Prophylaxis for Exposure to Human Immunodeficiency Virus
Kenneth L. Dominguez
Disclaimer: The use of trade names is for identification only and does not imply endorsement by the Public Health Service or the U.S. Department of Health and Human Services.
BACKGROUND
Postexposure prophylaxis (PEP) is the timely administration of antiretroviral (ARV) chemoprophylaxis to reduce the probability of becoming infected with HIV after an acute well-defined exposure and can be categorized as occupational (oPEP) or nonoccupational (nPEP). This chapter describes the epidemiology of various types of HIV exposures that may call into question use of PEP, recent animal and human studies supporting the use of PEP, current U.S. Public Health Service (USPHS)/Department of Health and Human Services (HHS) recommendations for oPEP and nPEP, and special considerations regarding pediatric nPEP. (See http://www.aidsinfo.nih.gov.easyaccess1.lib.cuhk.edu.hk for
most recent updates.) The USPHS oPEP recommendations continue to recommend a two-tiered system of three ARVs versus two ARVs, depending on the level of risk. The chapter highlights a change in the HHS nPEP recommendations, which now emphasize the importance of using three drug regimens, when feasible, to be consistent with the current standard of care regarding treatment of established HIV infection.
most recent updates.) The USPHS oPEP recommendations continue to recommend a two-tiered system of three ARVs versus two ARVs, depending on the level of risk. The chapter highlights a change in the HHS nPEP recommendations, which now emphasize the importance of using three drug regimens, when feasible, to be consistent with the current standard of care regarding treatment of established HIV infection.
oPEP
Current Centers for Disease Control and Prevention (CDC) oPEP guidelines define health care personnel (HCP) as persons whose activities involve contact with patients or with patients’ blood or other body fluids in a health care, laboratory, or public-safety setting. Occupational exposures that could place HCP at risk for HIV infection include (a) percutaneous injury (e.g., a needlestick or cut with a sharp object) or (b) contact of mucous membrane or nonintact skin (e.g., exposed skin that is chapped, abraded, or afflicted with dermatitis) with blood, tissue, or other body fluids that are potentially infectious. Nonintact skin exposures with potentially infectious body materials are not considered to be of risk except for direct contact (i.e., without barrier protection) with concentrated HIV in a research laboratory or production facility. Other body fluids include (a) semen, vaginal secretions, or other body fluids contaminated with visible blood that have been implicated in the transmission of HIV infection and (b) fluids with an undetermined risk of HIV transmission (i.e., cerebrospinal, synovial, pleural, peritoneal, pericardial, and amniotic fluids). In the absence of visible blood in the fluid or substance, exposure to saliva, tears, sweat, urine, or HIV feces is not considered to pose a risk for transmission of and does not require postexposure follow-up. Although mother-to-child transmission (MTCT) of HIV can occur through breast-feeding, exposure to breast milk has not been implicated in occupational transmission of HIV.
nPEP
Examples of nonoccupational exposures to HIV include exposure to HIV through unprotected sex or through sharing needles with HIV-infected persons. More common pediatric consultations for nPEP involve sexual abuse or exposure to discarded needles.
Studies of the Biologic Plausibility of PEP
In 1990, the USPHS published the first statement on oPEP at which time there was a lack of convincing data on the efficacy of PEP. Since then, additional data provide a stronger rationale for HIV PEP, including information regarding primary HIV pathogenesis, the biologic plausibility of the effectiveness of ARV drug administration for the PEP, and the effectiveness of ARV drugs for PEP in animal and human studies.
Primary HIV Pathogenesis and Biologic Plausibility of PEP Effectiveness
In primate models, simian immunodeficiency virus (SIV) travels within the inoculation site to dendritic-like cells during the first 24 hours, to regional lymph nodes in the next 24 to 48 hours, and to peripheral blood within 5 days of inoculation. Therefore, it seems biologically plausible that PEP, if started within hours after HIV exposure, could prevent spread of infection beyond the initially infected cells or lymph nodes.
