1. HIV and Pregnancy: Prevention of Mother-to-Child Transmission
4/19/2017
HIV and Pregnancy: Prevention of Mother-to-Child Transmission
Advances in Maternal and Neonatal Health
There are many issues that relate to HIV and pregnancy, but this talk will mainly focus on issues of preventing mother-to-child transmission, particularly the issue of breastfeeding.

2. 4/19/2017
Session Objectives
To discuss best practice for antenatal, intrapartum and postpartum care of the HIV-positive mother to reduce mother-to-child transmission
To review the evidence supporting these practices
HIV and Pregnancy

3. HIV-Related Counseling Issues During Pregnancy
4/19/2017
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
Counseling before pregnancy is important. It should focus on the effects of HIV on pregnancy, health of the mother, long-term health of the mother and child, how perinatal transmission occurs and how to prevent it with medicines.
HIV and Pregnancy

4. Pregnancy Effects on HIV
4/19/2017
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
Pregnancy does not the effects that HIV has on the body.
HIV and Pregnancy

5. Adverse Pregnancy Outcomes and Relationship to HIV Infection
4/19/2017
Adverse Pregnancy Outcomes and Relationship to HIV Infection
Pregnancy Outcome
Relationship to HIV Infection
Spontaneous abortion
Limited data, but evidence of possible increased risk
Stillbirth
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
Newborn mortality
Limited data in developed countries; evidence of increased risk in developing countries
Intra-uterine growth retardation
Evidence of possible increased risk
There may be association between HIV and:
Spontaneous abortion
Stillbirth
Maternal mortality
Newborn mortality
Low birth weight
Preterm delivery
Amnionitis
HIV and Pregnancy
Anderson 2001.

6. Relationship to HIV Infection
4/19/2017
Adverse Pregnancy Outcomes and Relationship to HIV Infection (continued)
Pregnancy Outcome
Relationship to HIV Infection
Low birth weight
Evidence of possible increased risk
Preterm delivery
Evidence of possible increased risk, especially w/ more advanced disease
Pre-eclampsia
No data
Gestational diabetes
Amnionitis
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
Oligohydramnios
Minimal data
Fetal malformation
No evidence of increased risk
HIV and Pregnancy
Anderson 2001.

7. Mother-to-Child Transmission
4/19/2017
Mother-to-Child Transmission
25–35% 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
Most HIV transmission (70%) occurs at the time of delivery, but a substantial amount (30%) occurs antenatally. A significant contributor to transmission is breastfeeding.
In 1998, 10% of all new HIV infections were in children, almost all mother-to-child transmissions (90%) were in Africa.
These statistics are given to emphasize that this is a serious worldwide problem, and a particular problem in Africa.
The percentages given are of all cases of HIV transmission, not of all pregnancies. It suggests to us that we should be focusing our efforts on interventions at the time of delivery and with breastfeeding.
In sub-Saharan Africa mortality rates for children under age 5 are now 1/3-2/3 higher than they would be in the absence of AIDS, contributing to the progressive reduction in life expectancy.
DeCock et al 2000; Dunn et al 1992; WHO/UNAIDS 1999.
HIV and Pregnancy

8. Risk Factors for Mother-to-Child Transmission
4/19/2017
Risk Factors for Mother-to-Child Transmission
Viral load (HIV-RNA level)
Genital tract viral load
CD4 cell count
Clinical stage of HIV
Unprotected sex with multiple partners
Smoking cigarettes
Substance abuse
Vitamin A deficiency
STDs and other coinfections
Antiretroviral agents
Preterm delivery
Placental disruption
Invasive fetal monitoring
Duration of membrane rupture
Vaginal delivery vs. cesarean section
Breastfeeding
HIV and Pregnancy
Anderson 2001.

9. Interventions to Reduce Mother-to-Child Transmission
4/19/2017
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
There are many interventions that may help reduce mother-to-child transmission, including obstetric interventions and newborn feeding. Antenatal care and antiretroviral agents play a significant role in reducing transmission.
HIV and Pregnancy

10. HIV Testing during Pregnancy
4/19/2017
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!
Discuss the advantages and disadvantages of HIV testing during pregnancy. There are many disadvantages to consider. A woman who is HIV positive, may be abandoned by her husband and family.
HIV and Pregnancy

11. Antenatal Care Most HIV-infected women will be asymptomatic
4/19/2017
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
When providing antenatal care, there is no need to increase the number of visits unless symptoms or complications develop. If available, antiretroviral agents given during antenatal care can benefit both the mother and child.
Good nutrition is important. Anemia is an independent predictor of progression and death in HIV-infected individuals. Vitamin A deficiency has also been associated with increased risk of mother-to-child transmission.
HIV and Pregnancy

