Approach
The first steps in assessing a patient's suitability for post-exposure prophylaxis (PEP) are to identify the timing and type of exposure, and to establish the HIV status and likelihood of detectable viremia of the source. All patients require a full medical and sexual history.
Timing of exposure
PEP must be initiated as soon as possible, ideally within 2 hours, and preferably within 24 hours of exposure.[3] PEP is not recommended if the exposure was more than 72 hours before presentation.[3][4]
Types of exposure
Nonoccupational exposure
Consider patient at potential risk for HIV acquisition if:
The source has HIV and is not receiving antiretroviral therapy (ART), is at high risk for HIV infection, or is from a group with high prevalence of detectable HIV viremia, AND
There has been exposure of vagina, rectum, mouth, or nonintact skin with blood, semen, vaginal secretions, rectal secretions, breast milk, or any body fluid that visibly contains blood.
Exposure with urine, nasal secretions, saliva, sweat, or tears without the presence of blood is considered negligible risk for acquisition of HIV.
For sexual exposures, it should also be ascertained whether there was ejaculation and whether there was trauma or visible blood.[37] If a condom was used, it should be established whether there was a breakage or slippage of the condom. There is no indication for PEP if an intact condom was used correctly.
Occupational exposure
If the exposure is occupational, the type of injury should be established. Occupational exposure is defined as:[3]
A percutaneous injury (e.g., a needlestick or cut with a sharp object). Deep injury, visible blood, or injury with a device that has been used intravascularly, all increase the risk of HIV transmission.
Contact of mucus membrane or nonintact skin (e.g., exposed skin that is chapped, abraded, or afflicted with dermatitis). If the skin remains intact, there is no risk of HIV transmission.
A bite if the skin is broken as a result of trauma.
With one of the following:[3]
Blood, semen, vaginal secretions, and other bodily fluids contaminated with visible blood
Tissue
Other body fluids that are potentially infectious such as cerebrospinal fluid, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid, and amniotic fluid.
Feces, nasal secretions, saliva, sputum, sweat, tears, urine, and vomitus are not considered potentially infectious unless they are visibly bloody. A systematic review identified no cases of HIV transmission associated with spitting.[38] The overall risk of acquiring HIV from a bite is negligible, but the risk is increased by the presence of blood in saliva or a high viral load in the source, or if deep wounds are inflicted.[3][38]
Evidence suggests that PEP may be effective even in high-risk populations, such as men who have sex with men (MSM) with ongoing drug use, but that high-risk behavior often continues after a course of PEP.[39][40] Presentation for PEP offers a unique opportunity for risk-reduction efforts that should be capitalized on by healthcare providers to provide in-depth counseling, and an opportunity to discuss pre-exposure prophylaxis (PrEP) for HIV.[41] In fact, the strategy of transitioning directly from PEP to PrEP is recommended for appropriate patients for whom HIV exposure events may continue to occur.[3][42][43]
Source characteristics
Every effort should be made to ascertain the HIV status and likelihood of detectable viremia of the source as soon as possible. If the source is known to be HIV-positive, the following should be considered: whether the HIV viral load is detectable, the number of copies/mL, and whether there is coinfection with hepatitis B or C or other sexually transmitted infections (STIs).
Robust evidence indicates that if an individual living with HIV has a suppressed HIV viral load <200 copies/mL, there is effectively no risk of sexual transmission.[44][45] Therefore, if the source patient is known to have HIV but is taking ART with confirmed and sustained (>6 months) undetectable plasma viral load (<200 copies/mL), PEP is not indicated.[3] If PEP is still indicated, it is important to document whether the source has taken any antiretrovirals and whether there is any known HIV viral resistance, as this is essential in drug selection.
