Prevention

HIV can be transmitted from an infected mother to her child during pregnancy or labor and postnatally through breast milk. Nearly 25 years after the first documented case of HIV infection, the decrease in perinatal HIV infections in the United States represents a major success in public health. Despite this achievement, several challenges remain in the effort to eliminate mother-to-child transmission of HIV infection. In the state of Nevada, the number of perinatally acquired HIV infections decreased to its lowest in 2003, with only 1 infected infant, compared with the peak in 1998 of 8 infected infants. We report 4 cases of mother-to-child HIV transmission that occurred in Las Vegas between October 2005 and June 2006 and that highlight some of the challenges in reducing the incidence of perinatal infections. A comprehensive, multidisciplinary program that allows for expanded access to prenatal care, rapid HIV testing in labor and delivery for women of unknown HIV serostatus, and close follow-up of exposed infants must be present to sustain the achievements made in the reduction of mother-to-child transmission of HIV infection. [AIDS Reader. 2007;17:33-38]

HIV can be transmitted from an infected mother to her child during pregnancy and labor and postnatally through breast milk. Although many accomplishments have been achieved in the United States in the prevention of mother-to-child transmission of HIV,^1,2 several challenges remain, including 4 major issues.

First, the estimated number of persons living with HIV/AIDS has steadily increased since 2000, and women now account for up to 27% of the total HIV cases.³ Second, approximately 25% of the estimated 850,000 to 950,000 persons living with HIV/AIDS in the United States are not aware of their HIV status.⁴ Third, in the United States, an estimated 6000 to 7000 HIV-infected women give birth each year, and nearly 40% have no documentation of their HIV serostatus because the majority do not seek prenatal care.⁵ Last, even though rapid HIV screening in the labor and delivery setting has been shown to be an acceptable and feasible method of screening mothers, many US hospitals do not have an established protocol.^4,6

These unresolved issues contributed to the 280 to 370 new perinatal HIV infections estimated to have occurred in the year 2000 alone.^7,8 We report 4 cases of mother-to-child HIV transmission that occurred in Las Vegas between October 2005 and June 2006 that highlight these challenges.

CASE SUMMARIESCase 1
A 29-year-old woman was admitted in labor at 33 weeks' gestation; she had not had prenatal care. Her HIV serostatus was unknown, and a blood sample was sent to an outside laboratory for an HIV enzyme-linked immunosorbent assay (ELISA). She delivered a live male infant 4 days later. The reactive result of the HIV ELISA was available at the outside laboratory before delivery, but it is unclear whether the clinician was aware of the result; thus neither mother nor infant received intervention to prevent mother-to-child transmission of HIV. The infant was hospitalized for 2 weeks; at discharge, maternal HIV serostatus was documented as unknown. Although the infant was seen on several occasions for recurrent oral candidiasis, it was not until he was 6 months old that appropriate testing with HIV DNA polymerase chain reaction (PCR) was performed, the result of which was reactive. HIV was diagnosed after the result of a repeated HIV DNA PCR test was reactive.

Case 2
A 36-year-old woman presented in labor with a history of limited prenatal care and unknown HIV serostatus. The result of an HIV ELISA done at admission was reactive. Intervention to reduce the risk of mother-to-child transmission was initiated, including treatment of the mother with zidovudine during labor and subsequent administration of zidovudine to the infant. At discharge, the infant was to continue receiving zidovudine, but treatment compliance was uncertain. Results of HIV DNA PCR tests performed at birth and at age 7 weeks were negative. Although the patient was seen on various occasions by his pediatrician for recurrent otitis media and failure to thrive, no subsequent testing was done until he was 18 months old. The result of an HIV ELISA performed at this time was reactive, and results of 2 follow-up HIV DNA PCR tests were positive, thus confirming HIV infection in the infant.

Case 3
A 26-year-old woman was admitted in labor at 38 weeks' gestation; she had had no prenatal care, and her HIV serostatus was unknown. The result of an HIV ELISA performed at admission was nonreactive. She delivered the next day and, at discharge, continued to breast-feed her newborn. The infant was seen multiple times for recurrent oral candidiasis and upper respiratory tract infections, beginning at age 6 months.

