Prenatal Care and Obstetrical Prenatal Care and Obstetrical Management of HIV+ WomenManagement of HIV+ Women

Deborah Cohan, MD, MPHBay Area Perinatal AIDS Center

National Perinatal HIV Consultation and Referral ServiceUCSF

Overview: Overview:

Antepartum management Antiretroviral therapy: Benefits, Risks

Intrapartum managementL&D managementMode of delivery

Post-partum management

Perinatal HIV in the U.S.Perinatal HIV in the U.S.

Perinatal HIV testing: Perinatal HIV testing: the key to preventionthe key to prevention

DHHS 2002; CDC 1998; CDC 2001; CDC 2002

Prenatal HIV Testing Strategies Prenatal HIV Testing Strategies Opt-in: voluntary, women sign consent to testOpt-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

Antepartum managementAntepartum management

Goals of prenatal careGoals of prenatal careOptimize 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

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

Maternal Risk FactorsMaternal Risk Factors 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

Other possible risk factorsOther possible risk factors STIs STIs Drug Use Drug Use Smoking Smoking AnemiaAnemia Vitamin A deficiencyVitamin A deficiency Clade D virus (vs. clade A)Clade D virus (vs. clade A) Monocyte/macrophage tropismMonocyte/macrophage tropism Viral homogeneityViral homogeneity Class I HLA concordanceClass I HLA concordance Certain HLA-B allelesCertain HLA-B alleles Rapid replication kinetics Rapid replication kinetics p24 antigenemiap24 antigenemia Primary HIV infectionPrimary HIV infection

www.wikipedia.org

HIV lifecycle and HIV lifecycle and drug targetsdrug targetsFusion inhibitors

NRTI and NNRTI

Integrase inhibitors

Protease Inhibitors

DHHS Guidelines for the Use of Antiretrovirals in HIV-Infected Adults and Adolescents, May 2006

When and How Should a When and How Should a non-pregnant non-pregnant Adult Be Treated?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

Antiretrovirals in pregnancyAntiretrovirals in pregnancy

All HIV+ pregnant women should get ART regardless of CD4 count and viral load.

But…When to startWhat to chooseWhat to avoid

Wright, SMFM, 2003; Thorne CROI 2005

ART: when to startART: when to startGoal: viral suppression by 3rd trimesterTypically start in 2nd trimesterExceptions 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

ART: what to chooseART: what to chooseSame 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 contraindicatedPurpose 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 Perinatal HIV Transmission U.S. Studies from 1993-2002U.S. Studies from 1993-2002

24.5%

7.6%5.0% 3.3% 2.0% 1.5%

0%

10%

20%

30%

40%

1993: 1994: 1997: 1999: 2001: 2002:WITS PACTG PACTG WITS PACTG PACTG 076 185 247 316

% T

ran

smis

sio

n

Adapted from Fowler 2004

ZDV HAART

Adverse effects of Adverse effects of antiretrovirals in pregnancyantiretrovirals in pregnancy

Maternal Risks and ARVsMaternal 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

Euro Collaborative Study and Swiss Mother+Child 2000; Thorne CROI 2004; Tuomala 2002; Cotter JID 2006; Wimalasundera Lancet 2002; Suy AIDS 2006

Obstetrical Risks and ARVsObstetrical Risks and ARVsPreterm 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?

Fetal/Neonatal RisksFetal/Neonatal Risks

DHHS 2005

FDA Drug ClassificationFDA 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

NelfinavirNelfinavir

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.

Benefits >>>> Potential RisksBenefits >>>> Potential Risks

Intrapartum ManagementIntrapartum Management

Shorten duration of ruptured membranesNo evidence of c/section to shorten ROMMinimize # exams to risk of chorioAvoid FSE, fetal scalp samplingPPROM???

Balancing MTCT vs. prematurityManagement should be based on maternal

viral load and NICU capabilities

Dorenbaum JAMA 2002

Standard Intrapartum ARTStandard Intrapartum ARTIntrapartum AZT regardless of antepartum

ART2mg/kg IV load, then 1mg/kg IV qhr until

deliveryLoading dose can be given over 20min-1hrD/C d4T when receiving AZTGive 3-4 hrs of IV AZT prior to elective c-section

Continue oral ART, even if getting cesarean

Cesarean Delivery and MTCTCesarean Delivery and MTCT

The European Mode of Delivery Collaboration, 1999; International Perinatal HIV Group 1999; Shapiro CROI 2004

Elective Cesarean and MTCTElective 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)

Read and Newell 2005

Elective Cesarean and MTCT: Elective Cesarean and MTCT: Cochrane CollaborationCochrane 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.”

Post-partum maternal carePost-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

Advisory Committee on Immunization Practices 1998; Brady CROI 2002

Post-partum vaccinationPost-partum vaccinationTdapComplete hepatitis A/B series prnFlu 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

ConclusionsConclusions

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)

ResourcesResourcesClinical 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

Thank youThank you