rj simonds, md
DESCRIPTION
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. The success of ACTG 076 led quickly to research that adapted its findings to resource-constrained settings. - PowerPoint PPT PresentationTRANSCRIPT
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