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Heterogeneity in neurocognitive change trajectories among people with HIV starting antiretroviral therapy in Rakai, Uganda

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Abstract

Considerable heterogeneity exists in patterns of neurocognitive change in people with HIV (PWH). We examined heterogeneity in neurocognitive change trajectories from HIV diagnosis to 1–2 years post-antiretroviral therapy (ART). In an observational cohort study in Rakai, Uganda, 312 PWH completed a neuropsychological (NP) test battery at two-time points (ART-naïve, 1–2 years post-ART initiation). All NP outcomes were used in a latent profile analysis to identify subgroups of PWH with similar ART-related neurocognitive change profiles. In a subset, we examined subgroup differences pre-ART on cytokine and neurodegenerative biomarkers CSF levels. We identified four ART-related change subgroups: (1) decline-only (learning, memory, fluency, processing speed, and attention measures), (2) mixed (improvements in learning and memory but declines in attention and executive function measures), (3) no-change, or (4) improvement-only (learning, memory, and attention measures). ART-related NP outcomes that are most likely to change included learning, memory, and attention. Motor function measures were unchanged. Subgroups differed on eight of 34 pre-ART biomarker levels including interleukin (IL)-1β, IL-6, IL-13, interferon-γ, macrophage inflammatory protein-1β, matrix metalloproteinase (MMP)-3, MMP-10, and platelet-derived growth factor-AA. The improvement-only and mixed subgroups showed lower levels on these markers versus the no-change subgroup. These findings provide support for the need to disentangle heterogeneity in ART-related neurocognitive changes, to focus on higher-order cognitive processes (learning, memory, attention) as they were most malleable to change, and to better understand why motor function remained unchanged despite ART treatment. Group differences in pre-ART CSF levels provide preliminary evidence of biological plausibility of neurocognitive phenotyping.

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Funding

This study was sponsored by the NIH (MH099733, MH075673, MH080661-08, L30NS088658, NS065729-05S2) with additional funding from the Johns Hopkins Center for Global Health. This study was also supported in part by the Division of Intramural Research, NIAID, NIH.

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Authors and Affiliations

  1. Department of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street/Meyer 6-113, Baltimore, MD, 21287-7613, USA

    Leah H. Rubin, Deanna Saylor, Raha Dastgheyb & Ned Sacktor

  2. Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Leah H. Rubin

  3. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Leah H. Rubin, Ronald H. Gray & Maria J. Wawer

  4. Rakai Health Sciences Program, Kalisizo, Uganda

    Gertrude Nakigozi, Alice Kisakye, James Batte, Richard Mayanja & Aggrey Anok

  5. Department of Psychiatry, Makerere University, Kampala, Uganda

    Noeline Nakasujja

  6. Department of Neurology, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA

    Kevin Robertson

  7. University of Minnesota, Minneapolis, MN, USA

    Sarah M. Lofgren & David R. Boulware

  8. Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA

    Steven J. Reynolds & Thomas C. Quinn

  9. Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Steven J. Reynolds & Thomas C. Quinn

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  1. Leah H. Rubin
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Correspondence to Leah H. Rubin.

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Rubin, L.H., Saylor, D., Nakigozi, G. et al. Heterogeneity in neurocognitive change trajectories among people with HIV starting antiretroviral therapy in Rakai, Uganda. J. Neurovirol. 25, 800–813 (2019). https://doi.org/10.1007/s13365-019-00768-5

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