Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Risk factors for treatment-limiting toxicities in patients starting nevirapine-containing antiretroviral therapy Anouk M. Kesselring a , Ferdinand W. Wit b , Caroline A. Sabin c , Jens D. Lundgren d , M. John Gill e , Jose M. Gatell f , Andri Rauch g , Julio S. Montaner h , Frank de Wolf a , Peter Reiss b , Amanda Mocroft c , on behalf of the Nevirapine Toxicity Multicohort Collaboration Background: This collaboration of seven observational clinical cohorts investigated risk factors for treatment-limiting toxicities in both antiretroviral-naive and experienced patients starting nevirapine-based combination antiretroviral therapy (NVPc). Methods: Patients starting NVPc after 1 January 1998 were included. CD4 cell count at starting NVPc was classified as high (>400/ml/>250/ml for men/women, respectively) or low. Cox models were used to investigate risk factors for discontinuations due to hypersensitivity reactions (HSR, n ¼ 6547) and discontinuation of NVPc due to treat- ment-limiting toxicities and/or patient/physician choice (TOXPC, n ¼ 10 186). Patients were classified according to prior antiretroviral treatment experience and CD4 cell count/viral load at start NVPc. Models were stratified by cohort and adjusted for age, sex, nadir CD4 cell count, calendar year of starting NVPc and mode of transmission. Results: Median time from starting NVPc to TOXPC and HSR were 162 days [inter- quartile range (IQR) 31–737] and 30 days (IQR 17–60), respectively. In adjusted Cox analyses, compared to naive patients with a low CD4 cell count, treatment-experienced patients with high CD4 cell count and viral load more than 400 had a significantly increased risk for HSR [hazard ratio 1.45, confidence interval (CI) 1.03–2.03] and TOXPC within 18 weeks (hazard ratio 1.34, CI 1.08–1.67). In contrast, treatment- experienced patients with high CD4 cell count and viral load less than 400 had no increased risk for HSR 1.10 (0.82 – 1.46) or TOXPC within 18 weeks (hazard ratio 0.94, CI 0.78–1.13). Conclusion: Our results suggest it may be relatively well tolerated to initiate NVPc in antiretroviral-experienced patients with high CD4 cell counts provided there is no detectable viremia. ß 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2009, 23:1689–1699 Keywords: CD4 cell count, HIV, nevirapine, toxicity, viral load Introduction Nevirapine is frequently used as part of combination antiretroviral therapy (cART) regimens, and is currently listed as one of the alternative options for cART in treatment-naive patients [1]. Nevirapine may also be used in patients with prior cART experience, for example, to minimize diarrhea or to reduce cardiovascular risks a HIV Monitoring Foundation, b Center for Poverty-Related Communicable Diseases, and Department of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands, c University College London Medical School, Royal Free Campus, London, UK, d Rigshospitalet and University of Copenhagen, Copenhagen HIV Programme, Copenhagen, Denmark, e University of Calgary, Calgary, Canada, f Infectious Diseases & AIDS Units, Hospital Clinic, University of Barcelona, Spain, g Division of Infectious Diseases, University Hospital Bern and University of Bern, Bern, Switzerland, and h British Columbia Centre for Excellence in HIV/AIDS, St. Paul’s Hospital, Vancouver, BC, Canada. Correspondence to Anouk M. Kesselring, MD, HIV Monitoring Foundation, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands. Received: 22 January 2009; revised: 20 April 2009; accepted: 21 April 2009. DOI:10.1097/QAD.0b013e32832d3b54 ISSN 0269-9370 Q 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins 1689