)[32] and instructed to seek medical care if they develop. Follow-up with a primary care provider or infectious disease physician should occur at 4-6 weeks, 3 months, and 6 months regardless of whether PEP was initiated in order to screen for medication side effects, to evaluate for symptoms of seroconversion, and to test for development of infections. If initiated, PEP adherence should be stressed, as overall adherence rates are around 60% but are commonly reported to be below 30%, often due to medication side effects such as nausea.[33]

Patients who are pregnant or become pregnant should be advised on the risk of HIV-transmission with breast feeding.

All patients should be advised to abstain from sexual encounters or stricly adhere to condom usage for all encounters (including oral sex) until 3 month follow up, as risk of secondary HIV transmission is highest during the acute phase of illness.

HIV PEP Regimens

Although the exact drug regimens for HIV PEP have changed in recent years, consensus remains that the preferred regimen is a 3-drug regimen given over a 28-day course.[1] Anyone prescribed PEP should be given the full 28-day course. On occasion, a 30-day supply will be dispensed due to the cost of adjusting manufacterer-supplied bottles, but no added benefits have been shown for continuation of the treatment course beyond 28 days.

The FDA announced in May 2018 that it was investigating correlations between dolutegravir use in early pregnancy and neural tube defects. Although such a correlation had not been shown definitively, guidance was issued at that time that women who were pregnant or of childebearing potential avoid dolutegravir and bictegravir while further evaluation was performed. Studies indicated that the increased rate of neural tube deficits seen in a cohort of HIV-infected individuals in Botswana[34] was not seen in the United States.[35]  Further, Raltegravir has a well-established safety profile for this use and remains a primary treatment option.[36]  In February of 2021, the Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission recommended the use of dolutegravir as a prefered agent both for women who are pregnant, and those attempting to get pregnant. This was based on the lack of neural tube defect in later cohorts, as well as the known benefits of dolutegrvir which include therapeutic efficacy, tolerance, and ease of administration with once daily dosing.[37]

Adults and adolescents

Patients older than 13 years with normal renal function (CrCl ≥60 mL/min), including pregnant individuals

The preferred 3-drug regimen is as follows:

• Tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg (Truvada) daily AND
• D olutegravir 50 mg once daily (regardless of pregnancy status  ^[37] )

OR

• Tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg (Truvada) daily  AND
• Raltegravir (Isentriss) 400 mg twice daily OR  Raltegravir (Isentriss HD) 600 mg once daily may be used outside of pregnancy.

Caution: Coadministration of raltegravir or dolutegravir with antacids or cations (iron, calcium, or magnesium) can reduce drug absorption and therefore efficacy of PEP.

An alternative regimen is as follows:

• Tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg (Truvada) daily AND
• Darunavir 800 mg daily AND
• Ritonavir 100 mg daily OR cobicistat 150 mg daily (as pharmacokinetic booster)

Patients older than 13 years with chronic kidney disease (CrCl < 60 mL/min)

The preferred 3-drug regimen is as follows:

• Renally dose-adjusted zidovudine and lamivudine daily AND
• Raltegravir 400 mg twice daily OR dolutegravir 50 mg once daily

Caution: Coadministration of raltegravir or dolutegravir with antacids or cations (iron, calcium, or magnesium) can reduce drug absorption and therefore efficacy of PEP.

An alternative regimen is as follows:

• Renally adjusted zidovudine and lamivudine daily AND
• Darunavir 800 mg daily AND
• Ritonavir 100 mg daily OR cobicistat 150 mg daily (as pharmacokinetic booster)

PEP is especially important in pregnant women and should not be avoided because of known or possible pregnancy.

Note that tenofovir alafenamide (TAF), a newer formulation of tenofovir, has not been specifically studied for HIV PEP and is not currently recommended for this indication. A TAF-containing co-formulation with emtricitabine (Descovy) is FDA-approved for the treatment of HIV infection in combination with other active agents, but its ultimate role in HIV PEP remains undefined at the time of this writing.

Infants and children

Children aged 2-12 years

Each drug dosed to age and weight

Preferred 3-drug regimen: Tenofovir DF AND emtricitabine AND raltegravir

Alternative regimens are as follows:

• Zidovudine AND lamivudine with raltegravir
• Lopinavir/ritonavir with raltegravir
• Tenofovir DF AND  emtricitabine AND lopinavir/ritonavir

Children aged 3-12 years: Tenofovir DF AND emtricitabine AND darunavir/ritonavir (darunavir is approved in children aged 3 years or older)

Children aged 4 week to < 2 years

Preferred 3-drug regimen: Zidovudine AND lamivudine with raltegravir or lopinavir/ritonavir

Alternative regimen: Zidovudine AND emtricitabine with raltegravir or lopinavir/ritonavir

Children aged birth to 27 days

Consult a pediatric HIV specialist.