HIV and Pregnancy: Prevention of Mother-to-Child Transmission

Advances in Maternal and Neonatal Health

Session Objectives

To discuss best practice for antenatal, intrapartum and postpartum care of the HIV-positive mother to reduce motherto-child transmission
To review the evidence supporting these practices

HIV and Pregnancy

HIV-Related Counseling Issues During Pregnancy

Educate/counsel regarding HIV and pregnancy before pregnancy:

Impact of HIV on pregnancy and pregnancy on HIV Maternal health Long-term health of mother and care for children Perinatal transmission Use of antiretrovirals and other drugs in pregnancy

HIV and Pregnancy

Pregnancy Effects on HIV

In all women, the absolute CD4 count decreases no matter whether HIV-positive or negative (pregnancy does not make HIV worse)
In HIV-positive women, percentage of CD4 cells should not change and viral load should not change because of pregnancy

HIV and Pregnancy

Adverse Pregnancy Outcomes and Relationship to HIV Infection

Pregnancy Outcome Spontaneous abortion Stillbirth Relationship to HIV Infection Limited data, but evidence of possible increased risk No association noted in developed countries; evidence of increased risk in developing countries

Perinatal mortality

No association noted in developed countries, but data limited; evidence of increased risk in developing countries
Limited data in developed countries; evidence of increased risk in developing countries Evidence of possible increased risk

Newborn mortality Intra-uterine growth retardation

Anderson 2001.

HIV and Pregnancy

Adverse Pregnancy Outcomes and Relationship to HIV Infection (continued)

Pregnancy Outcome Relationship to HIV Infection

Low birth weight

Preterm delivery Pre-eclampsia Gestational diabetes Amnionitis

Evidence of possible increased risk

Evidence of possible increased risk, especially w/ more advanced disease No data No data Limited data; more recent studies do not suggest an increased risk; some earlier studies found increased histologic placental inflammation, particularly in those with preterm deliveries Minimal data No evidence of increased risk
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Oligohydramnios Fetal malformation

Anderson 2001.

Mother-to-Child Transmission

2535% of HIV positive pregnant mothers will pass HIV to their newborns
In the absence of breastfeeding:

30% of transmission in utero

70% of transmission during the delivery

Meta-analysis showed 14% transmission with breastfeeding and 29% transmission with acute maternal HIV infection or recent seroconversion

DeCock et al 2000; Dunn et al 1992; WHO/UNAIDS 1999. HIV and Pregnancy 7

Risk Factors for Mother-to-Child Transmission

Viral load (HIV-RNA level)

Genital tract viral load CD4 cell count Clinical stage of HIV

STDs and other coinfections

Antiretroviral agents Preterm delivery Placental disruption

Unprotected sex with multiple partners

Smoking cigarettes Substance abuse Vitamin A deficiency

Invasive fetal monitoring

Duration of membrane rupture Vaginal delivery vs. cesarean section Breastfeeding

Anderson 2001.

HIV and Pregnancy

Interventions to Reduce Mother-to-Child Transmission

HIV testing in pregnancy

Antenatal care Antiretroviral agents Obstetric interventions

Avoid amniotomy Avoid procedures: Forceps/vacuum extractor, scalp electrode, scalp blood sampling Restrict episiotomy Elective cesarean section Remember infection prevention practices Newborn feeding: Breastmilk vs. formula

HIV and Pregnancy

HIV Testing during Pregnancy

Advantages:

Possible treatment of mother Reduce risk of mother-to-child transmission Future family planning issues

Precautions against further spread

If negative, advise about HIV prevention

Counseling is important!

