Prognostic model for HIV-1 disease progression in patients starting antiretroviral therapy was validated using independent data Margaret May a,b, * , Kholoud Porter c,d , Jonathan A.C. Sterne a,b , Patrick Royston d , Matthias Egger a,e a Antiretroviral Therapy (ART) Cohort Collaboration b Department of Social Medicine, University of Bristol, Bristol BS8 2PR, UK c CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) d MRC Clinical Trials Unit, London, UK e Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland Accepted 15 February 2005 Abstract Setting and Objective: The Antiretroviral Therapy (ART) Cohort Collaboration published models predicting progression to AIDS or death (the complement of AIDS-free survival) and death (the complement of absolute survival). The objective is to validate the model on independent data from CASCADE. Study Design: Discrimination was assessed using concordance statistics, and calibration was examined by comparing predicted survival curves with the corresponding Kaplan–Meier estimates. Accuracy was assessed by comparing predicted percentage probability of survival with the Kaplan–Meier estimate at yearly intervals after start of therapy. Results: There was little loss of model discrimination when applying the model to CASCADE. Overall predicted calibration curves agreed with Kaplan–Meier survival curves. Predicted probabilities of AIDS or death at 3 years after starting HAART ranged from 4.3% in the low-risk group to 20.5% in high-risk patients, with corresponding Kaplan–Meier estimates ranging from 4.0% to18.3%; for death predictions, the probabilities ranged from 1.2% to 7.3% and estimates from 1.1% to 8.6%. Conclusion: The predictions from the model agree with observed outcomes in CASCADE to within the 95% upper and lower Kaplan– Meier estimates. The prognostic model appears to be accurate in terms of discrimination and calibration, giving reliable and transportable predictions up to 3 years after the start of HAART. Ó 2005 Elsevier Inc. All rights reserved. Keywords: AIDS; Antiretroviral therapy; CD4; HIV; Prognosis; Validation 1. Introduction The prognosis for patients who are HIV-1 positive has substantially improved since the widespread introduction of highly active antiretroviral therapy (HAART) in 1996 [1]. The Antiretroviral Therapy (ART) Cohort Collaboration was set up in 2000 to allow prognostic modeling of progression to AIDS or death in patients who were HIV-1 positive and had started HAART with no previous exposure to antiretroviral treatment. Progression to AIDS in the context of this study is defined as first diagnosis of an AIDS event after starting HAART. Patients may or may not have had a diagnosis of AIDS prior to start of therapy. We are therefore modeling AIDS-free survival and absolute survival from initiation of HAART. In 2002, the collabo- ration reported the models and presented tables with probabilities for 80 different risk strata for progression to AIDS or death and to death from any cause up to 3 years after starting HAART, both in print [2] and on a website (http://www.art-cohort-collaboration.org). The CD4 cell count at commencement of HAART was the most strongly prognostic factor, with patients initiating HAART at ! 200 cells/mL at considerably higher risk of clinical progression. Viral load at commencement was as- sociated with clinical progression only if > 100,000 copies/ mL. Age 50 years or greater, a prior diagnosis of AIDS, and infection through injection drug use were also of prognostic importance. Estimated rates of progression to AIDS or * Corresponding author. Tel: 144-117-9287287; fax: 144-117- 9287325. E-mail address: m.t.may@bristol.ac.uk (M. May). 0895-4356/05/$ – see front matter Ó 2005 Elsevier Inc. All rights reserved. doi: 10.1016/j.jclinepi.2005.02.015 Journal of Clinical Epidemiology 58 (2005) 1033–1041