#AIDS2016 Adolescent Adherence and Retention: The Weakest Link Rashida A Ferrand Reader in International Health London School of Hygiene and Tropical Medicine Rashida Ferrand has no financial relationships with commercial entities to disclose.

#AIDS2016 The HIV care cascade HIV -ve HIV +ve HIV testing & counselling Linkage to HIV care Retention in care Treatment adherence HIV prevention Improved Health outcomes Virological suppression Reduced HIV transmission Retention in care and adherence to therapy are life-long 50% INCREASE in mortality in adolescents despite ART scale-up 90% virologically suppressed 90% on sustained ART 90% tested

#AIDS2016 Retention in HIV care among adolescents Bygrave PLoS One 2012; Evans AIDS Res Hum Retro 2013

#AIDS2016 Lost to follow-up after movement to next age-band: ZIMBABWE (n=3545: ) Age at ART start Rate of lost to follow-up per 100 person years (95% CI) Adjusted RR* (95% CI), p-value Before transition to next age-band After transition to next age-band 5 – 9y4.9 (3.95, 5.98)2.3 (1.47, 3.45) 0.7 (0.38, 1.11), p = – 14y3.2 (2.44, 4.15)4.9 (3.41, 7.07) 1.6 (0.96, 2.60), p = –19y9.1 (7.12, 11.5)16.7 (10.9, 25.6) 2.0 (1.19, 3.39), p = * Adjusted for gender, time on ART and calendar year Kranzer K et al, manuscript in preparation

#AIDS2016 Table: Immunological and virological responses at 6 and 12 months after antiretroviral therapy initiation, stratified by age category Maintaining HIV treatment As in other chronic diseases, adherence lower in adolescence – Key life events: medicines are not a priority – Period of experimentation & high-risk behaviours Nachega JAIDS 2009; Charles Bull WHO 2008; Bakanda PLoS One 2011; Evans AIDS Res Hum Retro 2013 TUAB01 ABSTRACTS M.Maskew A. Judd

#AIDS2016 Shubber et al: Poster THPEB074

#AIDS2016 Mental health and substance use Life-style (travel, forget, busy, daily routine) Lack of self-management skills Individual Lack of support and guidance Peer conformity Intense stigma Social Side-effects and palatability Pill burden Drug related Distance from clinic Drug stock-outs and waiting times Provider attitudes Structural Kim AIDS 2014; Dow AIDS Care 2016; Haberer PLoS One 2011; Biadgilign SAHARA J 2009; Nabukeera-Barungi Ann Trop Paediatr 2007 Correlates of poor adherence

#AIDS2016 ONCE DAILY REGIMENS ART REGIMENS WITH REDUCED TOXICITY AIDS 2015;29: FIXED-DOSE COMBINATIONS INNOVATIVE FORMULATIONS Drug related Margolis et al CROI Abs 31LB Musiime V et al 2014; 66:148–154

#AIDS2016 TREATMENT INTERRUPTIONS BREATHER: Lancet HIV 2016 N=199: virologically suppressed participants INCENTIVES Foster 2014 AIDS Patient Care STDS N=11: Incentives and motivational interviewing DIRECTLY OBSERVED THERAPY Gilkman Paediatrics 2007 N=9: Hospital admission Parsons 2006 AIDS Patient Care STDS N=14: 40 days admission HOLDING REGIMENS Linder V et al PIDJ 2016 N= 71: 3TC monotherapy KNOWLEDGE & EMPOWERMENT Berrien 2004 AIDS Patient Care STDS (N=37) Letourneau 2013 AIDS Care (N=34) Chokephaibulkit 2015 J Assoc Nur AIDS Care (N=139) Kaihin 2015 Behav Med (N=46) Bhana 2014 AIDS Care (N=65)  Home visits by nurses  Multisystemic therapy sessions  Individual and group sessions Individual

#AIDS2016 “ADOLESCENT FRIENDLY” SERVICES Lee AIDS 2016 Patient Care STDS Davila 2013 AIDS Care Teasdale 2016 JAIDS  Youth-friendly waiting area  Trained health providers  Text-messaging to providers  Evening clinics  Dedicated clinic day  Integrated SRH  Peer groups Structural Social PEER SUPPPORT Funck-Brentano AIDS 2005 N=30: Peer support group sessions  Decentralisation  Task Shifting  Home initiation  Home delivery  Same day ART initiation

#AIDS2016 The GAPS Few studies: 11 studies in 14 years; majority in high-income settings Limits of the evidence base: small sample sizes, no comparison groups, choice and definition of outcomes, selection bias Resource-intensive interventions applied at individual level: limited duration of effect Single-effect interventions for multi-dimensional determinants Needs of adolescents as individuals vs delivering long-term treatment at scale in low-resource settings with constrained health systems Macpherson P et al 2015 Trop Med Int Health Judd A et al 2016 Curr Opin HIV AIDS

#AIDS2016 Conclusions Adherence and retention are not one-off events- require maintenance life-long and critical to successful outcomes Adherence and retention determined by multiple factors: individual, social and structural Need a menu of interventions tailored to context and resources Interventions need to combine a public health approach AS WELL AS being responsive to individual needs

#AIDS2016 Moving forward Adolescents and communities empowered and active agents for change Interventions that address mental health-key determinant to adherence Caregiver support strategies as mediators for adolescents to achieving good outcomes School-based interventions plus focus on teachers

#AIDS2016 Acknowledgements LSHTM Richard Hayes Helen Weiss Katharina Kranzer Liz Corbett Joanna Busza Vicky Simms BRTI Ethel Dauya Tsitsi Bandason Grace McHugh Suba Dakshina ZENITH Study Team University of Zimbabwe Hilda Mujuru Kusum Nathoo Harare City Health Services Ministry of Health & Child Care Zimbabwe Population Services International Child Protection Society WHO David Ross Jane Ferguson Bruce Dick Rachel Baggaley