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Human immunodeficiency virus infections in pregnancy
GYNECOLOGY & OBSTETRICS International
Journal
of Gynecology
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ACOG educational bulletin
Human immunodeficiency
virus infections in pregnancy
Number 232, January 1997
This Educational Bulletin was developed under the direction of the Committeeon Educational Bulletins of the American College of Obstetriciansand Gynecologists as an aid to obstetricians and gynecologists. The College wishes to thank Howard L Minkoff, MD, for his assistancein the development of this bulletin. This document is not to be construedas establishinga standard of practice or dictating an exclusiie course of treatment. Bather, it is intended as an educationaltool that presentscurrent information on obstetric-gynecologic issues.
By mid- 1995,morethan half a million personsin the United Stateshad been reported ashaving acquired immunodeficiency syndrome(AIDS), of whom approximately 14% were women (1). For each patient with AIDS, there are many more patientsinfected with humanimmunodeficiency virus (HIV), the precursorto AIDS. In 1994,HIV infection wasthe third leadingcauseof death amongwomen 25-44 years old and the fifth leading causeof death in girls l-4 years old (2). The prevalenceof HIV infection in women giving birth in the United Statesin 1993 was about 1.6/1,000 (3). Ninety percent of HIV infections in children worldwide have beenthe result of perinatal transmission, and virtually all new casesin children are from perinatal transmission (4). Basedon a 25% perinataltransmissionrate, an estimated1,620 infected infants were born in the United Statesin 1993(3). Epidemiologic patternsshowbroad geographicdistribution of infection, and 85% of casesin adult women are among those aged 15 to 44 years old (5). Thus, obstetrician-gynecologistsare increasingly involved in caring for womenwith HIV (6). Obstetrician-gynecologistsshouldbe preparedto counsel patientsandrecommendtesting for the virus to all women who are pregnant or are seekingprepregnancycounseling.Zidovudine ([ZDV] formerly called azidothymidine, or AZT) therapy shouldbe recommendedto infected pregnant patientsto reducethe rate of perinatal transmission(7).
Pathophysiology Human immunodeficiency virus is a retrovirus. When infection occurs, the virus is incorporated into the host genome. Cells with the CD4+ antigen, particularly helperlymphocytes, arepreferentially infected. The virus can also infect macrophages,cells of the central nervoussystem,and possibly cells in the placenta (8). Infection with HIV leadsto progressivedebilitation of the immune system,rendering a patient susceptibleto opportunistic infections and neoplasmsthat rarely affect immunocompetentpatients. At the time of initial infection, the personmay be asymptomatic or may develop an acute syndrome similar to mononucleosiswith accompanying asepticmeningitis. Antibodies may be detected in most adults 6-12 weeks
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after exposure, but rarely, the latent period (“window phase”) before antibodies are detectable is longer (9, 10). After seroconversion, an asymptomatic period of variable length usually follows. Evidence of immune dysfunction may be followed by a wide range of clinical conditions that include: l
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Fever Weight loss Malaise Lymphadenopathy Central nervous system dysfunction Abnormal Pap tests Recurrent cervical intraepithelial neoplasia Oral and vaginal candidiasis
These nonspecific conditibns are usually progressive and are a prelude to opportunistic infections diagnostic of AIDS. The diagnosis of AIDS is based on the presence of certain conditions (see the box). Given the rapid development of new therapies for the myriad of clinical manifestations of HIV disease, it would be prudent for the obstetrician caring for a symptomatic patient to seek consultation from a clinician who has expertise in HIV disease. The primary modes of transmission of HIV are sexual activity, parenteral exposure to blood, and perinatal exposure of infants. There is no evidence of transmission through casual contact, water, food, or environmental surfaces. Because isolated cases of HIV infection acquired through donor insemination have been reported, donors should be screened at the time of donation and again 6 months later, before frozen semen is used (11).
Perinatal Transmission Mother-to-child transmission of HIV can occur during pregnancy or through breast-feeding. Infection can occur as early as the eighth week of gestation, although perhaps 50% or more of perinatal infections occur during labor and delivery (4). A number of maternal factors are associated with increased risk of perinatal transmission. These factors include low CD4 counts and intrapartum events that increase exposure of the fetus to maternal blood (4). Prolonged rupture of membranes has been linked to increased rates of mother-to-child transmission of HIV, with initial reports suggesting that 4 hours may be an important cut point (12, 13). Recent evidence suggestk that maternal viral load may correlate with the rate of mother-to-child transmission of HIV (14. 15). Although some investigators contest these findings (16), if the association is borne out, it may become
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AlDS-hdlcator Conditions* Bacterial infections, multiple or recurrent Candidiasis of bronchi, trachea, or lungs Candidiasis of esophagus Carcinoma, invasive cervical Coccidioidomycosis, disseminated or extrapulmonary Cryptococcosis, extrapulmonary Cryptosporidiosis, chronic intestinal Cytomegabvirus disease other than retinitis Cytomegalovirus retinitis Herpes simplex, with esophagitis, pneumonitis, or chronic mucocutaneous ulcers Histoplasmosis, disseminated or extrapulmonary HIV encephalopathy (dementia) HIV wasting syndrome Immunosuppression, severe HIV-related+ Isosporiasis, chronic intestinal Kaposi sarcoma Lymphoid interstitial pneumonia and/or pulmonary lymphoid hyperplasia Lymphoma,‘Burkii (or equivalent term) Lymphoma, immunoblastic (or equivalent term) Lymphoma, primary in brain Mycobacterium avium-intracellulare or Mycobacterium kansasii, disseminated or extrapulmonary Mycobacferium tuberculosis, disseminated or extrapulmonaty M tuberdosis, pulmonary Mycobacterial disease, other, disseminated, or extrapulmonary Pneumocystii carinii pneumonia Pneumonia, recurrent Progressive multiiocal leukoencephalopathy Sa/mone//a septicemia, recurrent Toxoplasmosis of brain ‘AIDS, acquired immunodeficienq syndrome; HIV, human immunode fKiency Virus value is defined as CD4+ T-lymphocyte cell count of less than ZOO/ mm’ or a CD4t percentage of less than I 4% in adults/adolescents who meet the AIDS surveillance case definition. Adapted from Centers for Disease Control and Prevention. HIV/AM Suweilbnce Repolt 1994$(4):16
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necessary to monitor viral loads in pregnancy and to tailor antiretroviral regimens to them so as to achieve the lowest possible level of virus. Current data, however, do not warrant any therapy other than ZDV to help lower the rate of transmission. Studies are ongoing to determine whether alternative drug regimens, incorporating newly approved drugs, will be more efficacious than ZDV alone. A large multicenter trial demonstrated that ZDV, begun between 14 and 34 weeks of gestation, can significantly reduce the rate of mother-to-infant transmission of HIV in women with CD4 cell counts higher than 200/mm3 who have not previously taken thedrug (17). The transmission rate was 25.5% among 183 children whose mothers received a placebo compared with 8.3% among 180 children whose mothers received ZDV (P = 0.00006). Drug toxicity was minimal, with only three women in each arm of the study discontinuing therapy because of side effects. The rates of major and minor malformations were similar in both groups, and only a mild, transient anemia was seen more often among ZDV-exposed neonates. Prospective studies show maternal-fetal transmission rates of 13-40% in the United States in the absence of treatment (4).
Testing and Counseling All pregnant women should receive counseling about HIV, and testing should be recommended as a part of their regular prenatal care. Specific information about HIV infection should be shared with the patient before and after testing.