Effectiveness of PEP in Animal and Human Studies
Animal and human data support the biologic plausibility of the effectiveness of HIV PEP. Animal models of the effectiveness of PEP vary by type of animal, type of virus, route and strength of inoculation, drug used for PEP, and the number, timing, and duration of doses of PEP. In primate models, macaques inoculated with SIV either intravenously or orally and treated with PEP at various time points using ZDV or (R)-9-(2-phosphonylmethoxypropyl) adenine (PMPA or tenofovir) exhibited a range of effectiveness in preventing infection or decreasing the severity of the initial infection, depending on the model. In general, early initiation of PEP, within a few hours of exposure, was associated with the highest effectiveness.
Human studies have been primarily observational. A case control study evaluated HIV seroconversion in HCP in the United States, France, and the United Kingdom with percutaneous exposure to HIV-infected blood. PEP (consisting of 1,000 mg/day of ZDV for 3 to 4 weeks) was received by 9 of 33 (27%) cases and 247 of 679 (36%) of controls. The likelihood of developing HIV infection among HCP who received PEP with ZDV was approximately 81% lower than among those who did not receive such PEP. Observational studies and registries designed to collect information about nPEP are being conducted and established, and thus far no seroconversions have been reported among registries in the United States, France, Switzerland, and Australia among individuals who received nPEP after exposure to HIV.
Studies of nPEP in Pediatric Practice
Few data exist regarding PEP in pediatric patients; however, nPEP surveys indicate that few hospitals or clinics have institutional policies for nPEP and patients often fail to complete a 4-week course of nPEP. Financial concerns, side effects, additional psychiatric and substance abuse issues, and the degree of parental involvement influenced whether PEP and HIV follow-up testing was completed. Many studies suggest that a successful PEP program should include psychosocial support, early follow-up with a physician knowledgeable about pediatric ARV therapy to assess compliance, and a written institutional protocol to provide a coordinated and standardized approach.
EPIDEMIOLOGY OF EXPOSURES TO HIV
Exposures in HCP
The average risk for HIV infection for HCP exposed to HIV-infected blood has been estimated at 0.3% for percutaneous exposures and 0.09% for mucous membrane exposures. The risk is unknown for skin exposures, but it is thought to be less than that for mucous membrane exposures. As of December 31, 2002, the CDC has received reports of 57 U.S. HCP with documented HIV seroconversion temporally associated with occupational HIV exposure and has been informed of an additional 139 HCP who report occupationally acquired HIV infection without such documentation. The risk of HIV transmission occurring from exposures that involve a larger volume of blood, especially when the source patient’s viral load is probably high, is estimated to exceed the average risk of 0.3%.
There are very limited epidemiologic data on the most common exposures to blood for HCP in pediatric health care settings. Up to 6 sharp object injuries (SOIs) per 100 employees per year have been reported in pediatric health care settings
involving mainly needles and most often among phlebotomists, nurses, and physicians. In addition, one-third of the approximately 12 human bite exposures per 10,000 occupied hospital beds that occur per year involved children and have failed to result in HIV seroconversion.
involving mainly needles and most often among phlebotomists, nurses, and physicians. In addition, one-third of the approximately 12 human bite exposures per 10,000 occupied hospital beds that occur per year involved children and have failed to result in HIV seroconversion.
BOX 141.1. Preventing and Managing Bottle Switches in Day Care Centers*
Make sure that parents label each child’s bottle of formula or breast milk with the child’s name and the date.
