Abstract
To report the status of switch rates and time-to-switch of antiretroviral therapy (ART) regimens by evaluating anchor drug classes and common switching patterns in Japanese people living with human immunodeficiency virus (HIV, PLWH). This cross-sectional cohort study extracted data of 28,089 PLWH from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), which contains data representing the entire population of Japan. PLWH with first prescription records of ART administered between January 2011 and March 2019 were identified (n = 16,069). The median time-to-switch and switch rates of anchor drug classes were estimated by Kaplan–Meier analysis. Brookmeyer–Crowley and Greenwood methods were used to estimate 95% confidence intervals for switch rates and median days, respectively. Switch rates were compared between anchor drug classes by year using log-rank tests. A total of 3108 (19.3%) PLWH switched anchor drug classes from first to second regimens. Switch rates increased continuously over 8 years for non-nucleoside reverse transcriptase inhibitors (NNRTIs) (14.9–65.5%) and protease inhibitors (PIs) (13.2–67.7%), with median time-to-switch of 1826 and 1583 days, respectively. Integrase strand transfer inhibitors (INSTIs) maintained a low switch rate (3.0–7.6%), precluding median-days calculation. Overall, the majority of patients treated initially with NNRTIs and PIs switched to INSTIs regardless of switching times (< 1 year: 67.3% and 85.9%, respectively; ≥ 1 year: 95.5% and 93.6%, respectively). The foremost switching strategies for first-to-second ART regimens are from NNRTIs or PIs to INSTIs regimens that maintain low switch rates long term. There was no observable difference in trend between sex, age and status of AIDS disease at first ART regimen. INSTIs HIV agents may be the most durable anchor drug class for PLWH receiving ART.
Highlights
Abbreviations ABC Abacavir antiretroviral therapy (ART) Antiretroviral therapy cART Combination regimens entry inhibitors (EIs) Entry inhibitors HIV Human immunodeficiency virus integrase strand transfer inhibitors (INSTIs) Integrase strand transfer inhibitors NDB National Database of Health Insurance Claims and Specific Health Checkups of Japan NNRTIs Non-nucleoside reverse transcriptase inhibitors protease inhibitors (PIs) Protease inhibitors PLWH People living with human immunodeficiency virus
Five classes of antiretroviral medications are used in Japan: nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand transfer inhibitors (INSTIs), and entry inhibitors (EIs)[3]
Of the 3108 patients who switched anchor drug classes from their first to second ART regimens, most patients treated initially with NNRTIs and PIs switched to INSTIs (67.3% [95% CI: 63.9%‒70.4%] and 85.9% [84.4%‒87.3%], respectively) < 1 year after starting the first regimen; 65.6% [95% CI: 63.1%‒68.0%) of patients treated initially with INSTIs switched to PIs in the second regimen (Fig. 1c)
Summary
Abbreviations ABC Abacavir ART Antiretroviral therapy cART Combination regimens EIs Entry inhibitors HIV Human immunodeficiency virus INSTIs Integrase strand transfer inhibitors NDB National Database of Health Insurance Claims and Specific Health Checkups of Japan NNRTIs Non-nucleoside reverse transcriptase inhibitors PIs Protease inhibitors PLWH People living with human immunodeficiency virus. PLWH frequently switch ART regimens during chronic HIV treatment. Five classes of antiretroviral medications are used in Japan: nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand transfer inhibitors (INSTIs), and entry inhibitors (EIs)[3]. The most recent guidelines for initiating an ART regimen recommend combination regimens (cART) consisting of two NRTIs as backbone therapy, with a third “anchor” drug from another class, most often NNRTIs, PIs, or I NSTIs1–3. Clinicians’ selection of an anchor drug is central to the treatment strategy because backbone choices are comparatively limited
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