Important note: Information in this article was accurate in November 2001. The state of the art may have changed since the publication date.Morbidity and Mortality Weekly Report, November 9, 2001 / 50(RR19);59-86
Centers for Disease Control and Prevention
Deborah Allen, Sc.D.
Division of Children With Special Health Needs
Bureau of Family and Community Health
Massachusetts Department of Public Health
Boston, Massachusetts
Arthur Ammann, M.D.
Global Strategies for HIV Prevention
San Rafael, California
Helen Bailey
AIDS Arms
Dallas, Texas
Cornelius Baker
National Association of People with AIDS
Washington, D.C.
Rosie Berger
United Health Care
New York, New York
Guthrie Birkhead, M.D., M.P.H.
Council of State and Territorial Epidemiologists
Albany, New York
Mary Boland, M.S.N., F.A.A.N.
University of Medicine & Dentistry of New Jersey
Newark, New Jersey
Cary Colman
Health Education Department
Kaiser Permanente
Panorama City, California
Ezra Davidson, Jr., M.D.
Charles R. Drew University of Medicine & Science
Los Angeles, California
Rebecca Denison
WORLD
Oakland, California
Maria Isabel Fernandez, Ph.D.
Department of Psychiatry & Behavioral Sciences
University of Miami School of Medicine
Miami, Florida
Toni Frederick, Ph.D.
Pediatric Spectrum of Disease Study
Los Angeles County Department of Health Services
Los Angeles, California
Donna Futterman, M.D.
Adolescent AIDS Program, Montefiore Medical Center and
Albert Einstein College of Medicine
Bronx, New York
Meliset Garcia
Disease Division
Children’s Hospital Pediatric Infectious
Springfield, Massachusetts
Randy Graydon
Division of Advocacy & Special Issues
Health Care Financing Administration
Baltimore, Maryland
David Harvey
AIDS Policy Center for Children, Youth, & Families
Washington, DC
Rashidah Hassan
Family Planning Council
Philadelphia, Pennsylvania
Catherine Hess
Association of Maternal & Child Health Programs
Washington, D.C.
Debra Hickman
Sisters Together & Reaching
Baltimore, Maryland
Roslyn Howard-Moss
Johns Hopkins OBGYN Department
Baltimore, Maryland
Jeanette Ickovics, Ph.D.
Department of Epidemiology
Yale University School of Medicine
New Haven, Connecticut
Ann Koontz, Dr.PH.
Division of Perinatal Systems/Women’s Health
Maternal & Child Health Bureau
Rockville, Maryland
Marlene LaLota, M.P.H.
Bureau of HIV/AIDS, Department of Health
Tallahassee, Florida
Zita Lazzarini, J.D., M.P.H.
Program in Medical Humanities, Health Law and Ethics
University of Connecticut Health Center
Farmington, Connecticut
Robert Levine, M.D.
Professor of Medicine
Yale University School of Medicine
Woodbridge, Connecticut
Michael Lindsay, M.D.
Department of OB-GYN
Emory University
Atlanta, Georgia
Katherine Luzuriaga, M.D.
University of Massachusetts Medical School
Worcester, Massachusetts
Miguelina Maldonado, M.S.W.
National Minority AIDS Council
Washington, D.C.
James McNamara, M.D.
National Institutes of Health
Rockville, Maryland
Lynne Mofenson, M.D.
National Institutes of Health/NICHD
Rockville, Maryland
Angus Nicoll, F.R.C.P.H., F.F.P.H.M., F.R.C.P.
HIV and STD Division, PHLS Communicable Disease Surveillance Centre
London, England
Deborah Parham, Ph.D.
Health Resources and Services Administration
Rockville, Maryland
Sindy Paul, M.D.
Division of AIDS Prevention and Control
New Jersey Department of Health
Trenton, New Jersey
Jim Pearson, Dr.PH.
Virginia Department of Health
Richmond, Virginia
Laura Riley, M.D.
Massachusetts General Hospital
Boston, Massachusetts
Gwendolyn B. Scott, M.D.
Division of Pediatric Infectious Diseases and Immunology, University of Miami
School of Medicine
Miami, Florida
Maureen Shannon
Association of Women’s Health, Obstetric, and Neonatal Nurses
San Francisco, California
Melissa Simmons
Children’s Diagnostic and Treatment Center
Sunrise, Florida
Christa-Marie Singleton, M.D., M.P.H.
Maternal and Child Health Policy
Association of State and Territorial Health Officers
Washington, D.C.
Sheperd Smith
The Children AIDS Fund
Herndon, Virginia
Pauline Thomas, M.D.
Office of AIDS Surveillance
New York City Department of Health
New York, New York
Kate Thomsen, M.D.
Planned Parenthood Federation of America
New York, New York
Deborah Von Zinkernagel
Office of HIV/AIDS Policy
Washington, D.C.
Diane Wara, M.D.
University of California, San Francisco
San Francisco, California
Theresa Watkins-Bryant, M.D.
