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Management of health care personnel exposed to HIV

Management of health care personnel exposed to HIV
Literature review current through: May 2024.
This topic last updated: Mar 13, 2023.

INTRODUCTION — Soon after the recognition of the HIV epidemic, the potential consequences of exposure to body fluids from persons with HIV 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 personal 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 a patient with HIV 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 a source with HIV 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 a source with HIV 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 (55.6 percent in 2021), followed by physicians who are residents or fellows (10.1 percent), attending physicians (6.3 percent), nonlab technologists (5.1 percent), and certified nursing assistants/home health aides (4.9 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 a source with HIV.

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 a source with HIV, 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]. In the UK, no cases of occupationally acquired HIV were reported from 2004 to 2013 [16].

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POST-EXPOSURE MANAGEMENT — The management of health care personnel (HCP) immediately after a significant exposure to blood or body fluids from patients with HIV 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 [17]. 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 [18].

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 have HIV, 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 [19]:

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) [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]. HIV RNA testing should be performed if acute HIV is suspected or if the source patient has been at increased risk for acquiring HIV in the past four weeks (eg, injection drug use, high-risk sexual behaviors) [21]. (See "HIV infection: Risk factors and prevention strategies", section on 'Modes of acquisition' and "Screening and diagnostic testing for HIV infection in adults", section on 'Overview of available 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 [22]. 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 in adults", section on 'Nucleic acid tests'.)

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.)

All percutaneous or sharps injuries from a source with HIV is considered an exposure (even if the HCP had no evidence of bleeding). Although the risk of HIV infection after a percutaneous injury averages 3/1000, it 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.

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 and better tolerated. 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 'Regimen selection' 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 the HCP 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 the HCP 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 persons of childbearing potential.

HCP who have childbearing potential need to be aware of the 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 the HCP for HIV — Baseline and follow-up testing for HIV should be performed in all HCP exposed to HIV to asses for evidence of HIV infection, even among those who receive PEP. The majority of individuals who acquire HIV will do so within the first three months. An antibody-antigen test is preferred since this test will detect infection earlier than those that just detect antibody. Detailed discussions of PEP and HIV diagnostic tests are presented separately. (See 'Post-exposure prophylaxis' below and "Screening and diagnostic testing for HIV infection in adults".)

Baseline testing – All exposed individuals should have a baseline HIV test immediately after the exposure.

Follow up testing – 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.

Extended follow-up for HIV testing (eg, for 12 months) is recommended for HCP who become infected with HCV after exposure to a source coinfected with HIV and HCV [23]. 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 [24]. 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 should not be performed to detect early infection in asymptomatic persons 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 nonimmune 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) [25]. 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, living with HIV. (See 'Definition of exposure' above and 'Indications for prophylaxis' below and 'Regimen selection' 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".)

Rationale — Data from animal models have supported the efficacy of zidovudine (AZT) alone in preventing transmission of HIV infection [26-28]. 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 [29]. (See "Antiretroviral selection and management in pregnant individuals 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 [30]. 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 [23]. 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. Three drug regimens have been shown to reduce the transmission rate to 0.5 percent [31]. (See "Prevention of vertical HIV transmission in resource-limited settings", section on 'Risk of vertical HIV transmission'.)

Improved efficacy is likely with combination ART for PEP as well. (See 'Regimen selection' 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, though the risk of side effects is much less with contemporary regimens. (See 'Preferred regimens for most HCP' below.)

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 [26-28].

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 a source patient with HIV). For such HCP, The United States Public Health Service suggests that PEP can be offered up to one week after the exposure [19].

Regimen selection — This section will review regimen selection for HCP who receive PEP. The duration of treatment and patient monitoring on treatment is discussed below. (See 'Duration of therapy' below and 'Patient monitoring' below.)

Preferred regimens for most HCP — We administer a three-drug regimen for 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 [19,32,33]. 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.

For most HCP, we suggest one of the following once-daily integrase strand transfer inhibitor (INSTI)-based regimens, provided the source does not have detectable virus with known resistance to these agents [33]:

Bictegravir-emtricitabine-tenofovir alafenamide

Dolutegravir in combination with either tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) or tenofovir alafenamide-emtricitabine (TAF/FTC).

An alternative INSTI-based regimen is raltegravir (400 mg twice daily) with either TDF/FTC or TAF/FTC administered once-daily. Although this regimen is likely to be as effective as one of the other INSTI-based regimens for PEP, it is more difficult to take since raltegravir requires twice daily dosing.

On the rare occasion an INSTI cannot be used (eg, due to cost or availability), TDF/FTC or TAF/FTC can be combined with the boosted protease inhibitor (PI) ritonavir-boosted darunavir.

For PEP, either formulation of tenofovir (tenofovir disoproxil fumarate [TDF] or tenofovir alafenamide [TAF]) can be used as part of the regimen since antiviral therapy is only administered for a short duration. This differs from persons with HIV who require life-long treatment; in such patients, TAF/FTC is typically preferred as part of a combination antiretroviral regimen to reduce the risk of kidney and bone toxicity.

