Public Health Service Guidelines for the Management of Health-Care Worker Exposures to HIV and Recommendations for Postexposure Prophylaxis

The rationale is provided here for the postexposure management and prophylaxis recommendations given at the end of the document. Additional details concerning the risk for occupational HIV transmission to HCWs and management of occupational HIV exposures are available elsewhere.^(16-18)

Risk for Occupational Transmission of HIV to HCWs

Prospective studies of HCWs have estimated that the average risk for HIV transmission after a percutaneous exposure to HIV-infected blood is approximately 0.3% (95% confidence interval [CI]=0.2%-0.5%)⁽¹⁶⁾ and after a mucous membrane exposure is 0.09% (95% CI=0.006%-0.5%).⁽¹⁹⁾ Although episodes of HIV transmission after skin exposure have been documented,⁽²⁰⁾ the average risk for transmission by this route has not been precisely quantified because no HCWs enrolled in prospective studies have seroconverted after an isolated skin exposure. The risk for transmission is estimated to be less than the risk for mucous membrane exposures.⁽²¹⁾ The risk for transmission after exposure to fluids or tissues other than HIV-infected blood also has not been quantified.

As of June 1997, CDC has received reports of 52 U.S. HCWs with documented HIV seroconversion temporally associated with an occupational HIV exposure. An additional 114 episodes in HCWs are considered possible occupational HIV transmissions; these workers reported that their infection was occupationally acquired and no other risk for HIV infection was identified, but transmission of infection after a specific exposure was not documented.⁽²²⁾ Of the 52 documented episodes, 47 HCWs were exposed to HIV-infected blood, one to a visibly bloody body fluid, one to an unspecified fluid, and three to concentrated virus in a laboratory. Forty-five exposures were percutaneous, and five were mucocutaneous; one HCW had both a percutaneous and a mucocutaneous exposure. The route of exposure for one person exposed to concentrated virus is uncertain. Of the percutaneous exposures, the objects involved included a hollow-bore needle (41), a broken glass vial (two), a scalpel (one), and an unknown sharp object (one) (CDC, unpublished data, 1998).

Epidemiologic and laboratory studies suggest that several factors may affect the risk for HIV transmission after an occupational exposure. The one retrospective case-control study of HCWs who had percutaneous exposure to HIV found that the risk for HIV transmission was increased with exposure to a larger quantity of blood from the source patient as indicated by a) a device visibly contaminated with the patient's blood, b) a procedure that involved a needle placed directly in a vein or artery, or c) a deep injury.⁽²³⁾ (A laboratory study that demonstrated that more blood is transferred by deeper injuries and hollow-bore needles lends further support for the observed variation in risk related to blood quantity^[24]). The risk also was increased for exposure to blood from source patients with terminal illness, possibly reflecting either the higher titer of HIV in blood late in the course of AIDS or other factors (e.g., the presence of syncytia-inducing strains of HIV). It was estimated that the risk for HIV transmission from exposures that involve a larger volume of blood, particularly when the source patient's viral load is probably high, exceeds the average risk of 0.3%.⁽²³⁾

The utility of viral load measurements from a source patient as a surrogate for estimating the viral titer for assessing transmission risk is not known. Plasma viral load measurement (e.g., HIV RNA) reflects only the level of cell-free virus in the peripheral blood. This measurement does not reflect the level of cell-associated virus in the peripheral blood or the level of virus in other body compartments (e.g., lymphatic tissue). Although a lower viral load, or results that are below the limits of viral quantification, in the peripheral blood probably indicates a lower titer exposure, it does not rule out the possibility of transmission; HIV transmission from persons with a plasma viral load below the limits of viral quantification (based on the assay used at the time) has been reported in instances of mother-to-infant transmission^(25,26) and in one HCW seroconversion (J.L. Gerberding, San Francisco General Hospital, unpublished data, May 1997).

There is some evidence that host defenses also may influence the risk for HIV infection. In one small study, HIV-exposed but uninfected HCWs demonstrated an HIV-specific cytotoxic T-lymphocyte (CTL) response when peripheral blood mononuclear cells were stimulated in vitro with HIV mitogens.⁽²⁷⁾ Similar CTL responses have been observed in other populations with repeated HIV exposure without resulting infection.^(28-33) Among several possible explanations for this observation, one is that the host immune response sometimes may be able to prevent establishment of HIV infection after a percutaneous exposure; another is that the CTL response simply may be a marker for exposure.

