Neurocognitive function in HIV infected patients on antiretroviral therapy

Alan Winston, Alejandro Arenas-Pinto, Wolfgang Stöhr, Martin Fisher, Chloe M Orkin, Kazeem Aderogba, Andrew De Burgh-Thomas, Nigel O'Farrell, Charles Jn Lacey, Clifford Leen, David Dunn, Nicholas I Paton, PIVOT Trial Team, Alan Winston, Alejandro Arenas-Pinto, Wolfgang Stöhr, Martin Fisher, Chloe M Orkin, Kazeem Aderogba, Andrew De Burgh-Thomas, Nigel O'Farrell, Charles Jn Lacey, Clifford Leen, David Dunn, Nicholas I Paton, PIVOT Trial Team

Abstract

Objective: To describe factors associated with neurocognitive (NC) function in HIV-positive patients on stable combination antiretroviral therapy.

Design: We undertook a cross-sectional analysis assessing NC data obtained at baseline in patients entering the Protease-Inhibitor-Monotherapy-Versus-Ongoing-Triple therapy (PIVOT) trial.

Main outcome measure: NC testing comprised of 5 domains. Raw results were z-transformed using standard and demographically adjusted normative datasets (ND). Global z-scores (NPZ-5) were derived from averaging the 5 domains and percentage of subjects with test scores >1 standard deviation (SD) below population means in at least two domains (abnormal Frascati score) calculated. Patient characteristics associated with NC results were assessed using multivariable linear regression.

Results: Of the 587 patients in PIVOT, 557 had full NC results and were included. 77% were male, 68% Caucasian and 28% of Black ethnicity. Mean (SD) baseline and nadir CD4+ lymphocyte counts were 553(217) and 177(117) cells/µL, respectively, and HIV RNA was <50 copies/mL in all. Median (IQR) NPZ-5 score was -0.5 (-1.2/-0) overall, and -0.3 (-0.7/0.1) and -1.4 (-2/-0.8) in subjects of Caucasian and Black ethnicity, respectively. Abnormal Frascati scores using the standard-ND were observed in 51%, 38%, and 81%, respectively, of subjects overall, Caucasian and Black ethnicity (p<0.001), but in 62% and 69% of Caucasian and Black subjects using demographically adjusted-ND (p = 0.20). In the multivariate analysis, only Black ethnicity was associated with poorer NPZ-5 scores (P<0.001).

Conclusions: In this large group of HIV-infected subjects with viral load suppression, ethnicity but not HIV-disease factors is closely associated with NC results. The prevalence of abnormal results is highly dependent on control datasets utilised.

Trial registry: ClinicalTrials.gov, NCT01230580.

Conflict of interest statement

Competing Interests: The authors have read the journal's policy and have the following conflicts: AW has received honoraria or research grants, or been a consultant or investigator, in clinical trials sponsored by Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Janssen Cilag, Roche, and Pfizer. All other authors have no conflict of interest. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Association between NPZ-5 score and…
Figure 1. Association between NPZ-5 score and Frascati score.

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