INTRODUCTION — Soon after the recognition of the HIV epidemic, the potentially grave consequences of exposure to body fluids from infected individuals prompted the development of policies and procedures designed to reduce the risk of HIV transmission in health care personnel (HCP). The incidence of needlestick injuries has subsequently been reduced by advances in education, safer sharps disposal, engineering changes (eg, needleless devices, safety needles) and personnel protection. However, institutions and health care professionals must continue to observe and improve these measures to minimize risk.
This topic will discuss the procedures to follow after HCP have had significant contact with body fluids from a patient infected with HIV. Other related topics include:
●(See "Prevention of hepatitis B virus and hepatitis C virus infection among health care providers".)
●(See "Management of nonoccupational exposures to HIV and hepatitis B and C in adults".)
●(See "Surgical issues in HIV infection".)
RISK OF TRANSMISSION OF HIV — The risk of transmission of HIV infection following inadvertent exposure varies widely depending upon the type of exposure. The risk is increased when the source has a high viral load, the volume is large, and the exposure is deep. All known seroconversions have occurred with exposure to blood, bloody fluids, or viral cultures. Health care personnel (HCP) at highest risk of transmission are those who have been inoculated percutaneously with blood from a source patient with HIV who is not on suppressive antiretroviral therapy and/or has a detectable viral load.
Risk by exposure type — The risk of becoming infected with HIV after exposure to body fluids from an HIV-infected patient is low. In the United States, there were 58 confirmed and 150 possible cases of occupationally acquired HIV reported to the US Centers for Disease Control and Prevention (CDC) from 1985 to 2013; there was only one confirmed case from 2000 to 2012 [1].
A review of prospective studies of seroconversion following occupational exposure to an HIV-infected source in the era before the introduction of potent antiretroviral therapy (ART) found the following [2]:
●HIV transmission occurred in 20 of 6135 cases (0.33 percent) following percutaneous exposure.
●One case of HIV was transmitted out of 1143 exposures (0.09 percent) on the mucosa of HCP.
●There were no cases after 2712 intact skin exposures.
A similar frequency of HIV seroconversion after needlestick injury (0.36 percent) was found in a later report from the CDC Cooperative Needlestick Surveillance Group [3] and in another meta-analysis (0.23 percent) [4]. The risk of HIV infection following an occupational mucosal exposure was subsequently estimated to be 0.03 percent [5].
Risk factors for seroconversion — A CDC case-control study of needlestick injuries from an HIV-infected source in the United States, the United Kingdom, France, and Italy included 33 cases who seroconverted and 655 controls [6]. The study found that the following factors, each of which presumably reflected exposure to a higher quantity of virus, increased the risk of acquiring HIV after a needlestick injury:
●Deep injury (odds ratio [OR] 15)
●A device visibly contaminated with the patient's blood (OR 6.2)
●Needle placement in a vein or artery (OR 4.3)
●Terminal illness in the source patient (OR 5.6)
The majority of cases were injured by a hollow bore as opposed to a solid needle.
The HIV viral load is another important risk factor for transmission based upon studies of sexual transmission in discordant couples and rates of perinatal transmission [7-10]. Early studies in HCP did not directly address this issue because they were based upon data obtained before viral load measurement was routinely available [3,6]. The observed correlation of transmission risk with a source with late-stage AIDS is thought to be a surrogate for high HIV viral load.
Risk of exposure by profession — Among HCP, nurses have reported the most frequent blood and body exposures (48.6 percent), followed by physicians who are residents or fellows (7.7 percent), attending physicians (7.7 percent), non-lab technologists (4.5 percent), respiratory therapists (3.6 percent), and certified nursing assistants/home health aides (3.2 percent) [11].
In a study conducted at five academic medical centers, fatigue associated with long work hours and sleep deprivation among medical trainees was associated with a threefold increase in the risk of needlestick injuries [12]. A survey performed among 699 surgeons-in-training at 17 medical centers found that the mean number of needlestick injuries by the fifth (final) year of residency was 7.7, and that 99 percent of residents had at least one needlestick injury [13]. Furthermore, approximately one-half had a needlestick injury involving a high-risk patient, and more than half of the most recent injuries had not been reported; the most common reason was lack of time. Despite the concerning number of exposures in this study, there has never been a confirmed case of HIV transmitted to a surgeon through occupational exposure in the United States.
Documented seroconversions — In the United States, 58 confirmed cases of occupationally acquired HIV infection were reported to the CDC between 1985 and 2013 [1,14]. A confirmed case required documentation that seroconversion occurred in the context of an occupational exposure to an HIV-infected source.
●Of these cases, 49 workers sustained a percutaneous exposure (puncture/cut injury), five had mucocutaneous exposures, two had both percutaneous and mucocutaneous exposures, and two had an unknown route of exposure. Forty-nine exposures were to blood from an HIV-infected source, one to visibly bloody fluid, four to an unspecified fluid, and four to concentrated virus in a laboratory.
