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Nucleoside Reverse Transcriptase Inhibitors

Safety and efficacy of zidovudine in pregnant women have been established and the drug appears to be well tolerated during pregnancy. In addition to zidovudine, data are available from clinical trials in pregnant women for didanosine, lamivudine, and stavudine; data regarding use of abacavir or tenofovir disoproxil fumarate (a nucleotide reverse transcriptase inhibitor) are not available to date.

Nucleoside Reverse Transcriptase Inhibitors

Follow-up of uninfected children born to women enrolled in study PACTG 076 (from birth to a median age of 4.2 years) has not revealed any difference in growth, neurodevelopment, or immunologic status among infants born to women who received zidovudine for prevention of maternal-fetal transmission of HIV compared with those born to women who received placebo. No malignancies have been observed in short-term (up to 6 years of age) follow-up of infants from study PACTG 076 or from a prospective cohort study involving infants with in utero exposure to zidovudine, but longer-term follow-up is necessary to provide a definitive assessment of carcinogenic risk in these infants.

NRTIs are known to induce mitochondrial dysfunction (possibly as the result of interference with mitochondrial replication resulting in mitochondrial DNA depletion), and it has been suggested that adverse effects related to mitochondrial toxicity possibly may be a concern for pregnant women and for infants exposed in utero to the drugs. Nonfatal lactic acidosis has occurred in pregnant women receiving antiretroviral regimens that included didanosine and stavudine. In addition, fatal lactic acidosis has been reported in at least 3 pregnant women who received an antiretroviral regimen that included both didanosine and stavudine.

Women receiving NRTIs appear to be at increased risk of lactic acidosis and severe hepatomegaly with steatosis, and it is unclear whether pregnancy potentiates this risk. Because pregnancy itself can mimic some of the early manifestations of the lactic acidosis/hepatic steatosis syndrome or be associated with other clinically important disorders of liver metabolism, clinicians caring for HIV-infected pregnant women who are receiving NRTIs should be alert for early diagnosis of lactic acidosis and/or hepatic steatosis.

Some experts recommend that hepatic enzymes and serum electrolytes be assessed more frequently during the last trimester of pregnancy, and any new manifestations evaluated thoroughly. In addition, it is recommended that a regimen that includes both didanosine and stavudine be used with caution in pregnant women and is recommended only if the potential benefits clearly outweigh the potential risks, such as when other NRTI combinations have failed or caused unacceptable toxicity or adverse effects.

Results of one retrospective study in France revealed indications of mitochondrial dysfunction (neurologic symptoms or abnormalities, symptomatic hyperkinetic hypertrophic cardiomyopathy) in 8 infants with in utero and neonatal exposure to zidovudine (without or without lamivudine); 2 infants exposed to a regimen of zidovudine and lamivudine developed severe neurologic disease and died. However, a causal relationship between exposure to NRTIs and these effects has not been established.

Evaluation of a large database containing information on children (with or without exposure to antiretroviral agents) born to HIV-infected women in the US has not revealed any similar deaths; most exposed children had been exposed to zidovudine alone rather than zidovudine and lamivudine; studies are ongoing to determine if there is any evidence of mitochondrial dysfunction among the living children in this US database. In a study in Africa evaluating regimens of zidovudine and lamivudine for prevention of maternal-fetal transmission of HIV, there was no evidence of increased risk of neurologic effects in children exposed to the drugs. In addition, results of another study in infants born to HIV-infected women found no evidence that in utero exposure to zidovudine causes cardiac abnormalities.

This study used longitudinal assessment of 4 measures of left ventricular structure and function as measures of adverse outcomes during the first 14 months of life, and included some infants who also received zidovudine after birth. Even if an association between in utero exposure to NRTIs and mitochondrial toxicity is substantiated in the future, it appears that the development of severe or fatal mitochondrial disease in exposed infants is extremely rare and the risk of such effects compared with the known benefits of a reduction in risk of perinatal transmission of HIV to the infant should be considered.

