TABLE 2.
Odds ratios for neurological diseases when exposed to ART 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 | |
| ART usage | ||||||||
| Non-ART use | 699 (27.19%) | 2,944 (28.63%) | 1 | Ref | Ref | 1 | Ref | Ref |
| ART use | 1872 (72.81%) | 7,340 (71.37%) | 1.09 | (0.98–1.21) | 0.117 | 1.08 | (0.97–1.2) | 0.148 |
| Timing of exposure to ART drugs | ||||||||
| Non-ART use | 699 (27.19%) | 2,944 (28.63%) | 1 | Ref | Ref | 1 | Ref | Ref |
| Current exposure (0 < YEAR ≤ 1) | 1,668 (64.88%) | 6,488 (63.09%) | 1.09 | (0.98–1.22) | 0.094 | 1.09 | (0.98–1.21) | 0.122 |
| Recent exposure (1 < YEAR ≤ 2) | 146 (5.68%) | 702 (6.83%) | 0.88 | (0.71–1.08) | 0.229 | 0.88 | (0.71–1.08) | 0.224 |
| Past exposure (2 < YEAR) | 58 (2.26%) | 150 (1.46%) | 1.67 | (1.21–2.30) | 0.002 | 1.68 | (1.22–2.32) | 0.002 |
| Cumulative defined daily dose (DDD) of ART drugs | ||||||||
| Non-ART use | 699 (27.19%) | 2,944 (28.63%) | 1 | Ref | Ref | 1 | Ref | Ref |
| Cumulative DDDs < 2,500 | 1,448 (56.32%) | 4,879 (47.44%) | 1.29 | (1.15–1.43) | <0.001 | 1.28 | (1.15–1.42) | <0.001 |
| Cumulative DDDs ≥ 2,500 | 424 (16.49%) | 2,461 (23.93%) | 0.54 | (0.46–0.63) | <0.001 | 0.53 | (0.45–0.62) | <0.001 |
| Adherence (ADH) of ART drugs | ||||||||
| Non-ART use | 699 (27.19%) | 2,944 (28.63%) | 1 | Ref | Ref | 1 | Ref | Ref |
| Low (0 < ADH ≤ 0.8) | 1,054 (41.00%) | 3,067 (29.82%) | 1.47 | (1.31–1.64) | <0.001 | 1.46 | (1.30–1.64) | <0.001 |
| High (0.8 < ADH) | 818 (31.82%) | 4,273 (41.55%) | 0.79 | (0.70–0.90) | <0.001 | 0.78 | (0.70–0.88) | <0.001 |
| Cumulative CPE scores of ART drugs | ||||||||
| Non-ART use | 699 (27.19%) | 2,944 (28.63%) | 1 | Ref | Ref | 1 | Ref | Ref |
| 0 ≦ Cumulative CPE score ≦ 10 | 911 (35.43%) | 3,770 (36.66%) | 1.03 | (0.92–1.16) | 0.576 | 1.03 | (0.92–1.15) | 0.632 |
| 10 < Cumulative CPE score ≦14 | 403 (15.67%) | 1716 (16.69%) | 1.03 | (0.89–1.19) | 0.694 | 1.02 | (0.88–1.18) | 0.785 |
| 14 < Cumulative CPE score ≦ 18 | 337 (13.11%) | 1,106 (10.75%) | 1.35 | (1.15–1.58) | <0.001 | 1.34 | (1.14–1.57) | <0.001 |
| 18 < Cumulative CPE score | 221 (8.60%) | 748 (7.27%) | 1.34 | (1.11–1.62) | 0.002 | 1.33 | (1.10–1.61) | 0.003 |
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; ART, antiretroviral therapy; DDD, defined daily dose; ADH, adherence of ART drugs; CPE score, central nervous system penetration effectiveness (CPE) score; 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), adherence (ADH), and central nervous system penetration effectiveness (CPE) score 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 claim 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). For the central nervous system penetration effectiveness (CPE) score, four categorized CPE scores were defined according to the sum of the ranks of each ART drug in the regimen administered to a patient from the start of drug usage to the first diagnosis date of neurological diseases (Table 2). The rank of each ART drug was determined according to previous studies (PubMed PMID number: 24907236, 31304188, 31823251, and 31385157). The CPE score for a particular regimen was determined by adding together the rankings of each ART drug included in the regimen. If the regimen was altered, the ranking of the newly added ART drug was added to the accumulated CPE score during the study period. Significant p-values (p < 0.05) are highlighted in bold italic font.