Division of Programs for Special Populations
Bureau of Primary Health Care
Bethesda, Maryland
Catherine Wilfert, M.D.
Duke University Medical Center
Chapel Hill, North Carolina
Carmen Zorilla, M.D.
University of Puerto Rico
San Juan, Puerto Rico
The following CDC staff members prepared this report:
Martha F. Rogers, M.D.
Mary Glenn Fowler, M.D., M.P.H.
Mary Lou Lindegren, M.D.
Division of HIV/AIDS Prevention — Surveillance and Epidemiology
National Center for HIV, STD, and TB Prevention
These guidelines replace CDC's 1995 guidelines, U.S. Public Health Service Recommendations for Human Immunodeficiency Virus Counseling and Voluntary Testing for Pregnant Women, and are for public- and private-sector service providers who provide health care for pregnant women. In 1998, the Institute of Medicine (IOM) published a report that recommended simple, routine, and voluntary human immunodeficiency virus (HIV) testing for all pregnant women in antenatal settings, given the effective interventions available to treat HIV-infected women and reduce risk for perinatal HIV transmission. In 1999, CDC convened consultation groups to discuss and comment on the IOM report. These guidelines are based on input from these meetings, the IOM report, and public comment on draft guidelines published in Fall 2000 in the Federal Register. These guidelines were also prompted by scientific and programmatic advances in the prevention of perinatally acquired HIV and care of HIV-infected women. These recommendations are consistent with the Revised Guidelines for HIV Counseling, Testing, and Referral.
Major revisions from the 1995 guidelines include
These guidelines recommend voluntary HIV testing to preserve a woman's right to participate in decisions regarding testing to ensure a provider-patient relationship conducive to optimal care for mothers and infants and to support a woman's right to refuse testing if she does not think it is in her best interest.
In 1994, after the announcement of the results of Pediatric AIDS Clinical Trials Group (PACTG) protocol 076 (1), the Public Health Service (PHS) published guidelines for zidovudine (ZDV) use to reduce perinatal human immunodeficiency virus (HIV) transmission (2). In 1995, PHS issued guidelines recommending universal counseling and voluntary HIV testing of all pregnant women and treatment for those infected (3). Publication of these recommendations was followed by rapid implementation by health-care providers, widespread acceptance of chemoprophylaxis by HIV-infected women, and a steep and sustained decline in perinatal HIV transmission (4,5). Observational studies have confirmed the effectiveness of ZDV in reducing the risk for perinatal transmission (6--8). This reduction in transmission risk resulted in an 83% decline in perinatal acquired immunodeficiency syndrome (AIDS) cases diagnosed in 1999, compared with the peak incidence of 907 cases in 1992 (7).
Despite this progress, children are still being infected perinatally. CDC estimates that 280--370 infants are born with HIV infection each year in the United States (CDC, unpublished data, 2000). These continued infections underscore the need for improved strategies to ensure that all pregnant women are offered HIV testing and, if positive, treatment to reduce their transmission risk and to safeguard their health and the health of their infants.
Several lessons have been learned from evaluation of the 1995 PHS guidelines. Many women, especially those who used illicit drugs, were not tested for HIV during pregnancy because of lack of prenatal care (8). In addition, many women refused testing because their health-care providers did not strongly recommend it. Some women declined testing because of perceived low risk, and some providers failed to offer testing because of perceived low risk, perceived difficulties and complexity of required counseling, and misunderstanding of counseling requirements. The logistics of testing, if too complex, also were considered a potential barrier to testing.
In December 1998, the Institute of Medicine (IOM) completed a study commissioned by Congress to assess the impact of current approaches for reducing perinatal HIV transmission, identify barriers to further reductions, and determine ways to overcome these barriers (9). IOM concluded that continued perinatal transmission was mainly caused by a lack of awareness of HIV status among some pregnant women. This problem was attributed to some health-care providers not offering HIV testing to all pregnant women because the providers believed they could predict which women were most at risk and that standard HIV testing protocols, particularly the requirement for extensive pretest counseling, were too burdensome to conduct for all women. IOM concluded that HIV testing should be simplified and made routine. They recommended that the United States adopt a national policy of universal HIV testing, with patient notification, as a routine component of prenatal care. That is, testing should be offered to all pregnant women as part of the standard battery of prenatal tests, regardless of risk factors and the prevalence rates in the community. IOM also recommended that women be informed when an HIV test is conducted and of their right to refuse testing.
Since 1994--1995, major scientific advances in the prevention of perinatal transmission and the care of HIV-infected persons have occurred. These advances increased the benefit of knowing one's HIV status, especially during pregnancy. More effective treatment has prolonged survival of HIV-infected persons and improved their quality of life (10). Clinical trials proved the effectiveness of prophylactic therapy for preventing perinatal transmission in women who are not treated until the time of delivery (11). Studies have indicated that women with nondetectable viral load rarely transmit HIV infection (12--14). Finally, new testing technologies (e.g., rapid testing, urine sampling) offer new options for HIV screening.
