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
 Mode of delivery
 Post-partum management
Perinatal HIV in the U.S.
Number of cases
Perinatal HIV testing:
the key to prevention
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
Antepartum management
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
 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 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
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
Fusion inhibitors
NRTI and NNRTI
Integrase inhibitors
Protease Inhibitors
www.wikipedia.org
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
 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
 Goal: viral suppression by 3rd trimester
 Typically start in 2nd trimester
 Exceptions to starting in 2nd trimester
 Continuing preconception regimen and nonteratogenic
 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
 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
40%
ZDV
30%
HAART 
24.5%
20%
7.6%
10%
5.0% 3.3%
2.0% 1.5%
0%
1993: 1994:
1997:
WITS PACTG PACTG
076
185
Adapted from Fowler 2004
1999: 2001: 2002:
WITS PACTG PACTG
247
316
Adverse effects of
antiretrovirals in pregnancy
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
 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
Fetal/Neonatal Risks
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
 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 Risks
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
 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
Cesarean Delivery 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 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 wellcontrolled HIV disease…the short-term risk of
the intervention may exceed the long-term
benefit.”
Read and Newell 2005
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




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
 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
 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
Thank you