Use only a bottle labeled for that child on that date
Never accept an unlabeled bottle from a parent
Do not use any unlabeled bottles that have beenaccepted accidentally
In the event that a child has mistakenly been given another child’s bottle of expressed breast milk, do the following:
Inform the parents of the child who was given the wrong bottle that:
Their child was given another child’s bottle ofexpressed breast milk
The risk of transmission of HIV is very small (see discussion below)
They should notify the child’s physician of theexposure
The child should have a baseline test for HIV
Inform the mother who expressed the breast milk of the bottle switch and ask:
If she has ever had an HIV test and, if so, if she would be willing to share the results with the parents
If she does not know if she has ever had an HIV test, if she would be willing to contact her obstetrician and find out and, if she has, share the results with the parents
If she has never had an HIV test, if she would be willing to have one and share the results with the parents and
When the breast milk was expressed and how it was handled prior to being brought to the facility
Provide the exposed child’s physician information on when the milk was expressed and how the milk was handled prior to being brought to the facility.
Risk of HIV transmission from expressed breast milk drunk by another child is believed to be low because:
In the United States, women who are HIV-infected and aware of that fact are advised not to breast-feed their infants
Chemicals present in breast milk act, together with time and cold temperatures, to destroy the HIV present in expressed breast milk.
Footnote
*Adapted from
Hale CM et al. The ABCs of safe and healthy child care: A handbook for child care providers. Atlanta: Department of Health and Human Service, Centers for Disease Control and Prevention Publication, 1996.
Prevention
Measures to prevent occupational HIV exposures include strict adherence to standard precautions and Office of Safety and Health Administration (OSHA) guidelines. Examples include the use of safer medical devices where appropriate, properly restraining patients when drawing lab samples, being well trained in doing procedures involving sharp objects, and using gloves when managing patients who might be combative or when manipulating the oral cavity. When handling breast milk, the use of gloves is not necessary except in situations where exposures to breast milk might be frequent, as in breast milk banking, or if the HCP has nonintact skin.
Exposures among Children in Health Care Settings
Children are present in hospitals either as patients or visitors and are subject to situations that could place them at risk for HIV infection. There have been case reports of children that were probably exposed inadvertently to blood from an HIV-infected person in the hospital or during in-home health care. Newborns have been inadvertently fed the expressed breast milk intended for another infant. Such exposures to breast milk would generally be considered to carry a low risk for HIV exposure unless the hospital is located in a geographic area with a high seroprevalence in women of child-bearing age.
Prevention
Measures to prevent pediatric exposures to HIV in health care settings include rapid disposal of used needles in sharps containers located out of the reach of children but readily accessible to HCP and use of standard procedures for labeling and dispensing bottles of expressed breast milk. Health care institutions may consider adapting existing recommendations related to bottles of expressed breast milk designed for day-care centers to hospital settings (Box 141.1). A bottle of expressed breast milk that has been properly labeled with the mother’s and infant’s hospital identifiers should always be checked against the infant’s identification bracelet prior to providing bottle-feedings of expressed breast milk. In addition, health care institutions that allow feeding of infants with human donor milk should use donor milk banks that adhere to existing state laws or regulations or national guidelines that ensure proper screening of donors and sterilization of milk.
Exposures among Children Outside the Health Care Setting
Children can be exposed to HIV outside the hospital setting. Examples of such exposures include sexual abuse involving oral, anal, or vaginal penetration by an HIV-infected perpetrator, needle sticks in the home or public areas with recently discarded syringes containing HIV-infected blood, exposures to HIV-containing breast milk, and human bites that compromise the skin’s integrity and involve an exchange of HIV-infected blood.
Sexual Abuse
There were 88,238 cases of various types of sexual abuse in children younger than 18 years of age reported in the United
States during 1999, including 26 cases of sexual abuse (17 confirmed, 9 suspected) among children with AIDS. These cases probably represent an underestimate due to the underreporting of such abuse.
States during 1999, including 26 cases of sexual abuse (17 confirmed, 9 suspected) among children with AIDS. These cases probably represent an underestimate due to the underreporting of such abuse.
