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

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

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

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

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

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

EFAVIRENZ: Unpublished primate data show high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 motherAntiretrovirals that should be avoided if possible:

AMPRENAVIR: Unpublished reports of abnormal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 motherAntiretrovirals that should be avoided if possible:

STAVUDINE/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.

Vertical TransmissionMaternal risk factors:

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:

Unknown! Exposure to

maternal secretions? Exposure to maternal blood at delivery?

Via the placenta?

Length of ruptured membranes(hours)

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

Route of deliveryInformed maternal choice:•Retrospective evidence of prevention of vertical transmission by elective cesarean deliveryin absenceof treatment

Hours of membrane rupture

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.

San Francisco, 1994-1999

Length of rupture of membranes,

(hours)

Shaffer et al., Viral Load and Transmission

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?

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?

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

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/ulmaternal 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