The result of an HIV ELISA obtained at 8 months-after the pediatrician became aware that HIV infection had been recently diagnosed in the father-was nonreactive. The mother was then tested and had a reactive HIV ELISA result. She was advised to stop breast-feeding. The result of a repeated HIV ELISA on the child obtained at 10 months was reactive, and HIV infection was confirmed with 2 HIV DNA PCR tests. The infant's subsequent HIV RNA PCR test revealed an HIV RNA level greater than 7.5 million copies/mL.

Case 4
A 26-year-old woman with known HIV infection was admitted for labor and delivery at 35 weeks' gestation. She was noted to have fever and premature rupture of her membranes. Her prenatal care had been erratic, and she reported being noncompliant with her antiretroviral medications during pregnancy. Intravenous zidovudine was started in addition to combination antiretroviral therapy. A cesarean section was performed in an attempt to reduce the risk of mother-to-child HIV transmission. The newborn was noted to have thrombocytopenia at birth, and the result of an HIV DNA PCR test was positive. HIV infection was confirmed with a repeated DNA PCR test 5 days later, and the HIV RNA PCR test results demonstrated greater than 750,000 copies/mL.

DISCUSSION
These 4 cases highlight challenges and barriers that hinder efforts to eliminate mother-to-child transmission of HIV infection. Lack of prenatal care and absence of rapid HIV diagnostic tests delay diagnosis of HIV in pregnant women and remain obstacles to initiating intervention in pregnant HIV-infected women. In 2003, the CDC set a goal that no child should be born in the United States with unknown HIV status and/or unknown maternal HIV serostatus. The CDC recommends routine opt-out prenatal HIV screening and rapid HIV testing during labor and delivery for all pregnant women with unknown HIV serostatus.4,9 The American College of Obstetricians and Gynecologists adopted this recommendation in its committee opinion on HIV testing in 2004.¹⁰

Despite these recommendations and the demonstrated feasibility of such programs,^6,11,12 many hospitals in the United States have no established protocol for rapid HIV testing of all pregnant women with unknown HIV serostatus at delivery. As a result, missed opportunities for the prevention of mother-to-child transmission of HIV continue to occur.¹³

The significant reduction of mother-to-child transmission of HIV in the United States has been attributed to routine HIV screening of pregnant women and the use of antiretroviral agents during pregnancy and delivery with subsequent prophylaxis for the infant as demonstrated by protocol ACTG (AIDS Clinical Trials Group) 076 and other clinical trials.^14,15 Many women of childbearing age are still unaware of their HIV serostatus, and a significant percentage of HIV-infected infants continue to be born to mothers who become aware of their HIV serostatus after delivery.² Many of these women are not familiar with the availability of treatment that could markedly decrease the chance of transmitting HIV to their children.⁴ As the number and proportion of women with HIV infection increase, adherence to antiretroviral therapy by HIV-positive pregnant women will remain an important part of the effort to eliminate mother-to-child transmission.

Individual Case Sentinel Events
The first case highlights the challenges faced when pregnant mothers do not seek prenatal care and rapid HIV testing during labor is unavailable. The absence of an established protocol for rapid HIV testing led to an HIV ELISA being performed at an outside laboratory with inadequate follow-up regarding the test result and the absence of an intervention. A rapid HIV test administered at admission would have provided results within a few hours, thus allowing the physicians to initiate appropriate intervention, including prophylactic therapy during the period before delivery, during labor, and subsequently to the infant. Studies have shown that point-of-care rapid HIV testing in a nonresearch setting is both feasible and cost-effective and helps reduce the rate of perinatal HIV transmission.^16-18

Guidelines are available regarding the use of antiretroviral therapy in HIV-infected women who have had no prior therapy as well as the follow-up management of their HIV-exposed infants.^8,19 In addition, appropriate initial HIV testing of the infant using PCR tests would have allowed early diagnosis of HIV infection and avoided the delay in initiating therapy.

