Clinical trial designConsiderations in the design of randomized controlled trials evaluating the optimal time to initiate antiretroviral therapy in previously untreated HIV-1-infected patientsBabiker, Abdel G; Gibb, Diana MAuthor Information Medical Research Council Trials Unit, London, UK Correspondence to Abdel G. Babiker, MRC CTU, 222 Euston Road, London, NW1 2DA, UK Tel: +44 0 207 670 4719; fax: +44 0 207 670 4818; e-mail: [email protected] Current Opinion in HIV and AIDS: November 2006 - Volume 1 - Issue 6 - p 488-494 doi: 10.1097/COH.0b013e328010f238 Buy Metrics Abstract Purpose of review This paper addresses design issues around ‘when to start’ trials in adults and children and in chronic and acute HIV infection. Issues for young children treated soon after birth and recently seroconverting adults differ, and are also discussed. Recent findings No trials have been published addressing this question for combination antiretroviral therapy in chronic HIV infection, and the evidence base for guidelines has largely been derived from observational studies. The biases inherent in observational data and recent results from the adult SMART trial may have moved the level of equipoise from ‘unstable certainty’ (mitigating against randomization) to a renewed call for a very large clinical endpoint trial of when to start therapy in the era of highly active antiretroviral therapy. Older children could also be enrolled in such a trial, as the predictive value of CD4 cell count values in children over 5 years and young adults. In acute infection, ongoing trials in adults and children is similar considering strategies of early short-term combination antiretroviral therapy compared with deferred therapy. Although not strictly ‘when to start trials’, these approaches could reduce life-long exposure to antiretroviral therapy while maintaining clinical and immunological well being. Summary Issues in the design of a future randomized trial of when to start antiretroviral therapy in chronic HIV infected adults and older children are discussed, while the role of early limited therapy in primary infection awaits results of ongoing trials. © 2006 Lippincott Williams & Wilkins, Inc.