Special considerations for regimen selection in selected patient populations are found below:

(See 'Persons with reduced kidney function' below.)

(See 'Persons of childbearing potential/persons who are pregnant' below.)

(See 'PEP options for drug-resistant virus' below.)

(See 'PEP in resource-limited settings' below.)

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.

PEP options for drug-resistant virus — If the source patient is known to have HIV, 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. Resistant strains that were documented in the past on a prior regimen should be considered in drug selection for PEP. 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 not immediately available [19]. In this situation, a regimen with a high barrier to resistance (dolutegravir-, bictegravir-, or darunavir-containing regimens) should be used pending the results. The regimen can then 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). An HIV specialist can help design the appropriate regimen. As examples:

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. In general, a regimen such as TDF/FTC plus boosted darunavir is a good option.

In one report, two HCP had significant blood exposure from a patient with HIV who had a history of extensive drug resistance mutations in the reverse transcriptase and protease genes [34]. 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 — First-line PEP regimens for persons who desire pregnancy and those who are pregnant are similar to those for nonpregnant persons.

These include:

Dolutegravir (50 mg once daily) or raltegravir (400 mg twice daily)

Plus

Tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) or tenofovir alafenamide-emtricitabine (TAF/FTC) administered once daily.

However, bictegravir-emtricitabine-tenofovir alafenamide is generally avoided in persons who are pregnant and persons of childbearing potential who are not on effective contraception since there is limited experience with the use of this agent during pregnancy. Such persons should also avoid elvitegravir/cobicistat/emtricitabine/tenofovir and other cobicistat-containing regimens due to decreased drug levels during pregnancy.

Previously, dolutegravir was avoided in persons who were early in their pregnancy or were able to become pregnant but were not using effective birth control [35]. This was based on 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 (the risk of a fetus developing a neural tube defect during the first 28 days) [36,37]. However, after accrual of further data, a subsequent analysis demonstrated no increased risk of neural tube defects [38]. Therefore, dolutegravir can be given at any stage of pregnancy and to persons attempting pregnancy, including for the purpose of post-exposure prophylaxis [33,39].

A more detailed discussion of the dosing and safety of antiretroviral agents in persons of childbearing potential and during pregnancy is presented elsewhere. (See "HIV and women" and "Safety and dosing of antiretroviral medications in pregnancy".)

Persons with reduced kidney function — For patients with reduced kidney function, TDF should be avoided in those with an eGFR < 60 mL/min/1.73 m2. However, if the eGFR is between 30 and 60 mL/min/1.73 m2, TAF/FTC can be used in combination with dolutegravir or bictegravir. We do not use two drug tenofovir sparing regimens (eg, dolutegravir-lamivudine) for PEP given lack of experience with this approach for prevention.

For those with an eGFR <30 mL/min/1.73m2 the approach must be individualized. As an example, for patients on hemodialysis, TAF/FTC plus an integrase inhibitor (dolutegravir, bictegravir, or raltegravir) can be used. However, for those not on dialysis, TAF and TDF should generally be avoided. In this setting, the integrase inhibitor can be combined with dose-reduced zidovudine and lamivudine [40]. Dosing recommendations for patients with reduced kidney function are found in the drug 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 [32]. PEP should not be delayed pending the source's HIV test results, especially in areas where HIV is prevalent in the general population (eg, HIV prevalence consistently exceeding 1 percent among pregnant women) [41]. In such settings, it should be presumed that sources with an unknown HIV status pose a risk of infection.

Similar to resource-rich settings, a three-drug regimen is preferred. The selection of agents reflects local availability; however, the combination of tenofovir dipivoxil fumarate, lamivudine, and dolutegravir is now widely available, both for treatment and post-exposure prophylaxis [42].

Drugs to avoid — Abacavir should be avoided for PEP since HLA-B*57:01 testing must first be performed to confirm the patients 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'.)

The NNRTI, nevirapine, should also be avoided for PEP given the risk of severe liver toxicity and Stevens-Johnson syndrome. In addition, efavirenz (another NNRTI), 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)'.)

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 [23,43]. PEP can be discontinued sooner if testing shows that the source patient is HIV negative. (See 'Determining HIV status of the source' above.)

Patient monitoring

Frequency of visits — 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. (See 'Side effects' below.)

Adherence to the PEP regimen should also be emphasized. A review of multiple studies showed a completion rate of only about 60 percent [44], though this figure is likely improved with the better-tolerated regimens that are now used. (See 'Preferred regimens for most HCP' above.)

Some exposed HCP should be seen again two weeks after the exposure and/or have laboratory testing to assess for drug toxicity. This includes persons experiencing side effects, medically complex persons who are at increased risk for toxicity (eg, those with reduced kidney function), those receiving an AZT containing regimen, as well as those who endorse difficulty adhering to their regimen. Many HCP benefit from added counseling.

Additional visits may also be warranted when follow up HIV testing is performed. (See 'Testing the HCP for HIV' above.)

