new pptct guidelines

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Perinatal Transmission and HIV:

Two Realities

National and International Perspectives

Tanya Zangaglia, MDMedical Director, Project Streetbeat

Curriculum Coordinator, NY/VI AETCColumbia Univ. School of Public Health


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What has been the mostsignificant accomplishment

of the HIV/AIDS era?


Two Realities


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The number of womenliving with HIV/AIDS

is growing


Two Realities


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Over four-fifths of all HIV-infected women in the U.S.

are of childbearing age


Two Realities


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HIV positive women are:

Living longer

Feeling more hopeful Choosing life


Two Realities


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HIV positive women

are choosing to become

pregnant


Two Realities


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Perinatal Transmissioncontinues to exist in the

United States


Two Realities


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Perinatal Transmission hasdeclined by at least 80%

between 1992 and 1999

JAMA1999; 282:531


Two Realities


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It is now possible to achieve

Perinatal Transmission ratesas low as 1-2%

this contrasted to 25-30%a decade ago

The Hopkins HIV Report

Jean R.Anderson, MDJuly 2001; p2


Two Realities


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Many women who are

pregnant are not offeredcounseling and testing and

remain undiagnosed many

of these women are not

perceived to be at risk


Two Realities


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Conducted in 7 states

Found that 20% of women with HIV-infection were not diagnosed beforedelivery

Reported that 36% of HIV-infectedwomen using illicit drugs during pregnancy

had no prenatal care

HIV SURVEILLANCE REPORT

Wortley, et. al.

MMWR 2001; 50:RR6-17


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Universal HIV testing with patient

notification as a routine part of

Prenatal care is currently supported

by the:

Institute ofMedicine

American College ofObstetricians andGynecologists

MANDATORY HIV TESTING OF

PREGNANT WOMEN


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Maternal plasma viral load is

viewed as perhaps the most

important correlate of perinatal

transmission in both antiretroviraltreated and nave women

Garcia, et. al. NEJM 1999; 341:394

Mofensen et. al.

NEJM 1999; 341:385

MATERNAL VIRAL LOAD


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MATERNAL VIRAL LOAD

A meta-analysis of 7 European and U.S.

prospective studies examined mother-to-

child transmission when maternal viralload was < 1000 c/ml

The study found that the risk of HIV

transmission was lowered from 9.8% inuntreated women to 1% in women

treated with antiretroviral therapy

(generally AZT

alone)Ionnides, et. al.

J. Infect Diseases

2001; 183:539


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In the past decade the clinical

thinking has shifted from being

reluctant to treat HIV positive

pregnant women to now

recommending antiretrovirals for allpregnant women with HIV

regardless of CD4 count or viral load

MATERNAL VIRAL LOAD


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PACTG 076STUDY PROTOCOL

AZT administered from week 14 of

gestation

AZT continued throughout pregnancy

AZT given as an IV infusion to the

mother during labor

AZT given to the newborn for 6 weeks


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Anger, skepticism, thoughts of genocide,

reluctance

Adverse fetal effects

Unethical to withhold AZT from some

women who might receive direct benefit

themselves, but instead were randomizedto receive a placebo

PACTG 076EARLY CONCERNS


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Study stopped prematurely

Review by the data and safetyMonitoring board found a highly

significant difference in transmission

rates between women who receivedAZT and those randomized to placebo

PACTG 076EARLY RESULTS


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VT was reduced by 66%

VT decreased from 22.6% (in placebo

recipients) to 7.6% (in those receiving

AZT)

PACTG 076IMPACT ON VERTICAL TRANSMISSION (VT)


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Immediate action taken

Study protocol became the standard of

care for pregnant women with HIV

infection

PACTG 076PUBLIC HEALTH RESPONSE


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Original study cohort consisted of

women with CD4 > 200 cells/mm3 and

no prior AZT exposure

Subsequent observational studies

confirmed the effectiveness of 076 inwomen with more advanced disease who

were not antiretroviral naive

PACTG 076


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Many women do not present for care until

much later in pregnancy (ex: 3rd trimester

rather than 2nd

trimester)