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Antenatal Care

Most HIV-infected women will be asymptomatic

Watch for signs/symptoms of AIDS and pregnancy-related complications Unless complication develops, no need to increase number of visits Treat STDs and other coinfections Counsel against unprotected intercourse Avoid invasive procedures and external cephalic version Give antiretroviral agents, if available Counsel about nutrition

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Antiretrovirals

Zidovudine (ZDV):

Long course Short course

Nevirapine

ZDV/lamivudine (ZDV/3TC)

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ZDV Perinatal Transmission Prophylaxis Regimen: ACTG 076 Trial

Antepartum Initiation at 1434 weeks gestation and continued throughout pregnancy PACTG 076 regimen: ZDV 5 times daily Acceptable alternative regimen: ZDV 2 or 3 times daily (depending on dose) During labor, ZDV IV over 1 hour, followed by a continuous infusion of IV until delivery Oral administration of ZDV to newborn for first 6 weeks of life, beginning at 812 hours after birth

Intrapartum Postpartum

Anderson 2000.

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Intrapartum vs. Postpartum Regimens for HIV-Infected Women in Labor with No Prior Antiretroviral Therapy
Drug Regimen Nevirapine Maternal Intrapartum Newborn Postpartum Data on Transmission Transmission at 6 weeks 12% with nevirapine compared to 21% with ZDV, a 47% (95% CI, 2064%) reduction

One oral One oral dose at dose at onset age 4872 hours (if of labor mother received nevirapine < 1 hour before delivery, newborn given oral nevirapine as soon as possible after birth and at 4872 hours)

Anderson 2001.

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Intrapartum vs. Postpartum Regimens for HIV-Infected Women in Labor with No Prior Antiretroviral Therapy (contd.)
Drug Regimen ZDV/3TC Maternal Intrapartum ZDV orally at onset of labor followed by dose orally every 3 hours until delivery AND 3TC orally at onset of labor, followed by dose orally every 12 hours
Anderson 2001.
HIV and Pregnancy 15

Newborn Postpartum ZDV orally every 12 hours AND 3TC orally every 12 hours for 7 days

Data on Transmission Transmission at 6 weeks 10% with ZDV/3TC compared to 17% with placebo, a 38% reduction

Intrapartum vs. Postpartum Regimens for HIV-Infected Women in Labor with No Prior Antiretroviral Therapy (contd.)
Drug Regimen ZDV Maternal Intrapartum Newborn Postpartum Data on Transmission Transmission 10% with ZDV compared to 27% with no ZDV treatment, a 62% (95% CI, 19-82%) reduction

IV bolus, followed Orally every 6 by continuous hours for 6 infusion of every weeks hour until delivery

Anderson 2001. HIV and Pregnancy 16

Intrapartum vs. Postpartum Regimens for HIV-Infected Women in Labor with No Prior Antiretroviral Therapy (contd.)
Drug Regimen ZDV and Nevirapine Maternal Intrapartum IV bolus, then continuous infusion until delivery AND Nevirapine single oral dose at onset of labor Newborn Postpartum Data on Transmission

Orally every 6 No data hours for 6 weeks AND Nevirapine single oral dose at age 4872 hours

Anderson 2001.

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Obstetric Procedures
Because of increased fetal exposure to infected maternal blood and secretions, increased transmission may come from:

Amniotomy Fetal scalp electrode/sampling Forceps/vacuum extractor Episiotomy Vaginal tears

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Delivery: Cesarean vs. Vaginal Birth

Risk of mother-to-child transmission increased 2% each hour after membranes have been ruptured
Cesarean section before labor and/or rupture of membranes reduces risk of mother-to-child transmission by 5080% compared with other modes of delivery in women on no antiretroviral therapy or on ZDV alone No evidence of benefit with cesarean section after onset of labor or membranes have been ruptured Cesarean section, however, increases morbidity and possible mortality to mother

Give antibiotic prophylaxis for cesarean section in HIV-infected women

International Perinatal HIV Group 1999; HIV and Pregnancy Semprini 1995.

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Recommended Infection Prevention Practices

Needles:

Take care! Minimal use Suturing: Use appropriate needle and holder Care with recapping and disposal

Wear gloves, wash hands with soap immediately after contact with blood and body fluids
Cover incisions with watertight dressings for first 24 hours

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Recommended Infection Prevention Practices (continued)

Use:

Plastic aprons for delivery Goggles and gloves for delivery and surgery Long gloves for placenta removal

Dispose of blood, placenta and waste safely

PROTECT YOURSELF!