What to monitor

Side effects — Integrase inhibitor-based PEP regimens typically have few side effects. PEP with TDF/FTC plus dolutegravir is well tolerated, with mild gastrointestinal symptoms and headache the most commonly reported side effects [45]. Dolutegravir can also be associated with insomnia, particularly when dosed in the evening; other neuropsychiatric symptoms, such as dizziness, anxiety, and depression, have been reported but are uncommon [46].

Small studies have also demonstrated that the integrase inhibitor raltegravir in combination with TDF/FTC was well tolerated as PEP, with mild gastrointestinal side effects in a minority of patients. Serious adverse effects were limited to a few cases of myalgias with elevation of creatinine kinase levels [47,48]. There have been rare reports of drug reaction with eosinophilia and systemic symptoms (DRESS) with raltegravir when used for treatment of established HIV infection [49].

In general, protease inhibitor-based PEP regimens are not as well tolerated. In a study that included 155 persons who received a PrEP regimen that included ritonavir boosted darunavir, 68 percent reported adverse drug reactions [50]

Adverse effects of specific agents are discussed in greater detail elsewhere. (See "Overview of antiretroviral agents used to treat HIV".)

Laboratory monitoring — Patients receiving PEP should be monitored for drug toxicity.

For those receiving a tenofovir-containing regimen, baseline testing should include serum creatinine and a liver enzyme panel. For patients with normal renal function, these labs should be repeated at the end of treatment. Patients with diabetes mellitus treated with a PI should also be monitored for hyperglycemia.

On the rare occasion that AZT is used (eg, patients with severe kidney disease not on dialysis), baseline testing should also include a complete blood count with differential. In such patients, these laboratory tests should be repeated two and four weeks after initiating therapy [19].

Significant abnormalities of laboratory values warrant follow-up testing, and on rare occasion, a switch in the antiretroviral regimen. Such patients should be managed in conjunction with an HIV specialist.

Follow up HIV testing — Patients receiving PEP should be monitored for evidence of new HIV infection. The approach to HIV testing is described above. (See 'Testing the HCP for HIV' above.)

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

Risk of acquiring HIV – For health care personnel (HCP), the risk of acquiring HIV after an exposure to body fluids from a patient with HIV is very low. The average risk of seroconversion after a needlestick injury from a source patient with HIV who is not receiving suppressive antiretroviral therapy is about 3 per 1000 with no prophylaxis. However, this 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. (See 'Risk of transmission of HIV' above.)

Initial management – 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.)

HIV testing after an exposure – HCP should promptly report possible HIV exposures to their occupational health department so the HCP and the source patient can be screened for HIV as soon as possible. All institutions should have a readily available policy for managing such exposures. (See 'Documentation of the exposure' above.)

Testing with a fourth-generation antibody-antigen test is usually sufficient. However, for source patients, testing for HIV RNA should also be performed if they are suspected of or are at risk for having acute HIV (eg, persons with symptoms of acute HIV infection, those who injected drugs or engaged in high-risk sexual behaviors in the last four weeks). (See 'Testing the HCP for HIV' above and 'Determining HIV status of the source' above.)

Indications for post-exposure prophylaxis (PEP) – 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. (See 'Indications for prophylaxis' above.)

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 results, particularly if the source patient has symptoms consistent with acute HIV infection or is at high risk for HIV infection.

If the source cannot be identified, we offer PEP if the exposure occurred in a setting where the source is at significant risk for HIV infection (eg, a needlestick from a sharps container in an HIV clinic or a needle exchange program).

Administration of PEP

Timing of PEP – If the decision is made to administer PEP, it should be started as early as possible after the exposure (ideally within one to two hours). For most HCP, we do not initiate PEP if more than 72 hours have elapsed after the initial exposure. (See 'Timing' above.)

Regimen selection for PEP – For most HCP, we suggest a three-drug regimen using an integrase strand transfer inhibitor (eg, dolutegravir or bictegravir) plus either tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) or tenofovir alafenamide-emtricitabine (TAF/FTC) (Grade 2C). An alternative regimen that combines tenofovir-emtricitabine with a boosted protease inhibitor (eg, ritonavir-boosted darunavir) is also acceptable. (See 'Regimen selection' above.)

However, there are special considerations for selected populations. As an example, bictegravir should be avoided in persons who are or could become pregnant. In addition, TDF should generally be avoided in persons with reduced kidney function. (See 'Persons of childbearing potential/persons who are pregnant' above and 'Persons with reduced kidney function' above.)

Duration of PEP – PEP should 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.)

Monitoring on PEP – People receiving PEP should be monitored for adverse reactions to the drugs and for drug toxicity. (See 'Patient monitoring' above.)

Follow up HIV testing – For all HCP who had an exposure to HIV, repeat HIV testing with an antibody-antigen test should be performed at six weeks and four months post-exposure. 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 the HCP for HIV' above.)

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. Management after an exposure to hepatitis B and C viruses is discussed separately. (See "Prevention of hepatitis B virus and hepatitis C virus infection among health care providers".)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges John G Bartlett, MD, and David J Weber, MD, MPH, who contributed to an earlier version of this topic review.

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Topic 3764 Version 29.0

References

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