IMPLEMENTATION AND OPERATIONAL RESEARCH:CLINICAL SCIENCE Nonadherence to Clinic Appointments Among HIV-Infected Children in an Ambulatory Care Program in Western Kenya Winstone Nyandiko, MBChB, MMed, MPH,*†‡ Rachel Vreeman, MD, MSc,†§ Hai Liu, PhD,†k Sylvia Shangani, Bsc, MPH,†‡ Edwin Sang, BSc,† Samuel Ayaya, MBChB, MMed,*†‡ and Paula Braitstein, PhD†¶#** Background: Nonadherence to clinic appointments is associated with poor outcomes in HIV-infected adults. We describe the effect of cumulative clinic adherence (CCA) to clinic appointments on mortality and loss to follow-up (LTFU) among HIV-infected children in Kenya. Methods: We analyzed retrospective clinical data from HIV- infected children in the United States Agency for International Development–Academic Model Providing Access to Healthcare Partnership in Kenya between 2001 and 2009. We defined CCA as the proportion of days adherent to clinic visits after enrollment. We examined the effects of CCA on both death and LTFU, controlling for demographic and clinical factors at enrollment and over time. Cox proportional hazards models with time-varying coefficients were used to calculate adjusted hazard ratios (AHR) associated with each 10% increase in CCA on mortality and LTFU. Results: Among 3255 HIV-infected children, 1668 (51.2%) were male, median enrollment age of 5.2 years (interquartile range: 3.6– 7.4). Of 2393 children with CD4 within 3 months after enrollment, 1125 (47.0%) were severely immune suppressed, 567 became LTFU, and 88 died. Children with higher CCA had a higher risk of both mortality and LTFU at 3 and 6 months. Higher CCA became protective at 24 months for mortality, AHR at 24 months: 0.7 (95% confidence interval: 0.6 to 0.9), and at 12 months for LTFU, AHR at 24 months: 0.7 (95% confidence interval: 0.7 to 0.7). Conclusions: Children adherence to clinic visits during the first 6 months of HIV care was associated with a higher risk of death and LTFU, but by 24 months, children with better CCA had a reduced risk of LTFU and mortality. Key Words: HIV infected, children, immune suppression, lost-to- follow-up, clinic adherence, CDC stage, WAZ and WHZ scores (J Acquir Immune Defic Syndr 2013;63:e49–e55) BACKGROUND Combination antiretroviral therapy (cART) effectively suppresses HIV replication, reduces mortality, and improves the lives of children and adults with HIV. 1–5 It is now recog- nized that nonadherence to clinic appointments is an indepen- dent risk factor for virologic failure in patients receiving cART. 6,7 If clinical nonadherence is coupled with poor adher- ence to medication adherence, viral resistance to drugs 8 and opportunistic infections can develop. 9 With 2.3 million chil- dren younger than 15 years currently living with HIV, 10 mea- suring and supporting long-term pediatric adherence to care and cART is a priority. A study of 2619 veterans in the United States starting cART after 1997 found that the frequency of visits (defined as using the number of 3 monthly intervals the patients honored an appointment with a visit during the first year of care) affected the patients’ subsequent survival. Those who made at least 1 visit in all 4 quarters had a rate of death almost half that of patients who had only a single visit during the first year. 11 In resource-limited settings (RLS), emerging studies among HIV-positive adults suggest a similar relationship between retention in care and mortality. In studies in China and South Africa, a direct relationship between missed visits and subsequent mortality was noted. From data from the China National Treatment Program, a direct relationship between missed visits during the first 6 months after engage- ment and subsequent mortality was noted. Adjusted for clin- ical and demographic factors including baseline CD4 level, missing 1–2 visits conferred a 1.27-fold rise in the hazard of death [95% confidence interval (CI): 1.08 to 1.48] and miss- ing 3–5 visits conferred a 1.72-fold rise in the hazard of death Received for publication October 14, 2012; accepted February 18, 2013. From the *Department of Child Health and Pediatrics, School of Medicine, College of Health Sciences, Moi University, Eldoret, Kenya; †United States Agency for International Development–Academic Model Providing Access to Healthcare, Eldoret, Kenya; ‡Moi Teaching and Referral Hospital, Eldoret, Kenya; §Department of Pediatrics, Children’s Health Services Research, Indiana University School of Medicine, Indianapolis, IN; kDepartment of Biostatistics, Indiana University School of Medicine, In- dianapolis, IN; ¶Department of Medicine, Indiana University School of Medicine, Indianapolis, IN; #Department of Medicine, School of Medicine, College of Health Sciences, Moi University, Eldoret, Kenya; and **Dalla Lana School of Public Health, University of Toronto, Toronto, Canada. Supported in part by a grant to the United States Agency for International Development–Academic Model Providing Access to Healthcare Partner- ship from the United States Agency for International Development as part of the President’s Emergency Plan for AIDS Relief, grant no. 623-A-00- 08-00003-00. The authors have no conflicts of interest to disclose. This is original research work done by the authors listed above all who have contributed to all or part of the following: the design, data collection, analysis, and article writing. Correspondence to: Winstone Nyandiko, MBChB, MMed, MPH, PO Box 2582 or 4606 Eldoret-30100, Kenya (e-mail: nyandikom@yahoo.com). Copyright © 2013 by Lippincott Williams & Wilkins J Acquir Immune Defic Syndr  Volume 63, Number 2, June 1, 2013 www.jaids.com | e49