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HIV In Mothers and
Children
2
What Is HIV/AIDS?
ā€¢ Acquired immunodeficiencysyndrome (AIDS) is caused
by the humanimmunodeficiencyvirus (HIV).
ā€¢ HIV attacks and destroys whiteblood cells, causinga
defect in thebodyā€™s immunesystem.
3
What Is HIV/AIDS?
ā€¢ The immunesystem of an HIV-infectedperson becomes
so weakenedthatit cannotprotect itself from serious
infections. Whenthishappens, theperson clinically has
AIDS.
ā€¢ AIDS may manifestas early as 2 years or as late as 10
years after infectionwith HIV.
4
Number ofPeoplewith
HIV/AIDSby Region
North America
890,000
Caribbean
330,000
Latin
America
1.4 million
Western Europe
500,000
Sub-Saharan
Africa
22.5 million
Eastern Europe &
Central Asia
270,000 East Asia
& Pacific
560,000
South and
South East Asia
6.7 million
Australia and New Zealand
12,000
North Africa &
Middle East
210,000
Source: UNAIDS/WHO 1998.
5
HIV Transmission Through SexualContact
ā€¢ Of every 100 HIV infectedadults, 75-85 have been
infectedthrough unprotected intercourse
ā€“ 70% of these infections are from heterosexual intercourse
ā€¢ STDs, especially ulcerative lesions in genitalia,increase
risk of transmission
Source: UNAIDS/WHO 1996.
6
Modesof HIV Transmission
ā€¢ Sexualintercourse
ā€¢ Accidental exposure to blood/blood products (e.g.,
blood transfusions,shared needles, contaminated
instruments)
ā€¢ Mother to childduring:
ā€“ pregnancy
ā€“ birth
ā€“ breastfeeding
7
Womenand HIV
Social Risk Factors
ā€“ Illiteracy
ā€“ Lackof awarenessof preventive measures
Biological risk factors
ā€“ Twiceas easy for women to contract HIVfrom men
ā€“ Physiology of women (e.g., menstruation, intercourse)
ā€“ Pregnancy-associated conditions (e.g., anemia, menorrhagia and
hemorrhage) increase the need for blood transfusion
8
HIV andContraception
ā€¢ Contraception withprotection
ā€“ Male condom (latex and vinyl)
ā€“ Female condom
ā€“ Nonoxynol-9 (antiviralspermicidal cream)1
ā€“ Diaphragm1
ā€¢ Methods appropriate for use by womenwith HIV. They should
use a condom for their partnerā€™s protection.
ā€“ Hormonals (COCs, Implants, PICs)
ā€“ Voluntary sterilization
1Partial protection if used without condom
9
Effectof AIDSon Pregnancy
ā€¢ Infertility
ā€¢ Repeated abortions
ā€¢ Prematurity
ā€¢ Intrauterinegrowth retardation
ā€¢ Stillbirths
ā€¢ Congenitalabnormalities
ā€¢ Embryopathies
10
HIV Transmission from Mother toInfant
ā€¢ Antenatal
ā€“ In utero bytransplacentalpassage
ā€¢ Intranatal
ā€“ Exposure to maternal blood and vaginalsecretions during labor
and delivery
ā€¢ Postnatal
ā€“ Postpartum through breastfeeding
Source: UNAIDS/WHO 1996; UNAIDS/WHO 1998.
11
HIV Transmission from Mother toInfant
ā€¢ 25-35% of all infantsborn to HIV-infected womenin
developing countriesbecome infected
ā€¢ 90% of HIV-infectedinfantsand children were infectedby
mother
Source: UNAIDS/WHO 1996; UNAIDS/WHO 1998.
ā€¢ approximately 600,000 HIV-infected infants
are born every yearā€“at least 1,600 every
dayā€“in resource-constrained countries.
ā€¢ Transmission occurs during pregnancy,
labor and delivery, and breastfeeding.
ā€¢ The rate of mother to child transmission has
been reduced to less than 5 percent
among the limited number of HIV-infected
women in developed countries.
ā€¢ high rates are largely due to
the lack of access to:
ā€“HIV voluntary counseling and
testing
ā€“ replacement feeding
ā€“selective caesarean section
ā€“antiretroviral drug therapy
14
HIV Transmission
HIV cannot be transmittedby:
ā€“ Casualperson to person contact at home or work or in socialor
public places
ā€“ Food, air, water
ā€“ Insect/mosquito bites
ā€“ Coughing, sneezing, spitting
ā€“ Shakinghands, touching, dry kissingor hugging
ā€“ Swimming pools, toilets, etc.
15
AIDSand Infants
ā€¢ Symptoms generallydevelop by 6 monthsof age
ā€“ Diarrhea
ā€“ Failure to thrive
ā€¢ Most of thesechildren diebefore their second birthday
ā€¢ Children born to HIV-infected parents are likely to become
orphans
Reducing pediatric HIV infection
and disease involves three
stages:
ā€¢ preventing HIV infection among women of
childbearing age
ā€¢ preventing unwanted pregnancy among
HIV-positive women
ā€¢ preventing mother to child transmission
during pregnancy, labor and delivery, and
breastfeeding
BENEFITS TO HIV TESTING
ā€¢ EARLY COUNSELING AND
TREATMENT OF HIV INFECTION
ā€¢ ABILITY TO MAKE DECISIONS
REGARDING PREGNANCY
ā€¢ IMPLEMENTATION OF STRATEGIES
TO ATTEMPT TO PREVENT
TRANSMISSION TO FETUS
WHO SHOULD WE
SCREEN?
ā€¢ ALL PREGNANT WOMEN
ā€¢ TARGETED TESTING FAILS TO
IDENTIFY A SUBSTANTIAL
PROPORTION OF HIV POSITIVE
WOMEN
ā€¢ zidovudine (AZT) administered to the
mother from 14 weeks of gestation and
to the child during the first seven days
after birth, reduced the risk of mother to
child transmission among non-
breastfeeding mothers by two-thirds.
ā€¢ Two similar studies conducted in CĆ“te
dā€™Ivoire and Burkina Faso among
breastfeeding mothers demonstrated a
37 percent reduction in mother to child
transmission.
Anti-Retroviral Based Prevention Strategies
ā€¢ A study in Uganda demonstrated a 47
percent reduction in mother to child
transmission following the
administration of a single dose of
nevirapine to the mother at onset of
labor and to the baby within 72 hours
after birth.
ā€¢ The combination of AZT and lamivudine
in a short-course regimen also has been
shown to reduce mother to child
transmission.