To address the lessons learned, IOM findings, and scientific advances, as well as the causes of continued HIV infection in children, PHS convened specialists in the field in April 1999 and sought widespread public comment in revising the 1995 guidelines for HIV counseling and testing for pregnant women. Consultation groups included researchers, professional health-care provider organizations (e.g., American Academy of Pediatrics, American College of Obstetricians and Gynecologists), clinicians, women living with HIV, and representatives from community organizations and PHS agencies overseeing care of HIV-infected pregnant women.
The resulting guidelines are presented in this document. They differ from the 1995 guidelines in that they
These guidelines maintain a voluntary approach to HIV testing. This voluntary approach preserves a woman's right to make decisions regarding testing and supports a woman's right to refuse testing if she does not think it is in her best interest.
This document replaces the 1995 PHS guidelines (3). These recommendations are primarily intended for providers of health care for women, with a focus on HIV screening of pregnant women to reduce mother-to-child transmission of HIV. This report does not address other concerns related to continued perinatal transmission (e.g., lack of prenatal care). CDC programs targeted to states with the highest incidence of perinatal HIV infection address these ongoing public health problems (information on these programs is available on the Internet at <http://www.cdc.gov/hiv/projects/perinatal/default.htm>). Other PHS guidelines address the importance of prevention interventions, including testing in the general population (see Revised Guidelines for HIV Counseling, Testing, and Referral). This report applies only to the United States; different recommendations, especially on breast-feeding, will apply in other countries.
Of the approximately 750,000 AIDS cases reported to CDC through the end of 1999, approximately 129,000 were in women. Approximately 64,000 women were living with AIDS in 1999, a 31% increase from 1996, reflecting improved survival with new combination treatment regimens (15). However, women with AIDS represent only a fraction of the number of HIV-infected women who need medical and social services. An estimated 120,000--160,000 HIV-infected women reside in the United States, 80% of whom are of childbearing age (16).
Most women with HIV/AIDS in the United States reside in the Northeast and the South. The highest numbers of cases were first observed in the Northeast, but the South has reported the greatest increases in recent years. African-American and Hispanic women are disproportionately affected by the epidemic and account for 80% of AIDS cases reported in U.S. women in 1999. Over time, the proportion of cases in women attributable to injection-drug use has declined, whereas the proportion of cases from heterosexual contact has increased, particularly among young women.
During 1985--1995, approximately 6,000--7,000 HIV-infected women gave birth in the United States each year (7). During the early 1990s, before perinatal chemoprophylaxis was available, an estimated 1,000--2,000 infants were born with HIV infection annually. By June 2000, a total of 8,027 perinatally acquired AIDS cases were recorded nationwide, most (85%) in African-American and Hispanic children (7,15). Before the results of the PACTG 076 trial using prenatal, intrapartum, and postpartum ZDV for perinatal prophylaxis, the risk for mother-to-child transmission ranged from 16% to 25% in studies from North America and Europe (17--19), up to 24% in Thailand (20), and 25--40% in Africa (21,22). Worldwide, approximately 600,000 infants each year become infected through mother-to-child transmission of the HIV virus.
In the United States, widespread implementation of the PHS guidelines for universal counseling and testing and perinatal use of ZDV has sharply reduced transmission risk and the number of perinatally acquired HIV infections (7). By 1995, several cohort studies had documented transmission rates of <11% (19,23). During 1996--2000, U.S. studies indicated that transmission rates had declined to 5%--6% (12,24) and <1% in women with nondetectable plasma viral loads (12,14,25). During 2000--2001, perinatal transmission rates of <2% have been achieved with combination antenatal antiretroviral drugs (26) or with ZDV combined with cesarean section (27--29). Analysis of U.S. perinatal AIDS surveillance data (15) reported through June 2000 indicated a sharp decline in the number of perinatal AIDS cases; this decline was temporally associated with increasing ZDV use among pregnant women aware of their HIV status (7). To more accurately monitor trends in perinatal HIV transmission and the implementation and impact of perinatal prevention programs (including HIV counseling and testing recommendations), CDC, the Council of State and Territorial Epidemiologists (CSTE), and the American Academy of Pediatrics (AAP) recommended national reporting of perinatal HIV exposure and HIV infection to help identify and target populations where prevention opportunities are missed (30,31).
Despite the declines, cases of perinatal HIV transmission continue to occur, largely because of missed opportunities for prevention, particularly among women who lack prenatal care or who are not being offered voluntary HIV counseling and testing during pregnancy. The estimated 280--370 infants born with HIV infection each year represent populations in which prevention efforts are impeded by lack of timely HIV testing and treatment of pregnant women (7). Of 329 children with perinatally acquired AIDS born during 1995--1996, a total of 112 (34%) were born to mothers not tested for HIV before the child's birth and 67 (20%) to mothers for whom the time of testing was not known.