HIV Seroconversion in HCWs

Data on the timing and clinical characteristics of seroconversion in HIV-exposed HCWs are limited by the infrequency of infection following occupational exposure, variations in postexposure testing intervals, and differences over time in the sensitivity of HIV-antibody testing methods. Among the HCWs with documented seroconversions reported to CDC for whom data are available, 81% experienced a syndrome compatible with primary HIV infection a median of 25 days after exposure (CDC, unpublished data, 1998). In a recent analysis of 51 seroconversions in HCWs, the estimated median interval from exposure to seroconversion was 46 days (mean: 65 days); an estimated 95% seroconverted within 6 months after the exposure.⁽³⁴⁾ These data suggest that the time course of HIV seroconversion in HCWs is similar to that in other persons who have acquired HIV through nonoccupational modes of transmission.⁽³⁵⁾

Three instances of delayed HIV seroconversion occurring in HCWs have been reported; in these instances, the HCWs tested negative for HIV antibodies >6 months postexposure but were seropositive within 12 months after the exposure ^(36,37) (J.L. Gerberding, San Francisco General Hospital, unpublished data, May 1997). DNA sequencing confirmed the source of infection in one instance. Two of the delayed seroconversions were associated with simultaneous exposure to hepatitis C virus (HCV)⁽³⁷⁾ (J.L. Gerberding, San Francisco General Hospital, unpublished data, May 1997). In one case, coinfection was associated with a rapidly fatal HCV disease course;⁽³⁷⁾ however, it is not known whether HCV directly influences the risk for or course of HIV infection or is a marker for other exposure-related factors.

Rationale for PEP

Considerations that influence the rationale and recommendations for PEP include the pathogenesis of HIV infection, particularly the time course of early infection; the biologic plausibility that infection can be prevented or ameliorated by using antiretroviral drugs and direct or indirect evidence of the efficacy of specific agents used for prophylaxis; and the risk/benefit of PEP to exposed HCWs. The following discussion considers each of these issues.

Role of Pathogenesis in Considering Antiretroviral Prophylaxis

Information about primary HIV infection indicates that systemic infection does not occur immediately, leaving a brief "window of opportunity" during which post-exposure antiretroviral intervention may modify viral replication. Data from studies in animal models and in vitro tissue studies suggest that dendritic cells in the mucosa and skin are the initial targets of HIV infection or capture and have an important role in initiating HIV infection of CD4+ T-cells in regional lymph nodes.⁽³⁸⁾ In a primate model of simian immunodeficiency virus (SIV) infection, infection of dendritic-like cells occurred at the site of inoculation during the first 24 hours following mucosal exposure to cell-free virus. During the subsequent 24-48 hours, migration of these cells to regional lymph nodes occurred, and virus was detectable in the peripheral blood within 5 days.⁽³⁹⁾ HIV replication is rapid (generation time: 2.5 days) and results in bursts of up to 5,000 viral particles from each replicating cell⁽⁴⁰⁾ (M.S. Saag, University of Alabama, personal communication, September 1997). The exponential increase in viral burden continues unless controlled by the immune system or other mechanisms (e.g., exhaustion of available target CD4+ T-cells). Theoretically, initiation of antiretroviral PEP soon after exposure may prevent or inhibit systemic infection by limiting the proliferation of virus in the initial target cells or lymph nodes.

Efficacy of Antiretrovirals for PEP

Studies in animals and humans provide direct and indirect evidence of the efficacy of antiretroviral drugs as agents for postexposure prophylaxis. In human studies and in most animal studies, ZDV was the antiretroviral agent used for prophylaxis.^(26,41-54) However, in more recent animal studies, newer agents also have been reported to be effective.^(55,56)

Data from animal studies have been difficult to interpret, in part because of problems identifying a comparable animal model for humans. Most studies use a higher inoculum for exposure than would be expected in needlestick injuries. Among the animal studies, differences in controlled variables (e.g., choice of viral strain [based on the animal model used], inoculum size, route of inoculation, time of prophylaxis initiation, and drug regimen) make attempts to apply these results to humans difficult. In the animal studies that showed efficacy of pre-exposure and/or postexposure prophylaxis, reported outcomes^(4,57) have included a) suppression of viremia or delayed antigenemia;^(41-47) b) drug-facilitated vaccine-type response (i.e., chemoprophylaxis sufficiently inhibited viral replication to permit formation of a long-lasting, protective cellular immune response);^(48-56) and c) definitive prevention of infection (i.e., chemoprophylactic efficacy).^(41,52-54) More recent refinements in methodology have enabled studies more relevant to humans; in particular, the viral inocula used in animal studies have been reduced to levels more analogous to human exposures.^(54,56) The results of these studies provide additional evidence of postexposure chemoprophylactic efficacy.

