Cohort study of HIV+ children in Southern Africa returning to care after being lost to follow up: Effect of interrupting care on mortality 26th July 2018.

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Presentation transcript:

Cohort study of HIV+ children in Southern Africa returning to care after being lost to follow up: Effect of interrupting care on mortality 26th July 2018

Introduction Loss to follow up in children presents us with challenges: Unknown medication use, no clinical or laboratory monitoring Increasingly, children are later returning to care, called a care interruption Little is known of the long-term outcome of a care interruption, and timing of the care interruption after ART start

objectives Describe the characteristics of children with a care interruption, and compare them to children that remained on treatment Describe the characteristics of the period of loss in children with a care interruption Evaluate the association between a care interruption and mortality

Iedea southern africa Period of study: 2004 - 2016 126 clinics across 6 countries: Lesotho, Malawi, Mozambique, South Africa, Zambia, and Zimbabwe Number of children in study: 46,356 Number of person-years: 180,446 Age range of children: birth to <16 y Number of children who died: 1,393

Lost in the first 6 months on ART and later returned: timeline Start ART treatment 46,356 No care interruption: 22,076 6 months Group 1 Group 2 Lost in the first 6 months on ART and later returned: 10,998 (24%)

Lost after 6 months on ART and later returned: timeline Start ART treatment 46,356 6 months Group 1 Group 2 Group 3 Lost after 6 months on ART and later returned: 13,282 (29%)

METHODS Main outcome of all cause mortality Care interruption was defined as the first period of no visit for >180 days Inclusion criteria: Treatment-naïve (baseline HIV-RNA >400 copies/ml) <16 years old initiating ART between 1 January 2004 and 2016 Alive for at least 180 days after ART initiation Poisson regression model with robust standard errors, controlling for confounding

Methods: person-time allocation Child hasn’t returned to clinic for 180 days: care interruption (theoretical clinic date) 180 days Child starts ART Database closes/ Child dies Child returns to clinic Clinic visits Child attends regular clinic visits Group 1: Time before a care interruption Group 2/3: Time after a care interruption

Characteristics of children with an interruption Total Care Interruption status No Care interruption (CI) CI before 6 months CI after 6 months N N (%) (n = 46,356 ) (n = 22,076 ) (n = 10,998 ) (n = 13,282 ) Sex Male 22,712 10,737 (49) 5,410 (49) 6,565 (49) Female 23,644 11,339 (51) 5,588 (51) 6,717 (51) Median (IQR) age at ART initiation 6.0 (2.2-10.1) 5.9 (2.1-10.1) 5.6 (1.9-9.9) 6.3 (2.6-10.2) Median (IQR) CD4% initiation 15.0 (9.6-22.6) 15.0 (9.3-22.2) 16.5 (10.7-24.5) 14.8 (9.3-22.0) Year of ART initiation 2004-2007 12,786 5,516 (25) 2,830 (26) 4,440 (33) 2008-2009 10,286 4,636 (21) 1,858 (17) 3,792 (29) 2010-2011 10,555 4,565 (21) 2,586 (24) 3,404 (26) 2012- 12,729 7,359 (33) 3,724 (34) 1,646 (12)

Characteristics of interruptions Group 2: Lost in the first 6 months on ART and later returned Group 3: Lost after 6 months on ART and later returned Length of first interruption (median) 322 days 244 days Proportion of follow-up time lost (median)* 71% 30% Percentage ultimately lost when the database closed 50% 35% * Calculated as Length of time out of care/ Total follow-up time

effect of a care interruption on mortality Variable Adjusted RR* (95% CI) P-value CI status No Care Interruption 1.00 <0.001 Care Interruption before 6 months 3.23 (2.56 to 4.08) Care Interruption after 6 months 1.19 (0.91 to 1.56) Current Age <2 years 2-5 years 0.27 (0.20 to 0.36) 6-9 years 0.10 (0.07 to 0.14) >=10 years 0.05 (0.03 to 0.08) Age at ART initiation 1.08 (0.83 to 1.40) 2.19 (1.50 to 3.20) 5.21 (3.37 to 8.06) Year of ART initiation 2004 – 2007 2008 – 2009 0.83 (0.69 to 0.99) 2010 – 2011 0.59 (0.47 to 0.74) 2012 – 2016 0.36 (0.26 to 0.49) * Also adjusted for gender, time in/out of care, baseline CD4% at ART initiation, cohort

