Moms, Babes and HIV: Perinatal
Transmission of HIV Can Be Prevented

Carol M Fulton, MSN, ARNP

Introduction

Over the past few years in the United States, news in the HIV epidemic has been fairly optimistic. People with HIV are living longer. Treatment protocols have improved the quality of life for many. Morbidity and mortality statistics have dramatically improved. At first glance, one might think the battle is won. However, the bad news is that people are still becoming infected with this deadly virus. Women and children are a very vulnerable population in the epidemic. AIDS rates in women of childbearing age rose 63% between 1991 and 1995. The Center for Disease Control and Prevention (CDC) documented over 114,000 women with AIDS by June, 1999.1 Seventy-nine thousand five hundred of those cases were in Florida and 1392 were pediatric cases. Of the pediatric cases, 96% were infected by perinatal transmission.2 Thirty-two percent of the people reported to have been infected with HIV between July, 1998 and June, 1999 were women.1 African American and Hispanic women are over represented in these numbers, but all ethnic groups are involved. Florida is the third in number of United States AIDS cases, the second in pediatric AIDS, and the first in HIV cases since July of 1997. It is estimated that 1 in 156 (0.6%) Floridians is currently living with HIV. This translates to 1 in 286 Whites, 1 in 50 African Americans, and 1 in 127 Hispanics. Remember, women are the fastest growing group within these statistical groups.

Approximately 6,000 to 7,000 HIV infected women give birth in this country every year.3 Without proper medical intervention 15 to 30% of those babies could potentially be born HIV positive, which would then translate into 900 to 2100 new HIV infected babies each year. Appropriate treatment decreases the rate of transmission from mother to baby dramatically. The incidence of pediatric AIDS attributed to mother-infant transmission decreased by 66% between 1993 and 1997 in the United States following the wide-spread use of the PACTG 076 ZDV regimen.4 Transmission rates as low as <2% have been reported among women with undetectable plasma VL. Providers of Women's Care can make a difference by appropriately counseling pregnant women and testing all pregnant women regardless of specific risk factors. Florida has required health care workers who attend pregnant women to counsel them about the benefits of HIV testing whenever routine prenatal care is offered. Right now research shows that as many as 15% of HIV positive women are not identified until labor.5

Voluntary HIV Testing and Counseling

The best way to prevent HIV infections in infants is to prevent HIV infection in women. In order to accomplish this, routine HIV risk assessment and counseling is essential. Many women do not know or believe they are at risk for HIV infection. Remember, the condition of pregnancy indicates at least some level of risk as the woman has had unprotected intercourse at least once. High-risk behaviors include injection or other illicit drug use, exchanging sex for money or drugs, and multiple sex partners during pregnancy. Risk-based testing has been shown to identify fewer women than routine voluntary testing of all pregnant women. When given the information about HIV, the majority of pregnant women accept HIV testing, especially, when it is recommended by their healthcare provider.6 Information about prevention of perinatal transmission and treatment options should also be included in the prenatal counseling.

HIV test results must be obtained and interpreted carefully. Several options are available. The most common is the ELISA, enzyme immunoassay (EIA). If this is repeatedly reactive, it is then confirmed by the Western Blot. Both the ELISA and Western Blot are highly sensitive and specific. A false positive result is very rare. Indeterminate (inconclusive) results can be caused by either incomplete antibody response in a newly infected person who is seroconverting or from a person with end stage HIV disease, and very rarely from an uninfected person. An indeterminate result, although rare, may be slightly more common in pregnancy.7, 8 Incorrect HIV test results occur primarily because of specimen handling errors, lab errors or failure to follow recommended testing algorithms. For rapid/expedited testing, the SUDS test (Single Use Diagnostic System) is the only rapid HIV test approved by the FDA. A negative result is most likely a true negative. False Positive results do occur. Therefore, all reactive rapid tests must be confirmed by a supplemental test. Consult with an HIV expert as needed.

Timing of Perinatal HIV Transmission

Perinatal transmission may occur during the prenatal period via an intrauterine or transplacental route, intrapartally during labor and delivery, or postpartally through breastfeeding. It is now clear that 70% to 80% of perinatal transmission occurs during or close to the time of birth.9 Micro-transfusion of maternal blood during labor contractions, infection after rupture of membranes, or direct contact of the fetus with infected secretions and blood from the genital tract have been implicated.