●Exposed HCP were nurses (24), clinical laboratory technicians (16), nonsurgical physicians (6), and others (11). Twenty-six of these HCP developed the acquired immunodeficiency syndrome (AIDS). There were no confirmed seroconversions in surgeons and no seroconversions after exposure from a suture needle.
In addition, 150 cases of possible occupationally acquired HIV infection occurred among HCP in the United States. These individuals lacked a documented workplace exposure, but their job responsibilities might have exposed them to HIV [1].
In Europe, 35 documented seroconversions following occupational exposure, and 85 possible occupationally acquired HIV infections were reported as of 2002 [15].
Cases of HIV seroconversion following occupational exposures are not systematically documented and reported in most other regions of the world.
POST-EXPOSURE MANAGEMENT — The management of health care personnel (HCP) immediately after a significant exposure to blood or body fluids from HIV-infected patients is critically important in reducing the likelihood of transmission and in ensuring that the legal rights of the employee and the institution are upheld.
All institutions should have a readily available policy for managing such exposures. In the United States, such a policy is required and must comply with regulations of the Occupational Safety and Health Administration (OSHA) (see "Prevention of hepatitis B virus and hepatitis C virus infection among health care providers", section on 'Minimizing risk'). The policy should be distributed to all employees and should be readily available in the Employee Health Service and the Emergency Department.
Initial actions following exposure — After an HCP has been exposed to blood or other body fluids, the initial response should be immediate cleansing of the exposed site. For skin exposures, the area should be washed with soap and water. Small wounds and punctures may also be cleansed with an antiseptic, such as an alcohol-based hand hygiene agent. Alcohol is virucidal to HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV); other antiseptics, such as iodophors, chloroxylenol (PCMX), and chlorhexidine (CHG) also inactivate HIV [16]. However, the efficacy of these agents in preventing HIV transmission is unknown.
For mucosal surface exposure, the exposed mucous membranes should be flushed with a copious amount of water. Eyes should be irrigated with saline or water. There is no evidence that expressing fluid by squeezing the wound will further reduce the risk of bloodborne pathogen transmission. Guidelines for hand washing and infection control can be accessed through the Centers for Disease Control and Prevention [17].
Documentation of the exposure — Clinical information on the source patient and the recipient HCP should be documented. This includes risk factors and serologic tests for HIV and hepatitis B and C. The nature and time of the exposure should also be described. If the source patient is known to be HIV infected, it is critical to determine the most recent viral load and antiretroviral treatment history, including any drug resistance.
Definition of exposure — In this topic and when evaluating HCP at risk for occupational infection with HIV, "exposure" is defined as contact with potentially infectious blood, tissue, or body fluids in a manner that allows for possible transmission of HIV and therefore requires consideration of post-exposure prophylaxis (PEP).
Such potentially infectious contacts are:
●A percutaneous injury (eg, a needlestick or cut with a sharp instrument used on a patient)
●Contact of mucous membrane or nonintact skin (eg, exposed skin that is chapped, abraded, or afflicted with dermatitis)
Body fluids of concern include:
●Body fluids implicated in the transmission of HIV: blood, semen, vaginal secretions, other body fluids contaminated with visible blood.
●Potentially infectious body fluids (undetermined risk for transmitting HIV): cerebrospinal, synovial, pleural, peritoneal, pericardial, and amniotic fluids.
Fluids that are not considered infectious unless they contain blood include feces, nasal secretions, saliva, gastric secretions, sputum, sweat, tears, urine, and/or vomitus.
In addition, any direct contact (ie, without barrier protection) to HIV in a research laboratory or production facility is considered an "exposure" that requires clinical evaluation and consideration of PEP.
Intact skin is an effective barrier against HIV infection, and contamination of intact skin with blood or other potentially contaminated fluids is not considered an exposure and does not require PEP.
These definitions of exposure are consistent with those detailed by the United States Public Health Service and Centers for Disease Control and Prevention (CDC) [18,19].
Determining HIV status of the source — If unknown, the presence of HIV infection in the source patient should be determined in an expedited manner, preferably with a fourth-generation combination antibody-antigen test [19,20]. (See "Screening and diagnostic testing for HIV infection", section on 'Tests'.)
If testing in the source patient is delayed, PEP should still be initiated while awaiting test results. If the source patient is found to be HIV negative, PEP can usually be discontinued unless acute HIV infection is suspected clinically. If acute HIV is suspected, testing for HIV RNA should be performed. (See "Acute and early HIV infection: Clinical manifestations and diagnosis".)
There have been rare case reports of occupational exposures in which the source patient was HIV seronegative by antibody assay but was found to have acute HIV infection [21]. In such cases, the viral load is usually high, so low results (eg, <1000 copies/mL) in the setting of negative antibody testing may reflect laboratory error or contamination and should be interpreted with caution. (See "Screening and diagnostic testing for HIV infection", section on 'Viral detection'.)
