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

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

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

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

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.

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

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 2003-2004 Source: Creek et al 2007

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

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

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

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

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“

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.

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

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