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A. Overview

  1. Pregnancy has no effect on progression of HIV
  2. Risk of prematurity or other adverse fetal outcome not affected by HIV infection
  3. Risk of transmission of HIV to fetus is ~20% without antiretroviral prophylaxis [2,3,4]
    1. Most transmission occurs from 36 weeks to labor (50% of cases)
    2. 30% of infections occur intrapartum, ~15% at 14-36 weeks, and ~5% in <14 weeks
    3. Breat feeding contributes another 14-20% of infections
  4. Antiretroviral Therapy (ART) [1,2]
    1. Antiretrovirals should be used during pregnancy to reduce perinatal transmission
    2. Triple ART including NNRTI can reduce transmission rates to <1.5%
  5. Cesarean Section [6]
    1. Reduces transmission >50% versus other delivery modes
    2. Should be offered to women with HIV RNA >1000/mL at week 38
    3. Amniocentesis is not recommended as it can increase risk of transmission
  6. Antiretroviral therapy is not associated with increased pregnancy complications
  7. Maternal-Fetal transmission rates are very high in underdeveloped countries
  8. Standards for treatment change rapidly: for updates, see http://www.hivatis.org
  9. All pregnant women at increased risk for HIV disease should be screened prior to birth [23]
  10. Group B streptococcal infection is increased in HIV+ persons; testing must be done

B. Risk Factors for Maternal-Fetal HIV Transmission [1]

  1. Transmission Rates [7,8,9]
    1. Maternal serum HIV-1 RNA levels is best overall predictor of transmission
    2. Transmission rate to infant is ~26% without antiretrovirals
    3. For women with HIV RNA <1000/mL, transmission rate is ~10% without treatment
    4. Women with HIV RNA levels <1000/mL treated with ZDV have ~1% rate of transmission to fetus (and no breast feeding)
  2. Low CD4 counts (typically <350/µL)
  3. HIV protein p24 antigen and serum anti-HIV neutralizing antibody not usually assessed
  4. Presence of sexually transmitted diseases peripartum
  5. Premature rupture of membranes (PROM): >4 hours before delivery increased risk ~2X
  6. Amniotic fluid color - bloody has 4-5 fold increased risk over clear fluid
  7. Breast Feeding (neonatal) - HIV is present in breast milk; ~3 fold increased risk [10]
  8. Vaginal delivery, particularly with maternal HIV RNA >1000/mL

C. HIV in Infants

  1. Detection of HIV Infection in Infants
    1. Maternal anti-HIV Abs may be present in infant serum up to 18 months
    2. For infants <18 months, HIV RNA, culture, or p24 antigen in serum can be used
    3. For infants >18 months, anti-HIV Ab (standard) detection is acceptable
  2. Without antiretroviral therapy, ~25% of infants develop full blown AIDS within 1 year
  3. Aggressive vaccinations and PCP prophylaxis are recommended regardless of CD4 count
  4. Major risk factors at birth for rapidly progressing HIV / AIDS [4]:
    1. Positive HIV antigenemia (p24 antigen) at birth: risk 3.5X for rapid progression
    2. HIV-1 positive culture or positive RT-PCR within 1 week at birth: risk 2.8X
    3. CD4+ T cells <30% at birth: risk 3.0X
    4. Abdominal organomegaly and/or lymphadenopathy: risk 2.5X
    5. High serum viral load is probably the best predictor

