ORIGINAL RESEARCH Determinants of response to first HAART regimen in antiretroviral-naı ¨ve patients with an estimated time since HIV seroconversion R Thie ´baut, 1,2 H Jacqmin-Gadda, 1 S Walker, 3 C Sabin, 4 M Prins, 5 J Del Amo, 6 K Porter, 3 F Dabis, 2 G Che ˆne 2 and the CASCADE Collaboration* 1 INSERM E0338 Biostatistics and 2 INSERM U593, ISPED, Bordeaux 2 University, Bordeaux, France, 3 MRC Clinical Trials Unit, London, UK, 4 Royal Free Centre for HIV Medicine and Department of Primary Care and Population Sciences, Royal Free and University College, London, UK, 5 Municipal Health Service, Cluster Infectious Diseases, Amsterdam, the Netherlands, and 6 Public Health Department, Miguel Herna´ndez University, San Juan-Alicante, Spain Objective To study the determinants of immunological and virological response to highly active antiretroviral therapy (HAART) in naı ¨ve patients, adjusting for time since HIV-1 seroconversion. Design Data from HIV-cohort studies where dates of seroconversion have been reliably estimated. Methods In previously untreated patients, short- and long-term marker responses from HAART initiation (three or more antiretroviral drugs) to the end of follow-up or any treatment modification were considered using mixed effects models accounting for undetectable HIV viral load and informative dropout. Results In total, 943 patients were treated with a first HAART regimen for a median of 29 months. In adjusted analyses, compared with a reference group of homosexual men without AIDS initiating treatment 4 years after seroconversion, injecting drug users (IDUs) were treated at similar CD4 and HIV RNA levels but had poorer short-term virological response (2.54 vs 2.13 log 10 HIV-1 RNA copies/mL at 1.5 months, P 5 0.03) and poorer long-term immunological response (522 vs 631 cells/ mL at 24 months, Po0.0001). Although individuals with AIDS at HAART initiation had lower CD4 counts (206 vs 382 cells/mL, Po0.0001), their immunological responses were similar to those of individuals without AIDS. Similarly, individuals further from seroconversion started HAART at lower CD4 counts (e.g. 311 vs 382 cells/mL at vs before 9 years from seroconversion, Po0.0001), but had similar CD4 responses. However, they experienced poorer long-term virological response (0.67 log 10 copies/mL/year smaller decline, Po0.0001) compared to those treated before 9 years from seroconversion. Conclusion Taking into account the time elapsed since seroconversion, this study suggests that careful choices of initial treatment should be made and intensive follow-up carried out in high-risk subgroups such as IDUs who have poorer responses. Keywords: CD4 T lymphocytes, HIV infection, HIV RNA, longitudinal study, seroconverters Received: 21 October 2004, accepted 29 March 2005 Introduction The clinical management of patients infected with HIV is mainly based on two markers – the CD4 T lymphocyte count and the plasma HIV RNA viral load – because of their Correspondence: Rodolphe Thie ´baut, INSERM E0338 & U593 – ISPED, Universite ´ Bordeaux 2 – Victor Segalen, 146 Rue Le ´o Saignat, 33076 Bordeaux Cedex, France. Tel: (33) 5 57 57 45 21; fax: (33) 5 56 24 00 81; e-mail: rodolphe.thiebaut@isped.u-bordeaux2.fr *See Appendix for the composition of the CASCADE Collaboration group. r 2006 British HIV Association HIV Medicine (2006), 7, 1–9 1