Counseling of health care personnel — Risk assessment is particularly important for HCP to make educated decisions about PEP, since the consequences are great and the stress is extraordinary. They should also be well informed of the benefits and risks of PEP and of the importance of close follow-up. Specifically, the following issues should be discussed with exposed HCP:
●HCP should be informed of the risk associated with the specific exposure experienced. (See 'Risk of transmission of HIV' above.)
•With percutaneous or sharps injuries from an HIV-infected source, the risk of HIV infection averages 3/1000, but varies greatly depending on the inoculum size (source viral load and volume of blood), the depth of penetration, and exposure to a hollow bore versus suture needle.
•Exposure of source blood to intact skin is considered "no risk." There are no confirmed cases of HIV transmission in HCP with skin abrasions, cuts, sores, or other breaches in skin integrity, but a theoretical risk is estimated at 1/1000.
•All documented transmissions have involved source blood, bloody body fluids, or laboratory cultures of HIV. Bites have never been implicated in transmission to HCP but have resulted in HIV transmission in other settings.
•The HCP may also be at risk for other bloodborne pathogens, such as hepatitis B or C.
•The HCP should be advised to practice safe sex or abstain until serologic testing in the source is reported negative.
●The efficacy and disadvantages of PEP should be discussed. (See 'Post-exposure prophylaxis' below.)
•A retrospective, case-control study found that PEP with zidovudine alone reduced the risk of HIV infection by about 80 percent [6]. Current multidrug regimens are likely much more effective in preventing infection. However, even when properly provided, PEP does not assure complete prevention of HIV infection.
•The goal is to initiate PEP within one to two hours of exposure; data from animal studies suggest decreased efficacy with delayed initiation. PEP is typically not recommended after a delay of more than 72 hours [19]. (See 'Timing' below.)
•Although available antiretroviral regimens are generally well tolerated, potential adverse effects remain an important consideration. (See 'Selection of antiretroviral therapy' below.)
●Risk reduction strategies should be employed to prevent transmission of HIV should the HCP acquire infection.
•In the event of HIV infection post-exposure, the greatest risk of transmission to other individuals is in the first 6 to 12 weeks, due to the high viral load of acute infection. Exposed HCP should be instructed on measures to reduce the potential risk of HIV transmission to others. This usually means condom use or abstinence from sex and refraining from blood, plasma, organ, tissue, and semen donation until the final follow-up HIV serology (four to six months post-exposure) is negative.
•There is no need to modify a health care provider's patient-care responsibilities after an exposure.
●Follow-up is important to identify HIV infection or adverse effects of the PEP regimen, if administered. (See 'Testing for HIV' below and 'Patient monitoring' below.)
•Baseline and follow-up testing for HIV should be performed to see if seroconversion occurred. The frequency and duration of follow-up testing depends upon the type of HIV test being used (eg, third- versus fourth-generation test). (See 'Testing for HIV' below.)
•Exposed HCP should report any febrile or "mononucleosis-like" illness so they can be evaluated for acute HIV infection. This should include testing for HIV RNA since early antiretroviral therapy has important potential benefits. (See "Acute and early HIV infection: Clinical manifestations and diagnosis".)
•For those who opt to take PEP, blood testing (complete blood count and renal and hepatic function tests) to evaluate for drug toxicity is recommended, at least at baseline and at two weeks post-exposure.
●Specific counseling is warranted for women of childbearing age.
•Female HCP who have childbearing potential need to be aware of the limited data on the safety of antiretroviral drugs, especially during the first trimester of pregnancy. A more detailed discussion on the use of PEP regimens in such patients is discussed below. (See 'Persons of childbearing potential/persons who are pregnant' below.)
•Women who are breastfeeding must weigh the risk of infant exposure to antiretroviral agents versus the risk of HIV transmission through breast milk if the mother becomes infected. There is no single preferred approach. One option is for temporary discontinuation of breastfeeding following exposure until the last follow-up serologic test is negative. Alternatively, if a woman chooses to continue breastfeeding, it is not a contraindication to PEP [19]. (See "Prevention of HIV transmission during breastfeeding in resource-limited settings".)
Testing for HIV — Baseline and follow-up serologic testing for HIV should be performed in all HCP exposed to HIV to see if seroconversion occurred. The majority of individuals who seroconvert will do so within the first three months. Testing should be performed even among those who receive PEP. (See 'Selection of antiretroviral therapy' below.)
All exposed individuals should have a baseline HIV test immediately after the exposure. Follow-up testing can be performed at six weeks and four months post-exposure if a fourth-generation antibody-antigen test is used [19]. By contrast, if a test that only measures antibody is used, repeat HIV testing should occur at six weeks, three months, and six months following exposure. An antibody-antigen test is preferred since this test will detect seroconversion earlier. A detailed discussion of the different types of HIV assays is found elsewhere. (See "Screening and diagnostic testing for HIV infection".)
