Postexposure Prophylaxis in Children and Adolescents for Nonoccupational Exposure to Human Immunodeficiency Virus

Type of Source Material

Not all body fluids from persons with HIV infection are equally infectious (Table 1). Blood and fluids contaminated with blood from persons with HIV infection should be assumed to contain HIV and are associated with the highest risk of HIV transmission. Semen or vaginal secretions, cerebrospinal fluid, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid, amniotic fluid, human milk, and unfixed tissue from persons with HIV infection also may contain HIV and should be considered infectious. However, exposure to these “other potentially infectious materials”¹ is associated with a lower risk of HIV transmission. Blood-free saliva, urine, feces (including diarrhea), and vomitus are highly unlikely to transmit HIV.

Volume of Source Material

Exposure to a large volume of infectious material carries a greater risk of HIV transmission than does exposure to a smaller volume. For example, in studies of health care professionals with percutaneous exposure to blood from persons with HIV infection (Table 2),⁴ injuries with large-gauge, hollow-bore needles were 14 times as likely to result in HIV transmission as were injuries with smaller-gauge, hollow needles; solid suture needles; or solid objects (such as a scalpel; Table 2).⁴ Risk is also greater after exposure to a needle on which blood is visible, compared with that after exposure to a needle on which blood is not visible.⁴

Concentration of Virus in Source Material

In addition to the volume of source material, the concentration of virus in the source material is an important factor in determining the risk of transmission after an exposure. The concentration of virus in blood is highest during early (primary) HIV infection, before the infected person has fully developed an immune response, and late in infection, when immunity wanes. Some persons with HIV infection have persistently high viral load. Percutaneous exposure to blood from a person with late-stage HIV infection increases transmission risk by more than fivefold (Table 2).⁴ For persons 15 to 24 years of age, for each act of heterosexual intercourse, risk of HIV transmission varies from 0.01% at viral loads less than 1700 copies/mL to 0.3% at viral loads more than 38 500 copies/mL.⁵ Risk of perinatal transmission is higher for mothers with late-stage HIV disease. Prenatal maternal HIV viral load is a critical factor in determining the risk of perinatal HIV transmission.^6,7 Treatment with antiretroviral drugs can decrease the concentration of virus in blood and body fluids, even in persons with primary or late-stage infection. Therefore, antiretroviral treatment of the HIV infected individual may be associated with decreased risk of sexual and perinatal HIV transmission. However, although antiretroviral therapy for an HIV-infected source patient may decrease viral load, transmission has occurred after exposure to blood or infectious body fluids from HIV-infected persons with plasma viral loads below the level of detection, perhaps from cell-associated virus. Although there is a correlation between plasma and genital viral load, HIV may be present in genital secretions even when undetectable in plasma.⁸

Viability of Virus in Source Material

The viability of virus in the source material also is an important consideration when evaluating the significance of a potential exposure to HIV, especially in the setting of a puncture wound from a needle found in the community setting.⁹ In most reports of HIV transmission by percutaneous injury, needlestick injury occurred shortly after needle withdrawal from the vein or artery of the source patient with HIV infection. HIV RNA was detected in only 3 (3.8%) of 80 discarded disposable syringes that had been used by health care professionals for intramuscular or subcutaneous injection of patients with HIV infection,¹⁰ indicating that most syringes will not contain HIV even after being used to draw blood from a person with HIV infection. HIV is susceptible to drying, and when HIV is placed on a surface exposed to air, the 50% tissue culture infective dose decreases by ∼6 logs in 72 hours (1 log every 9 hours).¹¹ The concentration of viable virus on a discarded needle will be related to the initial virus concentration and the time that contaminated material has been drying.¹² Such drying may not occur uniformly; if there are cells, tissue, or a blood clot inside the needle, drying and virus inactivation may be slower than for a thin uniform layer of fluid on the outside of a needle, and in the laboratory setting, HIV has been shown to survive for up to 28 days in syringes containing as little as 20 μL of blood.¹³ HIV survival may be less likely outside the laboratory, and HIV proviral DNA could not be found in 28 syringes discarded in public places and 10 syringes from a needle exchange program for injection drug users.¹⁴ Two small studies have found no evidence of HIV transmission after injuries from needles of discarded syringes.^15,16 There have been no confirmed reports of HIV acquisition from percutaneous injury by a needle found in the community (M.G. Fowler, Epidemiology Branch, Division of HIV/AIDS, Centers for Disease Control and Prevention [CDC], personal communication, June 15, 2002).