Perinatal transmission can occur during pregnancy (intrauterine), during labor and delivery (intrapartum), or after delivery through breast-feeding (postpartum). In the absence of breast-feeding, intrauterine transmission accounts for 25%--40% of infection, and 60%--75% of transmission occurs during labor and delivery (32). Among women who breast-feed, approximately 20%--25% of perinatal infections are believed to be associated with intrauterine transmission, 60%--70% with intrapartum transmission or very early breast-feeding, and 10%--15% with later postpartum transmission through breast-feeding (33). In a randomized trial of formula feeding versus breast-feeding, approximately 44% of HIV infection was attributed to breast-feeding (34). In breast-feeding populations, a shift toward an increasing proportion of transmission related to breast-feeding is likely to occur as a consequence of successful preventive interventions directed at late prenatal and intrapartum transmission.
Intrapartum transmission can occur during labor through maternal-fetal exchange of blood or during delivery by contact of the infant's skin or mucous membranes with infected blood or other maternal secretions (32). Several studies have indicated that most infections transmitted through breast-feeding probably occurred during the first few weeks to months of life (34--36). Risk factors during breast-feeding include viral load in breast milk (37,38), subclinical or clinical mastitis (37,39,40), breast abscesses (39,40), and maternal seroconversion during the lactation period (39,41).
Several risk factors are associated with perinatal HIV transmission. Clinical factors that increase the likelihood of transmission include immunologically or clinically advanced HIV disease in the mother, high plasma viral load (12,25,42), maternal injection-drug use during pregnancy, preterm delivery, nonreceipt of the PACTG 076 regimen, and breast-feeding (32). No link has been established between perinatal HIV transmission and maternal age, race/ethnicity, or history of having a previously infected child.
Obstetric factors also influence HIV transmission risk. The risk for perinatal trans-mission increases per hour duration of membrane rupture after controlling for other risk factors (43). Delivery >4 hours after the rupture of the fetal membranes can double the risk for HIV transmission (19,44). Maternal infection with another sexually transmitted disease (STD) during pregnancy and certain obstetrical procedures can also increase risk (45). Chorioamnionitis (i.e., uterine infection) has been associated with an increased risk for HIV transmission (23,46).
Most of these risk factors were identified before the recommended use of ZDV to prevent perinatal HIV transmission. Their effects are unknown now that most pregnant women infected with HIV are receiving ZDV chemoprophylaxis to prevent mother-to- child transmission, as well as combination therapy for their own health. Because of the sharp reductions in perinatal HIV transmission associated with effective antiretroviral interventions, factors that interfere with women or their infants receiving ZDV treatment (e.g., barriers to prenatal care, lack of HIV testing for some pregnant women) are increasingly important (9).
The birth of every perinatally HIV-infected infant is a sentinel health event signaling either a missed prevention opportunity or, more rarely, a failure of prophylaxis. An opportunity is missed whenever a woman of childbearing age is unaware of her HIV status or her risk for HIV or when an HIV-infected pregnant woman a) does not receive prenatal care, b) is not offered HIV testing, c) is unable to obtain HIV testing, d) is not offered chemoprophylaxis, e) is unable to obtain chemoprophylaxis, or f) does not complete the chemoprophylaxis regimen. Prophylaxis failures occur when an infant becomes infected despite chemoprophylaxis and other preventive interventions (9). Each of these missed opportunities or failures deserves attention from service providers and prevention programs.
Early Prenatal Care
Maximum reduction of perinatal transmission depends on preventing HIV infection in women or identifying HIV infection before pregnancy or as early as possible during pregnancy. Diagnosis allows a woman to receive effective antiretroviral therapies for her own health and preventive drugs (e.g., ZDV) to improve the chances that her infant will be born free of infection. Early knowledge of maternal HIV status is also important for decisions regarding obstetrical management. Achieving these goals requires increased access to and use of prenatal care.
Four states that conducted enhanced HIV surveillance reported that during 1993--1996, approximately 15% of HIV-infected pregnant women in the United States received no prenatal care, compared with only 2% of women in the general population (5). HIV-infected women who used illicit drugs during pregnancy were at the highest risk for not receiving prenatal care --- 35% compared with 6% for HIV-infected women who were not drug users. During 1997--1998, the HIV transmission rate among women in New York State was 17.5% (30/171) among those with no prenatal care, 16.2% (23/142) among those with 1--2 prenatal visits, and 8.0% (90/1,124) among those with >3 prenatal visits, indicating the importance of prenatal care in providing services that prevent perinatal transmission (47).
Offer and Acceptance of HIV Testing
Most women who have given birth since the 1995 PHS guidelines have received information or counseling regarding HIV infection and have been offered testing. This has occurred independently of state-to-state variations in application of recommended practices, type of prenatal health-care provider, type of patient insurance, or maternal demographic characteristics (9). A 14-state study of HIV counseling and testing data for 1996--1997 reported that the proportion of pregnant women voluntarily tested for HIV was 58%--81% (30). Women most likely to receive HIV counseling and testing during pregnancy were those who were African-American, had less than a high school education, were aged <25 years, received care in public rather than private health-care settings, and were Medicaid beneficiaries.
