Safety and Effectiveness of Dolutegravir/Rilpivirine in Japanese People Living with HIV: Final Report of 6-Year Post-marketing Surveillance Study

Previous phase 3 studies demonstrated that a two-drug combination of dolutegravir (DTG) and rilpivirine (RPV) was non-inferior to three-drug antiretroviral therapy (ART) regimens in people living with human immunodeficiency virus (HIV) with stable plasma HIV-1 RNA. In Japan, DTG/RPV was approved in 2018 for maintenance of HIV-1 suppression, but evidence on its long-term safety and effectiveness is limited. In this post-marketing surveillance, data on the real-world clinical use of DTG/RPV were obtained through the HIV-Related Drug Cooperative Survey, a national joint post-marketing program overseen by manufacturers of HIV medications in Japan. The data collection period was from November 26, 2018 to November 26, 2024. Adverse drug reactions (ADRs) and potential risk factors associated with their incidence were examined. Effectiveness was evaluated by longitudinal changes in plasma HIV RNA levels and peripheral CD4+ T cell counts. Forty-four participants were registered, of whom 43 were assessed for safety and 41 for effectiveness. Safety analyses included 39 men and 4 women, with a mean age of 53.3 years. All participants switched from other ART regimens. DTG/RPV treatment exceeded 2 years in 76.74% of participants. Four ADRs, all non-serious, occurred in three participants (6.98%): weight increased (n = 1), hypertension (n = 1), hyperuricemia (n = 1), and condition aggravated (n = 1, aggravated hyperuricemia in the participant with hyperuricemia). The incidence of ADRs differed by the following participant characteristics: treatment duration, hepatic disorder, and renal disorder. Plasma HIV RNA levels remained < 50 copies/mL for 3 years after switching to DTG/RPV in most participants. The mean (standard deviation) peripheral CD4+ T cell count was 563.3 (207.2) cells/mm3, which remained stable throughout 3 years. This 6-year post-marketing surveillance confirms the long-term safety and effectiveness of DTG/RPV in people living with HIV in Japan who were virologically suppressed and switched to this two-drug regimen. Previous clinical studies demonstrated that a two-drug combination of dolutegravir and rilpivirine was non-inferior to three-drug antiretroviral therapy regimens in people living with HIV (PLHIV) whose plasma HIV RNA levels were under control. Data on the long-term safety and effectiveness of dolutegravir/rilpivirine in Japan are limited. In this 6-year post-marketing surveillance (November 2018 to November 2024), we collected data on the clinical use of dolutegravir/rilpivirine through a national joint post-marketing program overseen by manufacturers of HIV medications in Japan. We assessed the safety of dolutegravir/rilpivirine by the occurrence of adverse drug reactions (ADRs), and its effectiveness by changes over time in plasma HIV RNA levels and peripheral CD4+ T cell counts after switching from prior antiretroviral therapy regimens to dolutegravir/rilpivirine. Of 43 participants assessed for safety, 42 were Japanese (97.67%), 39 were men (90.70%), and the mean age was 53.3 years. All participants switched from other antiretroviral therapy regimens. Four non-serious ADRs (weight gain, hypertension, hyperuricemia, and aggravated condition) occurred in three participants (6.98%). None of the participants had events related to hepatitis B virus infection or reactivation. Among 41 participants assessed for effectiveness, most participants maintained suppressed HIV RNA levels and stable CD4+ T cell counts for 3 years after switching to dolutegravir/rilpivirine. Our findings suggest that dolutegravir/rilpivirine is a safe and effective two-drug combination for PLHIV in Japan whose plasma HIV RNA levels are under control and who consider switching treatment.