Stavudine-containing regimens are not recommended for the initial treatment of antiretroviral-naive pregnant women because in vitro and in vivo antagonism has been demonstrated between stavudine and zidovudine. Stavudine-containing regimens may be considered in women who are unable to tolerate zidovudine. Regardless of the antepartum antiretroviral regimen used, the intrapartum component and the postpartum neonatal components of the zidovudine regimen for prevention of maternal-fetal transmission of HIV should be administered.

To monitor maternal-fetal outcomes of pregnant women who receive antiretroviral agents during their pregnancy, an antiretroviral pregnancy registry has been established, and physicians are strongly encouraged to contact the registry at 800-258-4263 or http://www.APRegistry.com to enroll such women. The registry, a collaborative project of pharmaceutical manufacturers with an advisory committee of obstetric and pediatric practitioners, is collecting observational, nonexperimental data on antiretroviral exposure during pregnancy for the purpose of assessing the potential teratogenicity of the drugs, and such data will be used to supplement animal toxicology studies and assist clinicians in weighing the potential risks and benefits of treatment for individual patients. Long-term follow-up of all infants born to women who received antiretroviral therapy during pregnancy is recommended to determine whether there are any late effects of such exposure.

Antiretrovirals for Prevention of Maternal-fetal Transmission of HIV

In the US, a 3-part zidovudine prophylaxis regimen that includes both antepartum and intrapartum zidovudine therapy in the pregnant woman and zidovudine therapy in the neonate (study PACTG 076 regimen) is recommended for all HIV-infected pregnant women to reduce the risk of maternal-fetal transmission of HIV. In other countries, zidovudine has been administered for prevention of maternal-fetal transmission of HIV in several different short-course regimens that involve initiating zidovudine therapy in the mother at 34-36 weeks of gestation or at the onset of labor (with or without zidovudine therapy in the neonate). In addition, an intrapartum and neonatal nevirapine regimen or an intrapartum and neonatal regimen of lamivudine and zidovudine has been used for prevention of maternal-fetal transmission of HIV. These short-course regimens have been well tolerated and appear to be cost-effective options for prevention of maternal-fetal transmission of HIV infection in areas with a high incidence of HIV seropositivity and limited availability of medical resources (e.g., sub-Saharan Africa) where the zidovudine study PACTG 076 regimen usually is not used. Some of these short-course regimens are acceptable alternatives for prevention of maternal-fetal transmission of HIV in the US for women in labor who have not received prior antiretroviral therapy.

Risk of Maternal-fetal Transmission of HIV

The rate of transmission of HIV infection from infected mothers (who have not received antiretroviral therapy) to their fetuses has been estimated to range from 7-65%, and appears to depend on a variety of factors, including the health status of the mother. In the US, the overall rate of maternal-fetal transmission of HIV from women who have not received antiretroviral therapy has been reported to be about 15-30%. The true incidence of perinatal HIV transmission has been difficult to establish, partly because the diagnosis of HIV infection in neonates and infants 18 months of age or younger was difficult prior to the availability of current tests and may be confounded by the presence of passively acquired maternal antibodies in the child’s serum.

Maternal-fetal transmission of HIV can occur in utero or intrapartum, or postpartum via breast-feeding. HIV has been detected in fetal tissue as early as 8-15 weeks of gestation. Based on presence or absence of HIV in cord blood or peripheral blood lymphocytes at birth, it has been estimated that HIV infection is acquired late in gestation or around the time of delivery in 50-70% of cases and earlier in the pregnancy in 30-50% of cases. HIV is distributed in milk, and postpartum transmission of HIV infection to infants can occur through breast-feeding, which is thought to be an important route of transmission in certain patient populations (e.g., in Africa, Haiti). Results of several studies in Africa indicate that the risk of HIV transmission through milk is continuous throughout the period of postpartum breast-feeding, but is greatest during the first 6 months postpartum.