There are multiple factors associated with increased risk of perinatal transmission of HIV infection. Maternal factors include advanced HIV disease as evidenced by low CD4 counts and/or high viral load, smoking during pregnancy, use of illicit drugs, frequent unprotected sexual intercourse with multiple partners, and anemia. Breaks in the placental barrier related to smoking, use of illicit drugs, STD and chorioamnionitis are a factor. The labor/birth process has already been mentioned previously. Premature rupture of the membranes, especially longer than 4 hours and maternal viral load >1000 copies have been identified as a risk factor. Evidence points to Caesarean section as an option to decrease vertical transmission.10 Invasive procedures including fetal monitoring and amniocentesis should be avoided. Prematurity/low gestational age and low birth weight are infant factors that should not be overlooked. Breast milk is not recommended for infants born to HIV positive women as there is a 14% addition risk with breastfeeding in established infections and a 29% increased risk with primary infection and sero-conversion in the post-partum period.11

What have we learned? - PACTG 076

PACTG 076 was a clinical trail of over 477 pregnant women with HIV infection. Women in the experimental group received zidovudine (ZDV) during pregnancy from 34 weeks gestation, during labor and delivery, and their infants received oral ZDV for 6 weeks after birth. The study halted in 1994 when interim results showed a significant difference in transmission rate between the ZDV and placebo groups.12 There are now six years of follow up on the infants studied in the PACTG Study 076. The only short-term adverse event noted was decreased hemoglobin in infants on ZDV at six weeks. The decreased levels were not clinically significant and resolved by 12 week. after cessation of the drug. Growth and development have been normal in the United States cohort. Table 1 spells out the recommended zidovudine perinatal transmission prophylaxis regimen.
 
Of course, all medications taken during pregnancy come with a risk to the unborn fetus. The FDA currently rates all antiretrovirals as either B (animal reproduction studies fail to demonstrate a risk to the fetus and adequate and well-controlled studies of pregnant women have not been conducted)

or C (safety in human pregnancy has not been determined, animal studies are either positive for fetal risk or have not been conducted and the drug should not be used unless the potential benefit outweighs the potential risk to the fetus).13 Phase I studies of many of the new medications are in progress and a national registry has been established. Recent non-human primate studies have shown teratogenicity associated with efavirenz (Sustiva), and recommendations are that it not be used during pregnancy. Although there are obvious benefits to therapy and proven efficacy for some agents, there are risks. Pregnant women must be informed about these risks before they make a decision. The support of a clinician with expertise in the treatment of HIV during pregnancy is strongly recommended. The issues are complex but the outlook is optimistic with current treatment modalities. One must also remember that untreated HIV disease carries significant risks for the mother and the unborn fetus.

Antiretroviral Treatment (ART) During Pregnancy

The updated Guidelines for the Use of Antiretrviral Agents in HIV-infected Adults and Adolescents recommend initiation of combination antiretroviral treatment for all symptomatic people and for asymptomatic people with a CD4 count >350/mm3, regardless of plasma HIV RNA. For asymptomatic people with CD4 counts >350/mm3 and plasma HIV RNA >30,000 copies/ml (bDNA) or >55,000 copies/ml (RT-PCR), some experts would initiate therapy, recognizing that the risk of developing AIDS within three years without treatment is 30%. For people with CD4 counts >350/mm3 and viral loads less than this, some experts would continue to monitor levels and observe. The reasoning behind this change in the guidelines is to decrease the incidence and duration of toxicities related to the antiretroviral drugs.

For pregnant women, their clinical, virologic and immunologic status should be of primary importance in guiding treatment decisions. Risks and benefits must be considered and options should be discussed. Perinatal transmission remains a concern since transmission of HIV has occurred even at undetectable levels of plasma HIV RNA. The risk of perinatal transmission is known to be minimal when the HIV RNA level is <1000 copies/ml. Therefore, many experts recommend standard combination therapy for women with HIV RNA >1000 copies /ml regardless of clinical and immunologic status.13 The goal of therapy for the pregnant woman is to suppress and maintain the viral load below the limit of detection and to raise the CD4 cell count. Clinicians are encouraged to register their patients in the Antiretroviral Pregnancy Registry (1-800-258-4263). The national registry has been established to provide follow up information on the outcome of the pregnancy and the effect of the drugs on outcome.

