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Gamaldo, Charlene E. MD, FAASM*; Gamaldo, Alyssa PhD; McArthur, Justin C. MBBS, MPH, FAAN*,‡; Smith, Michael T. PhD, CBSM§

JAIDS Journal of Acquired Immune Deficiency Syndromes: March 1st, 2014 - Volume 65 - Issue 3 - p e124–e125
doi: 10.1097/QAI.0000000000000042
Letters to the Editor

*Department of Neurology, Johns Hopkins University, Baltimore, MD

School of Aging Studies, University of South Florida, Tampa, FL

Departments of Pathology, Epidemiology, and Medicine, Johns Hopkins University, Baltimore, MD

§Department of Psychiatry and Behavioral Medicine, Johns Hopkins University, Baltimore, MD

Supported by NIH grant 5P30MH075673-S02, UL1 RR 025005.

The authors have no conflicts of interest to disclose.

To the Editors:

The reviewer points out correctly that we used a correlational approach and therefore cannot determine causality or establish the direction of the significant relationships observed between some of the sleep indices and cognitive performance in the HIV-positive individuals. However, given that this is one of the first studies exploring how sleep in HIV-positive individuals might impact cognitive performance, we believe that it is an acceptable scientific contribution to conduct an exploratory analysis to highlight any potential relationships. If there are acceptable relationships, then, as the reviewer mentions, one could expand and explore the underlying mechanisms for this relationship using an experimental approach. This article illustrates possible relationships between cognition and sleep in HIV participants. As mentioned in the article, we hope that future studies will be conducted that can confirm and/or expand on these findings.

This article represents the third article generated from a protocol that included HIV-seropositive and seronegative participants. As discussed in the methods section, more specific detail regarding the full protocol and methods has been published previously. This includes the protocol for measuring sleep based on well-established methods and validated tools including in laboratory polysomnography, 2 week ambulatory actigraphy monitoring, electronic sleep diaries, and clinical sleep evaluations conducted by sleep medicine trained experts.1–3 The reviewer's suggestions regarding the merit of including a control group in this subgroup analysis article raises an issue that the scientific community is now beginning to openly discuss. This issue has been raised in other disciplines, such as cognitive aging, particularly when exploring cross-ethnic groups in cognitive performance. For example, in the cognitive aging literature, researchers have often explored cognitive function in minority samples by conducting cross-group research in which a control group of white participants is included in the study. However, some researchers have proposed that these studies do not appreciate the unique cognitive attributes of the minority group of interest.4,5 Furthermore, they do not account for factors that may explain the within-group variability in cognitive function often observed in minority groups.6,7 As a result, these researchers suggest that within-group research is a more reliable and valid approach than cross-group research for identifying the underlying sources of poor cognitive functioning within minority samples, and subsequently, explaining the racial group differences in cognitive performance often reported in previous literature. This same theoretical perspective could also be applied to clinical samples, such as our HIV sample. Cognitive deficits have been long recognized as a being prevalent in HIV-seropositive individuals, even those who are aviremic. Indeed, the NeuroAIDS research community is actively searching for underlying pathophysiologic mechanisms, despite virological stability on combination anti-retroviral therapy. Furthermore, the cognitive functioning and/or deficits are likely to vary greatly within a diverse HIV cohort much less between HIV-seropositive subjects and seronegative “controls.” The within-group approach will be useful in identifying the factors that explain the within-group variability in cognitive function observed in HIV samples and, subsequently, will assist researchers in understanding the mechanisms for cognitive deficits within HIV individuals. The cross-group approach of making comparisons between an HIV sample and non-HIV control sample would ignore this within-group variability and would not adequately address the nature of variability in cognitive performance among the HIV individuals. As a result, a cross-group approach may limit the potential for identifying mechanisms for the cognitive deficits observed in HIV individuals and strategies of intervention for this population. In summary, we appreciate the interest in our article. As highlighted by the reviewer's comments, we believe that the overarching message is the need for further investigations into this relationship, as it certainly encompasses a complex inter-relationship physiologically, environmentally, and socio-culturally.

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The authors thank Dr Kawada for his thoughtful review to our submission and provide this response.

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