Comment 1956 www.thelancet.com Vol 367 June 17, 2006 It is startling to see how a seemingly insubstantial change in practice might affect long-term results for infants. When a medical text recommended immediate cord clam- ping in 1913, science was in its infancy and expert opinion guided practice. Today, we have the benefit of scientific evidence to advise our actions. The article in today’s Lancet by Camila Chaparro and colleagues 1 provides additional weight to the growing evidence that our haste to clamp the umbilical cord and pass the baby off is ill-advised. The mounting evidence that delayed cord clamping benefits both term and preterm infants continues to build. 2,3 Chaparro and colleagues’ international interdisciplinary study with 358 randomised infants shows that waiting 2 min before clamping the umbilical cord provided the infants with more body iron at 6 months of age without causing any harm at birth. The rationale for the study—the link between iron deficiency in infancy and neurodevelopmental delays—is well founded. The number of infants in the study was ambitious and the protocol for the 6-month follow-up was meticulously planned. The exclusion criteria were carefully selected to rule out women with conditions that negatively affect neonates. higher CD4 thresholds remains unclear but enthusiasm for that approach is likely to wane. 5,6 One recent large randomised clinical study of starting and stopping at CD4 cell counts above 350/µL revealed only slightly increased risk of minor HIV-related complications in the interruption arm (Staccato; table). 7 The implications for the individual management of antiretroviral therapy level are less clear. Because of the Trivacan and SMART studies, the most recent US Department of Health and Human Services guidelines state that treatment interruptions should be avoided in clinical practice and should only be done in a closely monitored clinical trial. 8 However, this is not practical because many patients in clinical practice have significant side-effects, pill fatigue, or treatment failure. Presumably any study that specifically focuses on those with strong reasons to stop therapy might show a benefit (or at least a lack of harm) in going on and off therapy. The fundamental challenge raised by Trivacan and SMART is how to translate data from broad heterogeneous study populations to an individual. For patients who are doing well on a stable regimen, the Trivacan and SMART data clearly indicate that uncontrolled HIV replication is more harmful than modern treatment regimens, and that well-tolerated drugs should be continued indefinitely. This finding is not surprising and was widely accepted even before these studies were done (at least it pertains to regions where treatment is widely available). At what point the harm associated with treatment in an individual outweighs the harm associated with uncontrolled HIV replication requires a careful understanding of treatment-related side-effects, HIV pathogenesis, and the consequences of interrupting therapy. The Trivacan and SMART studies provide a quantitative risk assessment of the consequences of stopping therapy and are therefore important studies for all treating clinicians. The task at hand now is to ensure that all patients—including those in resource-constrained regions, such as West Africa—have access to well-trained health-care providers who can readily adopt emerging data into any decision regarding when (if ever) to stop antiretroviral therapy. Steven G Deeks San Francisco General Hospital, San Francisco, California 94110, USA sdeeks@php.ucsf.edu I have received research support or honoraria from Boehringer Ingelheim, Bristol- Myers Squibb, GlaxoSmithKline, Pfizer, Roche, Tibotec, and Trimeris. 1 Gulick RM, Mellors JW, Havlir D, et al. Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. N Engl J Med 1997; 337: 734–39. 2 Levy AR, James D, Johnston KM, et al. The direct costs of HIV/AIDS care. Lancet Infect Dis 2006; 6: 171–77. 3 Danel C, Moh R, Minga A, for the Trivacan ANRS 1269 trial group. CD4-guided structured antiretroviral treatment interruption strategy in HIV-infected adults in west Africa (Trivacan ANRS 1269 trial): a randomised trial. Lancet 2006; 367: 1981–86. 4 El-Sadr W, Neaton J, for the SMART Study Investigators. Episodic CD4 guided use of antiretroviral therapy is inferior to continuous therapy: results of the SMART study. 13th Conference on Retroviruses and Opportunistic Infections. Denver, Colarado, USA; Feb 5–8, 2006: 106LB (abst). 5 Maggiolo F, Ripamonti D, Gregis G, Quinzan G, Callegaro A, Suter F. Effect of prolonged discontinuation of successful antiretroviral therapy on CD4 T cells: a controlled, prospective trial. AIDS 2004; 18: 439–46. 6 Cardiello PG, Hassink E, Ananworanich J, et al. A prospective, randomized trial of structured treatment interruption for patients with chronic HIV type 1 infection. Clin Infect Dis 2005; 40: 594–600. 7 Ananworanich J, Gayet-Ageron A, Le Braz M, et al. Program and abstracts of the 13th Conference on Retroviruses and Opportunistic Infections. Denver, Colarado, USA; Feb 5–8, 2006: 102 (abst). 8 Panel on Clinical Practices for Treatment of HIV Infection convened by the Department of Health and Human Services (DHHS). Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. May 4, 2006: http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf (accessed June 7, 2006). Delayed cord clamping increases infants’ iron stores See Articles page 1997