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. 2023 Jun 8;14:1110605. doi: 10.3389/fphar.2023.1110605

TABLE 4.

Odds ratios for neurological diseases when exposed to PI drugs.

Characteristics Patients with neurological diseases Patients with non-neurological diseases Crude Adjusted
(N = 2,571) (N = 10,284)
N (%) N (%) OR 95% CI p-value OR 95% CI p-value
PI usage
 Non-exposure 2,223 (86.46%) 8,987 (87.39%) 1 Ref Ref 1 Ref Ref
 Exposure 348 (13.54%) 1,297 (12.61%) 1.09 (0.96–1.24) 0.200 1.09 (0.95–1.24) 0.219
Timing of exposure to PI drugs
 Non-exposure 2,223 (86.46%) 8,987 (87.39%) 1 Ref Ref 1 Ref Ref
 Current exposure (0 < YEAR ≤ 1) 241 (9.37%) 813 (7.91%) 1.20 (1.03–1.40) 0.019 1.20 (1.03–1.39) 0.021
 Recent exposure (1 < YEAR ≤ 2) 43 (1.67%) 216 (2.1%) 0.80 (0.58–1.12) 0.200 0.80 (0.57–1.11) 0.184
 Past exposure (2 < YEAR) 64 (2.49%) 268 (2.61%) 0.96 (0.72–1.28) 0.788 0.96 (0.72–1.28) 0.788
Cumulative defined daily dose (DDD) of PI drugs
 Non-exposure 2,223 (86.46%) 8,987 (87.39%) 1 Ref Ref 1 Ref Ref
 Cumulative DDDs < 411 212 (8.25%) 611 (5.94%) 1.41 (1.20–1.66) <0.001 1.41 (1.19–1.66) <0.001
 Cumulative DDDs ≥ 411 136 (5.29%) 686 (6.67%) 0.79 (0.65–0.96) 0.018 0.78 (0.64–0.95) 0.015
Adherence (ADH) of PI drugs
 Non-exposure 2,223 (86.46%) 8,987 (87.39%) 1 Ref Ref 1 Ref Ref
 Low (0 < ADH ≤ 0.8) 290 (11.28%) 914 (8.89%) 1.29 (1.12–1.49) <0.001 1.29 (1.12–1.49) <0.001
 High (0.8 < ADH) 58 (2.26%) 383 (3.72%) 0.61 (0.46–0.81) <0.001 0.60 (0.46–0.80) <0.001

Follow-up years (mean ± SD) (the period between the HIV/AIDS diagnosis date and the neurological disease diagnosis date): 2.62 ± 2.31 years. N, number; PI, protease inhibitors; DDD, defined daily dose; ADH, adherence of ART drugs; OR, odds ratio; CI, confidence interval; Ref, reference. Model was applied using conditional logistic regression analysis adjusted by Charlson comorbidity number. Comorbidities were identified within the HIV/AIDS diagnosis date. Cumulative defined daily dose (DDD) and adherence (ADH) were calculated during the period between the HIV/AIDS diagnosis date and the neurological disease diagnosis date. The date of the first diagnosis of neurological disease was designated as the index date. The three categories included past exposure (2 < YEAR), recent exposure (1 < YEAR ≤ 2), and current exposure (0 < YEAR ≤ 1) according to the previous similar studies (PubMed PMID number: 31374345). Patients who received ART drugs during the time window of over 2 years before the index date but were currently non-users were defined as patients with past exposure. Patients who received ART drugs during the time window of 1–2 years before the index date were defined as patients with recent exposure. Patients who received ART drugs during the time window of 0–1 year before the index date were defined as patients with current exposure. Patients who had continuously received ART since their first diagnosis of HIV/AIDS were also defined as those with current exposure. The defined daily doses (DDDs) were those recommended by the Collaborating Center for Drug Statistics Methodology of the World Health Organization (WHO) (https://www.whocc.no/atc_ddd_index/). For the cumulative defined daily dose (DDD) of ART drugs, two categorized cumulative DDDs were defined according to (total amount of drug)/(amount of drug in a DDD) from the first date of ART treatment to the index date according to previous studies (PubMed PMID number: 31888519). For adherence (ADH) (electronic prescription claims data adherence) to ART drugs, two categorized ADHs were defined according to (total number of prescribed days)/(total number of observation days) from the first date of ART treatment to the index date according to previous studies (PubMed PMID number: 9681089). Significant p-values (p < 0.05) are highlighted in bold italic font.