In studies of HIV-2 or SIV in nonhuman primates in which ZDV or 3'-fluorothymidine was used, suppression or delay of antigenemia was the most common outcome; prevention of infection was infrequent.^{(43,52,58-60)} However, two other antiretroviral agents, 2',3'-dideoxy-3'-hydroxymethyl cytidine (BEA-005) and (R)-9-(2-phosphonylmethoxypropyl) adenine (PMPA), used to study PEP in primates have been more effective in preventing infection. When PMPA was administered 48 hours before, 4 hours after, or 24 hours after intravenous SIV inoculation to long-tailed macaques, a 4-week regimen prevented infection in all treated animals.⁽⁵⁵⁾ A 3-day regimen of BEA-005 prevented SIV infection in 12 of 12 pigtailed macaques when administered 1-8 hours after intravenous inoculation; infection also was prevented in four of four animals that received 3 days of BEA-005 within 10 minutes after HIV-2 inoculation.⁽⁵⁶⁾

Animal studies have demonstrated that early initiation of PEP and small inoculum size are correlates of successful PEP. ZDV initiated 1 hour or 24 hours after intravenous exposure to a rapidly lethal variant of SIV in pigtailed macaques prevented infection in one of three animals and modified SIV disease in three of six animals, respectively; PEP initiated at 72 hours had no effect.⁽⁵⁴⁾ In macaques administered ZDV or BEA-005 1 to 72 hours after SIV intravenous challenge, earlier initiation of PEP was correlated with delayed onset and peak of antigenemia, decreased duration of antigenemia, and reduction in SIV serum titer; the most potent effect was evident when PEP was initiated within 8 hours of exposure.^(43,56) Studies in primates and murine and feline animal models have demonstrated that larger inocula decrease prophylactic efficacy.^{(47,48,53,60)} In addition, delaying initiation, shortening the duration, or decreasing the antiretroviral dose of PEP, individually or in combination, decreased prophylactic efficacy.^{(42,43,45,47,50,55)}

There is little information with which to assess the efficacy of PEP in humans. Seroconversion is infrequent after an occupational exposure to HIV-infected blood; therefore a prospective trial would need to enroll many thousands of exposed HCWs to achieve the statistical power necessary to directly demonstrate PEP efficacy. During 1987-1989, the Burroughs-Wellcome Company sponsored a prospective placebo-controlled clinical trial among HCWs to evaluate 6 weeks of ZDV prophylaxis; however, this trial was terminated prematurely because of low enrollment.⁽⁶¹⁾ Because of current indirect evidence of PEP efficacy, it is unlikely that a placebo-controlled trial in HCWs would ever be feasible.

In the retrospective case-control study of HCWs, after controlling for other risk factors for HIV transmission, the risk for HIV infection among HCWs who used ZDV as PEP was reduced by approximately 81% (95% CI=43%-94%).⁽²³⁾ In addition, in a randomized, controlled, prospective trial (AIDS Clinical Trial Group [ACTG] protocol 076) in which ZDV was administered to HIV-infected pregnant women and their infants, the administration of ZDV during pregnancy, labor, and delivery and to the infant reduced transmission by 67%.⁽³⁾ Only 9%-17% (depending on the assay used) of the protective effect of ZDV was explained by reduction of the HIV titer in the maternal blood, suggesting that ZDV prophylaxis in part involves a mechanism other than the reduction of maternal viral burden.⁽²⁶⁾

The limitations of all of these studies must be considered when reviewing evidence of PEP efficacy. The extent to which data from animal studies can be extrapolated to humans is largely unknown, and the exposure route for mother-to-infant HIV transmission is not similar to occupational exposures; therefore these findings may not reflect a similar mechanism of ZDV prophylaxis in HCWs. Although the results of the retrospective case-control study of HCWs suggest PEP efficacy, the limitations of that study include the small number of cases studied and the use of cases and controls from different cohorts.

