Presented by: Caitlin Dugdale, MD The cost-effectiveness of integrating maternal ART into maternal & child health (MCH) services during the postpartum period in South Africa Presented by: Caitlin Dugdale, MD Tamsin K. Phillips, MPH; Landon Myer, MBChB, PhD; Emily P. Hyle, MD, MSc; Kirsty Brittain, MPH; Kenneth A. Freedberg, MD, MSc; Lucy Cunnama; Rochelle P. Walensky, MD, MPH; Allison Zerbe; Elaine J. Abrams, MD; Andrea L. Ciaranello, MD, MPH; and the MCH-ART trial team Supported by NICHD (R01HD079214 and R01HD074558), NIAID (R01AI058736, R37AI093269, and T32AI007433), NHLBI (K01HL123349), PEPFAR, the World Health Organization, the Elizabeth Glaser Pediatric AIDS Foundation, and the IMPAACT network

Disclosures We have no conflicts of interest to declare  

High rates of postpartum LTFU and non-adherence Postpartum loss to follow up (LTFU) and ART non-adherence contribute to adverse maternal and pediatric outcomes and MTCT among breastfeeding infants 12 months after delivery: 25-30% LTFU For those in care, 70% virologically suppressed Transfer of care from antenatal MCH services to separate postpartum maternal ART and infant HIV and well-child care is a vulnerable time for LTFU References: UNAIDS 2016, Nachega AIDS 2012, Kaplan AIDS 2008, Phillips JIAS 2014, Haas Lancet HIV 2016, Tenthani AIDS 2014, Myer HIV Med 2017, Myer CID 2016, Van Lettow JIAS 2014.

Strategies to Optimize ART Services for Maternal & Child Health MCH-ART Trial Strategies: Routine care: Referral to separate maternal ART and infant HIV and well-child care postpartum Integrated care: Co-located maternal ART and infant care integrated into MCH platform through the end of breastfeeding Maternal ART care References: Myer CROI 2017. Infant HIV/well-child care Delivery Delivery Maternal ART and infant care in MCH

MCH-ART Trial Results Results of integrated care: Improved maternal retention in care and viral suppression at 12 months Longer breastfeeding duration Low MTCT by 1 year, similar in both arms References: Myer CROI 2017.

Objective To use MCH-ART trial data to project the long-term clinical impact and cost-effectiveness of the integrated care intervention compared to routine care for postpartum mothers and infants in South Africa.

Cost-Effectiveness of Preventing AIDS Complications (CEPAC) CEPAC-International and CEPAC-Pediatrics: Monte Carlo simulation models of adult and pediatric HIV Simulated individuals from delivery through death MTCT by breastfeeding status and ART use HIV progression including VL and CD4 ART adherence, LTFU, and return to care Uses inputs from published literature and clinical trials to project long-term clinical and economic outcomes for mothers and children References: Walensky NEJM 2014. Ciaranello PLoS ONE 2013 & AIDS 2015. Francke JID 2016.

Model Methods Cohort: Postpartum mothers living with HIV and their breastfed infants in South Africa Strategies: Routine care: separate maternal ART/infant care Integrated care: co-located maternal ART/infant care in MCH services until end of breastfeeding Model-based outcomes: MTCT rates Maternal and infant life expectancy Per-person HIV-related health care costs

Cost-effectiveness analysis Incremental cost-effectiveness ratio (ICER): ICER <1x per-capita GDP/YLS considered “cost-effective” “Cost-effective” = additional health benefit worth the additional cost 2016 South Africa per-capita GDP= $5,260/YLS Additional resource use Additional health benefit $ Year of life saved (YLS) in Reference: IMF 2017

Key model inputs from MCH-ART Trial Maternal parameters Routine care Integrated care Age (mean, in years) 28.6 CD4 count <350 cells/µL before ART 49% Time on ART at delivery (median, in mo.) 4.3 Retention in care at 1 year 71% 81% HIV viral load <50 copies/mL at 1 year 66% Pediatric parameters Breastfeeding duration (mean, in mo.) 6 8 Economic parameters Additional integrated care intervention cost for mother-infant pair ----- $200

(HIV-infected and uninfected) Results Lifetime projections (undiscounted) Pediatric (HIV-infected and uninfected) Maternal MTCT (%) LE (years) HIV-related costs/person ($) LE from delivery (years) HIV-related costs/ person from delivery ($) Routine care 1.7 62.4 290 26.5 21,920 Integrated care 27.3 22,570 MTCT: mother to child transmission; LE: life expectancy. All costs reported in 2016 USD. The ICER of integrated care compared to routine care was $1,050/YLS* <20% South Africa per-capita GDP Considered cost-effective *Costs and LE discounted at 3%.

Trade offs: Breastfeeding, MTCT, and infant survival Integrated care led to: Improved maternal viral suppression: ↓ Risk of MTCT Longer breastfeeding: ↑ Risk of MTCT ↓ Non-AIDS mortality

BF 12m in both arms ICER = $990/YLS Sensitivity analysis BF 12m in both arms ICER = $990/YLS Integrated care was increasingly cost-effective with longer durations of breastfeeding

Additional sensitivity analyses Cost Integrated care was cost-effective unless the intervention cost was >$2,360/mother-infant pair Unlikely at ~12x estimated cost Effectiveness Integrated care remained cost-effective even if intervention impact on maternal retention and viral suppression reduced by 50% 50% effectiveness: ICER $1,310/YLS

Limitations Uncertainty in long-term projections Limited data on maternal retention and adherence beyond a few years postpartum Repeat pregnancies and their potential impact on maternal re-engagement not considered Exact intervention costs not yet known Detailed costing study of intervention pending* Costs and cost-effectiveness outcomes specific to South Africa *Lucy Cunnama and Edina Sinanovic, UCT

Conclusion Co-located maternal ART and infant care, integrated into maternal and child health services through the end of breastfeeding, is a cost-effective strategy to optimize postpartum maternal and infant outcomes in South Africa

CEPAC-Pediatric Team: Elaine Abrams, Ingrid Bassett, Alex Bulteel, Acknowledgements CEPAC-Pediatric Team: Elaine Abrams, Ingrid Bassett, Alex Bulteel, Andrea L. Ciaranello, Sophie Desmonde, Caitlin Dugdale, Lorna Dunning, Simone Frank, Emily P. Hyle, Taige Hou, Valeriane Leroy, Landon Myer, Anne Neilan, Robert Parker, Kunjal Patel, Martina Penazzato, George Seage, Djora Soeteman, Milton Weinstein, Rochelle P. Walensky, Kenneth A. Freedberg Supported by: Supported by NICHD (R01HD079214 and R01HD074558), NIAID (R01AI058736, R37AI093269, and T32AI007433), NHLBI (K01HL123349), PEPFAR, the World Health Organization, the Elizabeth Glaser Pediatric AIDS Foundation, and the IMPAACT network