Transcript Document

Of Mothers, Orphans and the
HIV Pandemic
Karen P. Beckerman, MD
New slides needed:
CSx data: 367, 316,
Models of HIV Rx in dev world
Tb Rx and dev world
Ask Ester if she might consider a
picture of herself and her daughter
Rupert and his son.
Associate Professor of Obstetrics
and Gynecology
New York University
Director of Obstetrics
Bellevue Hospital Center
25 October 2002
HIV disease in the U.S.
Pediatric AIDS incidence
Reproductive Health and HIV
Principles of care: universal
developed world
Preconceptional and early
pregnancy counseling
Vertical Transmission
Principles of care during pregnancy
The global epidemic
December 2001:
> 40 million
infected
>8,000 deaths
per day
600 new infections
per hour
a child dies
every minute
October 2002:
5 million new
infections in 2001
800,000 children
infected
44 million orphans
by 2010
Reproductive Health & HIV
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Pregnancy does not alter the course of HIV
disease in the west.
Data do not exist examining the effect of
pregnancy on HIV progression in the
developing world.
Prospective studies show that a pregnant
HIV infected mother has a 3% chance dying
before her baby’s first birthday and an 11%
chance of dying before the second birthday.
HIV in Africa
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DATA are VERY SCARCE
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The epidemic is
heterosexual.
After infection, rapid
progress to AIDS.
Less than half will remain
symptom-free at 3 years.
Median survival is 9 years.
Survival with AIDS is
“short.”
HIV and African Women
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55% of infected individuals are
women.
Male to female transmission is 10x
more efficient that female to male.
Women are infected early in their
reproductive lives,
Ususally by older men.
Rates of pregnancy and nursing are
high among African women with
asymptomatic HIV.
“The Population Chimney”
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HIV mortality will produce
population pyramids that
have never been seen
before.
By 2010, men will
outnumber women in each
5-year cohort between 15
and 49.
USAID, “Children on the Brink”
Largescale orphaning:
• Historically, sporadic and
short term.
HIV orphaning:
• Long term and chronic.
• Will worsen in coming
decades.
• Most will be uninfected.
• All will face extraordinary
risks:
Inadequate nutrition, housing
and health care.
Servitude, harshness & abuse
Acquisition of HIV
Proposed Solutions to the Orphan
Crisis:
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Strengthen coping capacities of families
Protection of property and inheritance rights
District AIDS committees
Community day-care centres
Waiving school fees
Support youth expression
Encourage political will
Reduction of stigma
Promote the rights of women and children
Encourage partnership and leadership
-USAID, 2001
Principles of care of the HIV-1
infected pregnant mother
First things first:
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Safe shelter
Adequate nutrition
Transportation
Self-determination
Self Determination:
Reproductive choice
OI Prophylaxis
Treatment
Delivery plan
Principles of care of the HIV-1
infected pregnant mother
Protection of mothers from mono- and dual
therapies likely to induce ART resistance:
Low Fidelity HIV-1 Replication
•Two polymerases without proofreading activity
HIV-1 reverse transcriptase
Cellular RNA polymerase
•Two RNA copies per virion
Insertions and deletions are common
•RNA strand breaks force template switching
•Uracil incorporation into proviral DNA
Especially in resting cells
Pregnancy and ART resistance
in Uganda
NVP single dose prophylaxis:
HIVNET 006 & 012
Single dose to mother + single dose to infant
Transmission fell from 25 to 13%
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of 46 mothers studied 6 weeks to 6
months later had detectable resistance
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the 36 infected infants, 8 had
detectable nnRTI resistance at 6 weeks
of age.
Pregnancy and ART resistance
in the developed world
Principles of care of the HIV-1
infected pregnant mother
Protection of mothers from mono- and dualtherapies likely to induce resistance:
•Nevirapine prophylaxis (even one dose)
is highly likely to result in nnRTI
resistance if not given in a safe
combination.
•In the U.S., nevirapine prophylaxis
given in addition to standard ART resulted
in no benefit to mother or baby, but did
cause significant induction of nnRTI
resistance.
(Dorenbaum, PACTG 316, CROI, 2001)
Pregnancy and ART resistance
in the developed world
•Zidovudine/lamivudine (AZT/3TC)
induces resistance (M184V) at same
frequencies in pregnant women as in
men
•In one study, 4 of 5 mothers developed
M184V (Clark, J Med Virol.59:364)
•M184V can be transmitted to neonates
Pregnancy and ART resistance
in the U.S. and England:
Are these data relevant to us today?
Unfortunately, YES.
ACTG 185: late 1990s
86%
received ZDV
14% received ZDV/3TC
30%
of mothers had nRTI resistance
by delivery
These
mothers were 3 times more
likely to transmit virus to their infant
(p=0.03)
Principles of care of the HIV-1
infected pregnant mother
Protection of mothers from mono- and dualtherapies likely to induce resistance:
•Women refusing 3 medications should be
offered zidovudine prophylaxis, never
Combivir alone.
Combivir
Alone
Priniciples of care of the HIV-1
infected pregnant mother
Aggressive use of combination
antiretroviral therapy to achieve durable
suppression of maternal HIV replication and
to protect mother from induction of
antiretroviral resistance:
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Offer 3 or more medications
Twice daily dosing