Failure of ZDV PEP to prevent HIV infection in HCWs has been reported in at least 14 instances^(62-64) (G. Ippolito, AIDS Reference Center, Rome, Italy, and J. Heptonstall, Communicable Disease Surveillance Center, London, United Kingdom, personal communication, 1997). Although eight of the 13 source patients had taken ZDV, laboratory assessment for ZDV resistance of the virus from the source patient was performed in only three instances, two of which demonstrated reduced susceptibility to ZDV. In addition to possible exposure to a ZDV-resistant strain of HIV, other factors that may have contributed to the apparent failures in these instances may include a high titer and/or large inoculum exposure, delayed initiation and/or short duration of PEP, and possible factors related to the host (e.g., cellular immune system responsiveness) and/or to the source patient's virus (e.g., presence of syncytia-forming strains).⁽⁶²⁾

Antiretroviral Agents for PEP

Several antiretroviral agents from at least three classes of drugs are available for the treatment of HIV disease. These include the nucleoside analogue reverse transcriptase inhibitors (NRTIs), nonnuceloside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) (See Appendix). Among these drugs, ZDV (an NRTI) is the only agent shown to prevent HIV transmission in humans.^(2,3) Although there are theoretical concerns that the increased prevalence of resistance to ZDV may diminish its utility for PEP,⁽⁶⁵⁾ no data are available to assess whether this is a factor for consideration. Clinical data from the ACTG protocol 076 study documented that despite genotypic evidence of maternal ZDV resistance, ZDV prevented perinatal transmission.⁽⁶⁶⁾ Thus, based on the available information, it is still reasonable that ZDV should continue to be the first drug of choice for PEP regimens.

There are no data to directly support the addition of other antiretroviral drugs to ZDV to enhance the effectiveness of the PEP regimen. However, in HIV-infected patients, combination regimens have proved superior to monotherapy regimens in reducing HIV viral load.^(67,68) Thus, theoretically a combination of drugs with activity at different stages in the viral replication cycle (e.g., NRTIs with a PI) could offer an additive preventive effect in PEP, particularly for occupational exposures that pose an increased risk for transmission.

Determining which agents and how many agents to use or when to alter a PEP regimen is largely empiric. Guidelines for the treatment of early HIV infection recommend the use of three drugs (two NRTIs and a PI);⁽⁶⁹⁾ however, the applicability of these recommendations to PEP remains unknown. In addition, the routine use of three drugs for all occupational HIV exposures may not be needed. Although the use of a highly potent regimen can be justified for exposures that pose an increased risk for transmission, it is uncertain whether the potential additional toxicity of a third drug is justified for lower-risk exposures. For this reason, the recommendations at the end of this report provide guidance for two- and three-drug PEP regimens that are based on the level of risk for HIV transmission represented by the exposure.

NRTIs that can be considered for use with ZDV for PEP are lamivudine (3TC), didanosine (ddI), and zalcitabine, each of which has been included in recommended regimens that include ZDV.⁽⁶⁹⁾ In previous CDC recommendations, 3TC was recommended as a second agent for PEP based on greater antiretroviral activity of the ZDV/3TC combination and its activity against many ZDV-resistant HIV strains without substantially increased toxicity.⁽⁶⁾ Also, data suggest that ZDV-resistant mutations develop more slowly in patients receiving the ZDV/3TC combination than those receiving ZDV alone,⁽⁷⁰⁾ and in vitro studies indicate that the mutation associated with 3TC resistance may be associated with reversal of ZDV phenotypic resistance.⁽⁷¹⁾ No additional information has emerged to warrant altering the original recommendation of 3TC as the second agent for PEP. In addition, because ZDV and 3TC are available in a combination formulation (Combivir™, manufactured by Glaxo Wellcome, Inc., Research Triangle Park, NC), the use of 3TC may be more convenient for HCWs. However, individual clinicians may prefer other NRTIs or combinations of other antiretroviral agents based on local knowledge and experience in treating HIV infection and disease.