If the HIV status of the source cannot be determined, many guidelines still recommend using local seroprevalence data of the population groups of the source to guide decision-making to offer PEP.[46][47] Higher-risk groups include injecting drug users, MSM, commercial sex workers, and recipients of blood transfusions with unscreened blood.[3] In settings with generalized HIV epidemics, it may be reasonable to assume all sources of unknown HIV status may pose a risk of infection. However, in settings where undiagnosed HIV infection is low and the vast majority of persons living with HIV are diagnosed and virally suppressed, using the prevalence of detectable HIV viremia in the source population may provide a more targeted approach.[3] Regional prevalence can be obtained from the Joint United Nations Programme on HIV/AIDS (UNAIDS). UNAIDS data 2020 Opens in new window
It may be reassuring if the source reports a recent negative HIV test. However, the 45-day window period for HIV when a recently infected person is infectious to others but still has a negative 4th-generation antigen-antibody test must be taken into account.[48] The window period is longer if 3rd-generation antibody tests (60 days) or point-of-care tests (90 days) are used.[48] If the source may have had new HIV exposure within the preceding window period, HIV viral load by RNA polymerase chain reaction (PCR) should also be tested to exclude HIV infection of the source.[49]
Clinical assessment: medical and sexual
A full medical history needs to be recorded to assess the patient's risk of HIV and to ascertain which medications are being taken. Antiretroviral medications have multiple drug interactions. Particularly important are tuberculosis (TB) and epilepsy in the history, but other important drug-drug interactions include antacids, multivitamins, and over-the-counter medications such as St John’s wort.
Taking antacids containing aluminum or magnesium salts significantly decreases plasma raltegravir and dolutegravir levels. Patients taking raltegravir should not take concomitant or staggered antacids containing aluminum and/or magnesium, and dolutegravir should be administered 2 hours before, or 6 hours after, medications containing polyvalent cations (e.g., magnesium, aluminum, iron, or calcium).[50][51]
Some medications, such as rifampicin and antiepileptics, reduce the efficacy of certain antiretroviral medications, and certain antiretroviral medications can reduce or increase systemic levels of other medications, such as oral contraceptives.[52] Any medication being taken should be checked for interactions, and the PEP regimen should be chosen accordingly. The drug history should also include a history of drug allergies.
The sexual history of the person presenting for PEP should be taken regardless of whether the exposure is sexual or occupational, and the person should be cautioned to practice safe sex until their HIV status is ascertained after 3 to 6 months.[4]
For those presenting for nonoccupational PEP, questions should be asked about previous sexual partners over the last 3 months to assess the patient's risk of being inside the HIV window period, because if the person is already infected the treatment will differ from standard PEP. Current STIs, especially genital ulcer disease, increase the risk of HIV transmission and should be inquired about.[53]
Children and adolescents who have been sexually assaulted should ideally be managed in the emergency room or other setting where age-appropriate resources are available to address the multiple medical, psychosocial, and legal issues.
Tests if PEP indicated
The following tests should be performed for all patients in which PEP is indicated:[3]
Baseline 4th-generation HIV antibody/antigen test (by blood enzyme-linked immunosorbent assay [ELISA] or enzyme immunoassay [EIA]) with a rapid HIV test: there is a possibility of a false-positive result, especially in low-prevalence populations. The window period must be considered. People already infected with HIV should not receive 28-day PEP but should instead be referred to HIV services to begin treatment. If PEP has already been initiated prior to HIV diagnosis, this should be continued until reviewed by an HIV specialist.
Renal function and urinalysis or urine protein:creatinine ratio: if renal dysfunction or significant proteinuria present avoid tenofovir disoproxil fumarate. Other antiretroviral medications may need dose-adjustment.
Liver enzymes: if elevated increases suspicion for chronic viral hepatitis or syphilis and would also prompt more frequent monitoring once PEP initiated.
Hepatitis B serology: hepatitis B surface antigen and core antibody should be done to determine chronic infection and hepatitis B surface antibody to determine immunity from prior vaccination. If antibody is negative, consider vaccination with the possible addition of hepatitis B immune globulin (HBIG) if the source is known to have hepatitis B or is at high risk for hepatitis B. If chronically infected with hepatitis B, this would impact choice of antiretrovirals as many medications active against hepatitis B are also active against HIV and must be carefully chosen with the assistance of an infectious disease specialist.
Hepatitis C antibody: where the index case is high risk for hepatitis C (e.g., a person who injects drugs), a hepatitis C PCR or core antigen should be performed. If positive, refer for specialist hepatitis management.
Syphilis serology: if positive, treat.
Pregnancy test.
Screening for other bacterial STIs (e.g., gonorrhea and chlamydia).
Viral load testing: not routinely done in patients undergoing PEP evaluation. It may be done when acute HIV seroconversion syndrome is suspected.[54][55]
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