Among adults, the probability of HIV transmission associated with a single act of unprotected receptive anal intercourse has been estimated to be between 0.008 and 0.032 and with vaginal intercourse to be between 0.0005 and 0.0015. The medical literature suggests that child sexual abuse may be a more efficient means of transmitting HIV than is adult sexual abuse because of anatomic differences and a higher frequency of repeated molestations and longer term abuse in children.
Any sexually assaulted child should be assessed within 72 hours of the assault. The clinician should (a) review the local HIV/AIDS epidemiology and assess risk for HIV infection in the assailant; (b) evaluate circumstances of the assault that may affect risk for HIV transmission; (c) consult with an HIV specialist if considering PEP; (d) discuss PEP, including its toxicity and unknown efficacy with the caregiver; (e) if indicated, provide enough medication to last until the return visit 3 to 7 days later, at which time the child can be reevaluated, including for his or her tolerance of the medication (if PEP is prescribed); and (f) perform HIV testing at baseline and then at 6 weeks, 3 months, and 6 months later.
The following situations are associated with a high risk of transmission of sexually transmitted infections (STIs), and HIV testing should be performed if (a) one or more children in a household has signs or symptoms of an STI; (b) the suspected assailant is known to have an STI or to be at high risk for STIs (e.g., the individual has multiple sexual partners or a history of STIs); (c) the patient or his or her parent(s) requests testing; (d) there is a high prevalence of STIs in the community; (e) there is evidence of genital, oral, or anal penetration or ejaculation; or (f) the assault involved traumatic mucosal injuries of the anus or vagina, associated with bleeding and contact with the semen of a known HIV-infected assailant. An example of a lower risk exposure is the sexual abuse of a child by a perpetrator with unknown HIV infection status in an area with low HIV seroprevalence.
Prevention
Examples of strategies to prevent the sexual abuse of children include (a) educating caretakers about teaching children to refuse to engage in abusive situations, to avoid keeping secrets related to abuse, and to disclose abusive situations to someone who is trusted; and (b) educating parents to select day-care centers with licensed day-care workers, open and visible play areas, and policies that allow parental visitation and do not allow for individual instruction in isolated settings.
Breast Milk Exposures
Globally, breast milk transmission of HIV represents an important mode of MTCT of HIV. In the United States, exposure to breast milk from an unknown or unscreened source is unlikely to result in HIV transmission, but each exposure must be considered on a case-by-case basis. Such exposures may occur through the switching or mislabeling of bottles containing expressed breast milk (e.g., in day-care settings), allowing an infant to breast-feed from a wet nurse with unknown HIV infection status, or using expressed, unpasteurized human milk that has not been screened for HIV or pasteurized. The likelihood that HIV is present in the breast milk of an unknown or unscreened source is low in the United States because the seroprevalence of HIV among pregnant women has been estimated at less than 2 per 1,000. The USPHS guidelines recommended that pregnant woman undergo HIV testing and that HIV-infected women should not breast-feed their infants. The risk of such an exposure would increase if the source individual is determined to have a history of behaviors that put her at risk for HIV transmission or comes from a community with a high HIV seroprevalence.
Prevention
The CDC recommends that prenatal HIV testing should be offered to all pregnant women and routine rapid HIV testing should be offered to all pregnant women whose HIV status is still unknown at the time of delivery. HIV-infected mothers in resource-rich settings should be counseled to avoid breast-feeding, and clinicians should provide education to HIV-infected mothers regarding feeding options. Every effort should be made to avoid exposure to HIV-contaminated breast milk. Other prevention strategies are listed in the section on pediatric exposures in health care settings.