Anti-Retroviral Based Prevention Strategies
21
Protecting HealthCareWorkersDuring Labor
and Delivery
ā€¢ Precautionsduringlabor:
ā€“ Protection from blood and amniotic fluids
ā€“ Protection from sharp instruments
ā€¢ Resuscitationof baby:
ā€“ Nomouth to mouth suction
ā€“ Nomouth to mouth breathing
ā€¢ Precautionsfollowinglabor:
ā€“ Proper disinfection of instruments
ā€“ Proper disposal of placenta and other items
PRETEST COUNSELING
ā€¢ TAKE RISK HISTORY AND COUNCIL
REGARDING RISK REDUCTION
ā€¢ DISCUSS REASONS FOR TEST
ā€¢ PROVIDE INFORMATION TO WOMEN
REGARDING TESTING & ILLNESS
ā€¢ RISKS & BENEFITS OF TESTING
ā€¢ CONFIDENTIALITY OF RESULTS
ā€¢ ASSESS WINDOW PERIOD
ā€¢ PERSON HAS RIGHT TO REFUSE
TESTING
POST-TEST COUNSELING
ā€¢ HIV RESULTS SHOULD BE GIVEN IN
PERSON
ā€¢ ASSESS PATIENTā€™S UNDERSTANDING
ā€¢ ENCOURAGE PATIENT TO EXPRESS
FEELINGS AND ASK QUESTIONS
ā€¢ NEGATIVE AND INDETERMINATE
RESULTS: DISCUSS NEED FOR REPEAT
TESTING
POSITIVE RESULT
ā€¢ IDENTIFY IMMEDIATE CONCERNS
ā€¢ IDENTIFY SUPPORTS
ā€¢ EFFECT OF HIV ON PREGNANCY
ā€¢ RISK OF TRANSMISSION TO FETUS
DURING PREGNANCY, L&D, BF
ā€¢ MEASURES TO DECREASE HIV
TRANSMISSION
CONCLUSIONS
ā€¢ ALLPREGNANTWOMEN SHOULD BE
OFFERRED HIV TESTING
ā€¢ PRE- & POST- TEST COUNSELING FOR
ALL PREGNANTWOMEN
ā€¢ TARGETED TESTING OF PREGNANT
WOMEN WHO REPORT HIGH RISK
BEHAVIOR NOT RECOMMENDED
ANTENATAL CARE
INTRODUCTION
ā€¢ MULTIDISCIPLINARY TEAM
APPROACH
ā€¢ MEDICAL NEEDS
ā€¢ SOCIAL AND PSYCHOLOGICAL
NEEDS
ANTENATAL CARE
ā€¢ SIMILAR TO CARE FOR HIV NEGATIVE
WOMEN
ā€¢ PREGNANCY NOT HIGH RISK
ā€¢ SAME NUMBER OF ANTENATAL VISITS
ā€¢ AVOID INVASIVE ANTENATAL TESTS OR
PROCEDURES
FIRST VISIT
ā€¢ PATIENT HISTORY
ā€¢ DATES OF 1ST POSITIVE HIV TEST
ā€¢ HIV RISK FACTORS
ā€¢ HIV CARE AT TIME OF CONCEPTION
ā€¢ SEROLOGIC STATUS OF PARTNER
ā€¢ OTHER STDā€™S
ā€¢ OPPORTUNISTIC INFECTIONS
ā€¢ DRUG HISTORY
FIRST VISIT
ā€¢ INVESTIGATIONS
ā€¢ CBC & DIFFERENTIAL
ā€¢ LYTES, GLUCOSE, RFTā€™S, LFTā€™S, LIVER
ENZYMES
ā€¢ CD4+ COUNT, CD8 COUNT, CD4/CD8
ā€¢ VIRAL LOAD
ā€¢ SEROLOGY FOR HEP A, B, C, SYPHILIS,
RUBELLA, TOXO, CMV
ā€¢ TB SKIN TEST
FOLLOW UP VISITS
ā€¢ STANDARD OBSTETRICAL ROUTINE
ā€¢ INCREASE SURVEILLANCE ONLY IF
WARRANTED
ā€¢ LABS EVERY 3 MONTHS
ā€¢ CD4+ COUNT
ā€¢ VIRAL LOAD
ā€¢ SEROLOGY FOR TOXOPLASMOSIS AND
SYPHILIS
OPPORTUNISTIC
INFECTIONS
ā€¢ PROPHYLAXIS SHOULD BE
OFFERED IN PREGNANCY FOR THE
FOLLOWING
ā€¢ PNEUMOCYSTIS CARINII PNEUMONIA
ā€¢ TOXOPLASMOSIS
ā€¢ TUBERCULOSIS
ā€¢ MYCOBACTERIUM AVIUM COMPLEX
ā€¢ VARICELLA ZOSTER
ā€¢ HEPATITIS A, B
CONCLUSION
ā€¢ HIV IN PREGNANCY SHOULD BE
MANAGED BY MULTIDISCIPLINARY
TEAM
ā€¢ ANTENATAL CARE IS SIMILAR TO
THAT OF HIV POSITIVE WOMEN
ā€¢ PREGNANCY NOT CONSIDERED
HIGH RISK SIMPLY BY VIRTUE OF
HIV INFECTION
ANTIRETROVIRAL USE
ANTEPARTUM
ANTIRETROVIRAL USE
ā€¢ GOALS:
ā€“ CONTROL DISEASE IN MOTHER
ā€“ REDUCE PERINATAL TRANSMISSION
ā€¢ VERY LITTLE DATA AVAILABLE ON
EFFECTS IN PREGNANCY
ā€¢ MOST DATA ASSESSES ZIDOVUDINE
ā€¢ LITTLE DATA ON OTHER DRUGS
CONCLUSIONS
ā€¢ ZIDOVUDINE REDUCES PERINATAL
TRANSMISSION IN WOMEN AT
DIFFERENT STAGES OF DISEASE
ā€¢ LONG AS WELL AS SHORTER
REGIMENS EFFECTIVE
ā€¢ STILL EFFECTIVE IN
BREASTFEEDING POPULATIONS
ā€¢ USE OF OTHER ANTIRETROVIRALS
IN COMBINATION WITH ZDV
PROMISING, STILL
IN UTERO
EXPOSURE
IN UTERO EXPOSURE
C
Skeletal
Abacavir
C
Hydrocephalu
s
Zalcitabine
B
Not
carcinogenic
Not
teratogenic
Didanosine
C
Liver and
urinary tumours
Not
teratogenic
Stavudine
C
Not
teratogenic
Lamivudine
FDA
Pregnancy
Category
Carcinogenicity
in animals
Teratogenicity
In animals
(rodents)
Drug
NRTIā€™s
IN UTERO EXPOSURE
B
Not teratogenic
Nelfinavir
C
Increased
hyperbilirubinemia
in monkeys -
neonatal
Incr.
supranumery &
cervical ribs
Indinavir
B
Not teratogenic
Saquinav
ir
B
Slight incr. in
cryptorchidism
Ritonavir
FDA
Pregnancy
Category
Non Teratogenic
Effects
Teratogenicity in
Animals
Drug
PIā€™s
ANTIRETROVIRAL
THERAPY DURING LABOR &
DELIVERY
IV ZIDOVUDINE
ā€¢ ZDV LOADING DOSE AT ONSET OF
LABOR 2MG/KG OVER 1 HR
ā€¢ CONTINUOUS INFUSION WHILE IN
LABOR 1MG/KG/HR
ā€¢ INCREASING EVIDENCE THAT MOST
PERINATAL TRANSMISSION
OCCURS NEAR TIME OF OR DURING
DELIVERY
ā€¢ REDUCTION OF PERINATAL
TRANSMISSION DUE TO SYSTEMIC
ANTIRETROVIRAL DRUG LEVELS IN
NEONATE AT TIME OF DELIVERY
IV ZIDOVUDINE
ā€¢ ZDV READILY CROSSES PLACENTA
ā€¢ INITIAL IV DOSE RESULTS IN
VIRUCIDAL LEVELS IN MOM &
INFANT
ā€¢ CONTINUOUS INFUSION ENSURES
STABLE DRUG LEVELS IN INFANT
DURING BIRTH
ORAL ZIDOVUDINE
ā€¢ IF IV ZDV NOT AVAILABLE, ORAL ZDV
MAY BE USED INTRAPARTUM
ā€¢ ZDV 600MG PO @ ONSET OF LABOR
ā€¢ 300MG PO Q3H IN LABOR
BANGKOK, LANCET 1999
ā€¢ RANDOMIZED PLACEBO
CONTROLLED
ā€¢ ZDV 300MG PO BID FROM 36WKS GA
UNTIL ONSET OF LABOR
ā€¢ 300MG PO Q3H WHILE IN LABOR
ā€¢ ALL WOMEN ADVISED NOT TO
BREASTFEED
ā€¢ TRANSMISSION RATES: 9.4% IN RX
GROUP; 18.9% IN CONTROL GROUP
ABIDJAN, LANCET 1999
ā€¢ SIMILAR TRIAL TO BANGKOK, BUT IN
BREASTFEEDING WOMEN
6 MONTHS 4.5 YEARS
ZDV 16.5% 21%
PLACEBO 26.1% 31%
EFFICACY 37% 30%
COTE Dā€™IVOIRE & BURKINA
FASO, LANCET 1999
ā€¢ PLACEBO VS ZDV STARTED @ 36-38
WKS GA
ā€¢ 300MG PO DAILY
ā€¢ 600MG PO AT ONSET OF LABOR
ā€¢ 300MG PO BID UNTIL 7 DAYS PP
ā€¢ >85% OF INFANTS BREASTFED
>3MOS
ā€¢ 18% VS 27.5 % TRANSMISSION @
6MOS (38% EFFICACY)
ā€¢ RESULTS SHOW SHORT-COURSE
PO ZDV SAFE & EFFECTIVE IN ļ‚ÆING
RISK OF MOTHER-TO-CHILD
TRANSMISSION
ā€¢ PREVENTION RATES NOT AS HIGH
AS WITH IV ZDV
ORAL NEVIRAPINE
ā€¢ NON-NUCLEOSIDE REVERSE
TRANSCRIPTASE INHIBITOR
ā€¢ VERY LONG HALF-LIFE
ā€¢ RAPID DEVā€™T OF DRUG RESISTANCE
HIVNET 012 STUDY
GUAY ET AL - 1999
ā€¢ 13626 ļ… RANDOMIZED - NVP VS ZDV
ā€¢ NVP REGIMEN
ā€¢ 200MG PO AT ONSET OF LABOR
ā€¢ 2MG/KG PO DOSE TO BABY ļ‚£72HR
DELā€™Y
ā€¢ ZDV REGIMEN
ā€¢ 600MG PO AT ONSET OF LABOR
ā€¢ 300MG PO Q3H DURING LABOR
ā€¢ 4MG/KG BID x7 DAYS TO INFANTS
HIVNET 012 - RESULTS
ZDV NVP
3 DAYS 10.4% 8.2%
6-8 WKS 21.3% 11.9%
14-16 WKS 25.1% 13.1%
SO WHAT?
