ORIGINAL ARTICLE The Coding Causes of Death in HIV (CoDe) Project Initial Results and Evaluation of Methodology Justyna D. Kowalska, a Nina Friis-Møller, a Ole Kirk, a,b Wendy Bannister, c Amanda Mocroft, c Caroline Sabin, c Peter Reiss, d John Gill, e Charlotte Lewden, f Andrew Phillips, c Antonella D’Arminio Monforte, g Matthew Law, h Jonathan Sterne, i Stephane De Wit, j and Jens D. Lundgren a,b ; for The CoDe Working Group and the D:A:D Study Group Background: The Coding Causes of Death in HIV (CoDe) Project aims to deliver a standardized method for coding the underlying cause of death in HIV-positive persons, suitable for clinical trials and epidemiologic studies. Methods: The project incorporates detailed data collection, a clas- sification system, and a centralized adjudication process performed by 2 independent reviewers. The methodology was tested in the Data Collection on Adverse events of Anti-HIV Drugs Study, and inde- pendent reviews of causes of death were compared. Logistic regres- sion models identified factors associated with initial agreement by reviewers on underlying cause of death. Results: A total of 491 reported fatal cases were adjudicated; in only 5% of cases the cause of death remained undetermined after adju- dication. Reviewers initially agreed on the underlying cause for 339 (69%) deaths. As compared with deaths due to AIDS-related causes, the odds of agreement were more than 80% lower when deaths were ultimately deemed to be due to non-AIDS-related causes (odds ratio = 0.17 95% confidence interval = 0.08 – 0.37) or undeter- mined causes (0.11 0.04 – 0.36). The odds of initial agreement were also lower for deaths occurring in subjects with hypertension (0.43 0.22– 0.85) and depression (0.43 0.23– 0.80). Conclusions: The extent and format of data collected in the CoDe Project appear to be sufficient for an informed review, and the proposed coding scheme is adequate for obtaining an underlying cause of death. (Epidemiology 2011;22: 000 – 000) S ince the introduction of combination antiretroviral therapy in 1996, there has been a substantial reduction in the incidence rates of death in the HIV-positive population. 1–3 As the number of deaths from AIDS-related causes has dropped, causes of death have become more variable, 4,5 with an increase in deaths from non-AIDS-related malignancies, liver, and cardiovascular disease, and other age-related comorbidities. 6 –10 It is important to monitor deaths in the HIV-infected population so that interventions can be targeted appropriately, should specific causes of death emerge or become predomi- nant. 11,12 Such monitoring is generally undertaken after clas- sifying causes of death using the International Classification of Diseases system (ICD; WHO), 13 the latest version of which (ICD-10) was endorsed in 1990. In contrast to ICD-9, the latest version includes more conditions that were consid- ered to have HIV as an underlying cause, resulting in a far greater number of conditions being coded as “HIV-related” 14 However, such an approach may not be optimal where the aim is to monitor emerging causes of death, particularly those that may be related to HIV or its treatment. In such a situation, it may be preferable to categorize causes of death according to organ system or etiology/pathology, rather than simply grouping all such death as being related to HIV. 15–19 National surveillance of HIV-related mortality is gen- erally performed using information from registries, with cause of death obtained from death certificates. However, it is well documented that death certificates alone, as well as site investigator self reporting, are often filled in erroneously (eg, with improper causal sequencing of diseases, or listing the mechanism of death rather than the underlying cause, which is insufficient to identify the underlying cause of death). 20 –22 In this situation, further adjudication is not possible because Submitted 13 September 2010; accepted 20 January 2011. From the a Copenhagen HIV Programme, University of Copenhagen, Faculty of Health Sciences, Copenhagen, Denmark; b Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark; c University College London Medical School, Royal Free Campus, London, United Kingdom; d HIV Monitoring Foundation, Academic Medical Center, Amsterdam, the Netherlands; e S Alberta HIV Clinic, Sheldon M Chumir Health Centre, Calgary, Canada; f Bordeaux School of Public Health, Institut de Sante ´ Publique, d’Epide ´miologie et de De ´veloppement, Bordeaux, France; g Hospital San Paolo, University of Milan, Milan, Italy; h National Centre in HIV Epidemiology and Clinical Research, Sydney, Australia; i Department of Social Medicine, University of Bristol, Bristol, United Kingdom; and j Department of Infectious Diseases, Centre Hospitalier Universitaire Saint-Pierre Hospital, Brussels, Belgium. Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article (www.epidem.com). Correspondence: Justyna D. Kowalska, Copenhagen HIV Programme, Uni- versity of Copenhagen, Faculty of Health Sciences, The Panum Institute/ Building 21.1, Blegdamsvej 3B, DK-2200 Copenhagen N, Denmark. E-mail: jko@cphiv.dk. Copyright © 2011 by Lippincott Williams & Wilkins ISSN: 1044-3983/11/2204-0001 DOI: 10.1097/EDE.0b013e31821b5332 Epidemiology • Volume 22, Number 4, July 2011 www.epidem.com | 1