Type of Contact

The type of contact between the infectious fluid and a susceptible person is an important determinant of the risk of HIV transmission (Table 3). Blood transfusion from an HIV-infected donor carries a 95% risk of HIV transmission.¹⁷ The risk of perinatal HIV transmission is between 13% and 45% in the absence of prophylaxis with antiretroviral medications.^18,19

The risk of HIV transmission from breastfeeding is associated with maternal stage of infection and duration of breastfeeding. For women who acquire HIV infection after giving birth, the transmission risk from breastfeeding is estimated to be 29% (95% confidence interval [CI], 16%–42%).²⁰ For women with chronic HIV infection, transmission risk from breastfeeding is estimated to be 10% to 16%.^20–23 The cumulative risk of transmission if breastfeeding for 5, 11, 17, and 23 months was 3.5%, 7.0%, 8.9%, and 10.3%.²¹ Using these estimates of cumulative risk and assuming that a mother breastfeeds 6 to 10 times per day, the per-episode risk of HIV transmission from a single exposure to human milk is estimated at ∼0.001% to 0.004% (Table 3). There are no reports of HIV transmission from a single episode of exposure to HIV-infected human milk in an individual handling human milk in a nursery or in an infant with a single enteral exposure to milk from a woman with HIV infection.²⁴

Sharp percutaneous exposure (needlestick, scalpel) to blood infected with HIV is associated with a much lower risk of transmission than that for perinatal or blood transfusion exposure. Prospective evaluation of 6202 health care professionals after percutaneous exposure to HIV-infected blood identified seroconversion in 20 persons, with an overall risk estimate of 0.32% (95% CI, 0.20%–0.50%).^4,25,26 Needle sharing in the context of injection drug use is estimated to have a transmission probability of 0.67% per injection (Table 3).²⁷

The risk of HIV transmission from sexual exposure is highest with unprotected receptive anal intercourse (0.5%–3.2%), intermediate with receptive vaginal intercourse (0.05%–0.15%), and lowest for insertive vaginal intercourse (0.03%–0.09%; Table 3).^28–33 The per-act risk of HIV transmission from oral sex is not known, although HIV rarely has been transmitted from orogenital sexual exposure.^34–39 The risk of sexual transmission of HIV is potentially modified by a variety of factors related to the type of sexual act and to biological variables in each partner (Table 4).^29,40 These factors may be important for younger children in the context of a single episode of sexual abuse and for adolescents who may have repeated sexual encounters that may put them at risk of HIV infection.

Transmission of HIV by human bites has been described,^41–44 although such transmission seems to be extremely rare, even when saliva is contaminated with the biter’s blood,²⁴ on the basis of the following observations:⁴⁵

• Saliva inhibits HIV infectivity.⁴⁶

• HIV is rarely isolated from saliva.⁴⁷

• Concentrations of HIV are low in the saliva of HIV-infected persons, even in the presence of periodontal disease.⁴⁸

• None of the approximately 500 000 cases of acquired immunodeficiency syndrome (AIDS) reported to the CDC by 1997 have been attributed to exposure to saliva.