ā€¢ EFFICACY OF SHORT-COURSE NVP
47% GREATER THAN SHORT
COURSE ZDV
ā€¢ CURRENTLY SHORT-COURSE PO
NVP NOT COMPARED TO IV ZDV
FOR TRANSMISSION PREVENTION
CONCLUSIONS
ā€¢ DURING LABOR - ZDV 2MG/KG IV
LOADING DOSE, THEN 1MG/KG/HR
ā€¢ IF IV ZDV NOT AVAILABLE CONSIDER
PO REGIMEN
ā€¢ MAY CONSIDER ADDITION OF
NVP 200MG PO TO IV ZDV @ ONSET
OF LABOR
OBSTETRICAL
PRACTICE
OBSTETRICAL PRACTICE
ā€¢ 70 % OF HIV TRANSMISSION
OCCURS INTRAPARTUM.
ā€¢ THE GOAL OF OBSTETRICAL
MANAGEMENT OF THE HIV PATIENT
IS TO AVOID THOSE PRACTICES
THAT INCREASE RISK OF
TRANSMISSION.
OBSTETRICAL PRACTICE
RUPTURE OF MEMBRANES
LANDESMAN ET AL., 1996
ā€¢ RUPTURED MEMBRANES ONE OF
MANY VARIABLES EXAMINED
ā€¢ 281 MOTHER-CHILD PAIRS WITH
MEMBRANES RUPTURED LESS
THAN 4 HOURS
ā€¢ 206 MOTHER-CHILD PAIRS WITH
MEMBRANES RUPTURED MORE
THAN 4 HOURS
RUPTURE OF MEMBRANES
LANDESMAN ET AL., 1996
0
5
10
15
20
25
% Infants Infected
less than 4 h
greater than 4 h
OBSTETRICAL PRACTICE
MODE OF DELIVERY - VAGINAL
ā€¢ ARTIFICIAL RUPTURE OF MEMBRANES
SHOULD BE AVOIDED
ā€¢ RUPTURE OF MEMBRANES PAST 4
HOURS SHOULD BE AVOIDED
ā€¢ FETAL SCALP SAMPLING AND THE USE
OF SCALP ELECTRODES SHOULD BE
AVOIDED
MODE OF DELIVERY:
EUROPEAN MODE OF DELIVERY
COLLABORATION ā€“ MARCH, 1999
ā€¢ RANDOMIZED CLINICAL TRIAL
ā€¢ 370 MOTHER-CHILD PAIRS
ANALYZED
ā€¢ 203 DELIVERED BY C-S
ā€¢ 167 DELIVERED VAGINALLY
MODE OF DELIVERY:
EUROPEAN MODE OF DELIVERY
COLLABORATION ā€“ MARCH, 1999
0
2
4
6
8
10
12
% INFANTS INFECTED
C-S
Vag.
MODE OF DELIVERY:
EUROPEAN MODE OF DELIVERY
COLLABORATION ā€“ MARCH, 1999
ā€¢ 203 C-S PERFORMED
ā€¢ 165 WERE PERFORMED
ELECTIVELY
ā€¢ 31 WERE PERFORMED
EMERGENTLY
MODE OF DELIVERY:
EUROPEAN MODE OF DELIVERY
COLLABORATION ā€“ MARCH, 1999
0
1
2
3
4
5
6
7
8
9
% Infected Infants
Elective
Emergency
MODE OF DELIVERY: META-ANALYSIS
THE INTERNATIONAL PERINATAL HIV
GROUP, APRIL 1999
ā€¢ 15 PROSPECTIVE COHORT STUDIES
ā€¢ 8533 MOTHER-CHILD PAIRS
ā€¢ REDUCTION OF TRANSMISSION 50% (OR
0.43, 95% CI, 0.33 ā€“ 0.56) WITH ELECTIVE
C-S VS. OTHER MODES OF DELIVERY
ā€¢ REDUCTION OF TRANSMISSION 87% (OR
0.13, 95% CI, 0.09 ā€“ 0.19) WITH ELECTIVE
C-S & PACTG 076
MODE OF DELIVERY ā€“ CAESAREAN
SECTION
ā€¢ HIV INFECTED WOMEN SHOULD BE
COUNSELLED ABOUT ELECTIVE C-S
ā€¢ VERTICAL TRANSMISSION IS REDUCED TO 2%
WITH PACTG 076 THERAPY AND ELECTIVE C-S
ā€¢ WOMEN WITH HIGH VIRAL LOADS MAY BENEFIT
MOST FROM C-S
ā€¢ TO AVOID SROM & ONSET OF LABOUR, ELECTIVE
C-S IS PERFORMED AT 38 WEEKS
ā€¢ AFTER SROM OR ONSET OF LABOUR C-S IS
LESS PROTECTIVE
ā€¢ TO AVOID C-S MORBIDITY, ANTIBIOTIC
PROPHYLAXIS SHOULD BE CONSIDERED
VIRAL LOAD
HIV IN PREGNANCY ā€“ VIRAL LOAD
WOMEN AND INFANTS TRANSMISSION STUDY (WITS): GARCIA ET
AL., 1999
26 of 64
Greater than
100,000
17 of 54
50,001 ā€“ 100,000
39 of 183
10,001 ā€“ 50,000
32 of 193
1,000 ā€“ 10,000
0 of 57
Less than 1,000
Number of HIV
Transmissions
HIV Viral Load
(Copies per mL)
HIV IN PREGNANCY ā€“ VIRAL LOAD
WOMEN AND INFANTS TRANSMISSION STUDY (WITS): GARCIA ET
AL., 1999
0
5
10
15
20
25
30
35
40
45
% INFANTS INFECTED
less than 1,000
1,001-10,000
10,001-50,000
50,001-100,000
more than 100,000
BREASTFEEDING IN HIV
POSITIVE WOMEN
INTRODUCTION
ā€¢ HIV DNA PRESENT IN BREAST MILK
ā€¢ HIV TRANSMISSION CAN OCCUR
THROUGH BREASTFEEDING
ā€¢ BREASTFEEDING IS AN
INDEPENDENT RISK FACTOR FOR
HIV TRANSMISSION
EVIDENCE TO SUPPORT
TRANSMISSION
ā€¢ ISOLATION OF HIV-1 FROM
CELLULAR & NON-CELLULAR
FRACTIONS OF BREAST MILK
ā€¢ CASE REPORTS OF INFECTED
CHILDREN BREASTFED BY
MOTHERS WHO ACQUIRED HIV
POSTPARTUM
EVIDENCE TO SUPPORT
TRANSMISSION
ā€¢ DOCUMENTATION OF OTHER
RETROVIRUSES TRANSMITTED
THROUGH BREAST MILK
ā€¢ CASE REPORTS OF BREAST FED
CHILDREN WHO WERE INITIALLY
HIV NEGATIVE BUT SEROCONVERTED
DURING BREASTFEEDING
POLICIES
ā€¢ AVOIDANCE OF BREASTFEEDING IS
CONTROVERSIAL AND DEPENDS ON
INTERNAL MILIEU
ā€¢ DEVELOPING COUNTRIES VS
INDUSTRIALIZED COUNTRIES
POLICIES
ā€¢ UNAIDS REVISED STATEMENT 1998:
WOMEN SHOULD BE OFFERED HIV