Certain clinical or biologic factors in the mother appear to influence the risk of maternal-fetal HIV transmission during pregnancy or delivery. The risk of maternal-fetal transmission of HIV in untreated women is greater in those with advanced symptomatic disease, high viral load, or low CD4+ T-cell counts than in those with less advanced disease. In pregnant women who receive zidovudine, viral load and CD4+ T-cell counts also appear to affect the risk of transmission of HIV333, 334 In one study of pregnant women, plasma HIV-1 RNA levels were significantly higher in those who transmitted the infection to their infants than in those who did not, and the risk of transmission generally increased with increasing maternal viral load. Results of another study indicate that maternal plasma HIV-1 RNA levels at the time of delivery are the strongest predictor of the risk of maternal-fetal transmission of the virus. However, a threshold for viral load below which there is no risk of transmission of HIV has not been identified.

Although none of the women in these studies who had plasma HIV-1 RNA levels less than 1000 copies/mL transmitted HIV to their infants, there have been reports of maternal-fetal transmission of the virus in women with all levels of plasma HIV-1 RNA, including those with levels below the limits of detection. Therefore, use of antiretroviral prophylaxis is recommended for all pregnant women with HIV infection, regardless of antenatal plasma HIV-1 RNA levels.

Certain conditions that expose the neonate to large amounts of HIV-infected maternal blood and/or cervicovaginal secretions during labor and delivery (e.g., premature membrane rupture, abruptio placentae, invasive monitoring procedures) may increase the risk of transmission of the virus, even in women with low viral load. There is some evidence that mode of delivery (elective cesarean section, vaginal delivery) may affect the rate of perinatal HIV transmission. 193, 201, 306 Several studies done before the availability of viral load testing and multiple-drug antiretroviral therapy indicate that cesarean section performed before the onset of labor and rupture of membranes (elective or scheduled cesarean) was associated with a 55-80% decrease in perinatal HIV-1 transmission compared with other types of delivery.

Meta-analysis of observational data from 15 prospective cohort studies indicated that the rate of perinatal HIV-1 transmission in women undergoing elective cesarean delivery was significantly decreased compared with similar women having either nonelective cesarean or vaginal delivery, whether or not they received zidovudine. In an international randomized study of mode of delivery, transmission was 1.8% in women randomized to elective cesarean delivery; many of these women received zidovudine. While the magnitude of the reduction in transmission after elective cesarean section compared to vaginal delivery among women receiving zidovudine in the randomized trial was similar to that seen in untreated women, this was not statistically significant. In both these studies, nonelective cesarean delivery (performed after onset of labor and/or rupture of membranes) was not associated with a significant decrease in transmission compared with vaginal delivery.

The maternal-fetal transmission rate reported for women who have plasma HIV-1 RNA levels below the limits of detection in late pregnancy are similar to those observed in women who receive zidovudine and undergo elective cesarean section, and it is unclear whether cesarean section offers any benefit to infants of women who are receiving potent multiple-drug antiretroviral therapy and have low or undetectable maternal plasma HIV-1 RNA levels late in pregnancy.

Some clinicians suggest that it is unlikely that scheduled cesarean section would further reduce the low rate of transmission in women with undetectable viral load nor would it prevent in utero transmission. Because there is some evidence that scheduled cesarean section may reduce the risk of perinatal HIV transmission in women who are not receiving antiretroviral therapy, the Perinatal HIV Guidelines Working Group suggests that these women should be counseled regarding the benefits and risks of elective cesarean section. In addition, these clinicians suggest that HIV-infected women who are receiving antiretroviral therapy but who have plasma HIV-1 RNA levels that remain substantially greater than 1000 copies/mL at 36 weeks’ gestation also should be counseled regarding the benefits and risks of elective cesarean section.

The guidelines published by the Perinatal HIV Guidelines Working Group (available at www.hivatis.org) should be consulted for specific information on maternal risks and risk of HIV transmission associated with mode of delivery and current recommendations regarding when a scheduled cesarean section should be considered in HIV-infected women.

Results of one retrospective study of twins born to HIV-infected mothers indicate that birth order may have some effect on the rate of transmission of the infection; HIV infection was diagnosed in 50% of first-born twins delivered vaginally, 38% of first-born twins delivered by cesarean section, and 19% of second-born twins delivered by either method.