• Transmission of HIV has not been documented in studies of nonsexual household exposure,⁴⁹ although unconfirmed transmission has been reported.⁵⁰

Risk of HIV transmission after mucous membrane exposure is low, probably near 0.1% or less.^51,52 Transmission has occurred after contact between blood and nonintact skin (eczema, abrasions, etc), but infectious blood in contact with intact skin has not been reported to result in HIV transmission and is not considered an exposure with risk of transmission.¹

Animal Models of PEP

Animal models of PEP suggest that antiretroviral therapy initiated after virus inoculation can prevent or ameliorate infection when drugs of adequate potency are administered immediately⁵⁷ or within a few hours of exposure^58–60 and continued for a few days⁶¹ to weeks.^62,63 PEP was most effective if begun immediately or within 24 hours⁶⁴ to 36 hours⁶⁵ and was less⁶⁵ or not⁶⁶ beneficial if begun after 72 hours. Animals developing HIV infection despite receiving PEP may have evidence of infection delayed for up to 16 weeks after virus inoculation.⁶⁵ However, even potent therapy may not be able to prevent transmission if the virus inoculum is high.^63,67,68

In animal models of PEP, antiretroviral drugs are most efficacious when continued for 28 days, compared with shorter durations.⁶⁴ This suggests that “prophylactic” therapy is not always truly preventing transmission but rather may be modifying the course of primary infection,^69,70 allowing the host to eliminate HIV early in infection. The development of a cellular immune response in HIV-exposed but ultimately uninfected animals^71–73 and humans^74–76 lends further support to this concept. If these regimens for prophylaxis are truly acting to abort early mucosal, submucosal, or subcutaneous infection, then antiretroviral regimens chosen for prophylaxis should be similar to those that have been shown to be effective for treatment of established HIV infection.

Prevention of Perinatal HIV Transmission as a Model of PEP

Single-drug preexposure plus postexposure antiretroviral therapy can decrease perinatal HIV transmission. In a randomized, placebo-controlled trial in 477 nonbreastfeeding women in the United States and Europe, zidovudine (ZDV [formerly called azidothymidine or AZT]) was administered to women during pregnancy and labor and to their infants for 6 weeks after birth. The rate of perinatal transmission of HIV was decreased by 67%, from 25.5% in the placebo group to 8.3% in the treatment group.⁷⁷ In a placebo-controlled trial in 626 breastfeeding women in Uganda, a single dose of nevirapine given to pregnant women at labor onset followed by a single dose to the infant after birth was compared with a very short course of ZDV. At 14 to 16 weeks of age, HIV infection was present in 25.1% of the nevirapine group, compared with 13.1% of the ZDV group, a 47% decrease in the rate of perinatal HIV transmission.⁷⁸

Prenatal use of combinations of antiretroviral agents may further decrease perinatal HIV transmission, compared with use of single-agent therapy. In a randomized, placebo-controlled trial in 1797 pregnant women with HIV infection in southern Africa, the rate of perinatal HIV transmission was decreased by 63%, from 15.3% in placebo-treated patients to 5.7% in women treated with the combination of ZDV plus lamivudine during pregnancy and labor and continued through 7 days after birth in women and their infants.⁷⁹ In an observational cohort study of 1542 pregnant women with HIV infection in the United States who delivered infants from 1990 to 2000, the rate of perinatal HIV transmission was 20.0% for women who received no antiretroviral therapy during pregnancy, 10.4% for those who received ZDV alone, 3.8% for women treated with 2-drug combination therapy, and 1.2% for women who received combination therapy that included protease inhibitors (PIs [highly active antiretroviral therapy]) during pregnancy.⁸⁰

Treating infants of HIV-infected women with ZDV exclusively, starting within 12 to 24 hours after birth and continued for 6 weeks, was associated with a decrease in the rate of perinatal HIV transmission in an observational study in New York.^81,82 However, observational data from North Carolina did not confirm the effectiveness of only postexposure treatment in preventing perinatal HIV transmission.^83,84 This suggests that combined pre- and postexposure therapy may more effectively prevent perinatal HIV transmission, at least when a single agent is used.

