Transcript Document

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
Principles of care of the HIV-1
infected pregnant mother
Cytochrome p4503A reductase activity:
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AUC8 for indinavir is markedly
suppressed late in pregnancy
p450 3A activity is significantly
increased in the third trimester
(Homma et al., 2001; Hayashi et al. 2001)
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Increased p450 3A activity in late
pregnancy is reversed by ritonavir,
allowing twice daily dosing,
for example,
RTV200mg/IDV800mg q 12 h
Principles 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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When likelihood of nonadherence is high, do not offer
nevirapine
If mother does not need therapy
for her own health, HAART can
be safely stopped post-partum
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:


Offer 3 or more medications
Twice daily dosing
Priniciples of care of the HIV-1
infected pregnant mother
Antiretrovirals that should be avoided
if possible:
EFAVIRENZ:
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Unpublished primate data show high
incidence of neural tube defects.
88 prospective cases in APR: no NTDs.
No indication, per se, to abort pregnancy.
Multiple ultrasound and blood tests can
rule out neural tube defects.
Consider a switch to nevirapine.
Priniciples of care of the HIV-1
infected pregnant mother
Antiretrovirals that should be avoided
if possible:
AMPRENAVIR:
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Unpublished reports of abnormal
calcification of bones.
Human data are lacking.
Consider a switch to another highly potent
agent or combination, such as
lopinavir/ritonavir.
Priniciples of care of the HIV-1
infected pregnant mother
Antiretrovirals that should be avoided
if possible:
STAVUDINE/DIDANOSINE (D4T/ddI):
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High potency nRTI combination.
Particularly effective in the setting of pan-resistance
and virologic breakthrough.
Given alone short term in South Africa, was highly
effective at preventing MCT, without lactic acidosis.
Reports of lactic acidosis during pregnancy.
If needed, requires very frequent monitoring of liver
transaminases.
Vertical Transmission
Maternal risk factors:
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Maternal immune status:
maternal CD4
Disease activity:
maternal viral load
(Garcia et al., NEJM 341:394)
Antiretroviral prophylaxis
Antiretroviral therapy
Prior infected child
Weight loss, Tb, OIs
Vertical Transmission
Mechanisms:
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Unknown!
Exposure to
maternal secretions?
Exposure to maternal blood at
delivery? Via the placenta?
Length of ruptured
Vertical Transmission
Obstetrical risk
factors:
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Length of ruptured
membranes
Prematurity, low
birth weight
Immune activation during
pregnancy or at delivery?
Evidence of chorioamnionitis:
infection or inflammation of membranes/placenta
Route of delivery
Informed maternal choice:
•Retrospective evidence of prevention of vertical
transmission
by elective
cesarean
delivery
in absence
of treatment
Hours of membrane rupture
Route of delivery
Informed maternal choice:
No data exist that demonstrate a
benefit of elective cesarean to
mother or baby when mother is
receiving potent combination
therapy.
San Francisco, 1994-1999
Shaffer et al.,
Viral Load and Transmission
Length of rupture of membranes,
(hours)
Control of maternal viral load appears to be
highly protective even in the setting of
prolonged rupture of membranes
How impossible is HIV treatment
for infected mothers in the
developing world?
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Today, although the challenges are enormous, we are
closer than ever before.
Ten years ago we could not even imagine HIV
therapy as it is today.
Availability of generic antiretrovirals, especially in
single pill formulations, holds great promise.
R&D for practical treatment strategies in the
developing world is ongoing.
How possible is mother to child
transmission prophylaxis?
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Theoretically, MTCT prevention with one or two drugs
is both possible and practical.
However,uptake of counseling and testing is low in
most settings where treatment is not available.
Uptake of prophylaxis is low (˜20%) even among
women who consent to testing in pilot projects.
Despite widespread assumption that induction of ART
resistance in mothers and infected infants will be
inconsequential, this remains to be proven.
Implementation of these strategies could result in the
induction of ART resistance on a massive scale.
Short-term RTI prophylaxis
strategies in Africa
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PETRA Arm A: Not significant at 18 months
HIVNET 012: 18 month data not published
Short term prophylaxis makes no significant difference
when:
maternal CD4<350 or >499 cells/ul
maternal plHIVRNA <50,000 copies/ml
High rates of repeat pregnancies after HIVNET 012
regimens noted in Harare
At best, regimens still result in transmission rates
>10%, a figure that is now unacceptable in the West.
“…the question is
no longer whether Asia will have
a major epidemic, but rather how massive it will be.” - P. Piot