Extended follow-up for HIV testing (eg, for 12 months) is recommended for any HCP who becomes infected with HCV after exposure to a source coinfected with HIV and HCV [18]. This recommendation is based upon a case report of delayed HIV seroconversion in an HCP who acquired HIV and HCV infection simultaneously through a needlestick exposure [22]. Extended follow-up may also be considered in exposed persons with a medical history suggestive of impaired humoral immunity; however, there are no data to determine a specific approach.
Routine monitoring of plasma HIV viral load to detect early infection should not be performed since there is a risk of false-positive test results. HIV viral load testing should only be obtained if there is clinical evidence of acute HIV infection. The most common manifestations of acute HIV infection are fever, lymphadenopathy, sore throat, myalgia/arthralgia, diarrhea, headache, nausea/vomiting, rash, oral/genital ulcers, and, when the illness is prolonged, weight loss. The usual time from HIV exposure to the development of symptoms is typically two to four weeks. A more detailed discussion on acute HIV infection is found elsewhere. (See "Acute and early HIV infection: Pathogenesis and epidemiology" and "Acute and early HIV infection: Clinical manifestations and diagnosis", section on 'Diagnosis'.)
Assessing risk of transmission of other bloodborne pathogens — HCP who have had a potential exposure to HIV are also at risk of exposure to hepatitis B and C virus. The risk of transmission of these bloodborne pathogens is higher than the risk of HIV. As an example, the risk of HBV to a non-immune individual (including those who have not responded to vaccine), is up to 100-fold (30 percent) higher than for HIV. The risk of hepatitis C virus transmission from an infected source is about sixfold greater (1.8 percent) [23]. Management of HCP exposed to these viruses, including PEP for HBV, is discussed separately. (See "Prevention of hepatitis B virus and hepatitis C virus infection among health care providers".)
POST-EXPOSURE PROPHYLAXIS — We offer post-exposure prophylaxis (PEP) using a three-drug regimen to health care personnel (HCP) with a percutaneous, mucous membrane, or nonintact skin exposure to body fluids of concern (eg, blood or blood-tinged fluids) if the source patient is, or is suspected to be, HIV infected. (See 'Definition of exposure' above and 'Indications for prophylaxis' below and 'Selection of antiretroviral therapy' below.)
PEP should be discontinued if testing shows that the source patient is HIV negative, unless there is concern that the source is acutely infected with HIV. (See "Acute and early HIV infection: Clinical manifestations and diagnosis".)
Efficacy — Data from animal models have supported the efficacy of zidovudine in preventing transmission of HIV infection [24-26]. In addition, the benefit of zidovudine in reducing maternal-infant transmission of HIV from 25.5 to 8.3 percent in a randomized controlled trial (the AIDS Clinical Trial Group Protocol 076) suggests that zidovudine could also have a beneficial role in PEP [27]. (See "Antiretroviral selection and management in pregnant women with HIV in resource-rich settings", section on 'Efficacy of ART in preventing transmission'.)
The best available clinical evidence for PEP comes from a case-control study that evaluated HCP with percutaneous exposures to HIV-infected blood in the United States and Europe between 1987 and 1994 [6]. There were 33 cases (HCP who became infected with HIV) and 665 controls (HCP who did not become infected). Risk factors for seroconversion were deep injury, injury by device with visible blood contamination, injury with needle from source blood vessel, and terminal illness in the source. In a multivariate analysis controlling for these risk factors, cases were significantly less likely to have taken zidovudine after exposure than controls (OR 0.19, 95% CI 0.06-0.52). This study has several methodological limitations, including retrospective design, heterogeneity of data source, and small number of events. Nevertheless, the cumulative data from this study in addition to the results from other prevention models (eg, studies of HIV perinatal transmission and PEP in primates) overall support the efficacy of PEP.
The mechanism by which zidovudine prevents HIV transmission is incompletely understood. The benefit in reducing maternal-infant transmission cannot be entirely explained by a reduction in plasma levels of HIV RNA [28]. It is known that older PEP regimens that included zidovudine were not perfect, since there have been at least six reported cases of HCP who contracted HIV infection despite receiving a zidovudine-containing combination regimen within two hours of exposure [18]. This drug is no longer generally recommended due to poor tolerance resulting in suboptimal adherence.
Subsequent data show that combination antiretroviral therapy (ART) is significantly better than zidovudine in reducing perinatal transmission rates from 8 to <2 percent [29]. Improved efficacy is likely with combination ART for PEP as well. (See 'Selection of antiretroviral therapy' below.)
Indications for prophylaxis — We offer PEP to HCP with a percutaneous mucous membrane or nonintact skin exposure to blood or bloody body fluids of a patient with known HIV infection. If the HIV status of the source patient is unknown, we offer PEP while awaiting HIV testing, particularly if the source patient is at high risk for HIV infection (eg, injection drug users, men who have sex with men) or has symptoms suggesting HIV infection. If the source patient cannot be identified (ie, HIV testing not possible), we offer PEP if the exposure occurred in a high-risk setting (eg, a needlestick from a sharps container in an HIV clinic or a needle exchange program).