Pretest Counseling Retest counseling should include information regarding the risk for HIV infection associated with sexual activity and intravenous drug use, the risk of transmission to the woman’s infant if she is infected, the availability of ZDV therapy to reduce this risk, as well as the risks and benefits of ZDV therapy to the woman (4). Counseling should include the potential social and psychologic implications of testing and a description of testing procedures. The legal requirements for HIV counseling and testing vary among states. Explaining the usefulness of ZDV in reducing mother-to-child transmission of HIV may encourage more pregnant women to learn their serostatus so that they can begin therapy to reduce the risk of infection to the fetus. The negative aspects of testing positive for HIV include mental anguishanddiscriminatory sequelae such as loss of employment or health care benefits. After receiving counseling, women should be asked to consent to testing. A number of experts in the field suggest having the patient sign a written informed consent form after she has been fully informed. If the patient elects to
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forego testing or ZDV treatment, her informed refusal should be documented in the medical record.
Testing The most common tests administered for HIV screening detect antibodies to the virus rather than the virus itself. Any adult who has antibodies to HIV must be considered infected and infectious. Standard testing procedures include an initial enzyme-linked immunosorbent assay followed by a contirmatory Western blot assay. No antibody test result should be considered positive unless it has been confirmed by a Western blot assay, particularly in low-risk populations. The specificity and sensitivity of standard testing procedures currently available in the United States are greater than 99.0%. Repeating each initial reactive test increases the specificity of the test sequence by reducing the possibility of technical laboratory error. The achievable falsepositive rate of sequentially performed enzyme-linked immunosorbent assay and Western blot tests can be less than 0.001%. Collection of specimens for testing (either blood or saliva) can be performed at home, although the specimens must still be sent on to laboratories for processing. Some patients may prefer the anonymity of this approach.
Posttest Counseling Patients who test negative for HIV antibodies should be informed that false-negative results can occur. The falsenegative rate is due to the prolonged latent phase, during which an exposed and infectious individual may test negative for the HIV antibody. The actual false-negative rate depends on the prevalence of risk-related behavior in the population tested, as well as the interval from risk-related behavior to the time of testing in a particular individual. Patients who test negative should be encouraged to practice low-risk behavior to minimize their risk of infection. A pregnant woman who has a positive test result should receive detailed, specific counseling at the time the results are relayed and in follow-up sessions. Management of HIV infection during pregnancy begins with counseling that will enable the patient to decide whether to continue the pregnancy and whether to use ZDV to reduce the risk of perinatal transmission. Counseling of HIV-positive patients should include the following points: l
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A description of the early clinical manifestations of HIV infection Current understanding of the prognosis of HIV infection The risks of perinatal transmission to the fetus and the value of ZDV
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Promotion of responsible sexual behavior, including use of latex condoms to prevent other sexually transmissible diseases Avoidance of intravenous drug use A prohibition from donating blood products and body organs Advice not to share toothbrushes, razors, and other implements that could be contaminated with blood The suggestion that sexual and needle-sharing partners be notified and advised of the availability of counseling and testing Referral to appropriate psychosocial support services Encouragement for the patient to share her HIV status with all of her health care providers
Management of Human Immunodeficiency Virus Infection During Pregnancy Management of HIV infection is directed toward stabilization of HIV disease, prevention of opportunistic infections, and prevention of perinatal transmission. Specific aspects of management are based on the clinical condition of the patient. Clinicians should balance the theoretic risks of fetal HIV inoculation posed by invasive procedures (eg, percutaneous umbilical cord blood sampling, chorionic villus sampling, amniocentesis) against the benefits of the procedures.
Prenatal Care The CD4 counts and the plasma viral load of pregnant women infected with HIV should be monitored each trimester if available. Low CD4 cell counts and high viral loads are predictive of the development of serious infections. Low CD4 counts should be used to tailor prophylactic therapies (eg, when count is less than 2OO/mn?initiate prophylaxis for Pneumocystis carinii pneumonia),and knowledgeof viral loadsmay help to guidethe initiation andmodificationof antiviral regimens.As CD4 countsget lower, prophylaxis againstother organismssuchasToxoplawna gondii and Mycobacterium avium-intracellulare complex may alsohave to be instituted.Ratesof preterm birth, low birth weight, and pregnancycomplicationsin asymptomaticHIV-infected womenhavenot differed significantly from thosein noninfectedmatchedcontrolsin moststudies.However, in studiesfrom African countries, in which up to 20% of infected womenhadAIDS, there were more pretetm births and lower birth weights in infected women(18, 19).
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Becausewomenwith HIV infection are at risk for a variety of infections,they shouldbetestedfor tuberculosis andother infections.Tuberculosistesting shouldbe done by an intradermal injection of five tuberculosisunits (Mantoux method) with two testsfor anergy (Candida albicans, tetanus,or mumps).A resultshowinginduration of 5 mm or more is consideredpositive for tuberculosis. HepatitisB virus, pneumococcal,and influenza vaccines arenotcontraindicatedin pregnancy,but thepossibilityof vaccine-associated HIV viremia shouldbe considered.
Opportunistic Infections pneumoniais the most commonopportunistic infection seenin patientswith AIDS. Prophylaxisis indicatedin patientswith CD4 cell levels lessthan 200/mm3 andthosewith symptomssuchas thrushor unexplained fever for greaterthan2 weeksat any CD4 level (20). The fist-line agentfor prophylaxisagainstP carinii pneumonia is trimethoprim-sulfamethoxazole(TMP-SMX). A US. Public Health Service task force recommendsone double-strength tablet of TMP-SMX (SMX, 800mg, and TMP, 160mg) daily but recognizesthat lower dosesmay be better toleratedin someindividuals (20); alternatives include dapsone.An acceptablealternative regimenfor patientsintolerantof TMP-SMX with severedisease(PO? ~70 mmHg) is intravenouspentamidine,which requires inpatienttreatmentinitially; steroidsshouldbeadded.For patientswith severediseasewho are intolerant of both TMP-SMX andpentamidine,alternativesincludeintravenoustrimetrexate or intravenousclindamycin plus oral primaquine.Severalalternativesare availablefor TMPSMX-intolerant patientswith milddisease: TMP-dapsone, atovaquone,and clindamycinplus primaquine.The relative efficacy of theseagentsis not well studied. None of thesedrugshave beenshownto be teratogenie, andthe risksof P carinii pneumoniafor the woman far outweightherisksto thefetus.Concernsaboutmaternal sulfonamidetherapy resulting in kemicterusin the newbornare not supportedby existing data(2 1). If apatientdevelopsP carinii pneumonia,oral therapy isreasonable for patientswith mild pulmonarydisease (PO, >70 mm Hg or percentoxygen saturationof >90%). For patientswho cannottoleratetheseagents,alternativesare available(20). Toxoplasmosisshouldbe treated with sulfadiazine andpyrimethamineisethionate.An alternativeregimenis clindamycin and pyrimethamine.Prolonged, persistent episodesof herpessimplexvirus infection may alsooccur andmay betreatedwith acyclovir. Oropharyngealcandid&is isthemostfrequentfungal infection in AIDS patients.Chronicvaginal candid&is is alsoseenoften in infectedwomen,althoughvaginalinfection haslittle perinatalsignificance.Symptomaticvaginal P carinii
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candidiasis may be treated initially with a topical antifungal medication. Recurrent or persistent candidiasis should be treated with oral ketoconazole, 400 mg/d for 14 days followed by 5&y courses each month for 6 months; careful monitoring of liver function tests is needed to assess adverse reactions (22). Fluconazole is being studied for prevention of vaginal candidiasis in women. While there are no formal recommendations for the use of fungal prophylaxis, many clinicians use fluconazole, 100 mg/d, for women who have had recurrent episodes of vaginal or esophageal candidiasis. Immunocompromised pregnant patients with pelvic inflammatory disease should be hospitalized and aggressively treated according to guidelines issued by the Centers for Disease Control and Prevention
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ZidomkeTlmpy AJltqmtum Oral administration of 100 mg of zidovudine (ZDV) five times daily, initiated assoon as possible beyond 14 weeks of gestation and continued throughout the pregnancy
LaboradDdlveq During labor, intravenous administration of ZDV in a lhour loading dose of 2 mg/kg of body weight, followed by a continuous infusion of 1 mg/kg of body weight per hour until delivery
(23).
