Editorial Commentary: under the Spell of the Red Queen.

A systematic review and meta-regression of temporal trends in adult CD4 cell counts at presentation to human immunodeficiency virus (HIV) care in highincome countries, by Lesko et al in this issue ofClinical Infectious Diseases, brings home a sobering message: Those counts have only risen minimally between 1992 and 2011, that is, from 307 cells/μL to 336 cells/μL(1.5 cells/μL/year).Moreover, during this time span there was negligible change in the proportion of subjects presenting with advanced HIV disease (CD4 count <200 cells/μL or AIDS) or late (CD4 count <350 cells/μL or AIDS). The study had the limitation of having to rely on quite diverse studies and data, and the results differ somewhat from an earlier study from the United States and Canada, covering the years 1997–2007, in which the estimated adjusted mean CD4 cell count at initial presentation for HIV care increased at a rate of 6 cells/ μL/year [1]. However, the level of precision of CD4 cell count estimates over time is not all that important: the fact of the matter remains that, even in recent years, many people with HIV infection in high-income countries present late for care and may start treatment even later [1–3]. In 2011, in the Netherlands the median CD4 count at HIV diagnosis was 390 cells/μL, 300 cells/μL at the start of antiretroviral therapy (ART), and 43% of those presenting for care did so with a CD4 count <350 cells/μL or an AIDSdefining event [4]. In 2012, the US Centers for Disease Control and Prevention reported that 41% of Americans who first received a diagnosis of HIV infection between 2006 and 2009 had no history of HIV testing [5]. The finding that so little has changed with regard to time of presentation to HIV care in a period that saw dramatic improvements in HIV treatment and monitoring options is astonishing. The study period spans the years of sequential monotherapy (1994 and earlier), dual therapy (1994–1995), and highly active antiretroviral therapy (HAART; 1996 and onward) and the introduction of HIV type 1 RNA monitoring (1995 and onward). Moreover, during the HAART years a major shift from complex and toxic regimens to simple, once-daily, well-tolerated, and less toxic first-line regimens occurred [6]. One would expect these respective developments to have had a major influence on earlier uptake of ART. Yet, we are reminded of what the Red Queen said to Alice: “Now, here, you see, it takes all the running you can do, to keep in the same place” [7]. The standstill is all the more astonishing as there can be little doubt that early treatment with current antiretroviral drugs, generally speaking, is of enormous benefit to the individual. Let us briefly recapitulate those benefits: (1) Increased survival:When ART is started early enough and the CD4 count is kept above 500 cells/μL, life expectancy appears to be similar to that of non-HIV-infected individuals [8, 9]. The results from another article in this issue of Clinical Infectious Diseases, by Mocroft et al from the COHERE Collaboration, indicate that the incidence of AIDS-defining illnesses (ADIs), in particular malignant ADIs, is higher in individuals with a CD4 count of 500–749 cells/μL compared to those with higher CD4 cell numbers. (2) It reduces tuberculosis incidence: This may not be of overriding importance in high-income countries, but is in countries with high tuberculosis incidence [10–12]. (3) It reduces the occurrence of immune reconstitution syndrome: This is an important cause of ART-related morbidity and mortality, in particular in resourcepoor settings [13]. (4) It may lead to a functional cure in some patients who are treated during primary or acute HIV infection [14, 15]. An ongoing study being conducted in Thailand shows that very early Received 6 June 2013; accepted 6 June 2013; electronically published 6 August 2013. Correspondence: Joep M. A. Lange, Amsterdam Institute for Global Health and Development (AIGHD), Academic Medical Center–University of Amsterdam, Pietersbergweg 17, Amsterdam 1105 BM, The Netherlands (j.lange@aighd.org). Clinical Infectious Diseases 2013;57(7):1048–50 © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/cid/cit425