COUNSELING AND TESTING, BE
INFORMED OF RISKS AND BENEFITS
OF BREASTFEEDING IF THE
MOTHER IS HIV POSITIVE, AND
SHOULD MAKE A DECISION THAT
TAKES INTO ACCOUNT THE
INDIVIDUAL &FAMILY SITUATIONS
MECHANISM OF
TRANSMISSION
ā€¢ EXACT MECHANISM OF
TRANSMISSION THROUGH BREAST
MILK STILL NOT WELL
UNDERSTOOD
ā€¢ INFECTION VIA CELL-FREE HIV IN
BREAST MILK OR VIA HIV-INFECTED
CELLS
ā€¢ SUSCEPTIBILITY OF IMMATURE
NEONATAL GI TRACT TO VIRUS
ā€¢ GI TRACT MUCOSAL DAMAGE
DURATION OF
BREASTFEEDING
ā€¢ STUDIES - ļ‚­ IN TRANSMISSION WITH
INCREASING DURATION OF
BREASTFEEDING
MALAWI, JAMA 1999
ā€¢ CUMULATIVE INFECTION RISK
WHILE BREASTFEEDING
ā€¢ 3.5% AT END OF 5 MONTHS
ā€¢ 7.0% AT END OF 11 MONTHS
ā€¢ 8.9% AT END OF 17 MONTHS
ā€¢ 10.3% AT END OF 23 MONTHS
ā€¢ NO FURTHER TRANSMISSION AFTER
BREASTFEEDING STOPPED
MULTICENTER STUDY,
LANCET 1998
ā€¢ CUMULATIVE INFECTION RISK
WHILE BREASTFEEDING
ā€¢ 0.7% AT END OF 6 MONTHS
ā€¢ 0.95% AT END OF 9 MONTHS
ā€¢ 2.5% AT END OF 12 MONTHS
ā€¢ 6.3% AT END OF 18 MONTHS
ā€¢ 7.4% AT END OF 24 MONTHS
ā€¢ 9.2% AT END OF 36 MONTHS
DURATION OF
BREASTFEEDING
ā€¢ ? EARLY WEANING POLICY
ā€¢ PROBLEMS WITH EARLY WEANING
ā€¢ ADVERSE NEONATAL EFFECTS
ā€¢ COLOSTRUM HIGHLY INFECTIOUS
EXCLUSIVITY OF
BRESTFEEDING
ā€¢ STUDIES - INFANTS EXCLUSIVELY
BREAST FED AT LOWER RISK OF
ACQUIRING HIV THAN THOSE FED
WITH OTHER TYPES OF MILK, TEA,
OR JUICE WHILE BEING BREAST
FED
BRAZIL STUDY, 1998
ā€¢ CHILDREN FED WITH OTHER TYPES
OF MILK WHILE BEING BREASTFED
WERE AT 2.2-FOLD GREATER RISK
OF HIV INFECTION THAN THOSE
EXCLUSIVELY BREASTFED
ā€¢ CHILDREN FED WITH TEA OR FRUIT
JUICE WHLE BEING BREASTFED
WERE AT 2.6-FOLD GREATER RISK
OF INFECTION
DURBAN (SOUTH AFRICA),
LANCET 1999
ā€¢ 3 GROUPS OF CHILDREN - NEVER
BREASTFED, EXCLUSIVELY
BREASTFED, MIXED FEEDING
ā€¢ NO SIGNIFICANT DIFFERENCE IN
TRANSMISSION BETWEEN NEVER
AND EXCLUSIVELY BREASTFED
GROUPS
ā€¢ SIGNIFICANTLY INCREASED RISK
OF TRANSMISSION FOR MIXED
INTERPRETATION
ā€¢ IMMUNE FACTORS IN BREAST MILK
ā€¢ GROWTH FACTORS IN BREAST MILK
ā€¢ MUCOSAL DAMAGE WITH MIXED
FEEDING
MATERNAL FACTORS
ā€¢ CRACKED NIPPLES
ā€¢ BLEEDING NIPPLES
ā€¢ PARITY
CONCLUSION
ā€¢ PRECISE RISK FACTORS AND
MECHANISM OF TRANSMISSION
STILL NOT WELL UNDERSTOOD
ā€¢ WOMEN WHO ARE HIV POSITIVE
SHOULD BE ADVISED TO AVOID
BREASTFEEDING
ā€¢ WOMEN WHO BREASTFEED
SHOULD BE INFORMED THAT
TRANSMISSION CAN OCCUR
SUMMARY
HIV SCREENING
ā€¢ ALL PREGNANT WOMEN SHOULD
BE OFFERRED HIV TESTING
ā€¢ PRE- & POST- TEST COUNSELING
FOR ALL PREGNANT WOMEN
ā€¢ TARGETED TESTING OF PREGNANT
WOMEN WHO REPORT HIGH RISK
BEHAVIOR NOT RECOMMENDED
ANTENATAL CARE
ā€¢ HIV IN PREGNANCY REQUIRES
MULTIDISCIPLINARY APPROACH
ā€¢ ANTENATAL CARE IS SIMILAR TO THAT OF
HIV -VE WOMEN
ā€¢ PREGNANCY NOT HIGH RISK
ā€¢ AVOID INVASIVE PROCEDURES
ā€¢ MONITOR CD4+ AND VIRAL LOAD AT
LEAST EVERY 3 MONTHS IF ABLE TO
PROVIDE ANTIRETROVIRAL THERAPY
ANTIRETROVIRAL USE
ā€¢ Zidovudine reduces perinatal
transmission in women at different
stages of disease
ā€¢ long (ante, peri, and postnatal) as well
as shorter regimens effective
ā€¢ still effective in breastfeeding
populations
ā€¢ Use of other antiretrovirals in
combination with ZDV promising, still
investigational
INTRAPARTUM
ANTIRETROVIRAL
THERAPY
ā€¢ DURING LABOR - ZDV 2MG/KG IV
LOADING DOSE, THEN 1MG/KG/HR
ā€¢ IF IV ZDV NOT AVAILABLE CONSIDER
PO REGIMEN
ā€¢ MAY CONSIDER ADDITION OF
NVP 200MG PO TO IV ZDV @ ONSET
OF LABOR
BREASTFEEDING
ā€¢ PRECISE RISK FACTORS AND
MECHANISM OF TRANSMISSION
STILL NOT WELL UNDERSTOOD
ā€¢ WOMEN WHO ARE HIV POSITIVE
SHOULD BE ADVISED TO AVOID
BREASTFEEDING
ā€¢ WOMEN WHO BREASTFEED
SHOULD BE INFORMED THAT
TRANSMISSION CAN OCCUR

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749-751.ppt

  • 1. HIV In Mothers and Children
  • 2. 2 What Is HIV/AIDS? ā€¢ Acquired immunodeficiencysyndrome (AIDS) is caused by the humanimmunodeficiencyvirus (HIV). ā€¢ HIV attacks and destroys whiteblood cells, causinga defect in thebodyā€™s immunesystem.