PEP: Potential for Failure

Although postexposure ZDV treatment of HIV-exposed health care professionals was associated with an 81% lower risk of HIV transmission in an analysis of observational data (Table 2),⁴ failures have occurred.⁸⁵ Such failures may result from large inoculum size,⁸⁶ late institution of therapy or failure to take prescribed therapy,⁸⁷ transmission of ZDV-resistant virus,^88,89 or other as yet unidentified factors.²

Although the feasibility of prophylaxis after nonoccupational exposure to HIV has been demonstrated,⁹⁰ there are no data measuring the efficacy or effectiveness of PEP in the nonoccupational setting, although this therapy is being offered in various communities.⁹¹ Failures of such prophylaxis have been reported,⁹² as have apparent successes.⁵⁴ The theoretic concern that offering PEP to sexually active persons would increase risk-taking behavior has not been identified in practice.⁹³ However, the cost of prophylaxis after nonoccupational exposures is high,⁹⁴ and adverse effects are relatively common⁹⁵ and can rarely be fatal.^2,96

General Considerations Regarding Recommendations for Prophylaxis

In evaluating the need for PEP, the following factors should be considered: the duration of time that has passed since the potential exposure, the likelihood of HIV infection in the exposure source, the risk of transmission given the source material and type of exposure, the effectiveness of therapy at modifying that risk, the toxicity of the therapy, and the burden of adherence to antiretroviral therapy.

Because PEP is only recommended for exposures to material from persons with HIV infection, efforts should be made to learn the infection status of the exposure source. If the HIV infection status of the exposure source is unknown, HIV testing should be requested of the person who is the source of the exposure, with consent as required by local laws or regulations. Although awaiting results of testing of the exposure source, PEP may be started for the potentially exposed person and stopped if the exposure source is found not to be infected with HIV.

According to USPHS recommendations for PEP in the nonoccupational setting,³ PEP should not be used for persons with HIV exposures that have a low risk of HIV transmission (eg, potentially infected body fluid on intact skin) or for persons who seek care too late for the anticipated interruption of transmission (more than 72 hours after reported exposure). Clinicians considering use of PEP after a nonoccupational HIV exposure should recognize that benefits likely would be restricted to situations in which the risk of transmission is high, the intervention can be initiated promptly, and adherence to the regimen is likely. If PEP is used, physicians experienced in the management of children and adolescents with HIV infection should be consulted.⁹⁷ Because PEP needs to be started within 72 hours of exposure, often the most feasible approach is to start PEP with a 3-day supply of medications and refer the patient to be evaluated by a consultant within 72 hours.

Recommendations for PEP in children and adolescents vary and include: 1) no PEP; 2) consider PEP; and 3) recommend PEP. Because of the absence of data documenting safety and efficacy of PEP, clinicians may make different, reasonable decisions in similar clinical circumstances. In individual cases of potential exposure, the perceived risks of HIV acquisition may be great enough to justify the burden and potential toxicity of PEP. The final decision to undertake PEP in a specific patient depends on the clinician’s recommendation and the exposed person’s and/or parent’s evaluation of the risk of transmission versus the toxicity of therapy.

If an exposure is serious enough to warrant PEP, 2-drug or 3-drug therapy can be chosen, balancing the theoretically improved efficacy of 3 drugs with the potentially lower toxicity of 2-drug regimens. The USPHS identifies the strength of their recommendations for PEP in the occupational setting by the number of drugs in the regimen.^1,97 The recommendations in this clinical report separate the decision to start PEP from the decision about the number of drugs to include in the regimen. CDC guidelines suggest that determining which agents and how many agents to use is largely empiric.¹ Complete recommendations from the CDC⁹⁷ are available online (www.hivpepregistry.org/pdf/pedipep.pdf). American Academy of Pediatrics recommendations follow.

