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

1. 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.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. 2 HIV and Pregnancy 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

3. 3 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 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.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.

4. 4 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 Pregnancy does not the effects that HIV has on the body. Pregnancy does not the effects that HIV has on the body.

5. 5 HIV and Pregnancy Adverse Pregnancy Outcomes and Relationship to HIV Infection There may be association between HIV and: Spontaneous abortion Stillbirth Maternal mortality Newborn mortality Low birth weight Preterm delivery AmnionitisThere may be association between HIV and: Spontaneous abortion Stillbirth Maternal mortality Newborn mortality Low birth weight Preterm delivery Amnionitis

6. 6 HIV and Pregnancy Adverse Pregnancy Outcomes and Relationship to HIV Infection (continued)

7. 7 HIV and Pregnancy 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.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.

8. 8 HIV and Pregnancy 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

9. 9 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 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.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.

10. 10 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! 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.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.

11. 11 HIV and Pregnancy 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.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.

12. 12 HIV and Pregnancy 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. 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): 1621-1629.) 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. 1999. Short-course ZDV for perinatal HIV-1 transmission in Bangkok, Thailand: A randomized controlled trial. Lancet 353: 773-780.) 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. 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.) Nevirapine. A single 200 mg dose at the onset of labor and a single 2 mg/kg dose to the newborn at 48-72 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. 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. 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): 1621-1629.) 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. 1999. Short-course ZDV for perinatal HIV-1 transmission in Bangkok, Thailand: A randomized controlled trial. Lancet 353: 773-780.) 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. 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.) Nevirapine. A single 200 mg dose at the onset of labor and a single 2 mg/kg dose to the newborn at 48-72 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.

13. 13 HIV and Pregnancy ZDV Perinatal Transmission Prophylaxis Regimen: ACTG 076 Trial

14. 14 HIV and Pregnancy Intrapartum vs. Postpartum Regimens for HIV-Infected Women in Labor with No Prior Antiretroviral Therapy Advantages of nevirapine include: Inexpensive Oral regimen Simple, easy to administer Can give directly observed treatment Disadvantages Unknown efficacy if mother has nevirapine-resistant virusAdvantages of nevirapine include: Inexpensive Oral regimen Simple, easy to administer Can give directly observed treatment Disadvantages Unknown efficacy if mother has nevirapine-resistant virus

15. 15 HIV and Pregnancy Intrapartum vs. Postpartum Regimens for HIV-Infected Women in Labor with No Prior Antiretroviral Therapy (cont�d.) Advantages: Oral regimen Compliance easier than 6 weeks of ZDV alone as newborn regimen is only 1 week Disadvantages: Potential toxicity of multiple drug exposureAdvantages: Oral regimen Compliance easier than 6 weeks of ZDV alone as newborn regimen is only 1 week Disadvantages: Potential toxicity of multiple drug exposure

16. 16 HIV and Pregnancy Intrapartum vs. Postpartum Regimens for HIV-Infected Women in Labor with No Prior Antiretroviral Therapy (cont�d.) Advantages: Has been standard recommendation based on clinical trial results Disadvantages: Requires IV administration, availability of ZDV IV formulation Compliance with 6 week newborn regimenAdvantages: Has been standard recommendation based on clinical trial results Disadvantages: Requires IV administration, availability of ZDV IV formulation Compliance with 6 week newborn regimen

17. 17 HIV and Pregnancy Intrapartum vs. Postpartum Regimens for HIV-Infected Women in Labor with No Prior Antiretroviral Therapy (cont�d.) 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 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

18. 18 HIV and Pregnancy 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.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.

19. 19 HIV and Pregnancy 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. 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.

20. 20 HIV and Pregnancy 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.Universal precautions to protect yourself are very important.

21. 21 HIV and Pregnancy 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!

22. 22 HIV and Pregnancy 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.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.

23. 23 HIV and Pregnancy 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.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.

24. 24 HIV and Pregnancy 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

25. 25 HIV and Pregnancy 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

26. 26 HIV and Pregnancy 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

27. 27 HIV and Pregnancy 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

28. 28 HIV and Pregnancy 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: 471�476. 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): 1175�1182. Dunn D et al. 1992. Risk of HIV-1 transmission through breastfeeding. Lancet 340(8819): 585�588. 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.

29. 29 HIV and Pregnancy 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): 977�987. 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): 661�667. Semprini AE et al. 1995. The incidence of complications after cesarean section in 156 women. AIDS 9:913�917. Shaffer N et al. 1999. Short-course ZDV for perinatal HIV-1 transmission in Bangkok, Thailand: A randomized controlled trial. Lancet 353: 773�780. 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): 1621�1629. 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.