The second case illustrates the importance of compliance with established intervention protocols using zidovudine. Although HIV infection could still have occurred, protocol ACTG 076 showed that this risk is reduced significantly when the 3-part regimen (zidovudine therapy during pregnancy and labor and then for the infant) is adhered to.¹⁴ Although maternal HIV serostatus was identified and early intervention initiated, the absence of a comprehensive maternal-child program may have led to ineffective monitoring of the family's adherence to prophylactic therapy and delayed the diagnosis of HIV infection in the infant.

Rapid HIV testing in labor allows for the provision of interventions to reduce the risk of transmission of HIV, even in the absence of treatment during pregnancy.² Close follow-up of the exposed infant with adherence to established management guidelines (Table) allows early identification of the infected infant. Once infection is confirmed, therapy can be initiated to reduce morbidity and mortality.

To confirm the absence of HIV infection in an infant exposed to HIV in utero, 2 negative HIV DNA PCR test results obtained after age 1 month are required, and 1 test should be at or later than age 4 months. Because of the complexities of testing for and treatment of perinatal HIV exposure and infection, an HIV specialist should be involved early in the process. A team approach that includes the obstetrician, pediatrician, HIV specialist, and case managers with active sharing of information among caregivers allows for coordinated intervention, close follow-up, early diagnosis, and more effective treatment.

The third case illustrates a peculiar problem when a woman acquires HIV infection late in pregnancy or after delivery; such a scenario justifies the recommendation for repeated HIV testing during pregnancy for women at risk (including those with absent or limited prenatal care).^7,10,16 It is still unclear at what point the mother acquired HIV infection. HIV was first diagnosed in her husband after the birth of the infant; however, the mother was reportedly unaware of this. Cases such as this serve as a reminder that pediatricians need to remain familiar with the presenting symptoms and signs of HIV infection in infants.

Again, a comprehensive program with effective communication between case managers and providers may identify mothers who are at risk for infection after an HIV-infected partner is identified. In such a case, cessation of breast-feeding should be recommended. With a negative result from the infant's ELISA at 8 months and rapid seroconversion at 9 months, postnatal transmission of virus from breast milk was seen as the most likely source of infection.

The fourth case highlights another major challenge in the effort to eliminate mother-to-infant transmission of HIV infection. Although medications are available to treat HIV infection and reduce the risk of transmission among HIV-positive pregnant mothers, they require dedication on the part of the mother and the support of the health care system to be successful. An intensive and often tedious program is required to adjust for barriers to adherence, including illicit drug use and mental health issues.

Although HIV infection in these 4 infants occurred under different circumstances, these cases illustrate the substantial challenges to the elimination of perinatal transmission of HIV infection. Between 1994 and 2003, only 44% of HIV-infected mothers in Nevada received antiretroviral medication, compared with a national average of 79% (Figure 1).²⁰ The number of HIV-infected infants in Nevada decreased to its lowest point in 2003, with only 1 infected infant, after reaching a peak in 1998 of 8 HIV-infected infants (Figure 2). The diagnosis of infection in 4 infants over a 6-month period represents a reversal in the trend seen from 1998 to 2003.
Comprehensive, multidisciplinary programs that allow expanded access to prenatal care, rapid HIV testing during labor for women with unknown HIV serostatus, and close follow-up of HIV-exposed infants are important in reducing the risk factors that hinder the elimination of mother-to-child transmission of HIV.²

CONCLUSION
Improved access to prenatal care and HIV testing for all pregnant women remain major strategies to help identify HIV-infected pregnant mothers and provide an opportunity to institute intervention aimed at reducing mother-to-child transmission of HIV infection. Women who do not seek prenatal care during pregnancy represent a special high-risk group. Programs that allow for retesting of such mothers who have had no or only limited prenatal care despite a nonreactive HIV ELISA result at delivery may be necessary to diagnose HIV infection in women who acquire the infection late in pregnancy or after delivery.