The addition of a PI as a third drug for PEP following high-risk exposures is based on the site of activity in the replication cycle (i.e., after viral integration has occurred) and demonstrated effectiveness in reducing viral burden. Previously, indinavir (IDV) was recommended as the PI for PEP because of its increased bioavailability when compared with saquinavir and its more favorable immediate toxicity profile compared with ritonavir.⁽⁷²⁾ In addition, requirements for dose escalation when initiating ritonavir make it less practical for use in PEP. Since the 1996 PEP recommendations were published, nelfinavir (NEL) was approved for use by FDA and is now included in regimens recommended for the treatment of primary HIV infection.⁽⁶⁹⁾ Also, FDA recently approved a soft-gel formulation of saquinavir (Fortovase™, manufactured by Hoffmann-LaRoche, Inc., Nutley, New Jersey) that has improved bioavailability relative to its hard-gel formulation (Invirase™, manufactured by Hoffmann-LaRoche, Inc.). However, the recommended dose of soft-gel saquinavir (1200 mg three times a day) is twice that of the hard-gel formulation (600 mg three times a day) and necessitates taking 18 pills a day, a factor that may influence HCW compliance if used for PEP. Based on these considerations, either IDV or NEL is recommended as first choice for inclusion in an expanded PEP regimen. If saquinavir is preferred by the prescribing physician, the soft-gel formulation (Fortovase™) should be used. Also, differences in the side effects associated with IDV and NEL, discussed below, may influence which of these agents is selected in a specific situation.

The NNRTIs (i.e., nevirapine and delavirdine) have not been included in these recommended regimens for PEP. As a class of antiretroviral agents, the NNRTIs are fast-acting and very potent, making them appealing in concept for PEP. In addition, there is some evidence of prophylactic efficacy.⁽⁷³⁾ However, concerns about side effects and the availability of alternative agents argue against routinely using this class of drugs for initial PEP, although with expert consultation, an NNRTI might be considered.

Side Effects and Toxicity of Antiretroviral Agents

An important goal of PEP is to encourage and facilitate compliance with a 4-week PEP regimen. Therefore, the toxicity profile of antiretroviral agents, including the frequency, severity, duration, and reversibility of side effects, is a relevant consideration. All of the antiretroviral agents have been associated with side effects (See Appendix). However, studies of adverse events have been reported primarily for persons with advanced disease (and longer treatment courses) and therefore may not reflect the experience of persons with less advanced disease or those who are uninfected.⁽⁷⁴⁾ Side effects associated with many of the NRTIs (e.g., ZDV or ddI) are chiefly gastro-intestinal (e.g., nausea or diarrhea), and in general the incidence of adverse effects has not been greater when these agents are used in combination.⁽⁷²⁾

All of the approved PIs may have potentially serious drug interactions when used with certain other drugs, requiring careful evaluation of concomitant medications being used by an HCW before prescribing a PI and close monitoring for toxicity when an HCW is receiving one of these drugs (See Appendix). PIs may inhibit the metabolism of nonsedating antihistamines and other hepatically metabolized drugs; NEL and ritonavir may accelerate the clearance of certain drugs, including oral contraceptives (requiring alternative or additional contraceptive measures for women taking these drugs). The use of PIs also has been associated with new onset of diabetes mellitus, hyperglycemia, diabetic ketoacidosis, and exacerbation of pre-existing diabetes mellitus.^(75-77) Nephrolithiasis has been associated with IDV use (including in HCWs using the drug for PEP);⁽⁸⁾ however, the incidence of this potential complication may be limited by drinking at least 48 oz (1.5 L) of fluid per 24-hour period (e.g., six 8 oz glasses of water throughout the day).⁽⁷²⁾ Rare cases of hemolytic anemia also have been associated with the use of IDV. NEL, saquinavir, and ritonavir have been associated with the development of diarrhea; however, this side effect usually responds to treatment with antimotility agents that can be prescribed for use, if necessary, at the time any one of these drugs is prescribed for PEP. The manufacturer's package insert should always be consulted for questions about potential drug interactions.

Among HCWs receiving ZDV PEP, usually at doses of 1,000-1,200 mg per day (i.e., higher than the currently recommended dose), 50%-75% reported one or more subjective complaints and approximately 30% discontinued the drug because of symptoms.^(7,78,79) Common symptoms included nausea, vomiting, malaise or fatigue, headache, or insomnia. Mild decreases in hemoglobin and absolute neutrophil count also were observed. All side effects were reversed when PEP was discontinued.

Preliminary information about HCWs receiving combination drugs for PEP (usually ZDV plus 3TC with or without a PI) suggests that approximately 50%-90% of HCWs report subjective side effects that caused 24%-36% to discontinue PEP.^(8-10) One study documented that combination regimens that included ZDV at a lower dose (600 mg per day) were better tolerated than high-dose ZDV used alone (1,000-1,200 mg per day).⁽¹⁰⁾ However, serious side effects, including nephrolithiasis, hepatitis, and pancytopenia, have been reported with the use of combination drugs for PEP^(9,80) (J.L. Gerberding, San Francisco General Hospital, personal communication, May 1997).