Peripartum Management

Careful planning for the delivery should be initiated during pregnancy. For women on combination therapy with a viral load (VL) below 1000 copies/ml and the CD4 is normal, a vaginal delivery is often allowed. In clinical situations such as this, the transmission risk is calculated to be <2%. If the pregnant woman chooses monotherapy with ZDV starting at 12 weeks gestation, or receives no ART or has a VL >1000 copies/ml, an elective C-section should be strongly considered.14 When delivery is via the vaginal route, careful management to minimize infant contact with maternal secretions should be implemented. Invasive procedures, including scalp electrodes, should be avoided. Rupture of membranes over 4 hours is associated with an increased risk of transmission. Generally, regardless of the mother's antiretroviral therapy (ART), ZDV is administered IV during labor and delivery in addition to her PO antiretroviral medications. Optimally, the drip should begin four hours before delivery. Unfortunately, some women do not receive prenatal care early in pregnancy or present in labor without prior treatment. Several alternative regimens starting in late pregnancy or labor have proved efficacious, although not as much as the full ACTG 076 protocol. Single dose nevirapine at the onset of labor followed by a single dose of nevirapine to the newborn at age 48 hours is one established protocol.10

All exposed newborn infants should begin ZDV therapy by mouth preferably within 6-12 hours of birth and continue the medication for 6 weeks (ZDV 2mg/kg every 6 hours) until HIV infection can be reasonably excluded, that is when the infant has had two negative HIV PCRs performed at >1 month of age and > 4 months of age. At least two negative serologic tests done after 14-16 months of age are recommended to confirm sero-conversion. (Guidelines)

Conclusion

The reality of HIV infection is a complex issue. Social, economic, psychologic, family, and health care issues all coalesce to create stress for the woman affected by this diagnosis. Adding pregnancy to the mix further complicates an already difficult situation. Preventing perinatal HIV transmission includes early access to prenatal care, education for women about the risk of HIV infection, access to antiretroviral medications and management of the pregnancy by clinicians conversant with both Obstetrical and HIV care.

Women can be at risk of infection from HIV and not be aware of it. Clinicians have a responsibility to assess for risk factors, educate clients, advocate for HIV testing as a routine for all pregnant women, provide risk reduction counseling and interventions while delivering compassionate care to these women. A multidisciplinary team is essential to the achievement of this goal. This is one area of HIV care in which we can win. Infants born to HIV infected women can be born free of the disease.

References

  1. Center for Disease Control and Prevention. HIV/AIDS Surveillance Report (1999). US Department of Health and Human Services. Public Health Service, 10: 1-40.
  2. Florida HIV/AIDS Surveillance Report. (2000). 12:1, December.
  3. Nielsen, K. (1999). Prevention is the best intervention: How far are we from eradication of perinatal HIV-1 transmission? Retrieved September 1999 from Medscape.
  4. Lindgren, M., Byers, R., Thomas, P., et al. (1999). Trends in perinatal transmission of HIV/AIDS in the US. JAMA. 282:531-538.
  5. Center for Disease Control. (2001, January). US Public Health Service Task Force recommendations for the use of antiretroviral drugs in pregnant HIV-1 infected women for maternal health and interventions to reduce perinatal HIV transmission in the US. http:// hivatis.org.
  6. Royce, R. Walter, E., Fernandez, M., et al. (2001). Barriers to universal prenatal HIV testing in 4 US locations in 1997. American Journal of Public Health. 91:727-733.
  7. Celum, C., Coombs, R., Jones, M., et al. (1994). Risk factors for repeatedly reactive HIV-1 EIA and indeterminate western blots. Archives of Internal Medicine, 154: 1129-1137.
  8. Gwinn, M., Redus, M., Granade, T., et al. (1992). HIV-1 serologic test results for one million newborn dried-blood specimens: Assay performance and implications for screening. Journal of Acquired Immune Deficiency Syndromes, 5: 505-512.
  9. The International Perinatal HIV Group. (1999). Mode of delivery the risk of vertical transmission of human immunodeficiency virus type 1, a meta- analysis of 15 prospective cohort studies. New England Journal of Medicine, 340: 977-987.
  10. Stein, E., Handelman, E. and Matthews, R. (2000). Reducing perinatal transmission of HIV: Early diagnosis and interventions during pregnancy. Journal of Midwifery & Women's Health, 45: 122-129.
  11. Fowler, M., Simonds, R., Roongpisuthipong, A. (2000). Update on Perinatal HIF Transmission. In M. Rogers (Ed), Pediatric Clinics of North America, 21-28.
  12. Connor, E., Sperling, R., Gelber, R., et al. (1994). Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. New England Journal of Medicine, 331, 1173.
  13. CDC. (2000). US Public Health Service Task Force 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. Available: http://www.hivatis.org/trtgdlns.html.
  14. ACOG Committee Opinion on Obstetric Practice. (2000). Scheduled cesarean delivery and the prevention of vertical transmission of HIV infection (234). Washington, DC: The American College of Obstetricians and Gynecologists.
June/July, 2001/ Jacksonville Medicine

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