Safety and Efficacy of Zidovudine for Prevention of Maternal-fetal Transmission of HIV

Results from study PACTG 076, a double-blind, placebo-controlled study in pregnant HIV-infected women, indicate that zidovudine therapy (initiated in the mother at 14-34 weeks of gestation and in the infant within 8-12 hours of birth) substantially decreases, but does not eliminate, the risk of perinatal transmission of HIV. Analysis of interim results of this study that determined the percentage of infants who were HIV infected at 18 months of age (as estimated by the Kaplan-Meier method) indicated that the rate of perinatal transmission of HIV was 8% in those who received the zidovudine regimen compared with 23% in those who received placebo.

Nucleoside Reverse Transcriptase Inhibitors

Because study PACTG 076 only included women who had not previously received antiretroviral therapy during the pregnancy and had CD4+ T-cell counts exceeding 200/mm3, it was suggested that these results cannot be used to predict efficacy of zidovudine therapy for prevention of maternal-fetal transmission of HIV in women with CD4+ T-cell counts of 200/mm3 or less, women who have previously received antiretroviral therapy, or women who have zidovudine-resistant strains of HIV. However, there now is some evidence that use of the PACTG 076 zidovudine regimen can decrease the risk of perinatal transmission of HIV in HIV-infected women with advanced disease, CD4+ T-cell counts less than 200/mm3, and prior zidovudine therapy.

Results of a recent study in Thailand evaluating 4 different zidovudine regimens (long-long, short-long, long-short, short-short) in pregnant HIV-infected women indicates that a short-short zidovudine regimen (zidovudine given to the mother from 35 weeks’ gestation through delivery in conjunction with a 3-day neonatal zidovudine regimen) is significantly less effective than a longer regimen similar to the study PACTG 076 regimen (zidovudine given to the mother from 28 weeks’ gestation through delivery in conjunction with a 6-week neonatal zidovudine regimen). Interim analysis revealed that the overall transmission rate with the short-short regimen was 10.% compared with 4.1% for the long-long regimen and that higher rates (43. and 13.%, respectively) were reported in those who delivered before 36 weeks’ gestation.

Based on these results, the short-short regimen was discontinued. In the final stratified analysis of study results, the rate of transmission for the long-long regimen was 7.8%; the rate of transmission for the long-short regimen (zidovudine given to the mother from 35 weeks gestation through delivery in conjunction with a 3-day neonatal zidovudine regimen) was 4.8%; and the rate of transmission for the short-long regimen (zidovudine given to the mother from 35 weeks’ gestation through delivery in conjunction with a 6-week neonatal zidovudine regimen) was 8.6%.

Safety and Efficacy of Multiple-drug Regimens for Prevention of Maternal-fetal Transmission of HIV

A short-term intrapartum and neonatal regimen of zidovudine and lamivudine has been evaluated for prevention of maternal-fetal transmission of HIV in a placebo-controlled study in Africa (PETRA study). Both zidovudine and lamivudine were initiated in the mother at onset of labor and continued postpartum for 7 days and a 7-day regimen of both drugs was used in the neonates.

At 6 weeks postpartum, the rate of transmission of HIV to the infants was about 9% in those who received the 2-drug regimen compared with 15% in those who received placebo. In a subgroup of women who received the intrapartum component but did not receive the postpartum component of the regimen, the rate of transmission was similar to that seen in the placebo arm. A 2-drug regimen involving use of antepartum and intrapartum zidovudine and lamivudine in the pregnant woman and a short-term regimen of both drugs in the neonate was evaluated in an observational cohort study in France.

Zidovudine was administered to the pregnant woman and neonate (the zidovudine study PACTG 076 regimen) in conjunction with oral lamivudine (150 mg twice daily in the mother beginning at 32 weeks gestation and continued until labor and 2 mg/kg twice daily in the neonate until 6 weeks of age). The rate of maternal-fetal transmission of HIV in those receiving the 2-drug regimen was 1.6% compared with a transmission rate of 6.8% reported for historic controls who received only the zidovudine study PACTG 076 regimen.