Antiviral Therapy Many new agents are now available for treatment of HIV, and polydrug therapy is often used for the treatment of HIV infection (24). It is particularly important, therefore, that obstetricians ensure that the choice of antiretroviral regimen for pregnant women not be based solely on the desire to prevent mother-to-child transmission of HIV. The need for optimal therapy of the mother’s infection must be part of the calculus upon which a therapeutic regimen is chosen. The use of ZDV is recommended to reduce the rate of perinatal transmission. It has been shown to reduce transmission in selected individuals. The full regimen includes antepartum, intrapartum, and neonatal therapy, and all three regimens should be used whenever possible (see the box). Concerns about the prophylactic use of ZDV remain, however, because the long-term effects are unknown. Zidovudine has not been shown to cause an increase in malformations in neonates born to mothers taking the drug. The few studies in animals thus far have not revealed malformations in conjunction with the use of ZDV, but increased resorption in preimplantation embryos has been reported in the mouse (25). Also, theoretically, women who take ZDV to reduce the possibility of mother-to-infant transmission may be risking future resistance to ZDV, compromising future care. The advent of new therapies may serve to mitigate this concern. The decision to use ZDV should be made by the patient only after discussing benefits and potential risks for herself and her child with her doctor. Prophylactic ZDV therapy should be recommended to infected patients at 14 weeks of gestation with a CD4 count equal to or greater than 200/mm3 (7). Although the utility of this approach is less well studied in individuals who begin ZDV therapy after 34 weeks of gestation and whose CD4 count is less than 2CO/mm3, the risks and benefits of ZDV therapy should still be discussed and the patient made
Oral administration of ZDV to the newborn (ZDV syrup at 2 mg/kg of body weight per dose every 6 hours) for the first 6 weeks of life, beginning 8-l 2 hours after birth
aware that there may be benefit no matter when therapy is started. If patients desire therapy and have not received it prior to delivery, therapy should be initiated in the neonate as soon as possible after delivery. If a woman has a history ofexposure to antiretroviral agents for more than 6 months, consideration of ZDV therapy is reasonable, but the possibility that resistant viral strains may emerge should be considered. New multiple antiretroviral regimens (ie, protease inhibitors and reverse transcriptase inhibitors) are available for the treatment of HIV. However, there are limited data on the safety or efficacy of these agents in pregnancy. If used, these agents should be administered after the first trimester, when organogenesis is completed.
Delivery A large percentage of mother-to-child transmission’occurs in the intrapartum period. Exposure to ruptured membranes may increase the transmission risk (12,13). Definitive data are lacking regarding the role of cesarean delivery in reducing the risk of transmission. Thus, obstetric practice should include steps other than cesarean delivery to reduce exposure to vaginal secretions. Artificial rupture of membranes should be avoided when possible, as should fetal scalp sampling and use of scalp electrodes. An effort should be made to avoid fetal-neonatal abrasions during delivery.
Postpartum Course Several reports have confirmed the vertical transmission of HIV during breast-feeding (26,27). Breast-feeding may
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increase the rate of transmission by lO-20% (4). Therefore, patients with HIV infection should be advised to avoid breast-feeding their infants. Because of the rapid changes in available therapeutic regimens (eg, protease inhibitors) for the treatment of HIV infection, both the mother and child should be referred to individuals with expertise in HIV care during the postpartum period. Current evidence does not support altering standard medical recommendations for contraceptive use among HIV-infected women. Use of latex condoms has been shown to be effective in limiting HIV transmission to uninfected partners. If HIV/sexually transmissible disease transmission is not an issue (eg, when both partners are infected with HIV), hormonal contraceptives or surgical sterilization are appropriate contraceptive options.
Infection Control in Obstetrics A number of health care workers have contracted HIV infection from accidental needle sticks, mucous membrane exposure, or percutaneous exposure to infected blood. Skin contact is a risk when exposed skin is chapped, abraded, or affected with dermatitis or the contact is prolonged or involves an extensive area (28). The risk of seroconversion in health care workers after needle stick exposure to HIV is approximately 0.3%; the risk after mucous membrane or skin exposure is lower (28). In caring for all patients, health care workers should use universal precautions to prevent skin, mucous membrane, and percutaneous exposure to all blood, secretions, and certain other fluids, including amniotic fluid. Goggles (protective eye covers) also should be used in all deliveries and in situations with the potential for conjunctival contact with bodily fluids. Double-gloving in the operating room can reduce skin exposure to blood after glove tears from 15% to 5% of cases (29). Because amniotic fluid may contain HIV, gloves should be used to handle the neonate as long as any maternal secretions remain. Devices operated by mouth suction that are used to clear the neonatal airway (DeLee suction devices) can pose arisk of transmission because blood or amniotic fluid in the neonate’s oropharynx may be infected. Thus, mouth suction should be avoided, and wall or bulb suction should be used. Keeping pressure less than 140 mm Hg will avoid damage to the neonate’s oropharynx. When mouth suction of the airway cannot be avoided, a trap should be placed in the line. Needles and other sharp instruments should be handled with care and disposed of properly. In particular, needles should never be resheathed, bent, or broken before they are discarded in a puncture-resistant container. If a health care worker sustains an injury with an HIV-contaminated needle, he or she should be counseled about the possible prophy-
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lactic use of antiretroviral medications. All institutions should orient health care workers to the availability of prophylaxis, its risks, and its benefits so that in the event of exposure, immediate use of antiretroviral therapy can be instituted (28). Recent case-control studies offer evidence that postexposure prophylaxis with ZDV, while not uniformly effective, does offer some protection, with lower rates of seroconversion seen among those being treated. Newly recommendedregimens involve the use of multidrug therapy (30). Conversely, a higher rate of seroconversion was seen among individuals whose exposure involved deep injuries, a device visibly contaminated with blood, or blood from a terminally ill source patient (3 1).
Ethical and Legal Issues Significant ethical and statutory issues are associated with HIV testing and infection. Laws and regulations for HIV screening, reporting, disclosure, and breach of confidence differ among states. Physicians should familiarize themselves with their state’s requirements. Issues of confidentiality are among the most problematic surrounding HIV antibody-positive patients. Although confidentiality has long been a cornerstone of medical care, it is now often difficult to ensure. Medical records are frequently reviewed by insurance companies, and many individuals are insured through their employers. Lawsuits have successfully challenged discrimination in employment and housing based on an individual’s HIV antibody status. Access to a patient’s serostatus should be limited to those with a medical need for this information. Unfortunately, simple solutions, such as keeping results in a secured area, may deprive members of the patient’s health care team of information necessary to administer appropriate care. Physicians also may be caught between a patient’s right to confidentiality and the duty to advise others of serious health risks. Every effort should be made to persuade the patient to disclose her status to those at risk as well as to all health care providers, including the baby’s physician. Most patients, with appropriate counseling and support, will inform their sexual partners of their infection. Physicians are also obligated to prevent stigmatization of these patients. Those pregnant women who decline prophylactic ZDV therapy should not be denied care or subjected to other punitive action (4). The Council on Ethical and Judicial Affairs of the American Medical Association has stated that “a physician may not ethically refuse to treat a patient whose condition is within the physician’s realm of competence solely because the patient is seropositive” for HIV infection (32). Pregnant women should receive information about all reproductive options and be supported in whatever decision they make (4).
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Summary The increasingrate of HIV infection amongwomen,the adventof therapyto reducemother-to-childHIV transmission,andthe uniquemanifestationsof HIV infection support the need for obstetrician-gynecologiststo play an active role in identifying and caring for HIV-infected women. Obstetrician-gynecologistsshouldcounselpatients andrecommendthat they be testedand,if appropriate, treated to reducethe risk of perinataltransmission. Obstetrician-gynecologistsunaccustomedto caring for patientswith HIV/AIDS shouldconsultwith physiciansor other obstetrician-gynecologistswho have expertise in managingHIV infection andAIDS.
