Effect of Early versus Deferred Antiretroviral Therapy for HIV on Survival

Replication paper
Original publication: New England Journal of Medicine
Original researchers: Mari M. Kitahata, Stephen J. Gange, Alison G. Abraham, Barry Merriman, Michael S. Saag, Amy C. Justice, Robert S. Hogg, Steven G. Deeks, Joseph J. Eron, John T. Brooks, Sean B. Rourke, M. John Gill, Ronald J. Bosch, Jeffrey N. Martin, Marina B. Klein, Lisa P. Jacobson, Benigno Rodriguez, Timothy R. Sterling, Gregory D. Kirk, Sonia Napravnik, Anita R. Rachlis, Liviana M. Calzavara, Michael A. Horberg, Michael J. Silverberg, Kelly A. Gebo, James J. Goedert, Constance A. Benson, Ann C. Collier, Stephen E. Van Rompaey, Heidi M. Crane, Rosemary G. McKaig, Bryan Lau, Aimee M. Freeman, Richard D. Moore
Current status: Unable to Replicate

The Original Study

The use of antiretroviral therapy reduces disease progression and death among patients with HIV infection. However, the optimal time to begin therapy is uncertain. This study examines the impact of early initiation of antiretroviral therapy on the risk of death among 17,517 asymptomatic patients with HIV infection in the United States and Canada who received medical care during the period from 1996 through 2005. The first analysis involved 8362 patients, comparing 2084 patients who initiated therapy at a CD4+ count of 351 to 500 cells per cubic millimeter to 6278 patients who deferred therapy. The second analysis compared 2220 patients who initiated therapy at a CD4+ count of more than 500 cells per cubic millimeter to 6935 patients that deferred treatment. The study uses multivariate Cox proportional-hazards models to examine the impact timing of treatment initiation has on disease patient mortality, adjusting for calendar year, cohort of patients and demographic and clinical characteristics. The first study shows that, among deferred therapy patients, there was an increase in the risk of death of 69 per cent, as compared to the early-therapy group. In the second analysis, deferred therapy patients experienced a 94 per cent increase in the risk of death.