Because there is evidence from a study in Africa (HIVNET 012) that a single 200-mg dose of nevirapine given to the mother at the onset of labor and a single 2-mg/kg nevirapine dose given to the neonate 48-72 hours after birth decreases the risk of perinatal HIV transmission by almost 50% compared with a very short regimen of zidovudine, studies are being done to determine whether adding the nevirapine regimen to a zidovudine regimen would further decrease the risk of transmission.

A study in non-breast-feeding women in Thailand is comparing efficacy of a short-course zidovudine regimen (oral zidovudine in the mother starting at 28 weeks gestation and zidovudine in the neonate for the first week of life) given with a single-dose intrapartum and neonatal nevirapine regimen with that of a short-course zidovudine regimen given with intrapartum nevirapine in the mother.

Although the study protocol initially included a treatment arm that involved use of the short-course zidovudine regimen alone, the first interim analysis indicated that the rate of HIV transmission was significantly higher in those receiving the short-course zidovudine regimen alone and this arm of the study was discontinued. A second open-label study in Africa reported a 7.1% transmission rate at 4 weeks following administration of a short-course zidovudine regimen (oral zidovudine in the mother starting at 36 weeks gestation and in the neonate for the first week of life) combined with a single-dose intrapartum and neonatal nevirapine regimen.

A study in the US, Europe, Brazil, and the Bahamas (PACTG 316) evaluated the benefits of adding the HIVNET 012 nevirapine regimen to standard antiretroviral therapy in 1506 pregnant women already receiving an antiretroviral regimen (at minimum the zidovudine study PACTG 076 regimen; 77% were receiving multiple-drug antiretroviral therapy). The women were randomized to receive the HIVNET 012 nevirapine regimen or placebo. Results indicated that the rate of HIV transmission was not significantly different between the 2 groups (1.% in those receiving placebo and 1.4% in those receiving the nevirapine regimen).

Current Recommendations for Prevention of Maternal-fetal Transmission of HIV in the US

The Perinatal HIV Guidelines Working Group of the US Centers for Disease Control and Prevention (CDC) and other clinicians recommend that all pregnant women in the US with documented HIV infection be offered the 3-part zidovudine study PACTG 076 regimen for prevention of maternal-fetal HIV transmission, regardless of the woman’s plasma HIV-1 RNA level. HIV-infected pregnant women should be informed that, while multiple-drug antiretroviral therapy may have substantial benefit for their own health, the potential benefits of the woman’s antiretroviral regimen to the fetus are unknown.

Therefore, identification of HIV-infected pregnant women before or as early as possible in the pregnancy and use of the complete 3-part zidovudine study PACTG 076 regimen is recommended regardless of whether or not the woman is receiving an antiretroviral regimen for her own health.

When the zidovudine PACTG 076 regimen is used for the prevention of maternal-fetal transmission of HIV, pregnant HIV-infected women should receive oral zidovudine in a dosage of 100 mg 5 times daily (or, alternatively, 200 mg 3 times daily or 300 mg twice daily) initiated at 14-34 weeks of pregnancy and continued until the start of labor. When labor begins, IV zidovudine therapy should be substituted and the mother should receive a 2-mg/kg loading dose of zidovudine given IV over 1 hour followed by 1 mg/kg per hour given by continuous IV infusion until the umbilical cord is clamped.

Nucleoside Reverse Transcriptase Inhibitors

The neonate should then receive oral zidovudine in a dosage of 2 mg/kg every 6 hours, initiated as soon as possible after delivery (preferably within 8-12 hours after birth) and continued through 6 weeks of age. In infants unable to receive oral therapy, IV zidovudine may be given in a dosage of 1.5 mg/kg every 6 hours administered IV over 30 minutes. Although not considered optimal, there is some evidence that initiation of zidovudine therapy in the mother even as late as 36 weeks’ gestation or after onset of labor or administration of only the postpartum neonatal component of the regimen to infants born to mothers who received no antiretroviral during pregnancy may provide some benefit.