References 1. Centers for Disease ControlandPrevention. First 500,000 AIDS cases-United States, 1995. MMWR 1995;44%49853 (Level III) 2. National Center for Health Statistics. Annual summary of births, marriages, divorces, and deaths: United States, 1994. Monthly vital statistics report; ~0143, no. 13. Hyattsville, Maryland: Department of Health and Human Services, Public Health Service (Level 11-2) 3. Davis SF, Byers RH, Lindegren ML, Caldwell MB, Karen JM, Gwinn M. Prevalence and incidence of vertically acquired HIV infection in the United States. JAMA 1995; 274:952-955 (Level III) 4. Centers for Disease Control and Prevention. U.S. Public Health Service recommendations for human immunodeficiency virus counseling and voluntary testing for pregnant women. MMWR 1995;44(RR-7):1-15 (Level III) 5. National Research Council. State of the epidemic. In: AIDS: the second decade. Washington, DC: National Academy Press, 1990:38-80 (Level III) 6. Centers for Disease Control. AIDS in women-United States. MMWR 1990;39:845-846 (Level III) 7. Centers for Disease Control and Prevention. Recommendations of the U.S. Public Health Service Task Force on the use of zidowdine to reduce perinatal transmission of human immunodeficiency virus. MMWR 1994;43(RR-ll):l-20 (Level III) 8. Maury W, Potts BJ, Rabson AB. HIV-l infection of firsttrimester and term human placental tissue: a possible mode of maternal-fetal transmission. J Infect Dis 1989;160:583588 (Level 11-2) 9. Centers for Disease Control. Public Health Service guidelines for counseling and antibody testing to prevent HIV infection and AIDS. MMWR 1987;36:509-515 (Level III) 10. Ranki A, Valle S-L, Krohn M, Antonen I, Allain J-P, Leuther M, et al. Long latency precedes overt seroconversion in sexually transmitted human-immunodeficiency-virus infection. Lancet 1987;2:589-593 (Level 11-2)
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11. American Fertility Society. New guidelines for the use of semenddnorinsemination: 1990. Fertil Sterill990;53(suppl 1): 1S-l 3s(LevelIII) 12. Landesman SH, Kalish LA, Bums DN, Minkoff H, Fox HE, Zorrilla C, et al. Obstetrical factors and the transmission of human immunodeficiency virus type 1 from mother tochild. N Engl J Med 1996;334:1617-1623 (Level 11-3) 13. Minkoff H, Bums DN, Landesman S, Youchah J, Goedert JJ, Nugent RP, et al. The relationship of the duration of ruptured membranes to vertical transmission of human immunodeficiency virus. Am J Obstet Gynecol 1995;173: 585-589 (Level 11-2) 14. Fang G, Burger H, Grlmson R, Tropper P, Nachman S, Mayers D, et al. Maternal plasma human immunodeficiency virus type 1 RNA level: a determinant and projected threshold for mother-to-child transmission. Proc Nat1 Acad Sci USA 1995;92:12100-12104 (Level 11-3) 15. Dickover RE, Garrany EM, Herman SA, Sim M, Plaeger S, Boyer P, et al. Identification of levels of maternal HIV-l RNA associated with riskof perinatal transmission: effect of maternal zidovudine treatment on viral load. JAMA 1996; 275:599-605 (Level 11-2) Lande.sman SH, Burns D. Quantifying HIV. JAMA 1996; 16. 275:640-641 (Level III) 17. Connor EM, Sperling RS, Gel&r R, Kiselev P, Scott G, O’Sullivan MJ, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovucline treatment. N Engl J Med 199&,331:1173-l 180 (Level I) 18. Bulterys M, Chao A, Muneyemana S, Kurawige J-B, Nawrocki P, Habimana P, et al. Maternal human immuoodeficiency virus 1 infection and intrauterine growth: a prospective cohort study in Butare, Rwanda. Pediatr Infect Dis J 1994;13:94-100 (Level 11-2) 19. Temmerman M, Chomba EN, Ndinya-Achola J, Plummer FA, Coppens M, Piot P. Maternal human immunodeficiency virus-l infection and pregnancy outcome. Obstet Gynecol 1994;83:495-501 (Level 11-2) 20. U.S. Public Health ServiceTaskForceon Antipneumocystis Prophylaxis in Patients with Human Immunodeficiency Virus Infection. Recommendations for prophylaxis against Pneumocystis carinii pneumonia for persons infected with human immunodeficiency virus. J Acquir Immune Defic Syndr Hum Retrovirol 1993;6:4&55 (Level III) 21. Sperling RS, Stratton P, and the members of the obstetricgynecologic working group of the AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. Treatment optionsfor humanimmunodeficiency virus-infected pregnant women. Obstet Gynecol 1992;79: 443-448 (Level III) 22. Sobel JD. Recurrent vulvovaginal candidiasis. A prospective study of the efficacy of maintenance ketoconazole therapy. N Engl J Med 1986;315:1455-1458 (Level I) 23. Centers for Disease Control and Prevention. 1993 sexually transmitteddiseasestreahnentguidelines. MMWR 1993;42 (RR-14):75-81 (Level III)
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24. Carpenter CCJ, Fischl MA, Hammer SM. Hirsch MS, Jacobsen DM, Katzenstein DA, et al. Antiretroviral therapy for HIV infection in 1996: recommendations of an intemational panel. JAMA 1996;276: 146154 (Level III) 25. Toltzis P, Mourton T. Magnuson T. Effect of zidovudine on preimplantation murine embryos. Antimicrob Agents Chemother 1993;37:1610-1613 (Level I) 26. Pizzo PA, Butler KM. In the vertical transmission of HIV, timing may beeverything. NEngl JMed 1991;325:652-654 (Level III) 27. Van de Perre P, Simonon A, Msellati P, Hitimana D-G, Vaira D, Bazubagira A, et al. Postnatal transmission of human immunodeficiency virus type 1 from mother to infant. A prospective cohort study inKigali, Rwanda. N Engl J Med 1991;325:593-598 (Level H-2) 28. Centers for Disease Control. Public health service statement on management of occupational exposure to human immunodeficiency virus, including considerations regarding zidovudine postexposure use. MMWR 1990;39(RR-1): 1-14 (Level III) 29. Gerberding JL, Littell C, Tarkington A, Brown A, Schecter WP. Risk of exposure of surgical personnel to patients’ blood during surgery at San Francisco General Hospital. N Engl J Med 1990;322: 1788-1793 (Level III) 30. Centers for Disease Control and Prevention. Update: provisional public health service recommendadons for chemoprophylaxis after occupational exposure to HIV. MMWR 1996;45:468472 (Level III) 31. Centers for Disease Control and Prevention. Case-control study of HIV seroconversion in health-care workers after percutaneous exposure to HIV-infected blood-France, United Kingdom, and United States, January 1988-August 1994. MMWR 1995;44:929-935 (Level H-2) 32. American Medical Association. Council on Ethical and Judicial Affairs. Ethical issues involved in the growing AIDS crisis. JAMA 1988;259:1360-1361 (Level III)
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The references in this bulletin are graded according to the method outlined by the U.S. Preventive Services Task Force: I
Evidence obtained from at least one properly designed randomized controlled trial II- 1 Evidence obtained from well-designed controlled trials without randomization II-2 Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than one center or research group II-3 Evidence obtained from multiple time series, with or without intervention, or dramatic results in uncontrolled experiments III Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees Requests for authorization to make photocopies should be dirEted to the Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923; telephone (508) 750-8400. Other publications from ACOG: l Committee Opinions, focused updates on emerging areas l Practice Patterns, evidence-based guidelines l Criteria Sets, baseline guidelines for review of diagnostic and management procedures Copyright Q January 1997 ISSN 1074-8628 The American College of Obstetricians and Gynecologists 409 12th Street, SW PO Box 96920 Washington, DC 20090.6920 1234Y10987
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ACOG educational bulletin
Human immunodeficiency
virus infections in pregnancy
Number 232, January 1997
This Educational Bulletin was developed under the direction of the Committeeon Educational Bulletins of the American College of Obstetriciansand Gynecologists as an aid to obstetricians and gynecologists. The College wishes to thank Howard L Minkoff, MD, for his assistancein the development of this bulletin. This document is not to be construedas establishinga standard of practice or dictating an exclusiie course of treatment. Bather, it is intended as an educationaltool that presentscurrent information on obstetric-gynecologic issues.
