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Prenatal Care and Obstetrical Management of HIV+ Women

Prenatal Care and Obstetrical Management of HIV+ Women. Deborah Cohan, MD, MPH Bay Area Perinatal AIDS Center National Perinatal HIV Consultation and Referral Service UCSF. Overview:. Antepartum management Antiretroviral therapy: Benefits, Risks Intrapartum management L&D management

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Prenatal Care and Obstetrical Management of HIV+ Women

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  1. Prenatal Care and Obstetrical Management of HIV+ Women Deborah Cohan, MD, MPH Bay Area Perinatal AIDS Center National Perinatal HIV Consultation and Referral Service UCSF

  2. Overview: • Antepartum management • Antiretroviral therapy: Benefits, Risks • Intrapartum management • L&D management • Mode of delivery • Post-partum management

  3. Perinatal HIV in the U.S.

  4. Number of cases

  5. Perinatal HIV testing: the key to prevention

  6. Prenatal HIV Testing Strategies • Opt-in: voluntary, women sign consent to test • Opt-out: voluntary, informed that test is standard, sign if decline testing (Tennessee, Canada) • Mandatory newborn screening: regardless of maternal consent (NY, Connecticut) • Uptake of HIV testing • Opt-in (25- 69%) vs. Opt-out (71-98%) approach • CA law mandates prenatal providers to offer HIV testing (opt-in) and explain that testing is routinely done unless pt declines • Likely change in CA law Jan 2008: opt-out DHHS 2002; CDC 1998; CDC 2001; CDC 2002

  7. Antepartum management

  8. Goals of prenatal care • Optimize woman’s health and psychosocial situation • ART: total viral suppression • Opportunistic Infection (OI) prophylaxis prn • Immunization prn • Prevent vertical transmission of HIV • ART, c/section in specific situations, Bottle-feeding • Minimize maternal risks • Viral resistance, Obstetrical outcomes • Minimize/assess risks to fetus/neonate • Teratogenicity, Genetic testing • Prepare for or prevent subsequent pregnancies 

  9. Maternal Risk Factors • Other possible risk factors • STIs • Drug Use • Smoking • Anemia • Vitamin A deficiency • Clade D virus (vs. clade A) • Monocyte/macrophage tropism • Viral homogeneity • Class I HLA concordance • Certain HLA-B alleles • Rapid replication kinetics • p24 antigenemia • Primary HIV infection • Plasma viral load @ delivery • per log : • OR 3.4 (1.7-6.8) • VL <1000: • 0.7%-0.9% transmission • Genital VL @ delivery • Cell-associated • per log  : OR 2.3 (1.1-4.8) • Cell-free • OR 3.4 (p=0.001) • CD4 count • Drug-resistant HIV • ZDV GT resist OR 5.16 • ZDV PT resist OR 1.25 Landesman 1996; Thea 1997; Shapiro 2002; Tuomala 2003; Chuachoowong 2000; Goedert 2001; O'Shea 1998; Mofeson 1999; Shapiro 1999; Monforte 1991; Ometto 1995; MacDonald 1998; Arroyo 2002; Winchester 2004; Yang 2003

  10. HIV lifecycle and drug targets • Fusion inhibitors • NRTI and NNRTI • Integrase inhibitors • Protease Inhibitors www.wikipedia.org

  11. When and How Should a non-pregnant Adult Be Treated? • When • Symptomatic, at any CD4 count • CD4 count <200 (AIDS) • CD4 count 200-350: Treatment offered • How • HAART: Highly Active Antiretroviral Therapy • 2 NRTI’s plus • PI or NNRTI • Monotherapy, dual therapy, and triple NRTI regimens no longer standard of care DHHS Guidelines for the Use of Antiretrovirals in HIV-Infected Adults and Adolescents, May 2006

  12. Antiretrovirals in pregnancy • All HIV+ pregnant women should get ART regardless of CD4 count and viral load. • But… • When to start • What to choose • What to avoid

  13. ART: when to start • Goal: viral suppression by 3rd trimester • Typically start in 2nd trimester • Exceptions to starting in 2nd trimester • Continuing preconception regimen and non-teratogenic • Needs ARV immediately for own health • If not tolerating preconception regimen in 1st trimester despite anti-emetics, d/c all at once • Stagger d/c of NVP-based ART Wright, SMFM, 2003; Thorne CROI 2005

  14. ART: what to choose • Same principles as non-pregnant HIV+ adults • Resistance/prior regimens, adherence/pill burden, S/E profile, degree of immunosuppression, viral hepatitis status • Except consider… • AZT-containing regimen unless contraindicated • Purpose of ART: her health vs. prophylaxis • If not needed for own health, less potent regimens may be acceptable • Triple NRTI regimens • AZT monotherapy for baseline viral load <1000?