12. Antiretrovirals Zidovudine (ZDV): Long course Short course Nevirapine
4/19/2017
Antiretrovirals
Zidovudine (ZDV):
Long course
Short course
Nevirapine
ZDV/lamivudine (ZDV/3TC)
Several antiretroviral regimens exist that have been shown to reduce mother-to-child transmission in clinical trials. Short-course ZDV and nevirapine are most affordable and are associated with good patient compliance.
Long course ZDV, given from 14 weeks of pregnancy orally, IV during labor and to the non-breastfed newborn for 6 weeks showed significant decrease in transmission (22.6% in placebo group vs. 7.6% in ZDV group). (Sperling RS et al Maternal viral load, ZDV treatment, and the risk of transmission of HIV type 1 from mother to infant. N Engl J Med 335 (22): ) There were no ill effects on the fetus except for mild and temporary anemia.
A short-course ZDV trial in Thailand compared placebo group with group given one tablet of ZDV 300 mg twice a day from 36 weeks gestation and every 3 hours from onset of labor until delivery. Newborns were not breastfed. This regimen reduced risk of transmission by 50% at a cost of $50 per patient. (Shaffer N et al Short-course ZDV for perinatal HIV-1 transmission in Bangkok, Thailand: A randomized controlled trial. Lancet 353: )
Combination of ZDV and lamivudine given in mostly breastfeeding population given at 36 weeks and onset of labor and for 1 week postpartum to newborn and mother reduced transmission by about 50% compared to placebo. (Gray G 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.)
Nevirapine. A single 200 mg dose at the onset of labor and a single 2 mg/kg dose to the newborn at hours resulted in a 47% decrease in transmission compared to ZDV during labor and for 1 week to newborn. The cost is approximately $4 to the patient.
HIV and Pregnancy

13. ZDV Perinatal Transmission Prophylaxis Regimen: ACTG 076 Trial
4/19/2017
ZDV Perinatal Transmission Prophylaxis Regimen: ACTG 076 Trial
Antepartum
Initiation at 14–34 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)
Intrapartum
During labor, ZDV IV over 1 hour, followed by a continuous infusion of IV until delivery
Postpartum
Oral administration of ZDV to newborn for first 6 weeks of life, beginning at 8–12 hours after birth
HIV and Pregnancy
Anderson 2000.

14. 4/19/2017
Intrapartum vs. Postpartum Regimens for HIV-Infected Women in Labor with No Prior Antiretroviral Therapy
Drug Regimen
Maternal Intrapartum
Newborn Postpartum
Data on Transmission
Nevirapine
One oral dose at onset of labor
One oral dose at age 48–72 hours (if mother received nevirapine < 1 hour before delivery, newborn given oral nevirapine as soon as possible after birth and at 48–72 hours)
Transmission at 6 weeks 12% with nevirapine compared to 21% with ZDV, a 47% (95% CI, 20–64%) reduction
Advantages of nevirapine include:
Inexpensive
Oral regimen
Simple, easy to administer
Can give directly observed treatment
Disadvantages
Unknown efficacy if mother has nevirapine-resistant virus
HIV and Pregnancy
Anderson 2001.

15. 4/19/2017
Intrapartum vs. Postpartum Regimens for HIV-Infected Women in Labor with No Prior Antiretroviral Therapy (cont’d.)
Drug Regimen
Maternal Intrapartum
Newborn Postpartum
Data on Transmission
ZDV/3TC
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
ZDV orally every 12 hours
AND
3TC orally every 12 hours for 7 days
Transmission at 6 weeks 10% with ZDV/3TC compared to 17% with placebo, a 38% reduction
Advantages:
Oral regimen
Compliance easier than 6 weeks of ZDV alone as newborn regimen is only 1 week
Disadvantages:
Potential toxicity of multiple drug exposure
HIV and Pregnancy
Anderson 2001.

16. 4/19/2017
Intrapartum vs. Postpartum Regimens for HIV-Infected Women in Labor with No Prior Antiretroviral Therapy (cont’d.)
Drug Regimen
Maternal Intrapartum
Newborn Postpartum
Data on Transmission
ZDV
IV bolus, followed by continuous infusion of every hour until delivery
Orally every 6 hours for 6 weeks
Transmission 10% with ZDV compared to 27% with no ZDV treatment, a 62% (95% CI, 19-82%) reduction
Advantages:
Has been standard recommendation based on clinical trial results
Disadvantages:
Requires IV administration, availability of ZDV IV formulation
Compliance with 6 week newborn regimen
Anderson 2001.
HIV and Pregnancy

17. 4/19/2017
Intrapartum vs. Postpartum Regimens for HIV-Infected Women in Labor with No Prior Antiretroviral Therapy (cont’d.)
Drug Regimen
Maternal Intrapartum
Newborn Postpartum
Data on Transmission
ZDV and Nevirapine
IV bolus, then continuous infusion until delivery
AND
Nevirapine single oral dose at onset of labor
Orally every 6 hours for 6 weeks
Nevirapine single oral dose at age 48–72 hours
No data
Advantages:
Potential benefit if maternal virus is resistant to either nevirapine or ZDV
Synergistic inhibition of HIV replication with combination in vitro
Disadvantages:
Requires IV administration, availability of ZDV intravenous formulation
Compliance with 6 week newborn regimen
Unknown efficacy and limited toxicity data
HIV and Pregnancy
Anderson 2001.

