RJ SIMONDS, MD

Transferring U.S. Domestic & Global Innovations to Combat HIV/AIDS

PMTCT

Turning the tide together to eliminate HIV in

children

July 22,2012

The success of ACTG 076 led quickly to research that adapted its findings to resource-

constrained settings.

Series1-5%0%5%

10%15%20%25%30%

7.6%

22.6%

ACTG 076 trial US/France 1994

Transm

issi

on R

isk

Placebo AZT

Short-course AZT trial Thailand1998

Single-dose NVP trial Uganda1999

Slide 2

Transmission Risk by Treatment Group

USA & Europe

Thailand

Africa

Moth

er-

Child

Tra

nsm

issi

on R

isk (

%)

0

5

10

15

20

25

30

35

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

Source: adapted from N. Shaffer, WHO, 2010

Research in Africa on ARV prophylaxis during breastfeeding

Research in US/Europe on ARV prophylaxis

Research in Africa and Thailand on shorter ARV prophylaxis

Slide 3

Combined efforts of the U.S. and other countries optimized PMTCT interventions.

Key organizations have linked U.S. and global PMTCT research, programs, and advocacy.

International Maternal Pediatric Adolescent AIDS Clinical Trials Group

Francois-Xavier Bagnoud Center(UMDNJ)

Elizabeth Glaser Pediatric AIDS Foundation

Slide 4

Technologies developed or researched in the U.S. have been critical to PMTCT programs in

resource-constrained settings.

Slide 5

The successful national PMTCT response in the U.S. informed and encouraged national-level

programs in other countries.

ARV coverage for PMTCT Thailand, 2001

Slide 6Sources: CDC surviellance slides; Amornwichet JAMA 2002

Early U.S. PMTCT policy experience helped inform policies in other countries.

Accept test Return for results

Given results0

102030405060708090

100Voluntary ("opt-in") testing

Routine ("opt-out") testing

Perc

ent

of

wom

en

HIV testing in 4 antenatal clinics using opt-in vs. opt-out testing strategies, Francistown, Botswana 2003-2004

Slide 7Source: Creek et al 2007

Programmatic issues emerging in the U.S. are alerting other countries to their future issues.

Dr. James Oleske and Long-Term SurvivorsUMDNJ Newark 2003

Aging of Perinatally HIV-InfectedChildren in the United States

30 years into the perinatal HIV epidemic in the US, HIV-infected children are now aging into adolescence and adulthood. HIV has become a chronic disease with challenges such as:

• adherence to therapy, psychosocial challenges

• late complications from chronic HIV infection and its therapy

• interaction of HIV and puberty• ARV resistance• mental health issues• sexual activity and pregnancy

Slide 8

WHO Simplified Pediatric Dosing Table Based on Modeling from PK Studies in Resource-Rich Countries

Drug Strength of paediatric tab

(mg)

Children 6 weeks of age and above Strength of adult tab (mg)

Number of tablets by weight-band

Number of tablets by weight-band morning and evening

3–5.9 kg 6–9.9 kg 10–13.9 kg 14–19.9 kg 20–24.9 kg 25–34.9 kg

am pm am pm am pm am pm am pm am pm

Single drugs

AZT 60 1 1 1.5 1.5 2 2 2.5 2.5 3 3 300 1 1

ABC 60 1 1 1.5 1.5 2 2 2.5 2.5 3 3 300 1 1

NVP 50 1 1 1.5 1.5 2 2 2.5 2.5 3 3 200 1 1

ddI 25 2a 2a 3 2 3 3 4 3 4 4 25 5 5

Combinations

AZT/3TC 60/30 1 1 1.5 1.5 2 2 2.5 2.5 3 3 300/150 1 1

AZT/3TC/NVP 60/30/50 1 1 1.5 1.5 2 2 2.5 2.5 3 3300/150/20

01 1

ABC/AZT/3TC 60/60/30 1 1 1.5 1.5 2 2 2.5 2.5 3 3300/300/15

01 1

ABC/3TC 60/30 1 1 1.5 1.5 2 2 2.5 2.5 3 3 b

d4T/3TC 6/30 1 1 1.5 1.5 2 2 2.5 2.5 3 3 30/150 1 1

d4T/3TC/NVP 6/30/50 1 1 1.5 1.5 2 2 2.5 2.5 3 3 30/150/200 1 1

LPV/r c 100/25 NR NR 2 1 2 2 2 2 100/25 3 3

U.S. research informs global guidance.

Slide 9

Slide 10

U.S. researchers help develop WHO guidelines.

Slide 10

Content experts: Elaine Abrams (The International Center for AIDS Care and Treatment Programs, Mailman School of Public Health, Columbia University, New York, USA), François Dabis, Laura A. Guay (Elizabeth Glaser Pediatric AIDS Foundation, Washington DC, USA), Louise Kuhn (Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, USA), Marc Lallemant (Programs for HIV Prevention and Treatment, Thailand), James McIntyre, Lynne M. Mofenson, Roger Shapiro (Harvard Medical School, Division of Infectious Diseases, Boston, USA) and Jeffrey S. A. Stringer (University of Alabama at Birmingham, Center for Infectious Disease Research in Zambia, Lusaka, Zambia).

2003 AfricaSIMBA: Infant ARV

2008 Ethiopia, India, Uganda SWEN: Infant

NVP

2009 Tanzania MITRA-plus:

Maternal ARV

2010 Malawi

BAN: Infant NVP vs

Maternal ARV

20102003

2010 Botswana

Mma Bana: Maternal

ARV

2008 MalawiPEPI-Malawi:

Infant NVP

Clinical Trials of Prevention of Postnatal

Mother-to-Child HIV Transmission via Breast

Feeding

Resource-constrained countries are researching issues no longer able to be studied in the U.S.

Slide 11

A growing body of global research informs USPHS guidelines in the U.S.

Slide 12

“Antiretroviral therapy (ART) should be initiated in HIV-infected infants <12 months of age, regardless of clinical status, CD4 percentage, or viral load“

CHER Study in South Africa

Continuing PMTCT effort in resource-constrained settings reminds the U.S. to remain

vigilant to maintain its success.

Slide 13

Zimbabwe

U.S.A.

Approaches to PMTCT in the U.S. and resource-constrained countries are coalescing.

Option B+

TREATMENT AS PREVENTIONAIDS-Free

Generation

Slide 14

Elimination of pediatric HIV infection worldwide requires continued efforts in the U.S. and in all

other countries.

Framework to Eliminate Mother-to-Child Transmission of HIV in the U.S.

Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and

Keeping Their Mothers Alive

Slide 15