  • 3. 3 What Is HIV/AIDS? ā€¢ The immunesystem of an HIV-infectedperson becomes so weakenedthatit cannotprotect itself from serious infections. Whenthishappens, theperson clinically has AIDS. ā€¢ AIDS may manifestas early as 2 years or as late as 10 years after infectionwith HIV.
  • 4. 4 Number ofPeoplewith HIV/AIDSby Region North America 890,000 Caribbean 330,000 Latin America 1.4 million Western Europe 500,000 Sub-Saharan Africa 22.5 million Eastern Europe & Central Asia 270,000 East Asia & Pacific 560,000 South and South East Asia 6.7 million Australia and New Zealand 12,000 North Africa & Middle East 210,000 Source: UNAIDS/WHO 1998.
  • 5. 5 HIV Transmission Through SexualContact ā€¢ Of every 100 HIV infectedadults, 75-85 have been infectedthrough unprotected intercourse ā€“ 70% of these infections are from heterosexual intercourse ā€¢ STDs, especially ulcerative lesions in genitalia,increase risk of transmission Source: UNAIDS/WHO 1996.
  • 6. 6 Modesof HIV Transmission ā€¢ Sexualintercourse ā€¢ Accidental exposure to blood/blood products (e.g., blood transfusions,shared needles, contaminated instruments) ā€¢ Mother to childduring: ā€“ pregnancy ā€“ birth ā€“ breastfeeding
  • 7. 7 Womenand HIV Social Risk Factors ā€“ Illiteracy ā€“ Lackof awarenessof preventive measures Biological risk factors ā€“ Twiceas easy for women to contract HIVfrom men ā€“ Physiology of women (e.g., menstruation, intercourse) ā€“ Pregnancy-associated conditions (e.g., anemia, menorrhagia and hemorrhage) increase the need for blood transfusion
  • 8. 8 HIV andContraception ā€¢ Contraception withprotection ā€“ Male condom (latex and vinyl) ā€“ Female condom ā€“ Nonoxynol-9 (antiviralspermicidal cream)1 ā€“ Diaphragm1 ā€¢ Methods appropriate for use by womenwith HIV. They should use a condom for their partnerā€™s protection. ā€“ Hormonals (COCs, Implants, PICs) ā€“ Voluntary sterilization 1Partial protection if used without condom
  • 9. 9 Effectof AIDSon Pregnancy ā€¢ Infertility ā€¢ Repeated abortions ā€¢ Prematurity ā€¢ Intrauterinegrowth retardation ā€¢ Stillbirths ā€¢ Congenitalabnormalities ā€¢ Embryopathies
  • 10. 10 HIV Transmission from Mother toInfant ā€¢ Antenatal ā€“ In utero bytransplacentalpassage ā€¢ Intranatal ā€“ Exposure to maternal blood and vaginalsecretions during labor and delivery ā€¢ Postnatal ā€“ Postpartum through breastfeeding Source: UNAIDS/WHO 1996; UNAIDS/WHO 1998.
  • 11. 11 HIV Transmission from Mother toInfant ā€¢ 25-35% of all infantsborn to HIV-infected womenin developing countriesbecome infected ā€¢ 90% of HIV-infectedinfantsand children were infectedby mother Source: UNAIDS/WHO 1996; UNAIDS/WHO 1998.
  • 12. ā€¢ approximately 600,000 HIV-infected infants are born every yearā€“at least 1,600 every dayā€“in resource-constrained countries. ā€¢ Transmission occurs during pregnancy, labor and delivery, and breastfeeding. ā€¢ The rate of mother to child transmission has been reduced to less than 5 percent among the limited number of HIV-infected women in developed countries.
  • 13. ā€¢ high rates are largely due to the lack of access to: ā€“HIV voluntary counseling and testing ā€“ replacement feeding ā€“selective caesarean section ā€“antiretroviral drug therapy
  • 14. 14 HIV Transmission HIV cannot be transmittedby: ā€“ Casualperson to person contact at home or work or in socialor public places ā€“ Food, air, water ā€“ Insect/mosquito bites ā€“ Coughing, sneezing, spitting ā€“ Shakinghands, touching, dry kissingor hugging ā€“ Swimming pools, toilets, etc.
  • 15. 15 AIDSand Infants ā€¢ Symptoms generallydevelop by 6 monthsof age ā€“ Diarrhea ā€“ Failure to thrive ā€¢ Most of thesechildren diebefore their second birthday ā€¢ Children born to HIV-infected parents are likely to become orphans
  • 16. Reducing pediatric HIV infection and disease involves three stages: ā€¢ preventing HIV infection among women of childbearing age ā€¢ preventing unwanted pregnancy among HIV-positive women ā€¢ preventing mother to child transmission during pregnancy, labor and delivery, and breastfeeding
  • 17. BENEFITS TO HIV TESTING ā€¢ EARLY COUNSELING AND TREATMENT OF HIV INFECTION ā€¢ ABILITY TO MAKE DECISIONS REGARDING PREGNANCY ā€¢ IMPLEMENTATION OF STRATEGIES TO ATTEMPT TO PREVENT TRANSMISSION TO FETUS
  • 18. WHO SHOULD WE SCREEN? ā€¢ ALL PREGNANT WOMEN ā€¢ TARGETED TESTING FAILS TO IDENTIFY A SUBSTANTIAL PROPORTION OF HIV POSITIVE WOMEN
  • 19. ā€¢ zidovudine (AZT) administered to the mother from 14 weeks of gestation and to the child during the first seven days after birth, reduced the risk of mother to child transmission among non- breastfeeding mothers by two-thirds. ā€¢ Two similar studies conducted in CĆ“te dā€™Ivoire and Burkina Faso among breastfeeding mothers demonstrated a 37 percent reduction in mother to child transmission. Anti-Retroviral Based Prevention Strategies