D. Reduction In Mother To Child Transmission [2]

  1. HIV testing is should be recommended in all new mothers at any increased risk [23]
  2. Breast Feeding MUST be Avoided
    1. Increases risk of transmission of HIV
    2. Short course ZDV may reduce transmission of HIV through breast milk [7,13]
    3. Formula feeding is superior to breast feeding even when ZDV is given [24]
  3. Benefits of ART [5,14]
    1. ZDV initially shown to significantly reduce transmission rates [8,9,24]
    2. Nevirapine is superior to ZDV in several settings [12,17]
    3. Nevirapine 200mg po x 1 for mothers prior to delivery and infant 2mg/kg x 1 within 72 hours of birth cuts transmission rate ~50% compared with ZDV [17,18]
    4. Nevirapine single dose to mother intrapartum and to neonate within 72 hours leads to
  4. 7% overall transmission rates at 18 months, compared with 25.8% for ZDV [12]
    1. Nevirapine single dose to mother added to standard oral ZDV prophylaxis beginning at 28 weeks reduced transmission from 6.3% to 2.8% [22]
    2. Nevirapine given to infant in addition to mother around delivery clearly reduces transmission more than that given to mother alone [22,26]
    3. Nevirapine of limited utility women already receiving antiretroviral therapy and where elective Cesarean section available [21]
    4. Starting ZDV even 3 days after delivery reduces transmission rate >30% [15]
    5. Short course ZDV+LAM beginning 36 weeks gestation and continuing 7 days after birth for mother and child had 5.7% transmission rate [16]
    6. Nevirapine+ZDV superior to nevirapine alone for treatment of HIV+ mothers who present within 2 hours of expected delivery (15.3% versus 20.9% transmission rates) [11]
    7. For infants of HIV+ mothers who are breast feeding, nevirapine ± ZDV for 14 weeks of life reduces HIV+ infant rate from 10.6% to 5.2% at age 9 months [26]
    8. Single dose tenofovir 300mg and emtricitabine 200mg added to intrapartum nevirapine and short-course ZDV reduced generation of NNRTI-resistance 6 weeks after delivery [25]
    9. Transmission during breast feeding must be considered in evaluation of prophylactic regimens [16]
  5. Combination ART [2,5]
    1. Should be recommended to all HIV-infected pregnant women regardless of HIV load or CD4
    2. Preference is to begin therapy before conception
    3. Many women delay therapy until after the first trimester to minimize exposure during organogenesis
    4. Most women should continue ART after delivery
    5. ZDV with lamivudine (Lam) combined with lopinavir+ritonavir is usually first choice
    6. Nelfinavir instead of lopinavir+ritonavir can be used
    7. Non-protease inhibitor containing regimen of ZDV+Lam with abacavir is also used
  6. Elective Cesarean delivery recommended for pregnant women with HIV RNA >1000/mL [13]
  7. Treatment of Mother at Delivery [5,6,21]
    1. Intravenous (IV) ZDV (prefer with LAM) is given during delivery or at membrane rupture
    2. Episiotomy should be avoided
    3. Midazolam or ergot alkaloids shold not be used with PI, efavirenz, delavirdine
    4. IV ZDV prophylaxis is most effective with elective Cesarean deliveries (compared with normal vaginal deliveries or emergent Cesarean deliveries)
    5. IV ZDV should be started within 3 hours of elective Cesarean delivery
    6. Combination C-section and antiretroviral therapy reduces transmission ~85% [6]
  8. Treatment of Infants [4,5]
    1. All infants should receive oral ZDV syrup for a minimum of 6 weeks (2mg/kg qid) [19]
    2. Some studies recommend up to 6 months of treatment [7]
    3. LAM 2mg/kg bid for 6 weeks should be added to ZDV [20]
    4. Short course ZDV+LAM for 7 days after birth reduced transmission rate from 8.9% to
  9. 7% in mothers given ZDV+LAM beginning at 36 weeks gestation [16]'
    1. For infants of HIV+ mothers who are breast feeding, nevirapine ± ZDV for 14 weeks of life reduces HIV+ infant rate from 10.6% to 5.2% at age 9 months [26]
  10. Role of anti-HIV globulin is unclear

References

  1. Watts DH. 2002. NEJM. 346(24):1879 abstract
  2. Riley LE and Yawetz S. 2005. NEJM. 353(16):1725 (Case Record) abstract
  3. Sexually Transmitted Disease Treatment Guidelines. 2002. MMWR. 51(RR6):1
  4. Kourtis AP, Bulterys M, Nesheim SR, Lee FK. 2001. JAMA. 285(6):709 abstract
  5. Drugs for HIV Infection. 2001. Med Let. 43(1119):103 abstract
  6. International Perinatal HIV Group. 1999. NEJM. 340(13):977 abstract
  7. Dabis F, Msellati P, Meda N, et al. 1999. Lancet. 353(9155):786 abstract
  8. Garcia PM, Kalish LA, Pitt J, et al. 1999. NEJM. 341(6):394 abstract
  9. Mofenson LM, Lambert JS, Stiehm ER, et al. 1999. NEJM. 341(6):385 abstract
  10. Leroy V, Newell ML, Dabis F, et al. 1998. Lancet. 352(9128):597 abstract
  11. Taha TE, Kumwenda NI, Gibbons A, et al. 2003. Lancet. 362(9391):1171 abstract
  12. Jackson JB, Musoke P, Fleming T, et al. 2003. Lancet. 362(9387):859 abstract
  13. Wiktor SZ, Ekpini E, Karon JM, et al. 1999. Lancet. 353(9155):781 abstract
  14. Shaffer N, Chuachoowong R, Mock Pa, et al. 1999. Lancet. 353(9155):773 abstract
  15. Wade NA, Birkhead GS, Warren BL, et al. 1998. NEJM. 339(20):1409 abstract
  16. Lange JMA and Petra Study Team. 2002. Lancet. 359(9313):1178 abstract
  17. Marseille E, Kahn JG, Mmiro F, et al. 1999. Lancet. 354(9181):803 abstract
  18. Guay LA, Musoke P, Fleming T, et al. 1999. Lancet. 354(9181):795 abstract
  19. Mofenson LM, Lambert JS, Stiehm ER, et al. 1999. NEJM. 341(6):385 abstract
  20. Mandelbrot L, Lanreau-Mascaro A, Rekacewicz C, et al. 2001. JAMA. 285(16):2083 abstract
  21. Dorenbaum A, Cunningham CK, Gelber RD, et al. 2002. JAMA. 288(2):189 abstract
  22. Lellemant M, Jourdain G, Le Coeur S, et al. 2004. NEJM. 351(13):217
  23. Chou R, Smits AK, Huffman LH, et al. 2005. Ann Intern Med. 143(1):38 abstract
  24. Thior I, Lockman S, Smeaton LM, et al. 2006. JAMA. 296(7):794 abstract
  25. Chi BH, Sinkala M, Mbewe F, et al. 2007. Lancet. 370(9600):1698 abstract
  26. Kumwenda NI, Hoover DR, Mofenson LM, et al. 2008. NEJM. 359(2):119 abstract