Vitamin D deficiency is associated with neurocognitive impairment in HIV-infected subjects
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Low vitamin D levels are associated with higher odds of cognitive dysfunction in the older population, and in subjects with mental disorders or with chronic neurologic diseases. With combination antiretroviral therapy (cART), incidence of HIV-associated dementia has reduced, while the prevalence of milder forms of neurocognitive impairment (NCI) persisted stable over time. Hypovitaminosis D is often found in HIV infection but its association with NCI has not been investigated yet. The aim was to explore this association in a clinic-based HIV-positive population.
A retrospective, cross-sectional analysis of an existing monocenter dataset obtained from patients undergoing neuropsychological assessment in routine clinical care between January, 2011 and December, 2016 was carried out. NCI was assessed through a standardized battery of 13 tests on 5 different cognitive domains and HIV-associated neurocognitive deficit (HAND) was classified according to Frascati’s criteria. Vitamin D deficiency was defined by 25 hydroxy-vitamin D 25(OH)D levels < 10 ng/mL. Logistic regression was adjusted for main associated covariates and seasonality.
542 patients were included: 96.7% were receiving cART, median CD4 count was 611/mmc (IQR, 421–809), HIV RNA was < 40 cp/mL in 85.8%. Median 25(OH)D was 23.2 ng/mL (IQR, 15.6–29.2), with vitamin D insufficiency 67.7% and deficiency in 9.4%. Overall, NCI was found in 37.1% and HAND in 22.7%. Compared to patients with higher vitamin D levels, subjects with vitamin D deficiency had increased proportions of NCI (52.9% versus 35.4%; p = 0.014) or of HAND (42.9% versus 24.9%; p = 0.012). Median NPZ-8 scores were significantly different based on vitamin D levels (p = 0.021). At multivariable analyses, vitamin D deficiency was the only risk factor of NCI (OR 2.05; 95% CI 1.04–4.05; p = 0.038) or of HAND (OR 2.12; 95% CI 0.99–4.54; p = 0.052).
In HIV-positive persons, severe hypovitaminosis D was independently associated with a higher risk of neurocognitive impairment in general, and of HIV-associated neurocognitive disorders in particular. Future studies are needed to elucidate causal relationship and whether vitamin D supplementation may reverse this risk.
KeywordsNeurocognitive impairment HAD Vitamin D HIV
The authors thank Dr Pietro Balestra and Dr Martina Ricottini as well as psychologists, physicians, nurses, laboratory staff of the National Institute for Infectious Diseases, L. Spallanzani, IRCCS and laboratory staff of the San Camillo- Forlanini Hospital for valuable collaboration.
Each author participated sufficiently in the work giving substantial contributions to realization; AAm, AAn, CP, SC and AV made contributions to the study conception and design, interpretation of data, drafting and revising the manuscript; ACB performed the neurocognitive assessment, RL, IM and ACB contributed to the acquisition of data, PL carried out the statistical analysis. All authors contributed to the intellectual content and gave their final approval to the submitted manuscript.
The study was supported by the INMI “Lazzaro Spallanzani” Ricerca Corrente grants (line 3d) from the Italian Ministry of Health 2016 and Gilead Fellowship 2017, awarded by Alessandra Vergori, MD.
Compliance with ethical standards
Conflict of interest
Adriana Ammassari (AAm) received speaker’s fees from AbbVie, BMS, Gilead, Janssen Cilag, Merck, ViiV and participated in Advisory Boards for Merck and Janssen; Andrea Antinori (AAn) received personal fees for consultancy and lectures from AbbVie, Bristol Myers Squibb, Gilead, Janssen, Merck, ViiV and research institutional grants from Bristol Myers Squibb, Gilead, Janssen, ViiV. Carmela Pinnetti (CP) participated in Advisory Boards for Janssen and received speaker’s fees from Gilead. For the remaining authors, none were declared.
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