18. 4/19/2017
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
During delivery, any procedures that either increase the chance of the mother bleeding or may cause breaks in the skin of the fetus through which there may be direct contact with the mother’s blood or vaginal secretions will increase the risk of transmission of HIV from mother to child.
Avoid amniotomy, fetal scalp electrode/sampling, operative vaginal delivery and episiotomy/vaginal trauma. These procedures can increase risk of transmission.
HIV and Pregnancy

19. Delivery: Cesarean vs. Vaginal Birth
4/19/2017
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 50–80% 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
Pregnancy may increase the risk of HIV shedding in maternal cervico-vaginal secretions.
In a recent meta-analysis from 15 prospective studies, the risk of mother-to-child transmission increased 2% each hour after membranes have been ruptured.
Cesarean section before the onset of labor or ruptured membranes can significantly reduce the risk of transmission from mother to child, especially if antiretroviral agents are not available. Cesarean sections however, have increased the risk of morbidity and possible mortality for the mother, particularly in low-resource settings because of anesthesia risks, blood loss, pain and increased recovery time.
International Perinatal HIV Group 1999; Semprini 1995.
HIV and Pregnancy

20. Recommended Infection Prevention Practices
4/19/2017
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
Universal precautions to protect yourself are very important.
HIV and Pregnancy

21. Recommended Infection Prevention Practices (continued)
4/19/2017
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!
HIV and Pregnancy

22. Newborn Wash newborn after birth, especially face Avoid hypothermia
4/19/2017
Newborn
Wash newborn after birth, especially face
Avoid hypothermia
Give antiretroviral agents, if available
Wash maternal blood and secretions off the newborn as soon as possible, particularly off the face. Beware of hypothermia!
If available, give antiretroviral agents to the newborn to reduce the risk of HIV transmission.
HIV and Pregnancy

23. Breasfeeding Issues Warmth for newborn Nutrition for newborn
4/19/2017
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
Breastfeeding is associated with a 14% risk of HIV transmission to newborns, yet provides nutrition for the newborn and an inexpensive method of feeding and contraception.
Formula feeding also poses risks to the newborn, such as diarrhea from contamination of formula with unclean water or malnutrition from formula being too dilute.
Factors associated with breastfeeding and mother-to-child transmission:
Cracked nipples/breast abscess or mastitis
Newborn oral thrush
Duration of breastfeeding
Exclusively breastfeeding versus breastfeeding and formula feeding.
HIV and Pregnancy

24. Breastfeeding Recommendations
4/19/2017
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
HIV and Pregnancy

25. South Africa Breastfeeding Trial: Objective and Design
4/19/2017
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.
HIV and Pregnancy

26. South Africa Breastfeeding Trial: Results and Conclusion
4/19/2017
South Africa Breastfeeding Trial: Results and Conclusion
Risk of transmission in:
156 newborns who were never breastfed: 18.8% (95% CI 12.6–24.9)
288 newborns who were breastfed and formula fed: 24.1% (95% CI 19.0–29.2)
103 newborns who were exclusively breastfed: 14.6 (95% CI 7.7–21.4)
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.
HIV and Pregnancy

27. Conclusion Voluntary counseling and testing
4/19/2017
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
HIV and Pregnancy

28. 4/19/2017
References
Anderson J (ed) 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 Influence of infant-feeding patterns on early mother-to-child transmission of HIV-1 in Durban, South Africa: A prospective cohort study. Lancet 354: 471–476.
DeCock K et al Prevention of mother-to-child transmission in resource-poor countries: Translating research into policy and practice. J Am Med Assoc 283(9): 1175–1182.
Dunn D et al Risk of HIV-1 transmission through breastfeeding. Lancet 340(8819): 585–588.
Gray G 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.
HIV and Pregnancy

29. References (continued)
4/19/2017
References (continued)
International Perinatal HIV Group The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type 1. N Engl J Med 340(14): 977–987.
Mandelbrot L et al 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): 661–667.
Semprini AE et al The incidence of complications after cesarean section in 156 women. AIDS 9:913–917.
Shaffer N et al Short-course ZDV for perinatal HIV-1 transmission in Bangkok, Thailand: A randomized controlled trial. Lancet 353: 773–780.
Sperling RS et al Maternal viral load, ZDV treatment, and the risk of transmission of HIV type 1 from mother to infant. N Engl J Med 335(22): 1621–1629.
UNICEF/UNAIDS/WHO Technical Consultation on HIV and Infant Feeding HIV and Infant Feeding: Implementation of Guidelines. WHO: Geneva.
World Health Organization (WHO)/Joint United Nations Programme on HIV/AIDS (UNAIDS) HIV In Pregnancy: A Review. WHO/UNAIDS: Geneva.
HIV and Pregnancy