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The baby at risk of HIV Dr.J.P.Dadhich New Delhi Outline of the - - PowerPoint PPT Presentation
The baby at risk of HIV Dr.J.P.Dadhich New Delhi Outline of the - - PowerPoint PPT Presentation
The baby at risk of HIV Dr.J.P.Dadhich New Delhi Outline of the Presentation Overview Review of evidence on risk factors HIV Transmission Efficiency Rates Type of Exposure Efficiency of single exposure Blood Transfusion > 95% Vertical
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HIV Transmission Efficiency Rates
14-20% Breast Milk 30% (12-40) Vertical Transmission > 95% Blood Transfusion Efficiency of single exposure Type of Exposure
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Timing of Mother-to-Child Transmission
Early Antenatal (<36 wks) Late Antenatal (36 wks to labor) Late Postpartum (6-24 months) Early Postpartum (0-6 months)
Adapted from N Shaffer, CDC
5-10% 10-20% 10-20% Labor and Delivery Breastfeeding Pregnancy <48hrs 7-90 days
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MTCT in 100 HIV+ Mothers by Timing of Transmission
10 20 30 40 50 60 70 80 90 100 Uninfected: 63 Breastfeeding: 15 Delivery: 15
Pregnancy: 7
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Risk Factors for HIV Transmission
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Maternal Risk Factors For Transmission of HIV
Immune/health status Plasma viral load Placental factors Breast milk virus Breast inflammation (mastitis, abscess, bleeding nipples) New HIV infection Viral Characteristics
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Placental Risk Factors for transmission of HIV
Transmission may occur through an intact placenta by transcytosis Risk increases if placental is damaged i.e. chorioamnionitis, smoking Usually in last trimester due to materno
- fetal transfusion
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Risk factors for Intrapartum Transmission
First born twin Vaginal Delivery PROM > 4 hrs Difficult labor, Instrumentation Genital Infection Fetal Scalp Electrodes
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Infant Risk Factors For Transmission of HIV Non-exclusive BF Age (first months) Lesions in mouth, intestine Infant immune response
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Maternal viral load
Indirect evidence of advanced maternal disease Important predictor of intra-partum MTCT
(Leroy et al, 2001; Semba et al, 1999)
Risk factor during breastfeeding The threshold below which there is no risk has not been identified
Kenya (Richardson et al, 2003), Tanzania(Fawzi et al, 2002),West Africa
(Leroy et al, 2003)
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Maternal Virus Load and Perinatal Transmission
40.6 > 100,000 30.9 50,001-100,000 21.3 10,001-50,000- 16.6 1000 –10000 < 1000 copies/ml Transmission Rate (%) Viral Load Garcia BM. NEJM, 1999
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Maternal Viral Load
Risk of HIV transmission per day of BF (%)
0.011 0.044
0.01 0.02 0.03 0.04 0.05 Low Viral Load High Viral Load
Richardson et al, 2003
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Maternal viral load
1.15 2.65 3.14 1 2 3 4 ZDV Plasma log10 viral load CD4 < 500
- Adj. Hazard Ratio
Leroy et al 2003
Adjusted HR for Postnatal Transmission in West Africa Combined Analysis
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Maternal immune status
HIV transmission from 6 w - 24 mo in West Africa by maternal baseline CD4
21.8 2 5 10 15 20 25 CD4 < 500 CD4 >= 500 Transmission (%)
Leroy et al 2003
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Maternal immune status
Hazard ratio for postnatal HIV transmission
8 3.7 1 5 10 CD4 < 200 CD4 200-499 CD4 >= 500
BHITS meta-analysis, Read et al (CROI 2003)
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Neonatal Period
higher prevalence of mastitis, breastfeeding
problems
infant gut more immature, permeable greater exposure (higher concentration of
cells)
(Nduati et al, 2000; John et al, 2001)
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Neonatal Period
4.5 1.9 2.9 1.8 1 2 3 4 5 Kenya Durban SAINT Study PETRA
Trasmission Risk (% per month)
Estimated postnatal transmission during the first month of life
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Multiple gestation
19% 38% Caesarian 19% 50% Vaginal Twin B Twin A Mode of Delivery
Goedert JJ. Lancet 1991;338:1471.
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Breastfeeding and HIV
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How does HIV transmission during breastfeeding occur?
Exact mechanisms unknown HIV virus in blood passes to breast milk
cell-associated, cell-free virus observed virus appears intermittently (undetectable ~ 25-
35%)
Virus may also come directly from infected cells in mammary gland
produced locally in mammary macrophages,
lymphocytes, epithelial cells (Becquart et al, 2002)
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How does HIV transmission during breastfeeding occur?
Infant consumes HIV
HIV enters/infects infant through permeable mucosal
surfaces, lymphoid tissues, and/or lesions in mouth, intestines
Although BF infant may consume >500,000 virons, >25,000
infected cells per day, majority do NOT become HIV infected (Lewis et al, 2001) Immune factors in BM, saliva play a role (Miller et al, 2002; Sabbaj et al, 2002; Farquhar et al, 2002; Van der Perre et al, 1999; 1993; 1988)
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Risk factors for postnatal transmission: Breast Pathology
Breast inflammation & mastitis increased risk of postnatal transmission (Embree et al; John et al;
Semba et al)
Nipple lesions, breast abscesses increased transmission (Fawzi et al, 2002;
Embree et al, 2000; Ekpini et al, 1997)
Sub-clinical mastitis higher viral load in BM (Willumsen et al, 2000; Semba et
al, 1999, Hoffman, 2003)
Estimated fraction of MTCT due to breast infection
18 20
5 10 15 20 25 Malawi Kenya
%
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Association between breast inflammation and breast milk virus
5.25 2.29
1 2 3 4 5 6 Viral Load Breast inflammation No breast inflammation
Hoffman et al, 2003
Log10 copies/mL
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Breast Pathology
Prevalence of breast pathologies in HIV+ women in Africa
Mastitis (clinical or sub-clinical):
Clinical exam: 7-11% (Embree, 2000; John et al, 2001) Na+/K > 1.0: 11-12% at 6, 14 wk (Willumsen et al, 2000) Na+ > 12 mmol/L: 16.4% at 6 wk (Semba et al, 1999)
Nipple lesions:
Clinical exam: 11-13% (Embree, 2000; John et al, 2001) Clinical exam: 10% (Ekpini et al, 1997) Hospitalized infants: 11% (Kambarami et al, 1997)
Breast abscesses:
Clinical exam: 12% (John et al, 2001) Clinical exam: 3% (Ekpini et al, 1997)
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Early Mixed breastfeeding
7 16 19 25 7 24 26 36
5 10 15 20 25 30 35 40 Birth 3 mo 6 mo 15 mo % EBF to 3 mo Partial BF
Coutsoudis et al, 1999; 2001
Cumulative HIV transmission Durban, SA
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Zidovudine Prophylaxis to mother and Rate of Perinatal transmission
22.6
(95% CI 17-29)
7.6
(95% CI 4.3-12.3)
Placebo Group
%
TEST Group
%
Pediatric AIDS clinical trial group protocol 076. NEJM 1994
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Maternal Malaria and MTCT
Among women dually infected with malaria and HIV, high-density placental malaria (>10,000 parasites/mL) was associated with increased risk for perinatal MTCT (ARR 2.0)
Ayisi JG, Emerg Infect Dis. 2004 Apr;10(4):643-52
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Conclusions
Perinatal Transmission of HIV is preventable Antenatal counseling and testing Prophylaxis Avoidance of various risk factors
In USA, rate of vertical transmission is less than 2%
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