Principles of care of the HIV1 infected pregnant mother Protection of mothers from mono and dual the

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Principles of care of the HIV-1 infected pregnant
motherProtection of mothers from mono- and
dual- therapies likely to induce resistance

• Women refusing 3 medications should be offered
  zidovudine prophylaxis, never Combivir alone.

Combivir Alone
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Priniciples of care of the HIV-1 infected
pregnant motherAggressive 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

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Principles of care of the HIV-1 infected pregnant
mother Cytochrome p4503A reductase activity

• 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)
• Increased p450 3A activity in late pregnancy is
  reversed by ritonavir, allowing twice daily
  dosing, for example, RTV200mg/IDV800mg q 12 h

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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

• When likelihood of non-adherence is high, do not
  offer nevirapine
• If mother does not need therapy for her own
  health, HAART can be safely stopped post-partum

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Priniciples of care of the HIV-1 infected
pregnant motherAggressive 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

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Priniciples of care of the HIV-1 infected
pregnant motherAntiretrovirals that should be
avoided if possibleEFAVIRENZ

• Unpublished primate data show high incidence of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.

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Priniciples of care of the HIV-1 infected
pregnant motherAntiretrovirals that should be
avoided if possibleAMPRENAVIR

• 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.

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Priniciples of care of the HIV-1 infected
pregnant motherAntiretrovirals that should be
avoided if possibleSTAVUDINE/DIDANOSINE
(D4T/ddI)

• 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.

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Vertical Transmission Maternal risk factors

• Maternal immune status maternal CD4
• Disease activity maternal viral load (Garcia
  et al., NEJM 341394)
• Antiretroviral prophylaxis
• Antiretroviral therapy
• Prior infected child
• Weight loss, Tb, OIs

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Vertical TransmissionMechanisms

• Unknown!
• Exposure to maternal secretions?
• Exposure to maternal blood at delivery? Via the
  placenta?

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Length of ruptured membranes(hours)?
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Vertical TransmissionObstetrical risk factors

• Length of ruptured membranes
• Prematurity, low birth weight
• Immune activation during pregnancy or at
  delivery?
• Evidence of chorioamnionitis infection or
  inflammation of membranes/placenta

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Route of deliveryInformed maternal choice

• Retrospective evidence of prevention of vertical
  transmission by elective cesarean deliveryin
  absenceof treatment

Hours of membrane rupture?
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Route of deliveryInformed maternal choice
No data exist that demonstrate a benefit of
elective cesarean to mother or baby when mother
is receiving potent combination therapy.
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San Francisco, 1994-1999
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Shaffer et al., Viral Load and Transmission
Length of rupture of membranes,(hours)
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Control of maternal viral load appears to be
highly protective even in the setting of
prolonged rupture of membranes
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How impossible is HIV treatment for infected
mothers in the developing world?

• 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.
• RD for practical treatment strategies in the
  developing world is ongoing.

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How possible is mother to child transmission
prophylaxis?

• 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.

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Short-term RTI prophylaxis strategies in Africa

• PETRA Arm A Not significant at 18 months
• HIVNET 012 18 month data not published
• Short term prophylaxis makes no significant
  difference when maternal CD4lt350 or gt499
  cells/ul maternal plHIVRNA lt50,000 copies/ml
• High rates of repeat pregnancies after HIVNET 012
  regimens noted in Harare
• At best, regimens still result in transmission
  rates gt10, a figure that is now unacceptable in
  the West.

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the question is no longer whether Asia will
have a major epidemic, but rather how massive it
will be. - P. Piot