By mid- 1995,morethan half a million personsin the United Stateshad been reported ashaving acquired immunodeficiency syndrome(AIDS), of whom approximately 14% were women (1). For each patient with AIDS, there are many more patientsinfected with humanimmunodeficiency virus (HIV), the precursorto AIDS. In 1994,HIV infection wasthe third leadingcauseof death amongwomen 25-44 years old and the fifth leading causeof death in girls l-4 years old (2). The prevalenceof HIV infection in women giving birth in the United Statesin 1993 was about 1.6/1,000 (3). Ninety percent of HIV infections in children worldwide have beenthe result of perinatal transmission, and virtually all new casesin children are from perinatal transmission (4). Basedon a 25% perinataltransmissionrate, an estimated1,620 infected infants were born in the United Statesin 1993(3). Epidemiologic patternsshowbroad geographicdistribution of infection, and 85% of casesin adult women are among those aged 15 to 44 years old (5). Thus, obstetrician-gynecologistsare increasingly involved in caring for womenwith HIV (6). Obstetrician-gynecologistsshouldbe preparedto counsel patientsandrecommendtesting for the virus to all women who are pregnant or are seekingprepregnancycounseling.Zidovudine ([ZDV] formerly called azidothymidine, or AZT) therapy shouldbe recommendedto infected pregnant patientsto reducethe rate of perinatal transmission(7).
Pathophysiology Human immunodeficiency virus is a retrovirus. When infection occurs, the virus is incorporated into the host genome. Cells with the CD4+ antigen, particularly helperlymphocytes, arepreferentially infected. The virus can also infect macrophages,cells of the central nervoussystem,and possibly cells in the placenta (8). Infection with HIV leadsto progressivedebilitation of the immune system,rendering a patient susceptibleto opportunistic infections and neoplasmsthat rarely affect immunocompetentpatients. At the time of initial infection, the personmay be asymptomatic or may develop an acute syndrome similar to mononucleosiswith accompanying asepticmeningitis. Antibodies may be detected in most adults 6-12 weeks
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after exposure, but rarely, the latent period (“window phase”) before antibodies are detectable is longer (9, 10). After seroconversion, an asymptomatic period of variable length usually follows. Evidence of immune dysfunction may be followed by a wide range of clinical conditions that include: l
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Fever Weight loss Malaise Lymphadenopathy Central nervous system dysfunction Abnormal Pap tests Recurrent cervical intraepithelial neoplasia Oral and vaginal candidiasis
These nonspecific conditibns are usually progressive and are a prelude to opportunistic infections diagnostic of AIDS. The diagnosis of AIDS is based on the presence of certain conditions (see the box). Given the rapid development of new therapies for the myriad of clinical manifestations of HIV disease, it would be prudent for the obstetrician caring for a symptomatic patient to seek consultation from a clinician who has expertise in HIV disease. The primary modes of transmission of HIV are sexual activity, parenteral exposure to blood, and perinatal exposure of infants. There is no evidence of transmission through casual contact, water, food, or environmental surfaces. Because isolated cases of HIV infection acquired through donor insemination have been reported, donors should be screened at the time of donation and again 6 months later, before frozen semen is used (11).
Perinatal Transmission Mother-to-child transmission of HIV can occur during pregnancy or through breast-feeding. Infection can occur as early as the eighth week of gestation, although perhaps 50% or more of perinatal infections occur during labor and delivery (4). A number of maternal factors are associated with increased risk of perinatal transmission. These factors include low CD4 counts and intrapartum events that increase exposure of the fetus to maternal blood (4). Prolonged rupture of membranes has been linked to increased rates of mother-to-child transmission of HIV, with initial reports suggesting that 4 hours may be an important cut point (12, 13). Recent evidence suggestk that maternal viral load may correlate with the rate of mother-to-child transmission of HIV (14. 15). Although some investigators contest these findings (16), if the association is borne out, it may become
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AlDS-hdlcator Conditions* Bacterial infections, multiple or recurrent Candidiasis of bronchi, trachea, or lungs Candidiasis of esophagus Carcinoma, invasive cervical Coccidioidomycosis, disseminated or extrapulmonary Cryptococcosis, extrapulmonary Cryptosporidiosis, chronic intestinal Cytomegabvirus disease other than retinitis Cytomegalovirus retinitis Herpes simplex, with esophagitis, pneumonitis, or chronic mucocutaneous ulcers Histoplasmosis, disseminated or extrapulmonary HIV encephalopathy (dementia) HIV wasting syndrome Immunosuppression, severe HIV-related+ Isosporiasis, chronic intestinal Kaposi sarcoma Lymphoid interstitial pneumonia and/or pulmonary lymphoid hyperplasia Lymphoma,‘Burkii (or equivalent term) Lymphoma, immunoblastic (or equivalent term) Lymphoma, primary in brain Mycobacterium avium-intracellulare or Mycobacterium kansasii, disseminated or extrapulmonary Mycobacferium tuberculosis, disseminated or extrapulmonaty M tuberdosis, pulmonary Mycobacterial disease, other, disseminated, or extrapulmonary Pneumocystii carinii pneumonia Pneumonia, recurrent Progressive multiiocal leukoencephalopathy Sa/mone//a septicemia, recurrent Toxoplasmosis of brain ‘AIDS, acquired immunodeficienq syndrome; HIV, human immunode fKiency Virus value is defined as CD4+ T-lymphocyte cell count of less than ZOO/ mm’ or a CD4t percentage of less than I 4% in adults/adolescents who meet the AIDS surveillance case definition. Adapted from Centers for Disease Control and Prevention. HIV/AM Suweilbnce Repolt 1994$(4):16
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necessary to monitor viral loads in pregnancy and to tailor antiretroviral regimens to them so as to achieve the lowest possible level of virus. Current data, however, do not warrant any therapy other than ZDV to help lower the rate of transmission. Studies are ongoing to determine whether alternative drug regimens, incorporating newly approved drugs, will be more efficacious than ZDV alone. A large multicenter trial demonstrated that ZDV, begun between 14 and 34 weeks of gestation, can significantly reduce the rate of mother-to-infant transmission of HIV in women with CD4 cell counts higher than 200/mm3 who have not previously taken thedrug (17). The transmission rate was 25.5% among 183 children whose mothers received a placebo compared with 8.3% among 180 children whose mothers received ZDV (P = 0.00006). Drug toxicity was minimal, with only three women in each arm of the study discontinuing therapy because of side effects. The rates of major and minor malformations were similar in both groups, and only a mild, transient anemia was seen more often among ZDV-exposed neonates. Prospective studies show maternal-fetal transmission rates of 13-40% in the United States in the absence of treatment (4).
Testing and Counseling All pregnant women should receive counseling about HIV, and testing should be recommended as a part of their regular prenatal care. Specific information about HIV infection should be shared with the patient before and after testing.