Prophylaxis with ZDV alone or in combination with other drugs was associated with at least 1 adverse effect in 49% of 674 health care professionals treated after occupational exposure to HIV, and 20% stopped prophylaxis prematurely because of adverse effects.⁹⁸ Adverse effects can be severe, including potentially fatal lactic acidosis and hepatitis from mitochondrial toxicity of nucleoside analog reverse transcriptase inhibitors (NRTIs)⁹⁹ and fatal hypersensitivity reactions from nevirapine.⁹⁶ Concern about adverse effects may contribute to low initiation rates for PEP,¹⁰⁰ and difficulty in adhering to complex drug regimens may lead to premature cessation of PEP.¹⁰¹

HIV antibody testing of the exposed person is recommended at baseline and at 6 weeks, 12 weeks, and 6 months after exposure. Such diagnostic testing will identify most persons who develop HIV infection after an exposure, although a small fraction of infected persons may not develop detectable antibody until more than 6 months after exposure.^102,103 Delay in HIV seroconversion may be more common if hepatitis C virus transmission occurs at the same time as HIV transmission.

Recommendation for Prophylaxis After Nonoccupational Exposure to HIV in Children and Adolescents

The risk of HIV transmission after an exposure varies by the type and severity of exposure (Tables 1–4) and by the likelihood that the source is infected with HIV (Table 5). Evaluation of both factors allows for estimation of the risk of HIV transmission after a potential exposure (Table 6). For an exposure to a person known to be infected with HIV, the baseline risk of transmission will be modified by the viral load in the exposure fluid.⁵ For an exposure to a person of unknown HIV infection status, the baseline risk of HIV transmission will be modified by the probability that the exposure source is infected with HIV (Table 5).

Once the risk of HIV transmission has been estimated, a decision whether to recommend PEP needs to be made. In the absence of specific data on efficacy of PEP outside of the health care setting, this decision is best made by experienced clinicians in collaboration with the exposed person and/or parents after a careful discussion of the risks of transmission and the burden and potential complications of antiretroviral therapy. The risk of transmission and potential benefits of PEP vary for different clinical situations, as outlined in Tables 6 through 8⇑⇓⇓ and Fig 1.

• Download figure
• Open in new tab
• Download powerpoint

Fig 1.

Possible exposure to HIV in children and adolescents: algorithm for decision-making for use of PEP.

Although PEP may be considered in many circumstances, it is only recommended for high-risk exposures to persons known to be infected with HIV (Table 8). No PEP is given if the exposure occurred more than72 hours previously, if the exposed person refuses PEP, or if the exposed person is unwilling or unable to commit to 28 days of therapy and appropriate follow-up (Table 7).

A careful discussion of the risks and benefits of therapy guides the decision-making regarding PEP and allows appropriate postexposure care (Table 9). If PEP is begun, it should be started as soon as possible after the exposure (within hours, and definitely within 72 hours), and therapy should be continued for 28 days. If consultation with a clinician experienced in the care of children and adolescents with HIV is not immediately possible, a supply of medications sufficient to last until consultation occurs could be dispensed to the patient.

Sexual Exposure

Sexual exposure can result in HIV infection (Tables 3 and 4), and sexual abuse has resulted in HIV transmission to children. Of 9136 children with HIV infection or AIDS reported to the CDC from 1981 through 1997, 26 were sexually abused, with confirmed HIV exposure in 17 and suspected HIV exposure in 9.¹⁰⁴ Of the 17 children with confirmed HIV exposure, 14 had no other risk of HIV infection, and 3 had multiple risk factors. Sexual abuse may be more likely to result in HIV transmission in girls than in women because of thin vaginal epithelium in children and cervical ectopy in adolescents and because children may be repeatedly abused by the same person over a long period.²⁴ In proven cases of sexual assault by a person known or suspected to have HIV infection, PEP may be considered up to 72 hours after the exposure but is likely to be most effective if given sooner, preferably within a few hours after exposure.^105–107 If the exposure source has genital ulcer disease or another sexually transmitted disease or if the exposure included tissue damage, the risk of HIV transmission is greater (Tables 3 and 4), increasing the potential benefit of PEP relative to the burden of therapy and risks of drug toxicity. Such modifying factors might strengthen the force of the recommendation in a given clinical setting.