Discarded Needles or Syringes
The risk of HIV transmission occurring from discarded needles in public places is thought to be low. It is estimated that the probability of HIV transmission associated with a puncture wound involving a known HIV-contaminated needle in a health care setting is 0.0032. It is likely that discarded needles in outdoor public settings have a lower risk for transmission due to the effect of environmental factors and the length of time between injection drug use and a subsequent, accidental puncture wound. The stability of HIV under various environmental conditions has been shown to decrease over time and rarely has been detected in needles used for intramuscular or subcutaneous injections in HIV-infected persons. At room temperature, survival of HIV in syringes is halved for every tenfold decrease in blood volume and HIV is detected in less than 1% of syringes after more than a week. The following factors are likely to increase the risk or are required for HIV transmission in needlestick injuries: presence of blood in a needle or syringe emptying into the wound, large needle bore size, deep puncture wounds, a needlestick injury directly into a vein or artery, a short lag time from time of discarding the needle or syringe to time of injury, positive HIV infection status of source individual, and a high seroprevalence among persons frequenting the geographic area where the needle was discarded (Table 141.1). For example, a child injured by picking up a freshly discarded syringe containing blood from a known HIV-infected injection drug user would be at higher risk of acquiring HIV infection. However, most pediatric needlestick injuries do not occur under such
circumstances and would be considered to have a very low risk for transmission.
circumstances and would be considered to have a very low risk for transmission.
TABLE 141.1. LOGISTIC REGRESSION ANALYSIS OF RISK FACTORS FOR HIV TRANSMISSION AFTER PERCUTANEOUS EXPOSURE TO HIV-INFECTED BLOOD* | |||||||||||||||||||||
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Prevention
Children should be educated to avoid playing in areas known to be frequented by injecting drug users and to avoid playing with discarded needles and syringes. Needle exchange programs may play a role in decreasing the number of discarded needles in public places.
Human Bites
It has been estimated that 250,000 human bites occur annually in the United States. Fifty percent of children at one day-care center were bitten at least once in a year. There is currently no evidence that human bites without the presence of blood-tinged saliva in the wound pose an HIV infection risk to the victim. Although biting has been cited as a possible mode of transmission in several case reports, in all of the well-documented reports, the bites were by adults and involved severe biting with blood exchange. Seroconversion was documented in a man bitten by an HIV-infected commercial sex worker with blood-tinged saliva.
Management of bite wounds should include an evaluation for breaks or abrasions in the skin of the bite victim. Should such breaks or abrasions occur, the person who inflicted the bite should be evaluated for the presence of blood in the mouth or oral lesions, which may cause the wound to be contaminated with blood. Proper wound care includes irrigation, debridement, immobilization, and elevation of the affected body part and antimicrobial prophylaxis.
Prevention
Biting in day-care centers may be deterred by setting limits for a child’s behavior, teaching and reinforcing coping skills, and providing other acceptable avenues or activities for children to release or redirect their anger.
Sports-Related and Day-Care–Related Bleeding Injuries
The risk of transmitting HIV or other bloodborne pathogens through sports-related injuries during athletic activities is considered to be low. To transmit a bloodborne pathogen during an athletic activity, blood from a bleeding wound or exudative skin lesion of an HIV-infected athlete would have to contaminate the skin lesion or exposed mucous membranes of another athlete. The likelihood of transmission of bloodborne pathogens in contact sports is estimated at 1 in 4 million/players/games for HIV. There have been no substantiated cases of HIV transmission and two cases of hepatitis B virus (HBV) transmission between athletes during an athletic event.
Similar to sports-related injuries, the incidence of injuries in day-care centers in the United States is low; the overall reported incidence of injuries in day-care settings has ranged from 0.25 to 2.50 per 100,000 child hours, with about one-third of such injuries requiring sutures in Washington state.
Prevention
Guidelines to prevent bloodborne pathogen transmission during athletic activities or at day-care facilities have been described. Once a child or athlete has suffered a bleeding injury, the physical activity associated with the injury should be stopped until the wound has been cleaned and dressed, the bleeding has stopped, blood-contaminated skin has been washed with soap and water, and blood-contaminated mucous membranes have been flushed with ample water. Gloves should be made available to staff in charge of cleaning wounds or surfaces contaminated with blood. Blood-contaminated surfaces should be cleaned with bleach solution (1 part bleach/ 100 parts water or 1 tablespoon bleach/1 quart water or ¼ cup of bleach/1 gallon of water) and allowed to dry before reusing.
