Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Slower CD4 cell decline following cessation of a 3 month course of HAART in primary HIV infection: findings from an observational cohort Sarah Fidler a , Julie Fox a , Giota Touloumi b , Nikos Pantazis b , Kholoud Porter c , Abdel Babiker c , Jonathan Weber a and the CASCADE Collaboration Objective: To investigate the effect of a short course of HAART during primary HIV infection (PHI) on rate of CD4 cell and viral load change. Methods: Data following HAART cessation from 89 individuals (seroconverting 1999 – 2003) who chose to take a 3 month course of HAART at PHI were compared with 179 untreated controls in CASCADE, using linear and nonlinear random effects models. Participants were non-randomized but frequency matched for age, sex, risk factor, year of seroconversion and presentation within the first 6 months of seroconversion. Time to CD4 cell count < 350 cells/ml and initiation of clinically indicated antiretroviral therapy (ART) were also compared as competing risks. Results: The rate of CD4 cell decline following therapy cessation appeared significantly slower among treated participants than untreated controls: losses of 51 cells/ml [95% confidence interval (CI), 32 – 69] and 77 cells/ml (95% CI, 65 – 89), respectively, 3 years after seroconversion (P ¼ 0.011). Based on extrapolated data, viral loads also differed significantly at this point (4.09 and 4.53 copies/ml, respectively). At 2 years, there was no significant difference in mean viral load levels: 4.31 copies/ml (95% CI, 4.14 – 4.48) and 4.47 copies/ml (95% CI, 4.28–4.66), respectively. CASCADE seroconverters were more likely to reach CD4 cell count < 350 cells/ml or initiate clinically indicated ART (hazard ratio, 1.45; 95% CI, 1.02–2.05; P ¼ 0.039). Conclusion: A short course of ART at PHI may delay CD4 cell decline. Confirmation of this requires a randomized clinical trial powered to address definitively the role of ART intervention in PHI (currently underway through SPARTAC). ß 2007 Lippincott Williams & Wilkins AIDS 2007, 21:1283–1291 Introduction The rate with which a host clears the initial viraemia during the early stages of HIV infection has been shown to play a key role in determining disease progression [1,2] and clinical outcome [3]. In-vitro data of HIV-specific CD4 cell responses mounted during this stage, often referred to as primary HIV infection (PHI), have been shown to correlate with enhanced virological control [4–6] although their relevance in vivo remains unknown. These immune responses are largely lost in chronic disease and fail to regenerate upon subsequent HAART initiation and virological suppression [7]. It has been hypothesized that intervention with HAART in PHI may, therefore, help to boost the host’s immunity to HIV-1 by preserving HIV-specific immune responses in CD4 cells and so delay disease progression [4]. Indeed, From the a Imperial College, St Mary’s Hospital, London, UK, the b Athens University Medical School, Greece, and the c MRC Clinical Trials Unit, London, UK. Correspondence to Dr S. Fidler, Imperial College, St Mary’s Hospital, London, UK. E-mail: s.fidler@imperial.ac.uk Received: 26 September 2006; revised: 4 December 2006; accepted: 18 January 2007. ISSN 0269-9370 Q 2007 Lippincott Williams & Wilkins 1283