The Perinatal HIV Guidelines Working Group of the CDC has made the following recommendations concerning use of antiretroviral agents in the US for prevention of maternal-fetal transmission of HIV in certain clinical situations:

  • HIV-infected pregnant women who have received no prior antiretroviral therapy. Standard clinical, immunologic, and virologic evaluations should be performed. A decision regarding initiation of antiretroviral therapy for the woman’s own health should be made based on the same parameters used for individuals who are not pregnant, although the known and unknown risks and benefits of such therapy during pregnancy must be considered and discussed. (See Guidelines for Use of Antiretroviral Agents: Antiretroviral Therapy during Pregnancy.) The 3-part zidovudine study ACTG 076 regimen for prevention of maternal-fetal transmission of HIV initiated after the first trimester should be recommended to the woman regardless of antenatal plasma HIV-1 RNA levels to reduce the risk for perinatal transmission of the virus. Use of a multiple-drug antiretroviral regimen in addition to the zidovudine prophylaxis regimen is recommended for HIV-infected women whose clinical, immunologic, and virologic status requires treatment or who have plasma HIV-1 RNA levels exceeding 1000 copies/mL, regardless of clinical or immunologic status. Women who are in the first trimester of pregnancy may consider delaying initiation of antiretroviral therapy until after 10-12 weeks’ gestation.
  • HIV-infected women receiving antiretroviral therapy at the time pregnancy is identified. If pregnancy is identified after the first trimester in an HIV-infected woman receiving antiretroviral therapy, therapy should be continued. If pregnancy is identified during the first trimester, the woman should be counseled regarding the benefits and potential risks of antiretroviral therapy during this period and continuation of therapy should be considered. If therapy is discontinued during the first trimester, all drugs should be stopped and reintroduced simultaneously to avoid development of resistance. If the current antiretroviral regimen does not contain zidovudine, the drug should be added or substituted for another NRTI after the first trimester of pregnancy whenever possible. Regardless of the antepartum antiretroviral regimen currently being used, the intrapartum component and postpartum neonatal component of the zidovudine regimen for prevention of maternal-fetal transmission of HIV should be administered.
  • HIV-infected pregnant women in labor who have received no prior antiretroviral therapy. Several different prophylaxis regimens involving intrapartum antiretroviral therapy in the woman and antiretroviral therapy in the neonate can be used in this situation. These regimens involve giving the mother a single 200-mg dose of oral nevirapine at the onset of labor and giving the neonate a single 2-mg/kg dose of oral nevirapine at 48 hours of age; giving the mother oral zidovudine (600 mg at onset of labor, followed by 300 mg every 3 hours until delivery) and oral lamivudine (150 mg at onset of labor, followed by 150 mg every 12 hours until delivery) and giving the neonate a 7-day regimen of oral zidovudine (4 mg/kg every 12 hours) and oral lamivudine (2 mg/kg every 12 hours); giving the mother IV zidovudine (2 mg/kg followed by 1 mg/kg given by continuous IV infusion) until delivery and giving the neonate a 6-week regimen of oral zidovudine (2 mg/kg every 6 hours); or giving the mother IV zidovudine (2 mg/kg followed by 1 mg/kg given by continuous IV infusion) until delivery and a single 200-mg dose of oral nevirapine at the onset of labor and giving the neonate a 6-week regimen of oral zidovudine (2 mg/kg every 6 hours) and a single 2-mg/kg dose of oral nevirapine at 48-72 hours of age. In the immediate postpartum period, the mother should undergo standard clinical, immunologic, and virologic evaluations and a decision regarding initiation of antiretroviral therapy for the woman’s own health should be made.
  • Infants born to HIV-infected women who received no antiretroviral therapy during pregnancy and no intrapartum zidovudine therapy. The postpartum neonatal component of the zidovudine regimen for prevention of maternal-fetal transmission of HIV should be discussed with the mother and offered for the neonate. Zidovudine should be initiated in the neonate as soon as possible after delivery (preferably within 6-12 hours after birth). In addition, some clinicians may choose to use a regimen of zidovudine in conjunction with other antiretroviral agents in the neonate, particularly if the mother is known or suspected of having zidovudine-resistant HIV; however, the efficacy of this approach for prevention of HIV transmission is unknown and appropriate dosing for such regimens are incompletely defined. The infant should undergo early diagnostic testing so that, if HIV-infected, antiretroviral treatment can be initiated as soon as possible. In the immediate postpartum period, the mother should undergo standard clinical, immunologic, and virologic evaluations and a decision regarding initiation of multiple-drug antiretroviral therapy for the woman’s own health should be made.
  • Antiretrovirals for Postexposure Prophylaxis following Occupational Exposure to HIV

