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.