Pretest Counseling Retest counseling should include information regarding the risk for HIV infection associated with sexual activity and intravenous drug use, the risk of transmission to the woman’s infant if she is infected, the availability of ZDV therapy to reduce this risk, as well as the risks and benefits of ZDV therapy to the woman (4). Counseling should include the potential social and psychologic implications of testing and a description of testing procedures. The legal requirements for HIV counseling and testing vary among states. Explaining the usefulness of ZDV in reducing mother-to-child transmission of HIV may encourage more pregnant women to learn their serostatus so that they can begin therapy to reduce the risk of infection to the fetus. The negative aspects of testing positive for HIV include mental anguishanddiscriminatory sequelae such as loss of employment or health care benefits. After receiving counseling, women should be asked to consent to testing. A number of experts in the field suggest having the patient sign a written informed consent form after she has been fully informed. If the patient elects to
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forego testing or ZDV treatment, her informed refusal should be documented in the medical record.
Testing The most common tests administered for HIV screening detect antibodies to the virus rather than the virus itself. Any adult who has antibodies to HIV must be considered infected and infectious. Standard testing procedures include an initial enzyme-linked immunosorbent assay followed by a contirmatory Western blot assay. No antibody test result should be considered positive unless it has been confirmed by a Western blot assay, particularly in low-risk populations. The specificity and sensitivity of standard testing procedures currently available in the United States are greater than 99.0%. Repeating each initial reactive test increases the specificity of the test sequence by reducing the possibility of technical laboratory error. The achievable falsepositive rate of sequentially performed enzyme-linked immunosorbent assay and Western blot tests can be less than 0.001%. Collection of specimens for testing (either blood or saliva) can be performed at home, although the specimens must still be sent on to laboratories for processing. Some patients may prefer the anonymity of this approach.
Posttest Counseling Patients who test negative for HIV antibodies should be informed that false-negative results can occur. The falsenegative rate is due to the prolonged latent phase, during which an exposed and infectious individual may test negative for the HIV antibody. The actual false-negative rate depends on the prevalence of risk-related behavior in the population tested, as well as the interval from risk-related behavior to the time of testing in a particular individual. Patients who test negative should be encouraged to practice low-risk behavior to minimize their risk of infection. A pregnant woman who has a positive test result should receive detailed, specific counseling at the time the results are relayed and in follow-up sessions. Management of HIV infection during pregnancy begins with counseling that will enable the patient to decide whether to continue the pregnancy and whether to use ZDV to reduce the risk of perinatal transmission. Counseling of HIV-positive patients should include the following points: l
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A description of the early clinical manifestations of HIV infection Current understanding of the prognosis of HIV infection The risks of perinatal transmission to the fetus and the value of ZDV
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Promotion of responsible sexual behavior, including use of latex condoms to prevent other sexually transmissible diseases Avoidance of intravenous drug use A prohibition from donating blood products and body organs Advice not to share toothbrushes, razors, and other implements that could be contaminated with blood The suggestion that sexual and needle-sharing partners be notified and advised of the availability of counseling and testing Referral to appropriate psychosocial support services Encouragement for the patient to share her HIV status with all of her health care providers
Management of Human Immunodeficiency Virus Infection During Pregnancy Management of HIV infection is directed toward stabilization of HIV disease, prevention of opportunistic infections, and prevention of perinatal transmission. Specific aspects of management are based on the clinical condition of the patient. Clinicians should balance the theoretic risks of fetal HIV inoculation posed by invasive procedures (eg, percutaneous umbilical cord blood sampling, chorionic villus sampling, amniocentesis) against the benefits of the procedures.
Prenatal Care The CD4 counts and the plasma viral load of pregnant women infected with HIV should be monitored each trimester if available. Low CD4 cell counts and high viral loads are predictive of the development of serious infections. Low CD4 counts should be used to tailor prophylactic therapies (eg, when count is less than 2OO/mn?initiate prophylaxis for Pneumocystis carinii pneumonia),and knowledgeof viral loadsmay help to guidethe initiation andmodificationof antiviral regimens.As CD4 countsget lower, prophylaxis againstother organismssuchasToxoplawna gondii and Mycobacterium avium-intracellulare complex may alsohave to be instituted.Ratesof preterm birth, low birth weight, and pregnancycomplicationsin asymptomaticHIV-infected womenhavenot differed significantly from thosein noninfectedmatchedcontrolsin moststudies.However, in studiesfrom African countries, in which up to 20% of infected womenhadAIDS, there were more pretetm births and lower birth weights in infected women(18, 19).
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Becausewomenwith HIV infection are at risk for a variety of infections,they shouldbetestedfor tuberculosis andother infections.Tuberculosistesting shouldbe done by an intradermal injection of five tuberculosisunits (Mantoux method) with two testsfor anergy (Candida albicans, tetanus,or mumps).A resultshowinginduration of 5 mm or more is consideredpositive for tuberculosis. HepatitisB virus, pneumococcal,and influenza vaccines arenotcontraindicatedin pregnancy,but thepossibilityof vaccine-associated HIV viremia shouldbe considered.
Opportunistic Infections pneumoniais the most commonopportunistic infection seenin patientswith AIDS. Prophylaxisis indicatedin patientswith CD4 cell levels lessthan 200/mm3 andthosewith symptomssuchas thrushor unexplained fever for greaterthan2 weeksat any CD4 level (20). The fist-line agentfor prophylaxisagainstP carinii pneumonia is trimethoprim-sulfamethoxazole(TMP-SMX). A US. Public Health Service task force recommendsone double-strength tablet of TMP-SMX (SMX, 800mg, and TMP, 160mg) daily but recognizesthat lower dosesmay be better toleratedin someindividuals (20); alternatives include dapsone.An acceptablealternative regimenfor patientsintolerantof TMP-SMX with severedisease(PO? ~70 mmHg) is intravenouspentamidine,which requires inpatienttreatmentinitially; steroidsshouldbeadded.For patientswith severediseasewho are intolerant of both TMP-SMX andpentamidine,alternativesincludeintravenoustrimetrexate or intravenousclindamycin plus oral primaquine.Severalalternativesare availablefor TMPSMX-intolerant patientswith milddisease: TMP-dapsone, atovaquone,and clindamycinplus primaquine.The relative efficacy of theseagentsis not well studied. None of thesedrugshave beenshownto be teratogenie, andthe risksof P carinii pneumoniafor the woman far outweightherisksto thefetus.Concernsaboutmaternal sulfonamidetherapy resulting in kemicterusin the newbornare not supportedby existing data(2 1). If apatientdevelopsP carinii pneumonia,oral therapy isreasonable for patientswith mild pulmonarydisease (PO, >70 mm Hg or percentoxygen saturationof >90%). For patientswho cannottoleratetheseagents,alternativesare available(20). Toxoplasmosisshouldbe treated with sulfadiazine andpyrimethamineisethionate.An alternativeregimenis clindamycin and pyrimethamine.Prolonged, persistent episodesof herpessimplexvirus infection may alsooccur andmay betreatedwith acyclovir. Oropharyngealcandid&is isthemostfrequentfungal infection in AIDS patients.Chronicvaginal candid&is is alsoseenoften in infectedwomen,althoughvaginalinfection haslittle perinatalsignificance.Symptomaticvaginal P carinii
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candidiasis may be treated initially with a topical antifungal medication. Recurrent or persistent candidiasis should be treated with oral ketoconazole, 400 mg/d for 14 days followed by 5&y courses each month for 6 months; careful monitoring of liver function tests is needed to assess adverse reactions (22). Fluconazole is being studied for prevention of vaginal candidiasis in women. While there are no formal recommendations for the use of fungal prophylaxis, many clinicians use fluconazole, 100 mg/d, for women who have had recurrent episodes of vaginal or esophageal candidiasis. Immunocompromised pregnant patients with pelvic inflammatory disease should be hospitalized and aggressively treated according to guidelines issued by the Centers for Disease Control and Prevention
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ZidomkeTlmpy AJltqmtum Oral administration of 100 mg of zidovudine (ZDV) five times daily, initiated assoon as possible beyond 14 weeks of gestation and continued throughout the pregnancy
LaboradDdlveq During labor, intravenous administration of ZDV in a lhour loading dose of 2 mg/kg of body weight, followed by a continuous infusion of 1 mg/kg of body weight per hour until delivery
(23).
