Comorbidities and Co-Medications Among 28 089 People Living With HIV

A Nationwide Cohort Study From 2009 to 2019 in Japan

Toshio Naito; Mai Suzuki; Shinichi Fukushima; Mayumi Yuda; Nobuyuki Fukui; Shotaro Tsukamoto; Kazutoshi Fujibayashi; Keiko Goto-Hirano; Ryohei Kuwatsuru


HIV Medicine. 2022;23(5):485-493. 

In This Article


Study Design and Data Source

This study is a multicentre retrospective observational cohort study. Based on Article 16, Paragraph 2 of the Act on Assurance of Medical Care for Elderly People,[16] and with the approval of Japan's Ministry of Health, Labour and Welfare, research data were strictly controlled in accordance with the ministry's guidelines.

Study Population

Between April 2009 and March 2019, patients with one or more documented ART prescriptions and one or more HIV-related illnesses were enrolled. Diseases were classified according to the reimbursement claim codes associated with the International Classification of Diseases, 10th Revision (ICD-10), codes B20–24. In the data extraction, medical fee claims that were paid with public funds, other than national health insurance, were excluded in advance. To avoid including doubtful PLWH, such as those poorly recorded or patients who appeared intentionally recorded only for the purpose of making a claim, patients were required to have a record of at least one ART prescription. Prescription of ART was defined as receiving any of the following antiretroviral drugs: nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand transfer inhibitors (INSTIs) and entry inhibitors.

Definitions of Measures

The presence of AIDS-defining illnesses was identified using ICD-10 codes and disease names, as follows: AIDS (B24); AIDS-related complex (B24); HIV disease resulting in mycobacterial infection (B20.0); HIV disease resulting in cytomegaloviral disease (B20.2); HIV disease resulting in other viral infections (B20.3); HIV candidiasis (B20.4); Pneumocystis jirovecii pneumonia (B20.6); Kaposi sarcoma (B21.0); Burkitt lymphoma (B21.1); non-Hodgkin lymphoma (B21.2); HIV encephalopathy (B22.0); HIV disease resulting in lymphoid interstitial pneumonitis (B22.1); Slim disease (B22.2); HIV disease resulting in other specified conditions (B23.8); and malignant neoplasm of the cervix uteri (C53). HIV infections among AIDS (B24) were excluded. HIV disease resulting in other conditions (B23.0, B23.1, 23.2, 23.3) were omitted.

Chronic comorbidities were defined based on ICD-10 codes and related diagnosis codes. If a specific code was recorded at least once during the study period, the patients was considered to have that chronic comorbidity. All comorbidity data during the study period were included, both prior to and after the ART was recorded, except for haemodialysis which only considered events after receiving ART. The chronic comorbidities and codes in this study include: type II diabetes (E11–14); hypertension (I10–15, except for I11/I13); lipid disorders (hypercholesterolaemia/hyperlipidaemia (E78.0–78.5); vascular diseases, including hypertensive heart and renal diseases (I11/I13), angina pectoris (I20), myocardial infarction (I21–22), stroke (I64 and related receipt diagnosis codes); chronic kidney disease (N18–19); malignancies (B21.0–21.2/C00–97); psychiatric disorders, including dementia (F01/F03), psychosis (F20–29), mania and depression (F30–32), and anxiety (F40–41); bone disorders [osteoporosis (M80–81)]; hepatitis B infection (B18.1); hepatitis C infection (B18.2); and psychoactive-substance-related disorders substance abuse (F19). Among malignancies, AIDS-defining cancers were identified according to the definition used in Ruzicka et al's. study[14] as Kaposi sarcoma (B21.0/C46); Burkitt lymphoma (B21.1/C83.7); non-Hodgkin lymphoma (B21.2/C82–85, exclude C83.7), and malignant neoplasm of cervix uteri (C53). All other malignancies were defined as non-AIDS-defining cancers.

Considering potential issues with long-term polypharmacy, this study limited the definition of co-medications to those drugs that were continuous prescriptions. In defining co-medication use, we considered both the number of medications prescribed over a period of three consecutive months and cumulative prescription days. Use of co-medication was defined as: (1) the number of concomitant non-ART medications prescribed for three consecutive months during January–March 2019; and (2) concomitant use of non-ART medications prescribed for a total of 90 days or more during the study period, based on the therapeutic subgroups (second level) of the Anatomical Therapeutic Chemical (ATC) codes.

Ethics Statement

This study complied with all relevant Ministry of Labour and Welfare of Japan guidelines and all research guidelines. The study protocol was approved by the Institutional Review Board (IRB) at Juntendo University School of Medicine's IRB (IRB no. 2019216). The need for informed consent was waived because the data used did not identify any individual.

Statistical Analysis

Patient's age was defined as the age at the time of the latest entry registered in the database. Patients were stratified into seven age groups: < 20, 20–29, 30–39, 40–49, 50–59, 60–69, and ≥ 70 years. Demographic characteristics and prescription drugs used during the study period were summarized descriptively, using the number and percentage of patients for categorical variables. All statistical analyses were performed in R 4.0.3 environment (R Core Team, 2020).[17]