When offered, most women (approximately 70% in most settings) will accept HIV testing. In a multicity study of prenatal clinic patients, 74%--95% of participants accepted HIV testing (48). Reasons most commonly cited for acceptance were a) belief that knowledge of positive HIV serostatus during pregnancy (and subsequent chemoprophylaxis) can be beneficial to both mother and infant and b) strong provider endorsement for prenatal HIV testing. The most common reasons for declining the test were no perceived risk, administrative scheduling difficulties, history of previous testing, and lack of provider endorsement.
Although most providers agreed that all women should be tested for HIV, some offered testing only to women whom they considered at risk for infection (49,50). Risk-based testing approaches identified fewer HIV-infected women than routine voluntary testing of all pregnant women (3) and also decreases in effectiveness as more women are infected through heterosexual contact without knowing their partner's HIV risk status.
Receipt of ZDV Chemoprophylaxis
The primary strategy to prevent perinatal transmission (in addition to avoidance of breast-feeding) is antiretroviral chemoprophylaxis using ZDV, now often part of a combined antiretroviral therapy regimen that reduces viral load as low as possible near the time of delivery. In the PACTG 076 protocol, chemoprophylaxis consisted of three components: ZDV administered orally to the mother during the second and third trimesters of pregnancy, intravenous administration of ZDV to the mother during labor and delivery, and administration of oral ZDV to the infant during the first 6 weeks of life (1).
Data from several sources demonstrated rapid implementation of the recommendations for ZDV prophylaxis by health-care providers and use of ZDV by HIV-infected pregnant women. One study analyzed approximately 6,800 perinatally exposed and infected children born during 1993--1998 in 32 states that reported HIV infection (51). Among those whose mothers were tested for HIV before or at birth of the infant, the percentage of infants receiving any component of the recommended ZDV regimen increased from 37% in 1994 to approximately 85% during 1996--1998. In a supplemental study of women diagnosed before delivery in four states, the proportion offered prenatal ZDV increased from 27% in 1993 to 85% in 1996, the proportion offered intrapartum ZDV increased from 5% to 75%, and the proportion offered neonatal ZDV increased from 5% to 76% (5). Fewer than 5% of women refused ZDV.
Abbreviated Antiretroviral Regimens
Given the complexity and cost of the PACTG 076 regimen, particularly for the developing world, other effective strategies to reduce the risk for perinatal HIV transmission have been identified. Results of randomized clinical trials in developing countries and observational data from the United States indicated that abbreviated perinatal antiretroviral regimens (20,52--54), regimens that begin as late as the onset of labor (11), and possibly antiretroviral chemoprophylaxis given only to the newborn (47) are effective in reducing the risk for perinatal transmission.
Abbreviated antiretroviral regimens have also proved effective in reducing the risk for transmission in resource-poor countries. In nonbreast-feeding women, a short antepartum/intrapartum regimen of ZDV reduced transmission by 50% (20); a similar regimen in breast-feeding populations was also effective, although efficacy was lower (52--54). Two other intrapartum/postpartum antiretroviral regimens were effective in reducing transmission in clinical trials among breast-feeding African women. One regimen was nevirapine given as a single dose to the woman in labor and to the infant at age 48 hours, and the other was ZDV plus lamivudine (3TC) given orally intrapartum and to the infant and mother for 1 week postpartum (11,36,55). Observational data and animal studies indicated that newborn prophylaxis alone offered some protection (24,56). Updated recommendations for use of these regimens in the United States, including for pregnant women who do not receive health care until near the time of delivery are available at the HIV/AIDS Treatment Information Service (ATIS) website at <http://www.hivatis.org> (57).
Other Strategies to Prevent Perinatal Transmission
Reducing exposure of the infant to maternal blood and secretions during the intrapartum period can prevent perinatal HIV transmission. Cesarean delivery performed before onset of labor and membrane rupture lowers the risk for HIV transmission compared with vaginal delivery in certain populations of women. Cesarean delivery resulted in a 50% reduction in perinatal HIV transmission overall among HIV-infected women who had cesarean deliveries compared with women delivering vaginally (28). A randomized clinical trial in Europe (27) demonstrated a benefit of elective cesarean section before onset of labor for both untreated HIV-infected women and infected women on antiretroviral therapy. However, cesarean delivery is associated with greater morbidity than vaginal delivery among both HIV-infected and noninfected women (58). In 1999 and 2000, the American College of Obstetricians and Gynecologists (ACOG) recommended offering scheduled cesarean delivery at 38 weeks gestation to reduce the risk for vertical transmission of HIV infection (57,59). Other intrapartum interventions alone (e.g., vaginal disinfection during labor and cleansing of the newborn) have not proven effective (60).
