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Post-exposure prophylaxis, also known as post-exposure prevention (PEP), is any preventive medical treatment started after exposure to a
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a g ...
in order to prevent the infection from occurring.


COVID-19

In 2021, the FDA has approved
bamlanivimab Bamlanivimab is a monoclonal antibody developed by AbCellera Biologics and Eli Lilly as a treatment for COVID-19. The medication was granted an emergency use authorization (EUA) by the US Food and Drug Administration (FDA) in November 2020, an ...
and
etesevimab Bamlanivimab/etesevimab is a combination of two monoclonal antibodies, bamlanivimab and etesevimab, administered together via intravenous infusion as a treatment for COVID-19. Both types of antibody target the surface spike protein of SARS� ...
for post-exposure prophylaxis against
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease quick ...
.


Rabies

PEP is commonly and very effectively used to prevent the onset of
rabies Rabies is a viral disease that causes encephalitis in humans and other mammals. Early symptoms can include fever and tingling at the site of exposure. These symptoms are followed by one or more of the following symptoms: nausea, vomiting, ...
after a bite by a suspected-rabid animal, since diagnostic tools are not available to detect rabies infection prior to the onset of the nearly always-fatal disease. The treatment consists of a series of injections of rabies vaccine and
immunoglobulin An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of th ...
. Rabies vaccine is given to both humans and animals who have been potentially exposed to
rabies Rabies is a viral disease that causes encephalitis in humans and other mammals. Early symptoms can include fever and tingling at the site of exposure. These symptoms are followed by one or more of the following symptoms: nausea, vomiting, ...
.


Tetanus

Tetanus Tetanus, also known as lockjaw, is a bacterial infection caused by ''Clostridium tetani'', and is characterized by muscle spasms. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually ...
toxoid can be given in case of a suspected exposure to tetanus. In such cases, it can be given with or without tetanus
immunoglobulin An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of th ...
(also called ''tetanus antibodies'' or ''tetanus antitoxin''"tetanus"
in the ''
Encyclopædia Britannica The (Latin for "British Encyclopædia") is a general knowledge English-language encyclopaedia. It is published by Encyclopædia Britannica, Inc.; the company has existed since the 18th century, although it has changed ownership various t ...
''. Last Updated 7-17-2013
). It can be given as
intravenous therapy Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutri ...
or by
intramuscular injection Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles hav ...
. The guidelines for such events in the United States for non-pregnant people 11 years and older are as follows:


HIV


History

AZT Zidovudine (ZDV), also known as azidothymidine (AZT), is an antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use in combination with other antiretrovirals. It may be used to prevent mother-to-child ...
was approved as a treatment for
AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ma ...
in 1987. Healthcare workers would occasionally be exposed to HIV during work. Some people thought to try giving health care workers AZT to prevent
seroconversion In immunology, seroconversion is the development of specific antibodies in the blood serum as a result of infection or immunization, including vaccination. During infection or immunization, antigens enter the blood, and the immune system begins t ...
. This practice dramatically decreased the incidence of seroconversion among health workers when done under certain conditions. Later the questions arose of whether to give HIV treatment after known exposure or high risk of exposure. Early data from
pre-clinical studies In drug development, preclinical development, also termed preclinical studies or nonclinical studies, is a stage of research that begins before clinical trials (testing in humans) and during which important feasibility, iterative testing and drug ...
established the efficacy of AZT in preventing transmission of HIV infection. AZT was also seen to reduce maternal-infant transmission of HIV in a
randomized controlled trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical t ...
, suggesting AZT's post-exposure prophylaxis (PEP) use. Subsequent data show combination antiretroviral therapy is significantly superior than AZT in reducing perinatal transmission rates. In addition, AZT is generally no longer recommended due to poor tolerance resulting in high rates of patient noncompliance. Non-occupational exposures include cases when a condom breaks while a person with HIV has sex with an HIV-negative person in a single incidence, or in the case of unprotected sex with an anonymous partner, or in the case of a non-habitual incident of sharing a syringe for injection drug use. Evidence suggests that PEP also reduces the risk of HIV infection in these cases. In 2005, the US DHHS released the first recommendations for non-occupational PEP (nPEP) use to lower risk of HIV infection after exposures. The recommendations were replaced with an updated guideline in 2016. Occupational exposures include needlestick injury of health care professionals from an HIV-infected source. In 2012, the US DHHS included guidelines on occupational PEP (oPEP) use for individuals with HIV exposures occurring in health care settings. Since taking HIV-attacking medications shortly after exposure was proven to reduce the risk of contracting HIV, this led to research into pre-exposure prophylaxis by taking medication before a potential exposure to HIV occurred. A report from early 2013 revealed that a female baby born with the HIV virus displayed no sign of the virus two years after high doses of three antiretroviral drugs were administered within 30 hours of her birth. The findings of the case were presented at the 2013 Conference on Retroviruses and Opportunistic Infections in
Atlanta Atlanta ( ) is the capital and most populous city of the U.S. state of Georgia. It is the seat of Fulton County, the most populous county in Georgia, but its territory falls in both Fulton and DeKalb counties. With a population of 498,7 ...
, U.S. and the baby is from
Mississippi Mississippi () is a state in the Southeastern region of the United States, bordered to the north by Tennessee; to the east by Alabama; to the south by the Gulf of Mexico; to the southwest by Louisiana; and to the northwest by Arkansas. Miss ...
, U.S. The baby—known as the " Mississippi baby"—was considered to be the first child to be "functionally cured" of HIV. However, HIV re-emerged in the child as of July 2014.