Antiretroviral agents are used for HIV postexposure prophylaxis (PEP) in health-care workers and other individuals exposed occupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with a risk for transmission of the virus.

The principal means of preventing occupationally acquired HIV infection is avoidance of blood exposures through the use of safety practices and strategies outlined in the CDC universal precautions for prevention of transmission of HIV, hepatitis B virus, and other bloodborne pathogens in health-care settings.

While compliance with these and other precautions decreases the incidence of occupational exposure to HIV, accidental exposures that put health-care workers and others at risk of infection can still occur. There is direct and indirect evidence from animal and human studies that antiretroviral PEP can reduce the risk of HIV transmission and data are accumulating regarding the tolerability and adverse effects reported with use of PEP in health-care workers.

Therefore, the CDC and other clinicians currently recommend use of PEP following occupational exposures associated with a risk for HIV transmission. Decisions concerning whether or not to administer an antiretroviral regimen for prophylaxis following an occupational exposure to HIV and the most appropriate regimen to use must be made on an individual basis, taking into consideration the type of exposure and associated risk of transmission and the potential toxicity of the antiretroviral agents.

Types of Occupational Exposure to HIV and Risk of Infection

The risk of acquiring HIV following occupational exposure varies depending on the type of exposure. Exposures to HIV that may place a health-care worker at risk for infection and require consideration of the need for PEP are percutaneous injuries (e.g., needlestick, cut with a sharp object) or contact of mucous membrane or nonintact skin (e.g., when the exposed skin is chapped, abraded, or afflicted with dermatitis) with blood, tissue, or other potentially infectious body fluids. In addition to blood and body fluids contaminated with visible blood, potentially infectious body fluids include semen and vaginal secretions (these fluids have been implicated in the sexual transmission of HIV infection but have not been implicated in occupational transmission) and CSF and synovial, pleural, peritoneal, pericardial, or amniotic fluids (the risk of transmission of HIV from these fluids has not yet been determined).

The risk of HIV infection after occupational exposure to other body fluids (e.g., urine, saliva, sputum, nasal secretions, feces, vomitus, sweat, tears) is presumed to be extremely low and these fluids are not considered potentially infectious unless they contain blood. There has been at least one case of documented HIV seroconversion in an individual unintentionally bitten by a patient with advanced HIV infection who, at the time of the bite, was having a tonic-clonic (grand mal) seizure and had saliva contaminated with visible blood.

Although transmission of HIV by this route is rare, clinical evaluation must include the possibility that both the person bitten and the person who inflicted the bite were potentially exposed to HIV. While human breast milk has been implicated in perinatal transmission of HIV, occupational exposure to human breast milk has not been implicated in HIV transmission to health-care workers and does not require postexposure follow-up. Any direct contact (i.e., without barrier protection) to concentrated HIV in a research laboratory or production facility is considered an exposure that requires clinical evaluation and consideration of the need for PEP.

While the true incidence of HIV transmission following occupational exposure to HIV-positive material is unknown, the risk of transmission of the virus is greater following percutaneous exposures than following mucous membrane or skin exposures. The risk of transmission of HIV after occupational exposure to body fluids or tissues other than HIV-infected blood is unknown, but probably is considerably lower than for blood exposures.

As of June 2000, the CDC had received 56 voluntary reports of US health-care workers with documented HIV seroconversion temporally associated with an occupational exposure to HIV. In addition, there have been an additional 138 episodes in health-care workers that were considered possibly related to occupational HIV transmission, but HIV seroconversion after a specific exposure was not documented.

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