Follow-Up Care for Infected Women and Perinatally Exposed Infants
Providing mothers and their infants with ongoing HIV-related care can maximize the benefits of prevention interventions. The medical care of HIV-infected women is a complicated task requiring use of potent combinations of antiretroviral drugs, monitoring of viral load and drug resistance, treatment and prophylaxis of opportunistic infections, and monitoring of immune status. In addition to conditions (e.g., Pneumocystis carinii pneumonia [PCP]) for which all immunocompromised HIV-infected persons are at risk, women experience specific manifestations of HIV disease (e.g., aggressive pelvic inflammatory disease and persistent and difficult-to-treat vaginal yeast infections requiring frequent screening and treatment) (61,62). HIV-infected women are also at increased risk for cervical dysplasia, which can result in cancer (63). With early detection and appropriate treatment, many of these complications can be prevented and treated. Improved health outcomes resulting from advances in HIV management and treatment depend not only on access to medical care but also on access to prevention and psychosocial support services. In the United States, most mothers and children with HIV/AIDS live in areas where poverty, illicit drug use, poor housing, and limited access to and use of medical care and social services add to the challenges of HIV disease (4,9). Women with HIV infection often have difficulty gaining access to health care and frequently are responsible for caring for children and other family members who might also be HIV-infected (64). They often lack social support and face other challenges that could interfere with their ability to gain access to and adhere to complicated treatment regimens. The complex medical and social problems of families affected by HIV are best managed by multidisciplinary case-management teams that integrate specialty medical care with prevention, psychosocial, and other HIV-related services (see Revised Guidelines for HIV Counseling, Testing, and Referral).
Postnatal evaluation of infants at risk for HIV infection that begins immediately after birth is the key to early diagnosis and optimal medical management of infected children. PCP is the most common opportunistic infection in children with AIDS and is often fatal (65). Because PCP occurs most often in perinatally infected children at ages 3--6 months (65), effective prevention requires that children born to HIV-infected mothers be identified promptly, preferably through maternal testing, so that PCP prophylactic therapy can be initiated at age 6 weeks. In 1995, CDC published revised guidelines recommending PCP prophylaxis for all perinatally exposed infants at ages 4--6 weeks until their infection status was determined (66). Perinatal screening can identify HIV-exposed infants early, making it possible to follow infected children closely and promptly diagnose other potentially treatable, HIV-related conditions (e.g., severe bacterial infections). This also allows antiretroviral treatment to be initiated as soon as indicated to prevent morbidity, prolong survival, and reduce the need for hospitalization (67).
Follow-up of infants, both infected and uninfected, who are exposed to antiretroviral drugs is critical to identifying potential short- and long-term toxicities. Data on the risks of antiretroviral drugs during pregnancy are summarized and updated regularly (57).
In 1996, Congress charged IOM with evaluating the extent to which state efforts had been effective in reducing perinatal HIV transmission and analyzing barriers to further reduction in such transmission. In 1999, IOM published its results, which addressed ways to increase prenatal testing, improve therapy for HIV-infected women and children, and generally reduce perinatal HIV infections (9).
Despite sharp reductions in perinatally transmitted AIDS cases that resulted from widespread implementation of the 1994 and 1995 PHS guidelines, IOM reported that the number of children born with HIV infection exceeded achievable prevention levels. Prenatal HIV testing was not universal, and many HIV-infected women were inadequately treated because they did not seek prenatal care, were not tested for HIV, or received treatment that did not reflect current standards. Even in settings where most prenatal-care providers agreed that HIV tests should be offered to all pregnant women, some reported that they did not offer the test to all women in their practices, mainly because pretest counseling recommended by CDC and promulgated in some state policies were too burdensome (9). Citing lack of time and skills for counseling, providers based testing decisions on their own, often inaccurate, assessments of maternal risk.
IOM recommended that the United States adopt a goal that all pregnant women be tested for HIV and all infected women receive optimal treatment for themselves and their children. To help meet this goal, IOM recommended that the United States adopt a policy of universal HIV testing, with patient notification, as a routine component of prenatal care (i.e., all pregnant women should be offered testing regardless of their risk factors or the prevalence rates where they live). Early diagnosis of HIV infection allows pregnant women to receive effective antiretroviral therapy for their own health and reduce the risk for transmitting HIV to their infants. Universal testing avoids stereotyping or stigmatizing any socioeconomic or ethnic group. Women should be told they are being tested for HIV and told of their right to refuse testing. Patient notification allows women to decline testing if they feel it is not in their best interest and simplifies the testing process by eliminating the need for extensive pretest counseling.
IOM's recommendations prompted reconsideration of the focus, implementation, and impact of PHS's guidelines for HIV screening of pregnant women. These guidelines recommended counseling all pregnant women regarding the risk for HIV infection, benefits of HIV testing, and voluntary testing. This approach was endorsed by most professional organizations representing prenatal, obstetrical, and perinatal-care providers. States quickly implemented the guidelines, but with substantial variability in strategy (68). Most states responded with policies on HIV counseling and testing of pregnant women; approximately 50% also enacted laws or regulations. Most policies and statutes are directed at pregnant women rather than newborns and focus on education, counseling, and consensual testing. New York and Connecticut are the only states that mandate newborn testing. No evidence exists to indicate that any legal approach is more successful than others in preventing perinatal transmission. No states require mandatory testing of pregnant women. In considering adopting the IOM guidelines, some states have implemented or are considering requiring some form of pretest counseling, routine testing with right of refusal, or universal or selective newborn screening. IOM's recommendation is for universal HIV testing with patient notification. As states consider implementing the IOM recommendations, other important considerations include availability of care and treatment for HIV-infected mothers and their infants, provider training needs, and confidentiality laws to protect positive test results reported to public health surveillance. States should consult with public health officials, health-care providers, and representatives of affected communities during this process.