Risk evaluation

Initiation of post-exposure prophylaxis with the use of antiretroviral drugs is dependent on a number of risk factors, though treatment is usually started after one high-risk event. In order to determine whether post-exposure prophylaxis is indicated, an evaluation visit will be conducted to consider risk factors associated with developing HIV. Assessments at this visit will include whether the at-risk person or the potential source-person are
HIV positive The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immu ...
, details around the potential HIV exposure event, including timing and circumstances, whether other high-risk events have occurred in the past, testing for sexually transmitted diseases, testing for hepatitis B and C (nPEP is also effective against hepatitis B), and pregnancy tests for women of childbearing potential. Risk factors for developing HIV includes exposure of mucous membranes (vagina, rectum, eye, mouth, broken skin or under the skin) of an HIV-negative person to
bodily fluids Body fluids, bodily fluids, or biofluids, sometimes body liquids, are liquids within the human body. In lean healthy adult men, the total body water is about 60% (60–67%) of the total body weight; it is usually slightly lower in women (52-55%). ...
(blood, semen, rectal secretions, vaginal secretions, breast milk) of a person known to be
HIV positive The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immu ...
. For example, having unprotected sex with
HIV positive The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immu ...
partner is considered risky, but sharing sex toys, spitting and biting considered to be negligible risks for initiating post-exposure prophylaxis. The highest non-sexual risk is
blood transfusion Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...
and the highest sexual contact risk is receptive anal intercourse. The timing of exposure does not affect the risk of developing HIV, but it does alter whether post-exposure prophylaxis will be recommended. Exposures that occurred 72 hours or less to beginning treatment are eligible for post-exposure prophylaxis. If the exposure occurred over 73 hours prior to treatment initiation, post-exposure prophylaxis is not indicated.


Testing

Initial HIV testing: Before initiating PEP after potential HIV exposure, persons should be tested for HIV1 and HIV2 antigens and antibodies in the blood using a
rapid diagnostic test A rapid diagnostic test (RDT) is a medical diagnostic test that is quick and easy to perform. RDTs are suitable for preliminary or emergency medical screening and for use in medical facilities with limited resources. They also allow point-of-care ...
. PEP should only be started if rapid diagnostic test reveals no HIV infection present or if tests results are not available. However, if HIV infection is already present then PEP should not be started. HIV test should be repeated four to six weeks and three months after exposure. People may experience signs and symptoms of
acute HIV infection The stages of HIV infection are acute infection (also known as primary infection), latency and AIDS. Acute infection lasts for several weeks and may include symptoms such as fever, swollen lymph nodes, inflammation of the throat, rash, muscle p ...
, including fever, fatigue, myalgia, and skin rash, while taking PEP. CDC recommends seeking medical attention for evaluation if these signs and symptoms occur during or after the month of PEP. If follow-up laboratory antibody tests reveal HIV infection, HIV treatment specialists should be sought out and PEP should not be discontinued until person is evaluated and treatment plan is established. STI and HBV testing: People with potential exposure to HIV are also at risk of acquiring STI and HBV.
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georg ...
(CDC) recommends STI-specific nucleic acid amplification testing ( NAAT) for gonorrhea and chlamydia and blood tests for
syphilis Syphilis () is a sexually transmitted infection caused by the bacterium '' Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, a ...
. PEP is also active against HBV infections so discontinuation of medication can cause the reactivation of HBV, though rare. Health care providers must monitor HBV status closely. Follow up testing: Serum creatinine and estimated creatinine clearance should be measured at baseline to determine the most appropriate PEP antiretroviral regimen. While on PEP, liver function,
renal function Assessment of kidney function occurs in different ways, using the presence of symptoms and signs, as well as measurements using urine tests, blood tests, and medical imaging. Functions of a healthy kidney include maintaining a person's flui ...
, and hematologic parameters should be monitored.