In all cases, the decision to administer PEP must weigh the risk of infection with HIV against the toxicity and inconvenience of PEP. The individual preferences of the exposed HCP will generally determine the decision about whether to proceed with PEP.
Timing — PEP should be initiated as soon as possible. The goal is to start within one to two hours (or earlier) after exposure, often using a "starter pack" with appropriate drugs that are immediately available. It is likely that a delay in initiating PEP can reduce efficacy. This concept is supported in primate models of PEP [24-26].
For most HCP, we do not initiate PEP if more than 72 hours have elapsed after the initial exposure; PEP is likely to be less effective when administered after that period of time [19]. However, we do offer PEP after a longer interval to patients with a very high-risk exposure (eg, sharps injuries from a needle that was in an artery or vein of an HIV-infected source patient). For such HCP, The United States Public Health Service suggests that PEP can be offered up to one week after the exposure [19].
Selection of antiretroviral therapy
Preferred antiretroviral regimens for PEP — We administer a three-drug regimen for all HCP who opt for post-exposure prophylaxis (PEP). This approach is supported by the United States Public Health Service, the International Antiviral Society-USA panel, and the World Health Organization [19,30,31]. Regimens for PEP include agents that have proven to be most potent and best tolerated in patients with HIV; most antiretroviral agents have not been studied with regards to their efficacy for PEP.
We suggest the following PEP regimens for HCP with an occupational exposure to HIV, provided the source does not have detectable virus with known resistance to these agents. The following regimens include a nucleoside/tide (NRTI) combination plus an integrase inhibitor:
●Tenofovir disoproxil fumarate-emtricitabine (300/200 mg once daily) plus dolutegravir (50 mg once daily)
●Tenofovir disoproxil fumarate-emtricitabine (300/200 mg once daily) plus raltegravir (400 mg twice daily)
We usually choose the dolutegravir-containing regimen for the convenience of once-daily dosing, except in persons who are pregnant or are of childbearing potential. More detailed discussions of regimen selection in this group and other patient populations are found below. (See 'Persons of childbearing potential/persons who are pregnant' below and 'PEP options for drug-resistant virus' below and 'Patients with reduced kidney function' below and 'PEP in resource-limited settings' below.)
Acceptable alternatives include tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) with a boosted protease inhibitor (PI) (eg, ritonavir-boosted darunavir or ritonavir-boosted atazanavir). Of these choices, we prefer TDF-FTC plus boosted darunavir, since darunavir appears to be better tolerated than atazanavir [32,33] and can be given with gastric acid-suppressing medications. Another acceptable alternative is a single-tablet regimen of TDF-FTC combined with cobicistat-boosted elvitegravir (an integrase inhibitor), which has been shown to be well tolerated [34]. This regimen has advantages (once daily, can be taken with gastric acid suppressants) and disadvantages (food requirement, multiple drug-drug interactions conferred by cobicistat) similar to those of a regimen containing ritonavir-boosted darunavir (table 1).
In the United States, assistance with choosing a regimen can be obtained by calling the National Clinicians' Post-exposure Prophylaxis Hotline (PEPline) at 888-448-4911.
Although the preferred regimen for postexposure prophylaxis in the United States is TDF-FTC with an integrase inhibitor, some international sites employ alternative regimens. For example, in France, the standard regimen for postexposure prophylaxis is the single-tablet regimen of TDF-FTC/rilpivirine [35]. In one report of 163 courses of this regimen in France, the regimen was well-tolerated with 86 percent completing the 28-day course with no seroconversions were reported [35]. However, this regimen needs to be taken with a meal and without agents that suppress gastric acid production.
Rationale for preferred PEP regimens — Since there are no data on the most efficacious postexposure prophylaxis (PEP) regimens for persons with exposure to HIV, selected medications are chosen based upon their known efficacy for the treatment of HIV, side effect profiles, patient convenience (eg, pill burden and dosing frequencies), and completion rates. Minor issues that may favor one or another regimen are as follows:
●Dolutegravir has potent anti-HIV activity, is administered once daily, has a high barrier to resistance, and is well tolerated [36-38].
●Raltegravir is well tolerated and has rare drug interactions. In addition, most experience with PEP has been with raltegravir [39]. However, this agent is dosed twice daily, and rare cases of skeletal muscle toxicity and severe systemic-cutaneous reaction resembling Stevens-Johnson syndrome have been reported [40,41].
●Boosted darunavir requires administration with food and may have more drug interactions and side effects compared with the integrase inhibitors.
Drugs to avoid — Nevirapine should not be used for PEP given the risk of severe liver toxicity and Stevens-Johnson syndrome. Efavirenz is rarely used for PEP because of the high risk of neuropsychiatric side effects and the risk of transmitted drug resistance. (See 'Side effects' below and "Overview of antiretroviral agents used to treat HIV", section on 'Non-nucleoside reverse transcriptase inhibitors (NNRTIs)'.).