For the individual woman, the substantial benefits of HIV testing must be weighed against the possible risks. Potential negative consequences of a diagnosis of HIV infection can include loss of confidentiality, job- or health-care--related discrimination and stigmatization, loss of relationships, domestic violence, and adverse psychological reactions (69). Providing HIV-infected women with or referring them to psychological, social, and legal services could help minimize these risks and allow more women to benefit from the health advantages of early HIV diagnosis without adverse consequences. The Americans with Disabilities Act (ADA) of 1990 and other federal, state, and local antidiscrimination provisions aim to protect persons with HIV/AIDS against discrimination in the workplace, housing, public services, and public accommodations (70). A 1998 U.S. Supreme Court decision provided further antidiscrimination protection by ensuring that persons with asymptomatic HIV disease are included under ADA and have access to nondiscriminatory and effective health care (70).
Testing of women before or during pregnancy is typically conducted according to the standard protocol for detection of antibody to HIV (71). For women with unknown HIV status during active labor, antiretroviral treatment can still be effective when given during labor and delivery, followed by treatment of the newborn (11). This expedited intervention requires the use of rapid diagnostic testing during labor or rapid return of results from standard testing.
Standard Testing Protocol
The HIV testing algorithm recommended by PHS consists of initial screening with an FDA-licensed enzyme immunoassay (EIA) followed by confirmatory testing of repeatedly reactive EIAs with an FDA-licensed supplemental test (e.g., Western blot). Although each test is highly sensitive and specific, using both increases the accuracy of results.
Indeterminate Western blot results can be caused by either incomplete antibody response to HIV in samples from infected persons or nonspecific reactions in samples from uninfected persons (72--74). Incomplete antibody responses that produce negative or indeterminate results on Western blot tests can occur among persons recently infected with HIV who have low levels of detectable antibodies (i.e., seroconversion), persons who have end-stage HIV disease, and perinatally exposed but uninfected infants who are seroreverting (i.e., losing maternal antibody). Nonspecific reactions producing indeterminate results in uninfected persons have occurred more frequently among pregnant or parous women than among other persons (73,74). No large-scale studies have been conducted to estimate the prevalence of indeterminate test results in pregnant women. However, a survey of 1,044,944 neonatal dried-blood specimens tested by EIA for maternally acquired HIV-1 antibody indicated a relatively low rate of indeterminate Western blot results (<1 in 4,000 specimens tested by EIA) (74). Overall, 2,845 Western blots were performed.
False-positive Western blot results (especially those with a majority of bands) are rare. For example, in a study that used a sensitive culture technique to test approximately 290,000 blood donors , no false-positive Western blot results were detected (75). In a study of the frequency of false-positive diagnoses among military applicants from a low-prevalence population (i.e., <1.5 infections/1,000 population), one false-positive result was detected among 135,187 persons tested (76).
An HIV test should be considered positive only after screening and confirmatory tests are reactive. A confirmed positive test result indicates that a person has been infected with HIV. False-positive results when both screening and confirmatory tests are reactive are rare. However, the possibility of a mislabeled sample or laboratory error must be considered, especially for a client with no identifiable risk for HIV infection. HIV vaccine-induced antibodies may be detected by current tests and may cause a false-positive result. Persons whose test results are HIV-positive and who are identified as vaccine trial participants should be encouraged to contact or return to their trial site or an associated trial site for HIV counseling, testing, and referral (CTR) services.
Incorrect HIV test results occur primarily because of specimen-handling errors, laboratory errors, or failure to follow the recommended testing algorithm (76). However, patients might report incorrect test results because they misunderstood previous test results or misperceived that they were infected (77). Although these occurrences are rare, increased testing of pregnant women will result in additional indeterminate, false-positive, and incorrect results. Because of the significance of an HIV-positive test result, its impact on a woman's reproductive decisions, and the resulting need to consider HIV therapeutic drugs for both a pregnant woman and her infant, previous guidelines have emphasized that HIV test results must be obtained and interpreted correctly. In some circumstances, correct interpretation might require consideration of not only additional testing but also the woman's clinical condition and history of possible exposure to HIV.
Diagnosis of HIV Infection in Newborns
The standard antibody assays used for older children and adults are less useful for diagnosis of infection in children aged <18 months. Nearly all infants born to HIV-infected mothers passively acquire maternal antibody and, in some cases, will test antibody positive until age 18 months regardless of whether they are infected. Definitive diagnosis of HIV infection in early infancy requires other assays, including nucleic acid amplification (e.g., polymerase chain reaction [PCR]) or viral culture. HIV infection is diagnosed by two positive assays (PCR or viral culture) on two separate specimens. Infant HIV testing should be done as soon after birth as possible so appropriate treatment interventions can be implemented quickly (67).
