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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




Perinatal hiv testing the key to prevention

Perinatal HIV testing: the key to prevention


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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