Guidelines for HIV postexposure prophylaxis (PEP) in at-risk patients have been issued by the Centers for Disease Control and Prevention (CDC) and Department of Health and Human Services (DHHS). Guidelines pertaining to nonoccupational 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.
The CDC Guidelines regarding HIV PEP were updated in 2016, as follows:
Transition to rapid antigen/antibody HIV tests
Revised PEP drug regimens
Updated testing schedules for both source and exposed patients
Antimicrobial treatment of sexually transmitted infections (STIs)
Evaluation for transition to preexposure prophylaxis (PrEP)
HIV PEP is indicated in all HIV-negative patients following 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 (infectious, traumatic, legal, 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 he or she is HIV-negative. Oral HIV tests are not recommended for use during this evaluation.
Substantial-risk fluids are as follows:
Any fluid visibly contaminated with blood
Negligible-risk fluids (if not visibly blood) are as follows:
Contact with a substantial-risk fluid to vagina, rectum, eye, mouth, nonintact skin (including dermatitis), or percutaneously is considered a significant exposure.
If the source patient is HIV-negative and not at a significant risk for acute HIV illness, PEP can often be discontinued after testing but should not be delayed while awaiting these tests. 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.
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. 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, but treatment is often not advisable in these situations.
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 of transmission, or if the exposure occurred more than 72 hours previously. 
Because nonoccupational postexposure prophylaxis (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. 
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 PEP 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 PEP 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 (PEP) for HIV remains controversial. It is unclear whether PEP is effective in preventing seroconversion after nonoccupational exposure to HIV. Justification of the efficacy, timing, and duration of nPEP has been extrapolated from 4 lines of evidence, as follows:
PEP is not 100% effective. PEP failures are more likely to be associated with zidovudine monotherapy, [1, 15, 16] infections with HIV strains that are resistant to the antiretroviral medications,  and ongoing exposures to HIV. [17, 14, 18, 19, 18] In patients who seroconvert despite nPEP, resistance testing should be considered to guide early and subsequent treatment decisions.
Other Sexually Transmitted Diseases
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 should be administered regardless of initial exposed patient testing and whether HIV PEP is administered following sexual assault.
Gonorrhea, as follows:
Chlamydia, as follows:
Azithromycin 1 gram orally, once OR
Doxycycline 100 mg orally, twice daily, for 7 days
Trichomoniasis (females only), as follows:
Human papillomavirus (HPV) infection, as follows:
In males and females aged 9-26 years, initiate HPV vaccine series (upon presentation and at 1-2 months and 4-6 months)
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
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.