Abacavir should also be avoided unless HLA-B*57:01 testing has been performed and the patient is negative for the allele. Severe hypersensitivity reactions to abacavir occur in 5 to 8 percent of patients who are HLA-B*57:01 positive. (See "Abacavir hypersensitivity reaction", section on 'Screening prior to abacavir exposure'.)
Specific populations
PEP options for drug-resistant virus — If the source patient is known to be HIV infected, it is important to obtain information about the patient's antiretroviral treatment history and review their past viral genotypes to see if drug-resistant virus is present. Standard PEP regimens may be inappropriate when the source is infected with a strain of HIV that is known or is likely to be resistant to antiretroviral medications [18]. Although there are no studies examining this issue, it is appropriate to tailor a regimen by selecting antiretroviral medications to which the source HIV is believed to be sensitive. (See "Interpretation of HIV drug resistance testing".)
However, PEP should not be delayed if information on resistance testing is unavailable [19]. In this situation, PEP regimens should include dolutegravir or boosted darunavir, and the regimen can be modified if needed when resistance testing is completed. These complex cases are best managed by an experienced HIV provider or with assistance from the HIV help-line (888-448-4911). If no resistance testing is available, an HIV specialist can often predict which mutations are likely to be present if the source patient has virologic failure on the current regimen [42]. This is particularly helpful since results from resistance testing performed after exposure will not be available soon enough to affect the choice of PEP [43]. (See "Overview of HIV drug resistance testing assays".)
An HIV specialist can help design the appropriate regimen by evaluating the results of resistance testing for the source patient on their current ART regimen. Some general principles can be applied when designing such a regimen:
●If the source patient has a history of drug resistance, but has viral suppression on the current ART, a PEP regimen using the same medications, or medications with similar patterns of susceptibility, is generally appropriate, if safe and well tolerated.
●If the source patient is taking ART but still has detectable viremia, it makes clinical sense to choose other medications that are unlikely to show cross-resistance when picking a PEP regimen while awaiting resistance testing on the source patient's virus.
●Resistant strains that were documented in the past on a prior regimen should be considered in drug selection for PEP.
The choice of drugs to which a resistant virus likely has no cross-resistance was exemplified in the cases of two HCP who had significant blood exposure from the same HIV-infected patient, who had a history of extensive drug resistance mutations in the reverse transcriptase and protease genes [44]. Both HCP were treated for one month with combination therapy that included raltegravir without evidence of seroconversion more than six months after initial exposure.
Persons of childbearing potential/persons who are pregnant — Dolutegravir should be avoided in:
●Persons of childbearing potential who are sexually active or have been sexually assaulted and who are not using an effective birth control method (eg, intrauterine contraception, injectable or oral contraception). (See "Contraception: Counseling and selection".)
●Persons early in pregnancy (eg, eight weeks since last menstrual period).
On May 18, 2018, the US Food and Drug Administration (FDA) released a safety alert regarding the use of dolutegravir in all persons who are able to become pregnant [45]. This was issued in response to a preliminary report suggesting an increased rate of neural tube defects in infants born to women in Botswana who were receiving dolutegravir at the time of conception [46,47]. The risk of a fetus developing a neural tube defect is during the first 28 days.
For persons who are or could become pregnant, a suitable PEP regimen appears to be tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) plus raltegravir. Although it is unknown whether other integrase strand inhibitors share the possible risk of neural tube defects reported with dolutegravir, raltegravir has been extensively used in pregnant women and individuals of childbearing potential for over a decade without any evidence to date of risk to the fetus. However, this uncertainty should be discussed with patients planning to initiate raltegravir. Tenofovir disoproxil fumarate-emtricitabine plus a ritonavir-boosted PI (eg, boosted darunavir) is another reasonable option (table 1).
If dolutegravir is still being considered and the patient was not using effective birth control at the time of exposure, a pregnancy test should first be obtained. If the test is positive or if the patient desires pregnancy, raltegravir or a ritonavir-boosted PI should be used as the third agent in combination with TDF-FTC. If the test is negative and the patient does not desire pregnancy, the patient can take dolutegravir but should use an effective contraception method until the nonoccupational PEP regimen is completed.
Persons who are pregnant and persons of childbearing potential who are not on effective contraception should also avoid elvitegravir/cobicistat/emtricitabine/tenofovir and other cobicistat-containing regimens due to decreased drug levels during pregnancy. Bictegravir should also be avoided because it is structurally similar to dolutegravir.
A detailed discussion of the dosing and safety of antiretroviral agents in persons of childbearing potential and during pregnancy is found elsewhere. (See "HIV and women" and "Safety and dosing of antiretroviral medications in pregnancy".)
Patients with reduced kidney function — For patients with reduced kidney function, the choice of NRTI combination is less clear since TDF is usually avoided in patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. In settings such as this, patients are best managed in consultation with an experienced HIV provider.