  • 20. ā€¢ A study in Uganda demonstrated a 47 percent reduction in mother to child transmission following the administration of a single dose of nevirapine to the mother at onset of labor and to the baby within 72 hours after birth. ā€¢ The combination of AZT and lamivudine in a short-course regimen also has been shown to reduce mother to child transmission. Anti-Retroviral Based Prevention Strategies
  • 21. 21 Protecting HealthCareWorkersDuring Labor and Delivery ā€¢ Precautionsduringlabor: ā€“ Protection from blood and amniotic fluids ā€“ Protection from sharp instruments ā€¢ Resuscitationof baby: ā€“ Nomouth to mouth suction ā€“ Nomouth to mouth breathing ā€¢ Precautionsfollowinglabor: ā€“ Proper disinfection of instruments ā€“ Proper disposal of placenta and other items
  • 22. PRETEST COUNSELING ā€¢ TAKE RISK HISTORY AND COUNCIL REGARDING RISK REDUCTION ā€¢ DISCUSS REASONS FOR TEST ā€¢ PROVIDE INFORMATION TO WOMEN REGARDING TESTING & ILLNESS ā€¢ RISKS & BENEFITS OF TESTING ā€¢ CONFIDENTIALITY OF RESULTS ā€¢ ASSESS WINDOW PERIOD ā€¢ PERSON HAS RIGHT TO REFUSE TESTING
  • 23. POST-TEST COUNSELING ā€¢ HIV RESULTS SHOULD BE GIVEN IN PERSON ā€¢ ASSESS PATIENTā€™S UNDERSTANDING ā€¢ ENCOURAGE PATIENT TO EXPRESS FEELINGS AND ASK QUESTIONS ā€¢ NEGATIVE AND INDETERMINATE RESULTS: DISCUSS NEED FOR REPEAT TESTING
  • 24. POSITIVE RESULT ā€¢ IDENTIFY IMMEDIATE CONCERNS ā€¢ IDENTIFY SUPPORTS ā€¢ EFFECT OF HIV ON PREGNANCY ā€¢ RISK OF TRANSMISSION TO FETUS DURING PREGNANCY, L&D, BF ā€¢ MEASURES TO DECREASE HIV TRANSMISSION
  • 25. CONCLUSIONS ā€¢ ALLPREGNANTWOMEN SHOULD BE OFFERRED HIV TESTING ā€¢ PRE- & POST- TEST COUNSELING FOR ALL PREGNANTWOMEN ā€¢ TARGETED TESTING OF PREGNANT WOMEN WHO REPORT HIGH RISK BEHAVIOR NOT RECOMMENDED
  • 27. INTRODUCTION ā€¢ MULTIDISCIPLINARY TEAM APPROACH ā€¢ MEDICAL NEEDS ā€¢ SOCIAL AND PSYCHOLOGICAL NEEDS
  • 28. ANTENATAL CARE ā€¢ SIMILAR TO CARE FOR HIV NEGATIVE WOMEN ā€¢ PREGNANCY NOT HIGH RISK ā€¢ SAME NUMBER OF ANTENATAL VISITS ā€¢ AVOID INVASIVE ANTENATAL TESTS OR PROCEDURES
  • 29. FIRST VISIT ā€¢ PATIENT HISTORY ā€¢ DATES OF 1ST POSITIVE HIV TEST ā€¢ HIV RISK FACTORS ā€¢ HIV CARE AT TIME OF CONCEPTION ā€¢ SEROLOGIC STATUS OF PARTNER ā€¢ OTHER STDā€™S ā€¢ OPPORTUNISTIC INFECTIONS ā€¢ DRUG HISTORY
  • 30. FIRST VISIT ā€¢ INVESTIGATIONS ā€¢ CBC & DIFFERENTIAL ā€¢ LYTES, GLUCOSE, RFTā€™S, LFTā€™S, LIVER ENZYMES ā€¢ CD4+ COUNT, CD8 COUNT, CD4/CD8 ā€¢ VIRAL LOAD ā€¢ SEROLOGY FOR HEP A, B, C, SYPHILIS, RUBELLA, TOXO, CMV ā€¢ TB SKIN TEST
  • 31. FOLLOW UP VISITS ā€¢ STANDARD OBSTETRICAL ROUTINE ā€¢ INCREASE SURVEILLANCE ONLY IF WARRANTED ā€¢ LABS EVERY 3 MONTHS ā€¢ CD4+ COUNT ā€¢ VIRAL LOAD ā€¢ SEROLOGY FOR TOXOPLASMOSIS AND SYPHILIS
  • 32. OPPORTUNISTIC INFECTIONS ā€¢ PROPHYLAXIS SHOULD BE OFFERED IN PREGNANCY FOR THE FOLLOWING ā€¢ PNEUMOCYSTIS CARINII PNEUMONIA ā€¢ TOXOPLASMOSIS ā€¢ TUBERCULOSIS ā€¢ MYCOBACTERIUM AVIUM COMPLEX ā€¢ VARICELLA ZOSTER ā€¢ HEPATITIS A, B
  • 33. CONCLUSION ā€¢ HIV IN PREGNANCY SHOULD BE MANAGED BY MULTIDISCIPLINARY TEAM ā€¢ ANTENATAL CARE IS SIMILAR TO THAT OF HIV POSITIVE WOMEN ā€¢ PREGNANCY NOT CONSIDERED HIGH RISK SIMPLY BY VIRTUE OF HIV INFECTION
  • 35. ANTEPARTUM ANTIRETROVIRAL USE ā€¢ GOALS: ā€“ CONTROL DISEASE IN MOTHER ā€“ REDUCE PERINATAL TRANSMISSION ā€¢ VERY LITTLE DATA AVAILABLE ON EFFECTS IN PREGNANCY ā€¢ MOST DATA ASSESSES ZIDOVUDINE ā€¢ LITTLE DATA ON OTHER DRUGS
  • 36. CONCLUSIONS ā€¢ ZIDOVUDINE REDUCES PERINATAL TRANSMISSION IN WOMEN AT DIFFERENT STAGES OF DISEASE ā€¢ LONG AS WELL AS SHORTER REGIMENS EFFECTIVE ā€¢ STILL EFFECTIVE IN BREASTFEEDING POPULATIONS ā€¢ USE OF OTHER ANTIRETROVIRALS IN COMBINATION WITH ZDV PROMISING, STILL
  • 38. IN UTERO EXPOSURE C Skeletal Abacavir C Hydrocephalu s Zalcitabine B Not carcinogenic Not teratogenic Didanosine C Liver and urinary tumours Not teratogenic Stavudine C Not teratogenic Lamivudine FDA Pregnancy Category Carcinogenicity in animals Teratogenicity In animals (rodents) Drug NRTIā€™s
  • 39. IN UTERO EXPOSURE B Not teratogenic Nelfinavir C Increased hyperbilirubinemia in monkeys - neonatal Incr. supranumery & cervical ribs Indinavir B Not teratogenic Saquinav ir B Slight incr. in cryptorchidism Ritonavir FDA Pregnancy Category Non Teratogenic Effects Teratogenicity in Animals Drug PIā€™s
  • 41. IV ZIDOVUDINE ā€¢ ZDV LOADING DOSE AT ONSET OF LABOR 2MG/KG OVER 1 HR ā€¢ CONTINUOUS INFUSION WHILE IN LABOR 1MG/KG/HR
  • 42. ā€¢ INCREASING EVIDENCE THAT MOST PERINATAL TRANSMISSION OCCURS NEAR TIME OF OR DURING DELIVERY ā€¢ REDUCTION OF PERINATAL TRANSMISSION DUE TO SYSTEMIC ANTIRETROVIRAL DRUG LEVELS IN NEONATE AT TIME OF DELIVERY
