1. PMTCT Turning the tide together to eliminate HIV in children
Transferring U.S. Domestic & Global Innovations to Combat HIV/AIDS
PMTCT
Turning the tide together to eliminate HIV in children
RJ Simonds, MD
July 22,2012

2. Transmission Risk by Treatment Group
The success of ACTG 076 led quickly to research that adapted its findings to resource-constrained settings.
ACTG 076 trial US/France
1994
Short-course
AZT trial Thailand
1998
Transmission Risk by Treatment Group
22.6%
Transmission Risk
Single-dose
NVP trial Uganda
1999
7.6%
Placebo
AZT

3. Mother-Child Transmission Risk (%)
Combined efforts of the U.S. and other countries optimized PMTCT interventions.
Research in US/Europe on ARV prophylaxis
Africa
Mother-Child Transmission Risk (%) 5 10 15 20 25 30 35
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
Thailand
Research in Africa and Thailand on shorter ARV prophylaxis
USA & Europe
Research in Africa on ARV prophylaxis during breastfeeding
Source: adapted from N. Shaffer, WHO, 2010

4. Key organizations have linked U. S
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

5. Technologies developed or researched in the U. S
Technologies developed or researched in the U.S. have been critical to PMTCT programs in resource-constrained settings.

6. ARV coverage for PMTCT Thailand, 2001
The successful national PMTCT response in the U.S. informed and encouraged national-level programs in other countries.
ARV coverage for PMTCT Thailand, 2001
Sources: CDC surviellance slides; Amornwichet JAMA 2002

7. Early U.S. PMTCT policy experience helped inform policies in other countries.
HIV testing in 4 antenatal clinics using opt-in vs. opt-out testing strategies, Francistown, Botswana
Source: Creek et al 2007

8. Programmatic issues emerging in the U. S
Programmatic issues emerging in the U.S. are alerting other countries to their future issues.
Aging of Perinatally HIV-Infected Children 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
Dr. James Oleske and Long-Term Survivors
UMDNJ Newark 2003

9. U.S. research informs global guidance.
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
Single drugs
AZT 60 1
1.5 2
2.5 3
300
ABC
NVP 50
200
ddI 25 2a 4 5
Combinations
AZT/3TC
60/30
300/150
AZT/3TC/NVP
60/30/50
300/150/200
ABC/AZT/3TC
60/60/30
300/300/150
ABC/3TC b
d4T/3TC
6/30
30/150
d4T/3TC/NVP
6/30/50
30/150/200
LPV/r c
100/25 NR

10. U.S. researchers help develop WHO guidelines.
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).
Slide 10

11. MITRA-plus: Maternal ARV PEPI-Malawi: Infant NVP
Resource-constrained countries are researching issues no longer able to be studied in the U.S.
2003 Africa
SIMBA: Infant ARV
2008 Ethiopia, India, Uganda
SWEN: Infant NVP
2009 Tanzania
MITRA-plus: Maternal ARV
2010 Malawi
BAN: Infant NVP vs
Maternal ARV
2010
2003
2010 Botswana
Mma Bana: Maternal ARV
2008 Malawi
PEPI-Malawi: Infant NVP
Clinical Trials of Prevention of Postnatal Mother-to-Child HIV Transmission via Breast Feeding

12. A growing body of global research informs USPHS guidelines in the U.S.
CHER Study in South Africa
“Antiretroviral therapy (ART) should be initiated in HIV-infected infants <12 months of age, regardless of clinical status, CD4 percentage, or viral load“

13. Continuing PMTCT effort in resource-constrained settings reminds the U
Continuing PMTCT effort in resource-constrained settings reminds the U.S. to remain vigilant to maintain its success.
Zimbabwe
U.S.A.

14. Treatment as Prevention
Approaches to PMTCT in the U.S. and resource-constrained countries are coalescing.
AIDS-Free Generation
Treatment as Prevention
Option B+

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