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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

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
Overview:
  • Antepartum management
    • Antiretroviral therapy: Benefits, Risks
  • Intrapartum management
    • L&D management
    • Mode of delivery
  • Post-partum management
prenatal hiv testing strategies
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

goals of prenatal care
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

maternal risk factors
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

hiv lifecycle and drug targets
HIV lifecycle and drug targets
  • Fusion inhibitors
  • NRTI and NNRTI
  • Integrase inhibitors
  • Protease Inhibitors

www.wikipedia.org

when and how should a non pregnant adult be treated
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

antiretrovirals in pregnancy
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
art when to start
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

art what to choose
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?
perinatal hiv transmission u s studies from 1993 2002
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

maternal risks and arvs
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
obstetrical risks and arvs
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

fda drug classification
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

nelfinavir
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.
intrapartum management
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
standard intrapartum art
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

elective cesarean and mtct
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

elective cesarean and mtct cochrane collaboration
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

post partum maternal care
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
post partum vaccination
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

conclusions
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)
resources
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
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