  • 43. IV ZIDOVUDINE ā€¢ ZDV READILY CROSSES PLACENTA ā€¢ INITIAL IV DOSE RESULTS IN VIRUCIDAL LEVELS IN MOM & INFANT ā€¢ CONTINUOUS INFUSION ENSURES STABLE DRUG LEVELS IN INFANT DURING BIRTH
  • 44. ORAL ZIDOVUDINE ā€¢ IF IV ZDV NOT AVAILABLE, ORAL ZDV MAY BE USED INTRAPARTUM ā€¢ ZDV 600MG PO @ ONSET OF LABOR ā€¢ 300MG PO Q3H IN LABOR
  • 45. BANGKOK, LANCET 1999 ā€¢ RANDOMIZED PLACEBO CONTROLLED ā€¢ ZDV 300MG PO BID FROM 36WKS GA UNTIL ONSET OF LABOR ā€¢ 300MG PO Q3H WHILE IN LABOR ā€¢ ALL WOMEN ADVISED NOT TO BREASTFEED ā€¢ TRANSMISSION RATES: 9.4% IN RX GROUP; 18.9% IN CONTROL GROUP
  • 46. ABIDJAN, LANCET 1999 ā€¢ SIMILAR TRIAL TO BANGKOK, BUT IN BREASTFEEDING WOMEN 6 MONTHS 4.5 YEARS ZDV 16.5% 21% PLACEBO 26.1% 31% EFFICACY 37% 30%
  • 47. COTE Dā€™IVOIRE & BURKINA FASO, LANCET 1999 ā€¢ PLACEBO VS ZDV STARTED @ 36-38 WKS GA ā€¢ 300MG PO DAILY ā€¢ 600MG PO AT ONSET OF LABOR ā€¢ 300MG PO BID UNTIL 7 DAYS PP ā€¢ >85% OF INFANTS BREASTFED >3MOS ā€¢ 18% VS 27.5 % TRANSMISSION @ 6MOS (38% EFFICACY)
  • 48. ā€¢ RESULTS SHOW SHORT-COURSE PO ZDV SAFE & EFFECTIVE IN ļ‚ÆING RISK OF MOTHER-TO-CHILD TRANSMISSION ā€¢ PREVENTION RATES NOT AS HIGH AS WITH IV ZDV
  • 49. ORAL NEVIRAPINE ā€¢ NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR ā€¢ VERY LONG HALF-LIFE ā€¢ RAPID DEVā€™T OF DRUG RESISTANCE
  • 50. HIVNET 012 STUDY GUAY ET AL - 1999 ā€¢ 13626 ļ… RANDOMIZED - NVP VS ZDV ā€¢ NVP REGIMEN ā€¢ 200MG PO AT ONSET OF LABOR ā€¢ 2MG/KG PO DOSE TO BABY ļ‚£72HR DELā€™Y ā€¢ ZDV REGIMEN ā€¢ 600MG PO AT ONSET OF LABOR ā€¢ 300MG PO Q3H DURING LABOR ā€¢ 4MG/KG BID x7 DAYS TO INFANTS
  • 51. HIVNET 012 - RESULTS ZDV NVP 3 DAYS 10.4% 8.2% 6-8 WKS 21.3% 11.9% 14-16 WKS 25.1% 13.1%
  • 52. SO WHAT? ā€¢ EFFICACY OF SHORT-COURSE NVP 47% GREATER THAN SHORT COURSE ZDV ā€¢ CURRENTLY SHORT-COURSE PO NVP NOT COMPARED TO IV ZDV FOR TRANSMISSION PREVENTION
  • 53. CONCLUSIONS ā€¢ DURING LABOR - ZDV 2MG/KG IV LOADING DOSE, THEN 1MG/KG/HR ā€¢ IF IV ZDV NOT AVAILABLE CONSIDER PO REGIMEN ā€¢ MAY CONSIDER ADDITION OF NVP 200MG PO TO IV ZDV @ ONSET OF LABOR
  • 55. OBSTETRICAL PRACTICE ā€¢ 70 % OF HIV TRANSMISSION OCCURS INTRAPARTUM. ā€¢ THE GOAL OF OBSTETRICAL MANAGEMENT OF THE HIV PATIENT IS TO AVOID THOSE PRACTICES THAT INCREASE RISK OF TRANSMISSION.
  • 56. OBSTETRICAL PRACTICE RUPTURE OF MEMBRANES LANDESMAN ET AL., 1996 ā€¢ RUPTURED MEMBRANES ONE OF MANY VARIABLES EXAMINED ā€¢ 281 MOTHER-CHILD PAIRS WITH MEMBRANES RUPTURED LESS THAN 4 HOURS ā€¢ 206 MOTHER-CHILD PAIRS WITH MEMBRANES RUPTURED MORE THAN 4 HOURS
  • 57. RUPTURE OF MEMBRANES LANDESMAN ET AL., 1996 0 5 10 15 20 25 % Infants Infected less than 4 h greater than 4 h
  • 58. OBSTETRICAL PRACTICE MODE OF DELIVERY - VAGINAL ā€¢ ARTIFICIAL RUPTURE OF MEMBRANES SHOULD BE AVOIDED ā€¢ RUPTURE OF MEMBRANES PAST 4 HOURS SHOULD BE AVOIDED ā€¢ FETAL SCALP SAMPLING AND THE USE OF SCALP ELECTRODES SHOULD BE AVOIDED
  • 59. MODE OF DELIVERY: EUROPEAN MODE OF DELIVERY COLLABORATION ā€“ MARCH, 1999 ā€¢ RANDOMIZED CLINICAL TRIAL ā€¢ 370 MOTHER-CHILD PAIRS ANALYZED ā€¢ 203 DELIVERED BY C-S ā€¢ 167 DELIVERED VAGINALLY
  • 60. MODE OF DELIVERY: EUROPEAN MODE OF DELIVERY COLLABORATION ā€“ MARCH, 1999 0 2 4 6 8 10 12 % INFANTS INFECTED C-S Vag.
  • 61. MODE OF DELIVERY: EUROPEAN MODE OF DELIVERY COLLABORATION ā€“ MARCH, 1999 ā€¢ 203 C-S PERFORMED ā€¢ 165 WERE PERFORMED ELECTIVELY ā€¢ 31 WERE PERFORMED EMERGENTLY
  • 62. MODE OF DELIVERY: EUROPEAN MODE OF DELIVERY COLLABORATION ā€“ MARCH, 1999 0 1 2 3 4 5 6 7 8 9 % Infected Infants Elective Emergency
  • 63. MODE OF DELIVERY: META-ANALYSIS THE INTERNATIONAL PERINATAL HIV GROUP, APRIL 1999 ā€¢ 15 PROSPECTIVE COHORT STUDIES ā€¢ 8533 MOTHER-CHILD PAIRS ā€¢ REDUCTION OF TRANSMISSION 50% (OR 0.43, 95% CI, 0.33 ā€“ 0.56) WITH ELECTIVE C-S VS. OTHER MODES OF DELIVERY ā€¢ REDUCTION OF TRANSMISSION 87% (OR 0.13, 95% CI, 0.09 ā€“ 0.19) WITH ELECTIVE C-S & PACTG 076
  • 64. MODE OF DELIVERY ā€“ CAESAREAN SECTION ā€¢ HIV INFECTED WOMEN SHOULD BE COUNSELLED ABOUT ELECTIVE C-S ā€¢ VERTICAL TRANSMISSION IS REDUCED TO 2% WITH PACTG 076 THERAPY AND ELECTIVE C-S ā€¢ WOMEN WITH HIGH VIRAL LOADS MAY BENEFIT MOST FROM C-S ā€¢ TO AVOID SROM & ONSET OF LABOUR, ELECTIVE C-S IS PERFORMED AT 38 WEEKS ā€¢ AFTER SROM OR ONSET OF LABOUR C-S IS LESS PROTECTIVE ā€¢ TO AVOID C-S MORBIDITY, ANTIBIOTIC PROPHYLAXIS SHOULD BE CONSIDERED
  • 66. HIV IN PREGNANCY ā€“ VIRAL LOAD WOMEN AND INFANTS TRANSMISSION STUDY (WITS): GARCIA ET AL., 1999 26 of 64 Greater than 100,000 17 of 54 50,001 ā€“ 100,000 39 of 183 10,001 ā€“ 50,000 32 of 193 1,000 ā€“ 10,000 0 of 57 Less than 1,000 Number of HIV Transmissions HIV Viral Load (Copies per mL)