For adolescents with a history of a single sexual exposure, PEP can be considered, and if given should be started as soon as possible after the exposure but certainly within 72 hours.^108,109 Such exposure might occur from sexual abuse or by accidental exposure in a consensual relationship (eg, a broken condom). For persons with ongoing consensual sexual exposure to HIV, PEP is not indicated, and behavioral interventions to decrease repeated exposure probably are more appropriate.^110,111

Percutaneous Exposures

Risk of HIV transmission from a puncture wound from a needle found in the community is significantly lower than the 0.3% HIV transmission risk after needlestick injury in a health care professional from a person with HIV infection. Although it is unlikely that a true estimate of risk can be established, transmission will be related to:

• The probability that the person who used the needle has HIV infection (Table 5);

• The time interval since the needle was in contact with blood of the source;

• The initial concentration of HIV on the needle, presence of blood or tissue that might delay drying (and, therefore, killing of the virus), or the presence of fresh blood or material that might contain viable virus; and

• The severity of the injury (skin contact without skin breakage, abrasion without bleeding, deeper skin penetration) in the exposed individual.

In evaluating a puncture wound, the following factors are considered in assessing potential for HIV transmission (presented as lower risk category followed by higher risk category for each attribute): the depth of the wound (superficial scratch or deep puncture); the presence of blood on the needle (no visible blood or visible blood); the characteristics of the blood on the needle (dried or fresh); the type of needle (solid or hollow bore); and the location the needle was used in the source patient’s body (not in artery or vein; or in artery or vein).

The risk of HIV transmission from a discarded needle in public places (often referred to as a “found” needle) seems to be low. Because data are not available on the efficacy of PEP in this circumstance for adults or children, the USPHS is unable to recommend for or against PEP in this circumstance. Furthermore, PEP is not without risk and often is associated with significant adverse effects. Therefore, PEP is not routinely recommended in this situation. However, if the needle and/or syringe are found to have visible blood and the source is known to be HIV infected, some experts recommend that PEP be considered. Testing the syringe for HIV is not practical or reliable and is not recommended.

Bite wounds are another percutaneous body fluid exposure that may occur in children, but the risk of HIV transmission after exposure to saliva is very low. In the absence of blood in saliva and blood in the bite wound, PEP is not indicated. However, if there is blood exchange from a bite, both the person bitten and the person biting should be considered at risk of transmission of HIV and considered for PEP. Use in this setting would be extremely unusual and is potentially indicated only when there is significant exposure to deep, bloody wounds in persons with HIV infection.

Adolescents may be percutaneously exposed to potentially infectious fluids by needle sharing for injection drug use (including anabolic steroids) or for body piercing. The per-contact probabilities of HIV transmission in Table 3 apply in this setting, and for a single percutaneous exposure to blood of a person at risk for or known to have HIV infection, PEP can be considered. For adolescents with ongoing needle sharing and potential exposure to HIV, PEP is not routinely recommended, and behavioral interventions to decrease repeated exposures are more appropriate than is postexposure drug therapy after a single episode.^110,111

Human Milk Exposures

Because HIV can be transmitted via human milk, even a single exposure to human milk should be considered to confer a potential (albeit very low) risk of HIV transmission (Table 3). Such exposure is possible in a hospital if stored, unpasteurized human milk is given to the wrong infant or if an infant is accidentally breastfed by a woman with HIV infection who is not the child’s mother. Exposure also could occur if a mother developed HIV infection while breastfeeding or if a breastfeeding mother with established HIV infection was not tested for HIV in the prenatal period. However, in most areas of the United States, the prevalence of HIV infection in pregnant women is less than 2 per 1000.¹¹² Most breastfeeding women will have been tested for HIV during pregnancy,^113,114 and women known to be HIV infected will have been counseled not to breastfeed.¹¹⁵ Therefore, the actual likelihood that exposure to HIV would occur by this route is extremely low.

