Prevention of Perinatal
Transmission of HIV
Amanda Cotter MD MRCOG MRCPI MSPH
Director of the Perinatal HIV Service
Division of Maternal Fetal Medicine
University of Miami
Disclosure of Financial Relationships
This speaker has no significant financial relationships with
commercial entities to disclose.
This slide set has been peer-reviewed to ensure that there are no conflicts of
interest represented in the presentation.
Learning Objectives
• Current pregnancy recommendations
• Preferred ART regimens
• Indications for cesarean delivery
• Complications of ART in pregnancy
Pediatric AIDS Cases by Age Group
and Year of Diagnosis, Florida, 1990-2006
N=1,304
Age Group
120
=2 yrs.
Number of Cases
80
60
40
20
0
90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06
Year of Diagnosis
Florida
2006 Florida
Pediatric HIV/AIDS Cases Population Estimates
By Race/Ethnicity (Ages 48 hr No AZT
Importance of Infant Pre- +/or Post-Exposure Prophylaxis
Possible Routes of Transmission
In-utero At Birth During Breastfeeding
Timing of Perinatal Transmission
In utero 25%–40% of cases
Intrapartum 60%–75% of cases
Addition risk with breastfeeding
14% risk with established infection
29% risk with primary infection
Current evidence suggests most transmission
occurs during the intrapartum period
Factors Influencing Perinatal
Transmission
• Maternal Factors • Obstetrical Factors
• HIV-1 RNA levels • Length of ruptured
• Low CD4 lymphocyte membranes/
count chorioamnionitis
• Other infections • Vaginal delivery
(hepatitis C, CMV, • Invasive procedures
bacterial vaginosis)
• Maternal injection drug • Infant Factors
use • Prematurity
• Lack of ZDV during
pregnancy
Risk Factors for Transmission
in Era of Antiretroviral Therapy:
Viral Load
Type of Antiretroviral Therapy
Mode of Delivery
Perinatal HIV Transmission and Maternal
HIV RNA Viral Load
Correlation between maternal VL and risk of transmission
even in pregnant women treated with ARV agents
Risk of transmission with VL ND is extremely low but
transmission has occurred at all VL levels
ZDV decreases transmission regardless of VL level
Delivery VL & Perinatal Transmission
40
32%
% Transmission
30
21%
20
11%
10 6%
1%
0
100000
40000 100000
Delivery Plasma HIV RNA
More Potent Antiretroviral Regimens
associated with Lower Perinatal Transmission
30
21%
% Transmission
20
10 8%
4%
1%
0
None AZT Less Potent Potent
Alone Combo Combo (PI)
Women & Infants Transmission Study, 1990-1999
Care Guidelines for All Pregnant Women with
HIV Infection
Clinical evaluation: HIV disease stage
Evaluate immunodeficiency: CD4+ count, CD4%
Assess risk of disease progression as determined by level
of plasma HIV-RNA
Document history of prior or current ARV use
Discuss known or unknown risks/benefits of therapy during
pregnancy
Develop strategy for long term evaluation and management
of mother and infant
ART in Pregnancy
• Reduce perinatal transmission
• Improve maternal health
ART in Pregnancy at UM/JMH
100%
90%
80% None
70% ZDV
HAART - PI
60%
HAART + PI
50%
40%
30%
20%
10%
0%
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002
Effects of ART in Pregnancy
• Pregnant woman
• Fetus
• Newborn
Lopinavir Exposure
120
100
LPV AUC (mcg*hr/mL)
50th percentile
80
60 10th percentile
40
20
0
Pregnancy Post Partum
Stek et al AIDS 2006
When to treat?
• After 1st trimester
• When the patient is “ready”
• When the patient can tolerate
• To keep the viral load 250;
in these women, use NVP based
regimens only if benefit outweighs
risk
•In women with CD4 1000
copies/mL regardless of clinical or immunologic
status
• Consider combination ART for women with
VL 1000 at 36 weeks gestation
• Continue ARV therapy—it’s working
• VL level falling but unlikely to be 1000 copies/mL;
unproven benefit in women on ART
Cesarean Section to Reduce
Perinatal HIV Transmission
• Unclear whether scheduled C/S offers any benefit to
women on ART with VL 34 weeks
Rapid Testing: Advantages
• Cost <$10
• Results in 20-30 minutes
• Positive – probably infected
• Oraquick high sensitivity & specificity
• Confirmation 24 hours - weeks
Rapid HIV Testing at Labor &
Delivery: the MIRIAD Study
• 24 hr counseling & rapid testing
• 16 hospitals in 6 US cities
• Nov 2001 - Nov 2003
• 84% consented
• 34 HIV+ (7/1000)
The MIRIAD Study
OraQuick
• Sensitivity/Specificity = 100% / 99.9%
• PPV 90%
• Median turn around time 70 mins
• 70% mothers received intrapartum ZDV
within 30-45 minutes
• 34 infants received ZDV±NVP
• 3/32 infants seroconverted
Rapid Testing : MIRIAD
• 10 received intrapartum AZT
• 8 received AZT + NVP
• 9 received no intrapartum ARV
• All infants received AZT
• 17 infants also received NVP
Rapid Testing : MIRIAD
Infection Status of Infants
• 3 infected
• 2 PCR positive day 1
• 1 PCR positive week 6
Early intervention is the key to prevention