IV catheters are not available to women in

labor in a large part of the world where

HIV predominates

The cost of the 076 regimen is prohibitive

for all but a few of the worlds nations

PACTG 076ONGOING DEBATE


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In this study AZT was started as late as36 weeks of pregnancy

AZT was given orally in labor

There was no neonatal component

Lancet

Shaffer, et. al.1999; 353:773

THAI SHORT-COURSE

AZT STUDY


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Still achieved significant reductions in

mother-to-child transmission

50% decline noted compared to placebo

in a non-breast feeding population

Lancet

Shaffer, et. al.1999; 353:773

THAI SHORT-COURSE

AZT STUDY


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Study also found that both plasma and

genital tract viral load were suppressedby AZT treatment

Both were independently correlated withtransmission

J. Infectious Diseases

Chuachoowong, et. al2000;181:99

THAI SHORT-COURSE

AZT STUDY


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Showed that the length of maternal

treatment is a significant variable in

reducing HIV transmission

Therapy started at 28 weeks gestation is

far superior to therapy started at 35weeks

NEJM

Lallemont, et. al.

2000; 343:1036

OTHER SHORT-COURSE

AZT STUDIES


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Studies highlighted the fact that

approximately 1/3 of transmissionoccurs earlier in pregnancy

Also studies demonstrated that the

effectiveness of therapy is blunted bybreastfeeding

NEJM

Lallemont, et. al.

2000; 343:1036

THAI SHORT-COURSE

AZT STUDY


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A single oral dose of Nevirapine was

given to a pregnant women at the onset

of labor

A single oral dose of Nevirapine was

given to her newborn within 48-72 hoursof birth

Lancet

Guay, et. al.

1999; 354:795

HIV NET 012 TRIAL


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Results show an approximate 50%

reduction in transmission compared withoral AZT given intrapartum and to theinfant for one week

Lancet

Guay, et. al.

1999; 354:795

HIV NET 012 TRIAL


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Less expensive

Offers the most realistic option for the

developing world

Allows women to be treated who first

present for medical care in labor

It can be given as directly observed

therapy (DOT)Lancet

Guay, et. al.1999; 354:795

HIV NET 012 TRIALTHE REGIMENTS


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No clinical trials evaluating HAART forthe purpose of reducing perinatal

transmission have been completed

Yet and still, HAART is the standard ofcare in the majority of HIV positive

pregnant women in the U.S.

This is especially true in women whorequire HAART for their own infection

HAART


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HAART is effective in reducing ViralLoad to undetectable levels

This in turn further lowers the likelihoodof transmission between mother and

fetus

HAART


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International Phase III trial

Compares:

Standard antiretroviral therapy(2-3 drug regimen)

Plus 2-dose Nevirapine

VS

Standard antiretroviral therapy

Plus placebo8th CROI [Abstract LB7]

Dorenbaum, et. al.Chicago 2/01

PACTG 316


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Very low rates of transmission in both

study arms

1.5% NVP

1.4% Placebo

Study concludes: Effective treatment of mom allows for

effective prophylaxis of the fetus8th CROI [Abstract LB7]

Dorenbaum, et. al.Chicago 2/01

PACTG 316


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Is Cesarean Section an appropriate

choice/option for preventing

Perinatal HIVTransmission?

CESAREAN SECTION


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Randomized clinical trial comparing:

Scheduled C-Section vs. Vaginal Delivery

Transmission Rates:

1.8% in women randomized to planned C-Section

10.6% in women with planned vaginal delivery

Lancet

The European Mode of Delivery Collaboration1999; 353:1035

CESAREAN SECTION


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Observational data from 15 prospective

cohort studies examined in a meta-analysis

A total of 7,800 mother-infant pairs in

the study

NEJM

The International Perinatal HIVG

roup1999; 340:9770

CESAREAN SECTION


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The study found that women undergoing