For women with known HIV infection, the best approach to preventing transmission is to avoid breastfeeding. For a woman who continues to breastfeed, potent antiretroviral therapy for herself may decrease viral load and decrease risk of transmission, but prolonged therapy for the mother or the infant so exposed is of unknown benefit. For an infant with a single exposure to human milk from a woman with HIV infection, the magnitude of risk is estimated to be approximately 100 times lower than that for other mucous membrane exposures (Table 3), and PEP is likely not warranted (Tables 6–8).

Choice of Antiretroviral Medications for PEP

No clinical studies are available to determine the best antiretroviral regimen for PEP. The most extensive data in terms of potential efficacy and safety are for ZDV monotherapy.^4,81 A clinician with experience in treatment of persons with HIV infection should be consulted before starting PEP.

Many clinicians would use the 3-drug combination of ZDV, lamivudine, and nelfinavir for PEP in children and adolescents (doses in Table 10).¹¹⁶ If the efficacy of PEP is in aborting early mucosal, submucosal, subcutaneous, or lymphatic HIV infection, then potent suppressive therapies, such as 2 NRTIs plus a PI, should be chosen, because such regimens have been shown to be more likely to suppress HIV replication than have monotherapy or dual therapy.

Taking the multiple medications required for PEP is a daunting task, and problems with drug toxicity (Table 11), patient adherence, and other factors severely limit the proportion of patients who finish PEP once they have started it.^{107,117–119} Completing 28 days of a 2-drug regimen is easier than completing a 3-drug regimen and may be associated with fewer medication adverse effects. Although the burden and toxicity of a 3-drug regimen may be warranted for treatment of persons with established HIV infection, the risk-benefit ratio for PEP may favor a 2-drug regimen for some patients. Therefore, some clinicians recommend 2-drug combinations of ZDV and lamivudine for PEP, hoping that the improved ease of use and potential decrease in toxicity will balance out the theoretic decrease in efficacy. It may be reasonable to consider a 2-drug regimen for treatment of some patients. The effectiveness of a drug regimen in practice will be related to the efficacy of the drugs and the probability of completion of the course of therapy.

ZDV and lamivudine are each available as syrups and are available together in a single tablet (Combivir [GlaxoSmithKline, London, United Kingdom]), enhancing ease of use for adolescents (doses in Table 10). If current and/or previous therapy used by the source patient is known and drug resistance is a concern, alternatives to the standard regimen might be considered in consultation with a specialist in HIV care in children and adolescents. Stavudine or didanosine are reasonable alternative NRTIs for use if resistance to ZDV or lamivudine is suspected. ZDV and stavudine should never be used in combination with one another because of intracellular antagonism. Because of the potential for a severe hypersensitivity reaction, the NRTI abacavir sulfate should be avoided in PEP regimens.

Nelfinavir is available as a powder for children who are unable to take pills, although some children prefer the crushed tablets to the powder. Indinavir is only available in capsule form, is associated with crystalluria and nephrolithiasis, and requires extra hydration and for these reasons is usually avoided for PEP in children and adolescents. Other PIs available in a liquid formulation appropriate for children include ritonavir, lopinavir/ritonavir (Kaletra [Abbott Laboratories, North Chicago, IL]), and amprenavir. However, gastrointestinal intolerance may be a problem with ritonavir and lopinavir/ritonavir. The liquid formulation of amprenavir has high levels of vitamin E, contains propylene glycol in a concentration that exceeds World Health Organization standards for use in infants, and should not be used in children under 4 years; therefore, it is not recommended for routine use in PEP regimens. PIs have multiple potential interactions with other drugs, and the package insert should always be consulted before prescribing any of these medications.

Nevirapine is a non-NRTI that has been shown to decrease mother-to-child transmission in a single-dose intrapartum and infant regimen.⁷⁸ The single-dose regimen has been shown to be safe for mothers and infants.¹²⁰ However, severe life-threatening cases of hepatotoxicity, including liver failure and death, have been reported in patients receiving nevirapine as part of a PEP regimen or as treatment of HIV infection. Therefore, nevirapine should not be used as part of a PEP regimen in children.^96,121

All antiretroviral agents have potential adverse effects (Table 11). It is critical to review the drug regimen, assess adherence, and evaluate the child for any symptoms of drug toxicity at all follow-up visits.