Antiviral Therapy Many new agents are now available for treatment of HIV, and polydrug therapy is often used for the treatment of HIV infection (24). It is particularly important, therefore, that obstetricians ensure that the choice of antiretroviral regimen for pregnant women not be based solely on the desire to prevent mother-to-child transmission of HIV. The need for optimal therapy of the mother’s infection must be part of the calculus upon which a therapeutic regimen is chosen. The use of ZDV is recommended to reduce the rate of perinatal transmission. It has been shown to reduce transmission in selected individuals. The full regimen includes antepartum, intrapartum, and neonatal therapy, and all three regimens should be used whenever possible (see the box). Concerns about the prophylactic use of ZDV remain, however, because the long-term effects are unknown. Zidovudine has not been shown to cause an increase in malformations in neonates born to mothers taking the drug. The few studies in animals thus far have not revealed malformations in conjunction with the use of ZDV, but increased resorption in preimplantation embryos has been reported in the mouse (25). Also, theoretically, women who take ZDV to reduce the possibility of mother-to-infant transmission may be risking future resistance to ZDV, compromising future care. The advent of new therapies may serve to mitigate this concern. The decision to use ZDV should be made by the patient only after discussing benefits and potential risks for herself and her child with her doctor. Prophylactic ZDV therapy should be recommended to infected patients at 14 weeks of gestation with a CD4 count equal to or greater than 200/mm3 (7). Although the utility of this approach is less well studied in individuals who begin ZDV therapy after 34 weeks of gestation and whose CD4 count is less than 2CO/mm3, the risks and benefits of ZDV therapy should still be discussed and the patient made
Oral administration of ZDV to the newborn (ZDV syrup at 2 mg/kg of body weight per dose every 6 hours) for the first 6 weeks of life, beginning 8-l 2 hours after birth
aware that there may be benefit no matter when therapy is started. If patients desire therapy and have not received it prior to delivery, therapy should be initiated in the neonate as soon as possible after delivery. If a woman has a history ofexposure to antiretroviral agents for more than 6 months, consideration of ZDV therapy is reasonable, but the possibility that resistant viral strains may emerge should be considered. New multiple antiretroviral regimens (ie, protease inhibitors and reverse transcriptase inhibitors) are available for the treatment of HIV. However, there are limited data on the safety or efficacy of these agents in pregnancy. If used, these agents should be administered after the first trimester, when organogenesis is completed.
Delivery A large percentage of mother-to-child transmission’occurs in the intrapartum period. Exposure to ruptured membranes may increase the transmission risk (12,13). Definitive data are lacking regarding the role of cesarean delivery in reducing the risk of transmission. Thus, obstetric practice should include steps other than cesarean delivery to reduce exposure to vaginal secretions. Artificial rupture of membranes should be avoided when possible, as should fetal scalp sampling and use of scalp electrodes. An effort should be made to avoid fetal-neonatal abrasions during delivery.
Postpartum Course Several reports have confirmed the vertical transmission of HIV during breast-feeding (26,27). Breast-feeding may
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increase the rate of transmission by lO-20% (4). Therefore, patients with HIV infection should be advised to avoid breast-feeding their infants. Because of the rapid changes in available therapeutic regimens (eg, protease inhibitors) for the treatment of HIV infection, both the mother and child should be referred to individuals with expertise in HIV care during the postpartum period. Current evidence does not support altering standard medical recommendations for contraceptive use among HIV-infected women. Use of latex condoms has been shown to be effective in limiting HIV transmission to uninfected partners. If HIV/sexually transmissible disease transmission is not an issue (eg, when both partners are infected with HIV), hormonal contraceptives or surgical sterilization are appropriate contraceptive options.
Infection Control in Obstetrics A number of health care workers have contracted HIV infection from accidental needle sticks, mucous membrane exposure, or percutaneous exposure to infected blood. Skin contact is a risk when exposed skin is chapped, abraded, or affected with dermatitis or the contact is prolonged or involves an extensive area (28). The risk of seroconversion in health care workers after needle stick exposure to HIV is approximately 0.3%; the risk after mucous membrane or skin exposure is lower (28). In caring for all patients, health care workers should use universal precautions to prevent skin, mucous membrane, and percutaneous exposure to all blood, secretions, and certain other fluids, including amniotic fluid. Goggles (protective eye covers) also should be used in all deliveries and in situations with the potential for conjunctival contact with bodily fluids. Double-gloving in the operating room can reduce skin exposure to blood after glove tears from 15% to 5% of cases (29). Because amniotic fluid may contain HIV, gloves should be used to handle the neonate as long as any maternal secretions remain. Devices operated by mouth suction that are used to clear the neonatal airway (DeLee suction devices) can pose arisk of transmission because blood or amniotic fluid in the neonate’s oropharynx may be infected. Thus, mouth suction should be avoided, and wall or bulb suction should be used. Keeping pressure less than 140 mm Hg will avoid damage to the neonate’s oropharynx. When mouth suction of the airway cannot be avoided, a trap should be placed in the line. Needles and other sharp instruments should be handled with care and disposed of properly. In particular, needles should never be resheathed, bent, or broken before they are discarded in a puncture-resistant container. If a health care worker sustains an injury with an HIV-contaminated needle, he or she should be counseled about the possible prophy-
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lactic use of antiretroviral medications. All institutions should orient health care workers to the availability of prophylaxis, its risks, and its benefits so that in the event of exposure, immediate use of antiretroviral therapy can be instituted (28). Recent case-control studies offer evidence that postexposure prophylaxis with ZDV, while not uniformly effective, does offer some protection, with lower rates of seroconversion seen among those being treated. Newly recommendedregimens involve the use of multidrug therapy (30). Conversely, a higher rate of seroconversion was seen among individuals whose exposure involved deep injuries, a device visibly contaminated with blood, or blood from a terminally ill source patient (3 1).
Ethical and Legal Issues Significant ethical and statutory issues are associated with HIV testing and infection. Laws and regulations for HIV screening, reporting, disclosure, and breach of confidence differ among states. Physicians should familiarize themselves with their state’s requirements. Issues of confidentiality are among the most problematic surrounding HIV antibody-positive patients. Although confidentiality has long been a cornerstone of medical care, it is now often difficult to ensure. Medical records are frequently reviewed by insurance companies, and many individuals are insured through their employers. Lawsuits have successfully challenged discrimination in employment and housing based on an individual’s HIV antibody status. Access to a patient’s serostatus should be limited to those with a medical need for this information. Unfortunately, simple solutions, such as keeping results in a secured area, may deprive members of the patient’s health care team of information necessary to administer appropriate care. Physicians also may be caught between a patient’s right to confidentiality and the duty to advise others of serious health risks. Every effort should be made to persuade the patient to disclose her status to those at risk as well as to all health care providers, including the baby’s physician. Most patients, with appropriate counseling and support, will inform their sexual partners of their infection. Physicians are also obligated to prevent stigmatization of these patients. Those pregnant women who decline prophylactic ZDV therapy should not be denied care or subjected to other punitive action (4). The Council on Ethical and Judicial Affairs of the American Medical Association has stated that “a physician may not ethically refuse to treat a patient whose condition is within the physician’s realm of competence solely because the patient is seropositive” for HIV infection (32). Pregnant women should receive information about all reproductive options and be supported in whatever decision they make (4).
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Summary The increasingrate of HIV infection amongwomen,the adventof therapyto reducemother-to-childHIV transmission,andthe uniquemanifestationsof HIV infection support the need for obstetrician-gynecologiststo play an active role in identifying and caring for HIV-infected women. Obstetrician-gynecologistsshouldcounselpatients andrecommendthat they be testedand,if appropriate, treated to reducethe risk of perinataltransmission. Obstetrician-gynecologistsunaccustomedto caring for patientswith HIV/AIDS shouldconsultwith physiciansor other obstetrician-gynecologistswho have expertise in managingHIV infection andAIDS.