C-Section before the onset of labor orruptured membranes had significantly

lower Perinatal HIVTransmission

NEJM


rou

p1999; 340:9770

CESAREAN SECTION


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These rates were compared to those

women having Vaginal Delivery or C-Section after membrane rupture,

regardless of AZT use

NEJM


rou

p1999; 340:9770

CESAREAN SECTION


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Current data is insufficient to evaluate

potential benefits of planned C-Sectionsin women treated with antiretroviral

therapy with viral loads less than 1000

c/ml

The Hopkins HIV Report

Jean R.Anderson, MD

July 2001

CESAREAN SECTION

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Resistance is increasing in frequency, evenamong antiretroviral-nave individualstheimplication for perinatal transmission is

unknown

The role of C-Sections in women with lowviral loads or with short duration of ruptured

membranes is not yet established Should serum concentrations of antiretrovirals

in pregnant women be monitored for purposesof safety and for efficacy?

OUTSTANDING ISSUES/

ONGOING DILEMNASDEVELOPED WORLD

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Are drugs toxicities more common in HIV

positive pregnant women?

What, if any, long term effects will we see

in exposed but uninfected infants?

What are the issues involved in the use ofrapid tests to make a diagnosis of HIV inlabor?

OUTSTANDING ISSUES/


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Issues in the developing world

are much more basic, yet more

overwhelming

OUTSTANDING ISSUES/


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The majority of AIDS

ORPHANS reside in the

developing world and is

estimated at 13.2 million globally

OUTSTANDING ISSUES/

ONGOING DILEMNASDEVELOPING WORLD

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Issues of access to antiretroviral therapy

continue to arise:

Resources are needed to offer HIV counselingand testing

Affordable and available drugs are needed

A healthcare infrastructure is needed to allowfor proper distribution and education

OUTSTANDING ISSUES/


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Breastfeeding (BF)

The mode of transmission in up to 50% of

newly infected children world-wide

Affordable alternatives are not widelyavailable

The general benefits in infant nutrition andinfant morbidity and mortality areestablished

OUTSTANDING ISSUES/


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Breastfeeding (BF)

BF vs. formula feeding (FF) in Kenya FF prevented 44% of infant infections

FF was associated with HIV-free survival

But FF is expensive

Clean water and the ability to sterilizeappropriately is not ubiquitous

Nduati, et. al.JAMA2000; 283:1167

OUTSTANDING ISSUES/


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Breastfeeding (BF)

In areas of the world where BF is common and HIV

remains highly stigmatized a real social pressure existsfor women to BF

By not BFing women signal that something is wrongand alienation from their families and their

communities ensues

So the debate no longer centers exclusively onwhether or not to BF in these countries, but perhaps

how long to BF and how best to BF

OUTSTANDING ISSUES/


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It has been shown that the longer the duration of BF

the higher the risk of HIV transmission

It has also been shown that mixed-feedingversus exclusivebreastfeedingalso leads to a higher risk of HIVtransmission

The conclusion from studies conducted to datesuggest that exclusive breastfeeding with early weaningmay be an appropriate alternative

Leroy et. al. Lancet 1998; 353:597

Coutsoudis et. al. Lancet 1999; 354:471

OUTSTANDING ISSUES/


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In the past, I never allowed myself to think

about having a baby or even look at a baby. I

was just waiting to die. But now, everything haschanged, and I suddenly have the opportunity

to have a child.Dr. Prager

A New Yorker living in Istanbul

She was infected with HIV 15 years ago after being pricked by a needleduring her medical residency

The New York Times, Health & Fitness

Tuesday, August 7th,2001 pF7


Two Realities

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AIDS 1998; 12:5241, Lorenzi, et al.

Obstet Gynecol 1999; 94:641, McGowan, et al.

Internat J. STD AIDS 2000; 11:200, Clarke, et al.

NEJM 1999; 341:205 Beckerman, et al.

T

he Women & InfantsT

ransmission Study InvestigatorsXIII International Conference 2000 Abstract LBOr4

Society for Maternal Fetal Medicine Annual Meeting 2000, Abstract289, Helfgott, et al.

REFERENCES

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U.S. Public Health Task Force

Guidelines for theManagement

of HIV in pregnancy:

http://www.hivatis.orghttp://hopkins-aids.edu

WEB RESOURCES

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