Treatment

In the case of HIV exposure, post-exposure prophylaxis (PEP) is a course of antiretroviral drugs which reduces the risk of
seroconversion In immunology, seroconversion is the development of specific antibodies in the blood serum as a result of infection or immunization, including vaccination. During infection or immunization, antigens enter the blood, and the immune system begins t ...
after events with high risk of exposure to HIV (e.g., unprotected anal or vaginal sex, needlestick injuries, or sharing needles). The
CDC The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georg ...
recommends PEP for any HIV-negative person who has recently been exposed to HIV for any reason. To be most effective, treatment should begin within an hour of exposure. After 72 hours PEP is much less effective, and may not be effective at all. Prophylactic treatment for HIV typically lasts four weeks. While there is compelling data to suggest that PEP after HIV exposure is effective, there have been cases where it has failed. Failure has often been attributed to the delay in receiving treatment (greater than 72 hours post-exposure), the level of exposure, and/or the duration of treatment (lack of adherence to the 28-day regimen). In addition, since the time and level of non-occupational exposures are self-reported, there is no absolute data on the administration timeframe to which PEP would be efficacious. The standard antibody window period begins after the last day of PEP treatment. People who received PEP are typically advised to get an antibody test at 6 months post-exposure as well as the standard 3 month test. The antiretroviral regimen used in PEP is the same as the standard highly active antiretroviral therapy used to treat AIDS. A typical prescription is a 28-day course of emtricitabine/tenofovir pills containing 200 mg of emtricitabine and 245 mg of tenofovir disoproxil to be taken once daily, and 400 mg pills of
raltegravir Raltegravir, sold under the brand name Isentress, is an antiretroviral medication used, together with other medication, to treat HIV/AIDS. It may also be used, as part of post exposure prophylaxis, to prevent HIV infection following potential ex ...
to be taken twice daily. People initiating nPEP treatment typically receive a 28-day starter pack, as opposed to a 3-7 day starter pack, to facilitate strong medication adherence. They should also be counseled on the unpleasant side effects including
malaise As a medical term, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. The word has existed in French since at least the 12th century. The term is often used ...
,
fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
,
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...
,
headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...
,
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of th ...
and
vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenter ...
. People at high risk for re-exposure due to unprotected intercourse or other behavioral factors should be given PrEP, which would begin immediately after the completion of the nPEP treatment course. Inversely, if a medically-adherent patient is already on PrEP upon non-occupational exposure, nPEP treatment is not necessary.


Hepatitis A

For exposure to
hepatitis A Hepatitis A is an infectious disease of the liver caused by ''Hepatovirus A'' (HAV); it is a type of viral hepatitis. Many cases have few or no symptoms, especially in the young. The time between infection and symptoms, in those who develop the ...
, human normal
immunoglobulin An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of th ...
(HNIG) and/or hepatitis A vaccine may be used as PEP depending on the clinical situation.


Hepatitis B

If the person exposed is an HBsAg positive source (a known responder to HBV vaccine) then if exposed to hepatitis B a booster dose should be given. If they are in the process of being vaccinated or are a non-responder they need to have hepatitis B immune globulin (HBIG) and the vaccine. For known non-responders HBIG and the vaccine should be given whilst those in the process of being vaccinated should have an accelerated course of HBV vaccine.


Hepatitis C

Persons exposed to
hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, ...
should be tested monthly with PCR, and if
seroconversion In immunology, seroconversion is the development of specific antibodies in the blood serum as a result of infection or immunization, including vaccination. During infection or immunization, antigens enter the blood, and the immune system begins t ...
occurs then treatment with
interferon Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten th ...
, or possibly ribavirin.


Anthrax

A 60-day course of oral
ciprofloxacin Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin i ...
should be given when exposure to
anthrax Anthrax is an infection caused by the bacterium '' Bacillus anthracis''. It can occur in four forms: skin, lungs, intestinal, and injection. Symptom onset occurs between one day and more than two months after the infection is contracted. The s ...
is suspected.


Lyme disease

A single 200 milligram oral dose of
doxycycline Doxycycline is a broad-spectrum tetracycline class antibiotic used in the treatment of infections caused by bacteria and certain parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus ...
may be used within 3 days of a deer tick bite in a high risk area (such as
New England New England is a region comprising six states in the Northeastern United States: Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, and Vermont. It is bordered by the state of New York to the west and by the Canadian provinces ...
), if the tick was attached for at least 36 hours.


Monkeypox and Smallpox

The smallpox vaccine decreases the incidence of infection with
monkeypox Monkeypox (also called mpox by the WHO) is an infectious viral disease that can occur in humans and some other animals. Symptoms include fever, swollen lymph nodes, and a rash that forms blisters and then crusts over. The time from exposu ...
and
smallpox Smallpox was an infectious disease caused by variola virus (often called smallpox virus) which belongs to the genus Orthopoxvirus. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) c ...
and the risk of severe illness even when administered after exposure. The CDC advises "that smallpox vaccine be given within 4 days from the date of exposure to prevent onset of the disease but should be offered up to 14 days post-exposure"; the NHS concurs with this but also urges to vaccinate as soon as possible after exposure.


See also

* Pre-exposure prophylaxis (PrEP)


References


Further reading

* * * *


External links


CDC on nonoccupational HIV postexposure prophylaxis
an article which summarizes more than 100 related research projects
HIV/AIDS Post-exposure prophylaxis
WHO
Occupational Postexposure Prophylaxis
: HRSA HIV/AIDS Bureau, The AIDS Education and Training Centers (AETC) {{DEFAULTSORT:Post-Exposure Prophylaxis Medical treatments HIV/AIDS Prevention of HIV/AIDS