Downloaded from http://journals.lww.com/aidsonline by BhDMf5ePHKbH4TTImqenVAHxkFJp/XpPk1L/H3vMGwqMxG9jwOd8eJPG+b4DlKuAX44qu/vwzmc= on 07/29/2018 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. EDITORIAL COMMENT HIV, the brain, children, HAART and ‘neuro-HAART’: a complex mix Bruce J. Brew AIDS 2009, 23:1909–1910 Keywords: children, HAART, HIV-encephalopathy Prior to the introduction of highly active antiretroviral therapy, the prevalence of HIV encephalopathy among the pediatric HIV-infected population was up to 50% [1]. For the purpose of this commentary, HIVencephalopathy will be the term used to delineate pediatric HIV-related cognitive impairment. The effect of HAART on HIV encephalopathy has not been studied in a large series, although several small series suggest significant benefit. In contrast, the adult population has seen several well documented studies showing that HAART has led to a very dramatic decline in the incidence of HIV-associated dementia (HAD) [2]. The prevalence, however, of milder forms of cognitive impairment, now captured under the broader terminology HIV-associated neurocognitive disorders (HAND), has not changed with HAART [3]. Of the several potential explanations, there is the controversial possibility that some HAART regimens may not adequately treat brain infection because of poor penetration into the brain, whereas others with better penetration may be more effective (neuro-HAART). Numerous studies have tried to address this issue with variable and at times conflicting results, although the weight of evidence is currently tending to favour benefit from neuro-HAARTover standard HAART [4,5]. In the pediatric HIV population, it would be expected that the need for such neuro-HAART should be more obvious than in adults, given the fragile nature of brain development. As such, the study of neuro-HAART in pediatric patients may be able to provide further insights and progress to resolve the controversy. The contribution from Patel et al. [6] addresses both the effect of HAART on pediatric HIV encephalopathy at a population level and the potential benefit of neuro-HAART. Drawing on a large multicenter cohort of 2398 perinatally HIV-infected children enrolled in the pre- HAART and HAART eras, Patel et al. found over a median follow-up of approximately 6 years, a 50% reduction in HIV encephalopathy with HAART. The reduction in HIV encephalopathy parallels adult studies of the effect of HAART on HAD. The result is exceptionally important not just at an individual clinical level. It suggests that the future social and working potential of the current pediatric infected population is likely to be good, with all the positive flow on societal benefits that that implies. Patel et al. [6] also found that neuro-HAART was associated with a very significant survival benefit (74% reduction in risk of death compared with nonneuro- HAART). Such a dramatic effect has not been seen in adults. The reason for the survival benefit is unknown, but clearly deserves further exploration. Surprisingly, however, neuro-HAART was not associated with a statistically significant reduction in HIV encephalopathy compared with nonneuro-HAART. Could the survival benefit of neuro-HAART in fact be related to better treatment of milder forms of HIV encephalopathy that may not have been particularly clinically apparent? Certainly, cognitive impairment per se is related to increased mortality at least in adults [7]. Departments of Neurology and HIV Medicine, St Vincent’s Hospital and University of New South Wales, Sydney, Australia. Correspondence to Professor Bruce J. Brew, Department of Neurology, Level 4 Xavier Building, 390 Victoria St, Darlinghurst, Sydney, NSW 2010, Australia. Tel: +61 2 8382 4100; fax: +61 2 8382 4101; e-mail: b.brew@unsw.edu.au Received: 17 May 2009; revised: 28 May 2009; accepted: 29 May 2009. DOI:10.1097/QAD.0b013e32832ec4c6 ISSN 0269-9370 Q 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins 1909