USPHS OPEP RECOMMENDATIONS
The USPHS oPEP recommendations underscore the need to balance the risk for infection against the potential toxicity or ARV agents. Because PEP is potentially toxic and side effects are common, its use is not justified for exposures that pose a negligible risk for transmission. For exposures that represent an increased risk for transmission, aggressive treatment using a highly active expanded regimen that includes three ARV drugs is recommended. However, most exposures do not represent an increased transmission risk and, for these exposures, the CDC recommends a basic two-drug regimen (Tables 141.2 and 141.3). In addition, the 2001 HIV oPEP recommendations also address oPEP for HBV and hepatitis C virus (HCV). (See http://www.aidsinfo.nih.gov.easyaccess1.lib.cuhk.edu.hk for the most recent updates.)
First Steps in Management of Exposures, Considerations for Determining the Level of Risk in Occupational Exposures, and the Appropriateness of Offering PEP
Care of the Exposure Site
Wound and skin sites exposed to blood or body fluids should be washed with soap and water. Mucous membranes should be flushed with water. PEP may be instituted immediately and discontinued at a later time should the detailed evaluation determine that the exposure does not warrant continued PEP prophylaxis.
TABLE 141.2. BASIC AND EXPANDED PEP REGIMENS FOR OCCUPATIONAL EXPOSURES | ||||||||||
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TABLE 141.3. DOSES OF ARVS USED FOR OCCUPATIONAL PEP | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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BOX 141.2. Recommendations for Contents of Occupational Exposure Report
Date and time of exposure
The procedure being performed
How and where exposure occurred and if a sharp device was involved, type of device
The exposure
Type of exposure: Percutaneous injury (e.g., needlestick or other penetrating sharps, etc.), mucous membrane exposure (e.g., splash in eye, etc.), nonintact skin exposure (e.g., broken or abraded skin, etc.), bites resulting in blood exposure to either person involved
Type and amount of fluid/tissue: Blood, fluids containing blood, or potentially infectious fluid or tissue (semen; vaginal, cerebrospinal, synovial, pleural, peritoneal, pericardial, and amniotic fluids)
Severity of exposure, depth of wound, duration of contact, condition of skin
Likelihood of presence of HIV, HBV, or HCV in source material
The source of exposure:
Infection status of person
HIV: presence of HIV antibody
HBV: presence of HbsAg
HCV: presence of HCV antibody
or other infectious disease
Stage of disease, history of antiretroviral therapy, antiretroviral resistance information, viral load, CD4+ T-cell count, liver enzymes (e.g., ALT)
If infectious status unknown, determine risk for HIV, HBV, or HCV infection.
Known sources: Consider medical diagnoses, clinical symptoms (e.g., acute syndrome suggestive of primary HIV infection), history of risk behaviors
Unknown sources: Consider likelihood of bloodborne pathogen infection among patients in the exposure setting
Susceptibility of exposed person
Hepatitis B vaccination and vaccine-response status
HIV, HBV, and HIV immune status
Details about care of exposed site: Washing of wound, flushing of mucous membranes
Details about counseling, postexposure management, and follow-up
Current medication history of exposed person and ability to swallow pills
Abbreviations: HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus.
Reprinted from Centers for Disease Control and Prevention. Updated U.S. Public Health Service Guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for post exposure prophylaxis. MMWR Morb Mortal Wkly Rep 2001;50:1.
The Occupational Exposure Report and Considerations for Determining Level of Risk
For the purposes of PEP, how does one determine whether the exposed person should be given PEP, and if so, whether the basic or expanded regimen should be given and how this should be documented? Box 141.2 contains a list of the details regarding the occupational exposure and the postexposure management, which should be noted in the exposed person’s medical record, in addition to any other local, state, or federal requirements.
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