For patients with moderately reduced kidney function, we prefer tenofovir alafenamide-emtricitabine after a potential occupational exposure. Tenofovir alafenamide (TAF) is a newer tenofovir pro-drug that has less bone and kidney toxicity compared with TDF and is approved for use in patients with an eGFR between 30 and 60 mL/min/1.73 m2. However, some experts prefer to avoid TAF in the setting of PEP, particularly after nonoccupational exposures (eg, mucosal exposures), because available data suggest that TAF results in lower mucosal tenofovir levels compared with TDF, although intracellular levels of tenofovir are higher [48,49]. Another option is zidovudine-lamivudine (adjusted for eGFR), which can also be used in patients with an eGFR <30 mL/min/1.73 m2. However, zidovudine (AZT) has considerable toxicity, including fatigue and anemia. Dose-adjusted TDF-FTC is also an option, and some UpToDate experts prefer to initiate this NRTI combination after nonoccupational exposures, but the risk of worsening renal function must be discussed with the patient. If an AZT- or TDF-containing regimen is initiated, it may be reasonable to transition the patient to abacavir-lamivudine if testing for HLA-B*57:01 is negative. (See "Abacavir hypersensitivity reaction".)
Dosing recommendations for patients with reduced kidney function are found in the Lexidrug information program within UpToDate.
PEP in resource-limited settings — The World Health Organization (WHO) recommends PEP for HCP following an exposure to potentially infectious body fluids from a patient who is or is suspected to be HIV infected [30]. PEP should not be delayed pending the source's HIV test results, especially in areas where HIV is firmly established in the general population (eg, HIV prevalence consistently exceeding 1 percent among pregnant women) [50]. In such settings, it should be presumed that sources with an unknown HIV status pose a risk of infection. The WHO guidelines suggest a three-drug regimen using TDF-FTC as the preferred NRTI combination and a ritonavir-boosted protease inhibitor (lopinavir or atazanavir) as the third agent. These agents are widely available in low- and middle-income countries. Where available, raltegravir, boosted darunavir, or dolutegravir can also be used as a third agent. The WHO guidelines also list efavirenz as a potential third drug; however, we avoid efavirenz whenever other recommended third drugs are available, given its neuropsychiatric side effects. If a three-drug regimen is not available, a dual nucleoside regimen with TDF-FTC can be used. (See 'Selection of antiretroviral therapy' above.)
Duration of therapy — The recommended duration of PEP is four weeks because a course of zidovudine for this duration appeared protective in some studies, and shorter courses of PEP in primate studies were less effective; however, the optimal duration of PEP is unknown [18,51]. PEP can be discontinued if testing shows that the source patient is HIV negative. (See 'Determining HIV status of the source' above.)
Patient monitoring — HCP should be seen in follow-up within 72 hours of the exposure and starting PEP [19]. At that visit, clinicians can evaluate if PEP should be continued and if side effects are present. Exposed HCP should be seen again two weeks after the exposure and have laboratory testing to assess for drug toxicity (see 'Laboratory monitoring' below). Adherence to the PEP regimen should be emphasized at each visit; a review of multiple studies showed a completion rate of only about 60 percent [52], though this figure is likely to improve with the better-tolerated regimens that are now used.
Side effects — Integrase inhibitor-based PEP regimens typically have few side effects. Small studies have demonstrated that raltegravir in combination with TDF-FTC was well tolerated as PEP, except for a few cases where patients developed myalgias and elevation of creatinine kinase levels [39,53].
Prior to the use of integrase inhibitors, side effects were reported by about half of patients who receive PEP [54-58]. Most side effects were mild, but about one-third of patients discontinued treatment because of adverse reactions [54,55,59,60]. The most common ones were nausea and fatigue; headache, vomiting, and diarrhea were also common [54-58]. Rare but serious side effects included hepatitis, hyperglycemia, fevers, rashes, and pancytopenia [54,55]. PEP with nevirapine resulted in severe adverse events, including at least one case of hepatotoxicity requiring liver transplantation and three confirmed or possible cases of Stevens-Johnson syndrome; thus, this agent is not recommended for PEP [54,61-64]. (See 'Drugs to avoid' above.)
One program that provided four weeks of PEP to 401 people with exposures outside the health care setting (94 percent were sexual exposures) also found a high rate of side effects including nausea (52 percent), fatigue (44 percent), headache (24 percent), diarrhea (15 percent), and anorexia (12 percent) [65]. Side effects were more common with triple-drug PEP regimens that include a PI than with dual-NRTI PEP regimens [66]. The regimens that are now used for PEP are better tolerated, though gastrointestinal side effects, while usually mild, are still fairly common.
Adverse effects of specific agents are discussed in greater detail elsewhere.
Laboratory monitoring — Patients who receive PEP should be monitored for drug toxicity. Testing should include a complete blood count including differential, and tests of hepatic and renal function at baseline and at two and four weeks after initiation of PEP [18]. Patients treated with a PI should also be monitored for hyperglycemia. Additional testing may be indicated depending on the PEP regimen selected. (See "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach".)