  15. Perinatal HIV Transmission U.S. Studies from 1993-2002 ZDV HAART  % Transmission 1993: 1994: 1997: 1999: 2001: 2002: WITS PACTG PACTG WITS PACTG PACTG 076 185 247 316 Adapted from Fowler 2004

  16. Adverse effects of antiretrovirals in pregnancy

  17. Maternal Risks and ARVs • Lactic acidosis and d4T (and ddI) • 12 reports of maternal LA (3 fatal) • Avoid d4T and ddI if possible • Think of LA if • N/V, abdominal pain, SOB, leg and arm weakness • Hepatic Toxicity and NVP • 1st 6 wks NVP, may persist even when d/c NVP • Distinguished from other etiologies (ob and non-ob) • Avoid starting NVP if CD4 > 250 • Gestational DM and PIs • Conflicting data, most studies don’t find association • Not a reason to avoid using PIs

  18. Obstetrical Risks and ARVs • Preterm delivery and ARVs? • Conflicting data; all based on observational cohorts • Europ Collaborative & Swiss Mother+Child HIV: yes • U.S. Collaborative (n=2123): no • Meta-analysis: PTD only if preconception or 1st trimester ARV • Pre-Eclampsia and ARVs? • Conflicting preliminary data • ARVs increase risk? • ARVs restore immune system to allow Pre-E to occur? Euro Collaborative Study and Swiss Mother+Child 2000; Thorne CROI 2004; Tuomala 2002; Cotter JID 2006; Wimalasundera Lancet 2002; Suy AIDS 2006

  19. Fetal/Neonatal Risks

  20. FDA Drug Classification • A • B • NRTI: ddI, FTC, TDF (monkey osteomalacia @ high dose) • PI: ATV, NFV, RTV, SQV • FI: T-20 • C • NRTI: ABC (rats 35x dose), 3TC, d4T, ddC, ZDV • NNRTI: NVP • PI: APV (rat thymic elongation/ skeletal ossification), f-APV, IDV, LPV/r • D • EFV (monkey 15% CNS malformations; 3 human NTD, 1 Dandy Walker) • Avoid using preconception/1st trimester EFV • 2nd/3rd trimester EFV only if no other options DHHS 2005

  21. Nelfinavir • Sept. 2007, Pfizer sent a letter to providers regarding the presence of low levels of ethyl methane sulfonate (EMS) in nelfinavir. EMS is teratogenic, carcinogenic, and mutagenic in animals. No human data exist. • Not recommended unless no other alternative is available.

  22. Benefits >>>> Potential Risks

  23. Intrapartum Management • Shorten duration of ruptured membranes • No evidence of c/section to shorten ROM • Minimize # exams to  risk of chorio • Avoid FSE, fetal scalp sampling • PPROM??? • Balancing MTCT vs. prematurity • Management should be based on maternal viral load and NICU capabilities

  24. Standard Intrapartum ART • Intrapartum AZT regardless of antepartum ART • 2mg/kg IV load, then 1mg/kg IV qhr until delivery • Loading dose can be given over 20min-1hr • D/C d4T when receiving AZT • Give 3-4 hrs of IV AZT prior to elective c-section • Continue oral ART, even if getting cesarean Dorenbaum JAMA 2002

  25. Cesarean Delivery and MTCT

  26. Elective Cesarean and MTCT • 38 weeks, no labor, no ROM • Benefit seen in early studies • AZT alone, observ studies didn’t adjust for VL • Studies in the HAART era: limited benefit • PACTG 367 cohort, 1998-2001; 72 U.S. sites, n=2875 singleton births • Transmission 2.9% overall • MTCT by pre-delivery maternal viral load • <1000: 0.7% vs. 1000-9999: 2.1% vs. 10,000+: 5.9% • Elective c/s vs. vaginal delivery by maternal VL • <1000: 0.8% vs. 0.7% • 1000-9999: 2.8% vs. 1.9%: OR 1.5 (0.4-5.0) • 10,000+: 4.1% vs. 7.3%: OR 0.5 (0.2-1.5) • No RNA in chart: 8.3% vs. 22.4%: OR 0.3 (0.1-0.9) The European Mode of Delivery Collaboration, 1999; International Perinatal HIV Group 1999; Shapiro CROI 2004

  27. Elective Cesarean and MTCT: Cochrane Collaboration • “Elective c/section is a good intervention for the prevention of MTCT among HIV-infected women not taking antiretrovirals or taking only zidovudine… • Among women with less advanced or well-controlled HIV disease…the short-term risk of the intervention may exceed the long-term benefit.” Read and Newell 2005

  28. Post-partum maternal care • For those continuing on ART post-partum: • Reinforce medication adherence • Dose maternal and neonatal ART on similar schedules • Remove breastfeeding literature from educational packs • Contraception

  29. Post-partum vaccination • Tdap • Complete hepatitis A/B series prn • Flu vax (if didn’t get antepartum) • Rubella vax • MMR: live-attenuated vaccine • Case report of measles pneumonitis • Advisory Committee on Immunization Practices: • Recommends in susceptible, asymptomatic HIV • Not recommended if cd4 <200 or <14% • Check titers at 3 months and revaccinate prn Advisory Committee on Immunization Practices 1998; Brady CROI 2002

  30. Conclusions • Prevent perinatal HIV transmission through 1° prevention among women • Ensure access to HIV testing: preconception and during pregnancy • Ensure access to contraception and abortion services • Keep woman healthy and preserve future ART options • HIV-specific prenatal care • Consider Cesarean • if high viral load, no HAART, no labor/rupture of membranes • Avoid intrapartum interventions • Bottle feed (formula or banked human milk)

  31. Resources • Clinical consultation • National Perinatal HIV Consultation and Referral Service (NCCC) • 24/7 coverage, based at SFGH • 1-888-448-8765 (1-888-HIV-8765) • Bay Area Perinatal AIDS Center (BAPAC) • 415-206-8919 (M-F, 8a-5p) • Reproductive Infectious Disease Fellows • 719-8726 (24/7 coverage) • Web-based resources • www.aidsinfo.nih.gov (Perinatal HIV Guidelines) • www.womenchildrenhiv.org

  32. Thank you

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