References:

References

1. Lindegren ML, Byers RH Jr, Thomas P, et al. Trends in perinatal transmission of HIV/AIDS in the United States. JAMA. 1999;282:531-538.
2. Centers for Disease Control and Prevention. Achievements in public health: reduction in perinatal transmission of HIV infection-United States, 1985–2005. MMWR. 2006;55:592-597.
3. Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report: Cases of HIV infection and AIDS in the United States, 2004. Available at:

http://www.cdc.gov/hiv/topics/surveillance/resources/reports/2004report/pdf/2004SurveillanceReport.pdf

. Accessed June 20, 2006.
4. Centers for Disease Control and Prevention. Advancing HIV prevention: new strategies for a changing epidemic-United States. MMWR. 2003;52:329-332.
5. Centers for Disease Control and Prevention. Quick Facts: Perinatal April 2003–March 2005. Available at:

http://www.cdc.gov/hiv/topics/prev_prog/AHP/resources/factsheets/QF_Perinatal.pdf

. Accessed June 20, 2006.
6. Bulterys M, Jamieson DJ, O'Sullivan MJ, et al. Rapid HIV-1 testing during labor: a multicenter study. JAMA. 2004;292:219-223.
7. Centers for Disease Control and Prevention. Revised recommendations for HIV screening of pregnant women. MMWR. 2001;50(RR-19):59-86.
8. Centers for Disease Control and Prevention. US Public Health Service Task Force recommendation for use of antiretroviral drugs in pregnant HIV-1–infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States. MMWR. 2002;51(RR-18):1-38.
9. Centers for Disease Control and Prevention. Rapid HIV-1 antibody testing during labor and delivery for women of unknown HIV status: a practical guide and model protocol. January 30, 2004. Available at:

http://www.cdc.gov/hiv/topics/testing/resources/guidelines/pdf/Labor&DeliveryRapidTesting.pdf

. Accessed December 8, 2006.
10. ACOG Committee on Obstetric Practice. ACOG committee opinion number 304, November 2004. Prenatal and perinatal human immunodeficiency virus testing: expanded recommendations. Obstet Gynecol. 2004;104:1119-1124.
11. Minkoff H, O'Sullivan MJ. The case for rapid HIV testing during labor. JAMA.1998;279:1743-1744.
12. Cohen MH, Olszewski Y, Branson B, et al. Using point-of-care testing to make rapid HIV-1 tests in labor really rapid. AIDS. 2003;17:2121-2124.
13. Peters V, Liu KL, Dominguez K, et al. Missed opportunities for perinatal HIV prevention among HIV-exposed infants born 1996-2000, pediatric spectrum of HIV disease cohort. Pediatrics. 2003;111:1186-1191.
14. Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. N Engl J Med. 1994;331:1173-1180.
15. Wade NA, Birkhead GS, Warren BL, et al. Abbreviated regimens of zidovudine prophylaxis and perinatal transmission of the human immunodeficiency virus. N Engl J Med. 1998;339:1409-1414.
16. Sansom SL, Jamieson DJ, Farnham PG, et al. Human immunodeficiency virus retesting during pregnancy: cost and effectiveness in preventing perinatal transmission. Obstet Gynecol. 2003;102:782-790.
17. Mrus JM, Tsevat J. Cost-effectiveness of interventions to reduce vertical HIV transmission from pregnant women who have not received prenatal care. Med Decis Making. 2004;24:30-39.
18. Aaron E, Levine AB, Monahan K, Biondo CP. A rapid HIV testing program for labor and delivery in an inner-city teaching hospital. AIDS Reader. 2006;16:22-24, 28-30, 37.
19. Recommendations for the use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States. Updated October 12, 2006. Available at:

http://aidsinfo.nih.gov/ContentFiles/PerinatalGL.pdf

. Accessed December 5, 2006.
20. Nevada State Health Division. A profile of children born to HIV infected mothers in Nevada: 1994-2003. November 2005. Available at:

http://health2k.state.nv.us/nihds/publications/SpecialRptChildBornHIVPosMothersNev.pdf

. Accessed November 29, 2006.
21. Handford CD, Tynan AM, Rackal JM, Glazier RH. Setting and organization of care for persons living with HIV/AIDS. Cochrane Database Syst Rev. 2006;3:CD004348.