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Newborn

Wash newborn after birth, especially face

Avoid hypothermia Give antiretroviral agents, if available

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Breasfeeding Issues

Warmth for newborn

Nutrition for newborn Protection against other infections Safety unclean water, diarrheal diseases Risk of HIV transmission Contraception for mother Cost

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Breastfeeding Recommendations
If the woman is:

HIV-negative or does not know her HIV status, promote exclusive breastfeeding for 6 months HIV-positive and chooses to use replacements feedings, counsel on the safe and appropriate use of formula HIV-positive and chooses to breastfeed, promote exclusive breastfeeding for 6 months

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South Africa Breastfeeding Trial: Objective and Design

Objective: To assess whether pattern of breastfeeding is a critical determinant of early mother-to-child transmission of HIV
549 HIV-infected women studied Compared newborns at 3 months that had been:

Exclusively breastfed Breastfed and formula-fed Never breastfed

Coutsoudis et al 1999.

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South Africa Breastfeeding Trial: Results and Conclusion

Risk of transmission in:

156 newborns who were never breastfed: 18.8% (95% CI 12.624.9) 288 newborns who were breastfed and formula fed: 24.1% (95% CI 19.029.2) 103 newborns who were exclusively breastfed: 14.6 (95% CI 7.721.4)

Conclusion: Newborns who were exclusively breastfed for at least 3 months did not have any excess risk of HIV infection compared to newborns who were not breastfed

Coutsoudis et al 1999.

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Conclusion

Voluntary counseling and testing

Antenatal, intrapartum and postpartum care to mother can decrease risk of mother-to-child transmission

Antiretroviral therapy can also reduce risk of transmission

Newborn care: Feeding

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References
Anderson J (ed). 2001. A Guide to the Clinical Care of Women with HIV, 2nd ed. U.S. Department of Health and Human Services, Health Resources and Services Administration: Rockville, Maryland. Coutsoudis A et al. 1999. Influence of infant-feeding patterns on early mother-to-child transmission of HIV-1 in Durban, South Africa: A prospective cohort study. Lancet 354: 471476. DeCock K et al. 2000. Prevention of mother-to-child transmission in resource-poor countries: Translating research into policy and practice. J Am Med Assoc 283(9): 11751182. Dunn D et al. 1992. Risk of HIV-1 transmission through breastfeeding. Lancet 340(8819): 585588. Gray G. 2000. The PETRA study: Early and late efficacy of three short ZDV/3TC combinations regimens to prevent mother-to-child transmission of HIV-1. XIII International AIDS Conference, Durban, South Africa.

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References (continued)
International Perinatal HIV Group. 1999. The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type 1. N Engl J Med 340(14): 977987. Mandelbrot L et al. 1996. Obstetric factors and mother-to-child transmission of human immunodeficiency virus type 1: The French perinatal cohorts. Amer J Obstet Gynecol 175(3 pt 1): 661667. Semprini AE et al. 1995. The incidence of complications after cesarean section in 156 women. AIDS 9:913917. Shaffer N et al. 1999. Short-course ZDV for perinatal HIV-1 transmission in Bangkok, Thailand: A randomized controlled trial. Lancet 353: 773780. Sperling RS et al. 1996. Maternal viral load, ZDV treatment, and the risk of transmission of HIV type 1 from mother to infant. N Engl J Med 335(22): 16211629. UNICEF/UNAIDS/WHO Technical Consultation on HIV and Infant Feeding. 1998. HIV and Infant Feeding: Implementation of Guidelines. WHO: Geneva. World Health Organization (WHO)/Joint United Nations Programme on HIV/AIDS (UNAIDS). 1999. HIV In Pregnancy: A Review. WHO/UNAIDS: Geneva. HIV and Pregnancy 29