Implementation and Follow-up

The HIV infection status of the exposure source should be sought. If the source person is known but HIV status unknown, then HIV testing with appropriate counseling and consent should be requested.

Wounds should be washed completely with soap and water. Mucous membranes should be flushed with water or saline solution. Tetanus booster and other wound care should be provided as needed (Table 9).

A discussion of risks and benefits of PEP with the family of an exposed toddler will differ from the discussion with a potentially exposed adolescent, whose family may be specifically excluded from knowledge of the whole event. Treating adolescents in this setting should follow state and local laws regarding confidentiality of medical care. Because of the need to begin prophylaxis as quickly as possible after an exposure, office or clinic staff should be instructed to act immediately on telephone calls concerning possible HIV exposure, and the clinician should not wait until the end of the clinic day to return a call. Such staff education might be incorporated into OSHA-mandated bloodborne pathogen training.

Emergency departments should have protocols concerning possible need for postexposure HIV prophylaxis, and a “starter kit” of 3 days of antiretroviral medicines should be available at all times to ensure immediate institution of PEP therapy. Careful follow-up is crucial to ensure that the rest of the medications can be obtained easily and that consultation with a specialist in pediatric and adolescent HIV care occurs, to monitor toxicity, and to provide support for medication adherence and psychologic stress.

Initial follow-up of the exposed child is recommended within 2 to 3 days to review drug regimen, assess adherence, evaluate for any symptoms of toxicity, assess psychosocial status of the child and family, and arrange appropriate referrals if needed. To support patient adherence to medications, visits to the clinician’s office or clinic or patient-clinician telephone calls should occur at weekly intervals.

Laboratory testing for drug toxicity should be performed at baseline and 2 weeks (optional) and 4 weeks after starting therapy, and at a minimum should include complete blood cell count and alanine transaminase concentration. Persons treated with indinavir should be monitored for hematuria because of the risk of nephrolithiasis. Careful attention needs to be paid to complaints of abdominal pain, which might prompt evaluation for pancreatitis.

Monitoring for seroconversion to HIV includes testing for HIV by enzyme immunoassay, indicated at baseline and 6 weeks, 12 weeks, and 6 months after exposure. For patients coinfected with hepatitis C virus, HIV enzyme immunoassay should also be performed 12 months after the potential exposure. Testing for hepatitis B and hepatitis C should be performed as appropriate, following standard guidelines.¹²²

In a significant exposure, the person at risk of HIV acquisition also becomes a potential source of HIV transmission to others. This needs to be discussed, and methods of preventing possible secondary transmission of HIV should be outlined, including abstinence or use of condoms for sexually active adolescents.

The potential for acquisition of HIV infection can lead to psychologic stress, which may require intensive counseling during the immediate postexposure period and until follow-up testing is negative 6 months after the exposure.

If local experts in the use of antiretroviral agents in children are unavailable for consultation, the University of California-San Francisco has a hot line (1–888-HIV-4911) that is supported by the CDC and the Health Resources and Services Administration and is staffed 24 hours a day to help clinicians through the decision pathways and to provide information on choice of therapy.

In selected instances of possible HIV exposure, legal or administrative issues may be raised, and careful documentation is important. For exposures in the hospital setting, hospital administrative policies should be consulted. For adolescents, support from family or friends might be encouraged, but the adolescent’s right to privacy should be respected.

Reporting of Exposures and Therapy

Exposures that are considered for PEP should be reported to the nonoccupational HIV PEP registry, which is run by the John Snow Institute under the auspices of the CDC. The registry can be accessed online (www.hivpepregistry.org), by telephone (1–877-HIV-1PEP), or by fax (1–877-HIV-7PEP).