effect of a care interruption on mortality Variable Adjusted RR* (95% CI) P-value CI status No Care Interruption 1.00 <0.001 Care Interruption before 6 months 3.23 (2.56 to 4.08) Care Interruption after 6 months 1.19 (0.91 to 1.56) Current Age <2 years 2-5 years 0.27 (0.20 to 0.36) 6-9 years 0.10 (0.07 to 0.14) >=10 years 0.05 (0.03 to 0.08) Age at ART initiation 1.08 (0.83 to 1.40) 2.19 (1.50 to 3.20) 5.21 (3.37 to 8.06) Year of ART initiation 2004 – 2007 2008 – 2009 0.83 (0.69 to 0.99) 2010 – 2011 0.59 (0.47 to 0.74) 2012 – 2016 0.36 (0.26 to 0.49) * Also adjusted for gender, time in/out of care, baseline CD4% at ART initiation, cohort

Sensitivity analysis: Interruption Length Sensitivity analysis adjusting the duration of care interruption in those with a care interruption within 6 months on ART

Sensitivity analysis: time on art Figure 1: Sensitivity analysis of the time on ART prior to a care interruption

Cohort analysis

implications Care interruptions are important Need to strengthen retention of children in the early period after ART initiation

Acknowledgements – IeDEA-SA Funding acknowledgement Research reported in this publication was supported by the National Institute Of Allergy And Infectious Diseases of the National Institutes of Health under Award Number U01AI069924. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Site investigators and cohorts: Gary Maartens, Aid for AIDS, South Africa; Michael Vinikoor, Centre for Infectious Disease Research in Zambia (CIDRZ), Zambia; Monique van Lettow, Dignitas, Malawi; Robin Wood, Gugulethu ART Programme, South Africa; Nosisa Sipambo, Harriet Shezi Clinic, South Africa; Frank Tanser, Africa Centre for Health & Population Studies (Hlabisa), South Africa; Andrew Boulle, Khayelitsha ART Programme, South Africa; Geoffrey Fatti, Kheth’Impilo, South Africa; Sam Phiri, Lighthouse Clinic, Malawi; Cleophas Chimbetete, Newlands Clinic, Zimbabwe; Karl Technau, Rahima Moosa Mother and Child Hospital, South Africa; Brian Eley, Red Cross Children's Hospital, South Africa; Josephine Muhairwe, SolidarMed Lesotho; Anna Jores, SolidarMed Mozambique; Cordelia Kunzekwenyika, SolidarMed Zimbabwe, Matthew P Fox, Themba Lethu Clinic, South Africa; Hans Prozesky, Tygerberg Academic Hospital, South Africa. Data centers: Nina Anderegg, Marie Ballif, Lina Bartels, Julia Bohlius, Frédérique Chammartin, Benedikt Christ, Cam Ha Dao Ostinelli, Matthias Egger, Lukas Fenner, Per von Groote, Andreas Haas, Taghavi Katayoun, Eliane Rohner, Lilian Smith, Adrian Spörri, Gilles Wandeler, Elizabeth Zaniewski, Kathrin Zürcher, Institute of Social and Preventive Medicine, University of Bern, Switzerland; Andrew Boulle, Morna Cornell, Mary-Ann Davies, Victoria Iyun, Leigh Johnson, Mmamapudi Kubjane, Nicola Maxwell, Tshabakwane Nembandona, Patience Nyakato, Ernest Mokotoane, Gem Patten, Michael Schomaker, Priscilla Tsondai, Renee de Waal, School of Public Health and Family Medicine, University of Cape Town, South Africa.