References 1. Centers for Disease ControlandPrevention. First 500,000 AIDS cases-United States, 1995. MMWR 1995;44%49853 (Level III) 2. National Center for Health Statistics. Annual summary of births, marriages, divorces, and deaths: United States, 1994. Monthly vital statistics report; ~0143, no. 13. Hyattsville, Maryland: Department of Health and Human Services, Public Health Service (Level 11-2) 3. Davis SF, Byers RH, Lindegren ML, Caldwell MB, Karen JM, Gwinn M. Prevalence and incidence of vertically acquired HIV infection in the United States. JAMA 1995; 274:952-955 (Level III) 4. Centers for Disease Control and Prevention. U.S. Public Health Service recommendations for human immunodeficiency virus counseling and voluntary testing for pregnant women. MMWR 1995;44(RR-7):1-15 (Level III) 5. National Research Council. State of the epidemic. In: AIDS: the second decade. Washington, DC: National Academy Press, 1990:38-80 (Level III) 6. Centers for Disease Control. AIDS in women-United States. MMWR 1990;39:845-846 (Level III) 7. Centers for Disease Control and Prevention. Recommendations of the U.S. Public Health Service Task Force on the use of zidowdine to reduce perinatal transmission of human immunodeficiency virus. MMWR 1994;43(RR-ll):l-20 (Level III) 8. Maury W, Potts BJ, Rabson AB. HIV-l infection of firsttrimester and term human placental tissue: a possible mode of maternal-fetal transmission. J Infect Dis 1989;160:583588 (Level 11-2) 9. Centers for Disease Control. Public Health Service guidelines for counseling and antibody testing to prevent HIV infection and AIDS. MMWR 1987;36:509-515 (Level III) 10. Ranki A, Valle S-L, Krohn M, Antonen I, Allain J-P, Leuther M, et al. Long latency precedes overt seroconversion in sexually transmitted human-immunodeficiency-virus infection. Lancet 1987;2:589-593 (Level 11-2)
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11. American Fertility Society. New guidelines for the use of semenddnorinsemination: 1990. Fertil Sterill990;53(suppl 1): 1S-l 3s(LevelIII) 12. Landesman SH, Kalish LA, Bums DN, Minkoff H, Fox HE, Zorrilla C, et al. Obstetrical factors and the transmission of human immunodeficiency virus type 1 from mother tochild. N Engl J Med 1996;334:1617-1623 (Level 11-3) 13. Minkoff H, Bums DN, Landesman S, Youchah J, Goedert JJ, Nugent RP, et al. The relationship of the duration of ruptured membranes to vertical transmission of human immunodeficiency virus. Am J Obstet Gynecol 1995;173: 585-589 (Level 11-2) 14. Fang G, Burger H, Grlmson R, Tropper P, Nachman S, Mayers D, et al. Maternal plasma human immunodeficiency virus type 1 RNA level: a determinant and projected threshold for mother-to-child transmission. Proc Nat1 Acad Sci USA 1995;92:12100-12104 (Level 11-3) 15. Dickover RE, Garrany EM, Herman SA, Sim M, Plaeger S, Boyer P, et al. Identification of levels of maternal HIV-l RNA associated with riskof perinatal transmission: effect of maternal zidovudine treatment on viral load. JAMA 1996; 275:599-605 (Level 11-2) Lande.sman SH, Burns D. Quantifying HIV. JAMA 1996; 16. 275:640-641 (Level III) 17. Connor EM, Sperling RS, Gel&r R, Kiselev P, Scott G, O’Sullivan MJ, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovucline treatment. N Engl J Med 199&,331:1173-l 180 (Level I) 18. Bulterys M, Chao A, Muneyemana S, Kurawige J-B, Nawrocki P, Habimana P, et al. Maternal human immuoodeficiency virus 1 infection and intrauterine growth: a prospective cohort study in Butare, Rwanda. Pediatr Infect Dis J 1994;13:94-100 (Level 11-2) 19. Temmerman M, Chomba EN, Ndinya-Achola J, Plummer FA, Coppens M, Piot P. Maternal human immunodeficiency virus-l infection and pregnancy outcome. Obstet Gynecol 1994;83:495-501 (Level 11-2) 20. U.S. Public Health ServiceTaskForceon Antipneumocystis Prophylaxis in Patients with Human Immunodeficiency Virus Infection. Recommendations for prophylaxis against Pneumocystis carinii pneumonia for persons infected with human immunodeficiency virus. J Acquir Immune Defic Syndr Hum Retrovirol 1993;6:4&55 (Level III) 21. Sperling RS, Stratton P, and the members of the obstetricgynecologic working group of the AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. Treatment optionsfor humanimmunodeficiency virus-infected pregnant women. Obstet Gynecol 1992;79: 443-448 (Level III) 22. Sobel JD. Recurrent vulvovaginal candidiasis. A prospective study of the efficacy of maintenance ketoconazole therapy. N Engl J Med 1986;315:1455-1458 (Level I) 23. Centers for Disease Control and Prevention. 1993 sexually transmitteddiseasestreahnentguidelines. MMWR 1993;42 (RR-14):75-81 (Level III)
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24. Carpenter CCJ, Fischl MA, Hammer SM. Hirsch MS, Jacobsen DM, Katzenstein DA, et al. Antiretroviral therapy for HIV infection in 1996: recommendations of an intemational panel. JAMA 1996;276: 146154 (Level III) 25. Toltzis P, Mourton T. Magnuson T. Effect of zidovudine on preimplantation murine embryos. Antimicrob Agents Chemother 1993;37:1610-1613 (Level I) 26. Pizzo PA, Butler KM. In the vertical transmission of HIV, timing may beeverything. NEngl JMed 1991;325:652-654 (Level III) 27. Van de Perre P, Simonon A, Msellati P, Hitimana D-G, Vaira D, Bazubagira A, et al. Postnatal transmission of human immunodeficiency virus type 1 from mother to infant. A prospective cohort study inKigali, Rwanda. N Engl J Med 1991;325:593-598 (Level H-2) 28. Centers for Disease Control. Public health service statement on management of occupational exposure to human immunodeficiency virus, including considerations regarding zidovudine postexposure use. MMWR 1990;39(RR-1): 1-14 (Level III) 29. Gerberding JL, Littell C, Tarkington A, Brown A, Schecter WP. Risk of exposure of surgical personnel to patients’ blood during surgery at San Francisco General Hospital. N Engl J Med 1990;322: 1788-1793 (Level III) 30. Centers for Disease Control and Prevention. Update: provisional public health service recommendadons for chemoprophylaxis after occupational exposure to HIV. MMWR 1996;45:468472 (Level III) 31. Centers for Disease Control and Prevention. Case-control study of HIV seroconversion in health-care workers after percutaneous exposure to HIV-infected blood-France, United Kingdom, and United States, January 1988-August 1994. MMWR 1995;44:929-935 (Level H-2) 32. American Medical Association. Council on Ethical and Judicial Affairs. Ethical issues involved in the growing AIDS crisis. JAMA 1988;259:1360-1361 (Level III)
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The references in this bulletin are graded according to the method outlined by the U.S. Preventive Services Task Force: I
Evidence obtained from at least one properly designed randomized controlled trial II- 1 Evidence obtained from well-designed controlled trials without randomization II-2 Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than one center or research group II-3 Evidence obtained from multiple time series, with or without intervention, or dramatic results in uncontrolled experiments III Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees Requests for authorization to make photocopies should be dirEted to the Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923; telephone (508) 750-8400. Other publications from ACOG: l Committee Opinions, focused updates on emerging areas l Practice Patterns, evidence-based guidelines l Criteria Sets, baseline guidelines for review of diagnostic and management procedures Copyright Q January 1997 ISSN 1074-8628 The American College of Obstetricians and Gynecologists 409 12th Street, SW PO Box 96920 Washington, DC 20090.6920 1234Y10987