Serious abnormalities of laboratory values warrant a switch in the antiretroviral regimen. (See "Switching antiretroviral therapy for adults with HIV-1 and a suppressed viral load".)
SOURCES FOR FURTHER INFORMATION — A 24-hour hotline is available through the National Clinicians' Post-Exposure Prophylaxis Hotline, phone number 1-888-448-4911.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: HIV prevention".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Blood or body fluid exposure (The Basics)")
SUMMARY AND RECOMMENDATIONS
●The risk to health care personnel (HCP) of contracting HIV from exposure to body fluids from an HIV-infected patient is very low. The average risk of seroconversion after a needlestick injury is about 3 per 1000 with no prophylaxis. (See 'Risk of transmission of HIV' above.)
●The first response to a percutaneous exposure should be to wash the area thoroughly with soap and water; for punctures and small lacerations, cleaning the area with an alcohol-based hand hygiene agent is reasonable. Exposed mucous membranes should be irrigated copiously with water or saline. (See 'Initial actions following exposure' above.)
●HCP should report exposures promptly to obtain HIV screening for both the HCP and the source patient (according to institution guidelines), and to discuss the need for post-exposure prophylaxis (PEP). (See 'Documentation of the exposure' above.)
●Because of the stress and emotional impact of an occupational exposure to HIV, explicit counseling on the actual risk of the exposure and the benefits and disadvantages of PEP is important. Exposed HCP should also be instructed on reducing the risk of potential transmission of HIV and means of monitoring for seroconversion. (See 'Counseling of health care personnel' above.)
●HIV screening of the exposed individual should be performed at baseline. If a fourth-generation antibody-antigen test is used, follow-up testing can be performed at six weeks and four months post-exposure. By contrast, if a test that only measures antibody is used, repeat HIV testing should occur at six weeks, three months, and six months following exposure. (See 'Testing for HIV' above.)
●For HCP with a percutaneous, mucous membrane, or nonintact skin exposure to potentially infectious body fluids, the decision to administer PEP must weigh the risk of HIV infection with the potential toxicity of PEP.
•We offer PEP if the source has known HIV infection. If the HIV status of the source patient is unknown, we offer PEP while awaiting HIV testing, particularly if the source patient is at high risk for HIV infection (eg, injection drug users, men who have sex with men) or has symptoms suggesting HIV infection.
•If the source patient cannot be identified, we offer PEP if the exposure occurred in a setting where the source is at high risk for HIV infection (eg, a needlestick from a sharps container in an HIV clinic or a needle exchange program). (See 'Indications for prophylaxis' above.)
●If the decision is made to administer PEP, it should be started as early as possible after an exposure (ideally within one to two hours). We administer PEP while awaiting the results of HIV testing if the HIV status of the source patient is unknown and the source patient is at elevated risk for HIV infection. (See 'Timing' above.)
●For most patients, we suggest a three-drug regimen using tenofovir disoproxil fumarate-emtricitabine plus an integrase strand transfer inhibitor (eg, raltegravir or dolutegravir) (Grade 2C). Alternative regimens that combine tenofovir disoproxil fumarate-emtricitabine with a boosted protease inhibitor (eg, ritonavir-boosted darunavir) are also acceptable. (See 'Selection of antiretroviral therapy' above.)
•For many patients we prefer a dolutegravir-containing regimen for the convenience of once-daily dosing. In addition, it may be particularly effective if there is concern for transmission of drug-resistant virus. (See 'Preferred antiretroviral regimens for PEP' above and 'PEP options for drug-resistant virus' above.)
•However, for persons who are or could become pregnant, we administer tenofovir disoproxil fumarate-emtricitabine in combination with either raltegravir or a ritonavir-boosted protease inhibitor. Dolutegravir should be avoided in persons of childbearing potential who were not using an effective birth control method at the time of exposure and in persons early in pregnancy; preliminary data suggest a potential risk of neural tube defects in infants born to women who received dolutegravir at the time of conception. (See 'Preferred antiretroviral regimens for PEP' above and 'Persons of childbearing potential/persons who are pregnant' above.)
●It is recommended that PEP be continued for four weeks, although the duration needed to achieve maximal benefit is not known. PEP can be discontinued if testing shows that the source patient is HIV negative. (See 'Duration of therapy' above and 'Determining HIV status of the source' above.)
●People receiving PEP should be monitored for adverse reactions to the drugs and for drug interactions. (See 'Patient monitoring' above.)
●The Occupational Safety and Health Administration requirements in the United States and the management of exposure to hepatitis B and C viruses are discussed separately. (See "Prevention of hepatitis B virus and hepatitis C virus infection among health care providers".)
ACKNOWLEDGMENTS — The editorial staff at UpToDate would like to acknowledge John G Bartlett, MD, and David J Weber, MD, MPH, who contributed to an earlier version of this topic review.