Resistance to Antiretroviral Agents

Known or suspected resistance of the source virus to antiretroviral agents, particularly to one or more agents that might be included in a PEP regimen, is a concern for those making decisions about PEP. Resistance of HIV has been reported with all available antiretroviral agents.⁽⁶⁵⁾ However, the relevance of exposure to a resistant virus is not understood. Although transmission of resistant strains has been reported,^(81-85) in the perinatal clinical trial that studied vertical HIV transmission (ACTG protocol 076), ZDV prevented perinatal transmission despite genotypic resistance of HIV to ZDV in the mother.⁽⁶⁶⁾ In addition, patients generally take more than one antiretroviral drug and, unless testing is performed, often it is difficult to know to which drug(s) resistance exists. The complexity of this issue is further compounded by the frequency of cross-resistance within drug classes.

Resistance should be suspected in source patients when there is clinical progression of disease or a persistently increasing viral load and/or a decline in CD4 T-cell count despite therapy, or a lack of virologic response to a change in therapy. Nevertheless, in this situation it is unknown whether a modification in the PEP regimen is necessary or will influence the outcome of an occupational exposure.

Antiretroviral Drugs in Pregnancy

Considerations for the use of antiretroviral drugs in pregnancy include their potential effect on the pregnant woman and on her fetus or neonate. The pharmacokinetics of antiretroviral drugs has not been completely studied in pregnant women. Some of the antiretroviral drugs are known to cross the placenta, but data for humans are not yet available for others (particularly the PIs). In addition, data are limited on the potential effects of antiretroviral drugs on the developing fetus or neonate.⁽⁸⁶⁾ Decisions on the use of specific drugs in pregnancy also are influenced by whether a drug has specific adverse effects or might further exacerbate conditions associated with pregnancy, (e.g., drugs that cause nausea may be less tolerated when superimposed on the nausea normally associated with pregnancy).

There are data on both ZDV and 3TC from clinical trials in HIV-infected pregnant women. The most extensive experience has been with the use of ZDV after 14 weeks of gestation in pregnant HIV-infected women in phase I studies and the perinatal ACTG protocol 076.^(4,87) The dose of ZDV for pregnant women is the same as that in nonpregnant persons, and ZDV appears safe and well tolerated in both women and their infants who have had a follow-up period of several years.^(88-90) Data from the Antiretroviral Pregnancy Registry have not documented an increased risk for birth defects in infants with in utero exposure to ZDV.⁽⁹¹⁾ There are limited data on use of 3TC alone or in combination with ZDV in late gestation in pregnant HIV-infected women. As with ZDV, the pharmacokinetics and dose of 3TC appear to be similar to those for nonpregnant persons. The drug appears safe during pregnancy for women and infants, although long-term safety is not known.^(92,93)

Carcinogenicity and/or mutagenicity is evident in several in vitro screening tests for ZDV and all other FDA-licensed nucleoside antiretroviral drugs. In some in vivo rodent studies, high-dose lifetime continuous ZDV exposure⁽⁹⁴⁾ or very high dose in utero ZDV exposure has been associated with the development of tumors in adult females or their offspring.^(95,96) The relevance of these animal data to humans is unknown. However, in 1997 an independent panel reviewed these data and concluded that the known benefits of ZDV in preventing perinatal transmission, where the risk for transmission without ZDV is 25%-30%, outweigh the hypothetical concerns about transplacental carcinogenesis.⁽⁹⁷⁾

No data are available regarding pharmacokinetics, safety, or tolerability of any of the PIs in pregnant women. The use of PIs in HIV-infected persons has been associated with hyperglycemia; it is unknown whether the use of these agents during pregnancy will exacerbate the risk for pregnancy-associated hyperglycemia. Therefore, close monitoring of glucose levels and careful instruction regarding symptoms related to hyperglycemia are recommended for pregnant HCWs receiving a PI for PEP. IDV is associated with infrequent side effects in adults (i.e., hyperbilirubinemia and renal stones) that could be problematic for the newborn. As the half-life of IDV in adults is short, these concerns may be relevant only if the drug is administered shortly before delivery.

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