  • 67. HIV IN PREGNANCY ā€“ VIRAL LOAD WOMEN AND INFANTS TRANSMISSION STUDY (WITS): GARCIA ET AL., 1999 0 5 10 15 20 25 30 35 40 45 % INFANTS INFECTED less than 1,000 1,001-10,000 10,001-50,000 50,001-100,000 more than 100,000
  • 69. INTRODUCTION ā€¢ HIV DNA PRESENT IN BREAST MILK ā€¢ HIV TRANSMISSION CAN OCCUR THROUGH BREASTFEEDING ā€¢ BREASTFEEDING IS AN INDEPENDENT RISK FACTOR FOR HIV TRANSMISSION
  • 70. EVIDENCE TO SUPPORT TRANSMISSION ā€¢ ISOLATION OF HIV-1 FROM CELLULAR & NON-CELLULAR FRACTIONS OF BREAST MILK ā€¢ CASE REPORTS OF INFECTED CHILDREN BREASTFED BY MOTHERS WHO ACQUIRED HIV POSTPARTUM
  • 71. EVIDENCE TO SUPPORT TRANSMISSION ā€¢ DOCUMENTATION OF OTHER RETROVIRUSES TRANSMITTED THROUGH BREAST MILK ā€¢ CASE REPORTS OF BREAST FED CHILDREN WHO WERE INITIALLY HIV NEGATIVE BUT SEROCONVERTED DURING BREASTFEEDING
  • 72. POLICIES ā€¢ AVOIDANCE OF BREASTFEEDING IS CONTROVERSIAL AND DEPENDS ON INTERNAL MILIEU ā€¢ DEVELOPING COUNTRIES VS INDUSTRIALIZED COUNTRIES
  • 73. POLICIES ā€¢ UNAIDS REVISED STATEMENT 1998: WOMEN SHOULD BE OFFERED HIV COUNSELING AND TESTING, BE INFORMED OF RISKS AND BENEFITS OF BREASTFEEDING IF THE MOTHER IS HIV POSITIVE, AND SHOULD MAKE A DECISION THAT TAKES INTO ACCOUNT THE INDIVIDUAL &FAMILY SITUATIONS
  • 74. MECHANISM OF TRANSMISSION ā€¢ EXACT MECHANISM OF TRANSMISSION THROUGH BREAST MILK STILL NOT WELL UNDERSTOOD ā€¢ INFECTION VIA CELL-FREE HIV IN BREAST MILK OR VIA HIV-INFECTED CELLS ā€¢ SUSCEPTIBILITY OF IMMATURE NEONATAL GI TRACT TO VIRUS ā€¢ GI TRACT MUCOSAL DAMAGE
  • 75. DURATION OF BREASTFEEDING ā€¢ STUDIES - ļ‚­ IN TRANSMISSION WITH INCREASING DURATION OF BREASTFEEDING
  • 76. MALAWI, JAMA 1999 ā€¢ CUMULATIVE INFECTION RISK WHILE BREASTFEEDING ā€¢ 3.5% AT END OF 5 MONTHS ā€¢ 7.0% AT END OF 11 MONTHS ā€¢ 8.9% AT END OF 17 MONTHS ā€¢ 10.3% AT END OF 23 MONTHS ā€¢ NO FURTHER TRANSMISSION AFTER BREASTFEEDING STOPPED
  • 77. MULTICENTER STUDY, LANCET 1998 ā€¢ CUMULATIVE INFECTION RISK WHILE BREASTFEEDING ā€¢ 0.7% AT END OF 6 MONTHS ā€¢ 0.95% AT END OF 9 MONTHS ā€¢ 2.5% AT END OF 12 MONTHS ā€¢ 6.3% AT END OF 18 MONTHS ā€¢ 7.4% AT END OF 24 MONTHS ā€¢ 9.2% AT END OF 36 MONTHS
  • 78. DURATION OF BREASTFEEDING ā€¢ ? EARLY WEANING POLICY ā€¢ PROBLEMS WITH EARLY WEANING ā€¢ ADVERSE NEONATAL EFFECTS ā€¢ COLOSTRUM HIGHLY INFECTIOUS
  • 79. EXCLUSIVITY OF BRESTFEEDING ā€¢ STUDIES - INFANTS EXCLUSIVELY BREAST FED AT LOWER RISK OF ACQUIRING HIV THAN THOSE FED WITH OTHER TYPES OF MILK, TEA, OR JUICE WHILE BEING BREAST FED
  • 80. BRAZIL STUDY, 1998 ā€¢ CHILDREN FED WITH OTHER TYPES OF MILK WHILE BEING BREASTFED WERE AT 2.2-FOLD GREATER RISK OF HIV INFECTION THAN THOSE EXCLUSIVELY BREASTFED ā€¢ CHILDREN FED WITH TEA OR FRUIT JUICE WHLE BEING BREASTFED WERE AT 2.6-FOLD GREATER RISK OF INFECTION
  • 81. DURBAN (SOUTH AFRICA), LANCET 1999 ā€¢ 3 GROUPS OF CHILDREN - NEVER BREASTFED, EXCLUSIVELY BREASTFED, MIXED FEEDING ā€¢ NO SIGNIFICANT DIFFERENCE IN TRANSMISSION BETWEEN NEVER AND EXCLUSIVELY BREASTFED GROUPS ā€¢ SIGNIFICANTLY INCREASED RISK OF TRANSMISSION FOR MIXED
  • 82. INTERPRETATION ā€¢ IMMUNE FACTORS IN BREAST MILK ā€¢ GROWTH FACTORS IN BREAST MILK ā€¢ MUCOSAL DAMAGE WITH MIXED FEEDING
  • 83. MATERNAL FACTORS ā€¢ CRACKED NIPPLES ā€¢ BLEEDING NIPPLES ā€¢ PARITY
  • 84. CONCLUSION ā€¢ PRECISE RISK FACTORS AND MECHANISM OF TRANSMISSION STILL NOT WELL UNDERSTOOD ā€¢ WOMEN WHO ARE HIV POSITIVE SHOULD BE ADVISED TO AVOID BREASTFEEDING ā€¢ WOMEN WHO BREASTFEED SHOULD BE INFORMED THAT TRANSMISSION CAN OCCUR
  • 86. HIV SCREENING ā€¢ ALL PREGNANT WOMEN SHOULD BE OFFERRED HIV TESTING ā€¢ PRE- & POST- TEST COUNSELING FOR ALL PREGNANT WOMEN ā€¢ TARGETED TESTING OF PREGNANT WOMEN WHO REPORT HIGH RISK BEHAVIOR NOT RECOMMENDED
  • 87. ANTENATAL CARE ā€¢ HIV IN PREGNANCY REQUIRES MULTIDISCIPLINARY APPROACH ā€¢ ANTENATAL CARE IS SIMILAR TO THAT OF HIV -VE WOMEN ā€¢ PREGNANCY NOT HIGH RISK ā€¢ AVOID INVASIVE PROCEDURES ā€¢ MONITOR CD4+ AND VIRAL LOAD AT LEAST EVERY 3 MONTHS IF ABLE TO PROVIDE ANTIRETROVIRAL THERAPY
  • 88. ANTIRETROVIRAL USE ā€¢ Zidovudine reduces perinatal transmission in women at different stages of disease ā€¢ long (ante, peri, and postnatal) as well as shorter regimens effective ā€¢ still effective in breastfeeding populations ā€¢ Use of other antiretrovirals in combination with ZDV promising, still investigational
  • 89. INTRAPARTUM ANTIRETROVIRAL THERAPY ā€¢ DURING LABOR - ZDV 2MG/KG IV LOADING DOSE, THEN 1MG/KG/HR ā€¢ IF IV ZDV NOT AVAILABLE CONSIDER PO REGIMEN ā€¢ MAY CONSIDER ADDITION OF NVP 200MG PO TO IV ZDV @ ONSET OF LABOR
  • 90. BREASTFEEDING ā€¢ PRECISE RISK FACTORS AND MECHANISM OF TRANSMISSION STILL NOT WELL UNDERSTOOD ā€¢ WOMEN WHO ARE HIV POSITIVE SHOULD BE ADVISED TO AVOID BREASTFEEDING ā€¢ WOMEN WHO BREASTFEED SHOULD BE INFORMED THAT TRANSMISSION CAN OCCUR