Rapid Tests for Expedited Screening
For certain HIV-infected pregnant women, the labor and delivery setting is the first opportunity for HIV testing and interruption of mother-to-child transmission. Although results of conventional EIAs and Western blots are typically not available for 1--2 weeks, rapid tests for detecting antibody to HIV can produce results in 10--60 minutes (78). The sensitivity and specificity of rapid assays are comparable with EIAs. However, the predictive value of a single screening test varies with the prevalence of HIV infection among the population tested. Because HIV prevalence is low in most perinatal testing settings, the negative predictive value of a single rapid test (i.e., the probability that a negative test accurately indicates that the person tested is uninfected) is high. A negative rapid test does not require further testing. In contrast, the positive predictive value of a single test (i.e., the probability that a positive test represents true infection) will be low among populations with low prevalence (71). Therefore, a reactive rapid test must be confirmed by a supplemental test (e.g., Western blot). However, necessary peripartum interventions to reduce the risk for perinatal transmission might need to be based on the preliminary results of rapid testing at labor and delivery. Decisions regarding use of antiretroviral drugs to prevent perinatal transmission among women who are repeatedly reactive on a single rapid HIV test require clinical judgment regarding initiation of prophylactic treatment before results of a confirmatory test are available.
Only one FDA-approved rapid HIV test (Abbott Murex Single Use Diagnostic System [SUDS] HIV-1 test, Abbott Laboratories, Inc., Abbott Park, Illinois) is commercially available in the United States, although other rapid tests are being considered for approval. This test can provide definitive negative and preliminary positive test results at the time of testing and identify women who might need antiretroviral treatment and whose infants might benefit from chemoprophylaxis. A careful risk assessment could help make treatment decisions. The predictive value of a reactive rapid test is higher among persons with risk for HIV infection, especially in areas with high HIV prevalence (79). Use of a second screening test (either rapid test or EIA) can also improve the positive predictive value of a single reactive rapid HIV test. In studies conducted outside the United States, specific combinations of >2 different screening assays provided results as reliable as those from the conventional EIA/Western blot combination (80).
Expedited EIA testing that produces results within a few hours can also aid decisions regarding antiretroviral therapy. Although results from standard testing are not likely to be available during labor and delivery, they could be available within 12 hours of an infant's birth. Because neonatal prophylaxis might be effective in reducing risk for transmission (24), expedited application of the standard testing protocol is another way to reduce mother-to-child infection.
Research and programmatic studies are underway to assess the feasibility of offering voluntary HIV counseling and rapid testing at labor and delivery to women of unknown serostatus in the United States. Implementation of rapid testing and expedited EIA approaches should address several ethical and logistical considerations, including
A CDC-funded, multicenter initiative called Mother-Infant Rapid Intervention at Delivery (MIRIAD) is underway to address these considerations among women with inadequate prenatal care in communities with high HIV seroprevalence among women of childbearing age (81). If successful, this initiative will offer crucial peripartum interventions to reduce the risk for HIV transmission among HIV-infected women first identified at labor and delivery.
The following revised recommendations for HIV screening of pregnant women are based on scientific and clinical advances in preventing perinatally acquired HIV and caring for HIV-infected women, recommendations from IOM, consultations with specialists in the field, and public opinion. They reflect the need for universal HIV testing of all pregnant women and simplification of the pretest process so that operational procedures do not impede women from benefitting from proven measures to prevent perinatal transmission and from other advances in the care and treatment of HIV disease. Although universal testing is recommended, testing should remain a voluntary decision by the pregnant woman.
When the pretest process is simplified to providing essential information, the value of prevention counseling should not be lost. For some women, the prenatal care period could be an ideal opportunity for HIV prevention and subsequent behavior change to reduce risk for acquiring HIV infection. Thus, the following steps are recommended:
Recommendations for HIV-Infected Pregnant Women
Although pregnancy is not an adequate reason to defer therapy for HIV infection, unique considerations exist regarding use of antiretroviral drugs during pregnancy, including the potential need to alter dosing because of physiologic changes associated with pregnancy, the potential for adverse short- or long-term effects on the fetus and infant, and the effectiveness in reducing the risk for perinatal transmission (57).
Because of recent advances in both antiretroviral and obstetrical interventions, pregnant women infected with HIV who know their status prenatally can reduce their risk for transmitting HIV to their infants to <2%. The guidelines in this report are intended to reduce barriers to voluntary HIV testing for all pregnant women in the United States and to make the voluntary counseling and testing process simple and routine in prenatal settings. The recommendations underscore the importance of HIV-infected pregnant women (and their health-care providers) knowing their status to protect their own health and reduce the risk for transmitting HIV to their infants.
We are grateful for the contributions of Ida Onorato, M.D., CDC.
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