Safety and Effectiveness Analysis of Dolutegravir and Dolutegravir/Abacavir/Lamivudine in Japanese People Living with HIV: 10 years of Post-Marketing Surveillance

Dolutegravir (DTG), an integrase strand transfer inhibitor, is recommended as a first-line antiretroviral therapy (ART) for HIV/AIDS in international guidelines. In Japan, approved DTG-containing formulations include the single-agent DTG (Tivicay® tablets) and the fixed-dose combination of DTG, abacavir sulfate, and lamivudine (DTG/ABC/3TC, Triumeq® combination tablets). Although overseas clinical trials have demonstrated the favorable safety and effectiveness of these DTG-containing products, evidence specific to Japanese people living with HIV/AIDS (PLHIV) has remained limited. This report presents the final findings from a decade-long, prospective, post-marketing surveillance of single-agent DTG and DTG/ABC/3TC initiated in 2014. Data on the real-world clinical use of the single-agent DTG and DTG/ABC/3TC were obtained through the HIV-Related Drug Cooperative Survey, a national joint post-marketing program overseen by Japanese manufacturers of HIV therapies. Adverse drug reactions (ADRs) were captured and classified using the Medical Dictionary for Regulatory Activities. Associations between ADR incidence and potential risk factors were examined. Effectiveness was evaluated by longitudinal changes in plasma HIV RNA copy number and peripheral CD4+ cell counts. Among 2345 PLHIV included in the safety analysis, 652 patients (27.80%) reported ADRs. The most frequently reported ADRs were increased blood creatinine (4.78%), abnormal hepatic function (2.43%), and nausea (2.30%). ADR incidence was higher in participants with baseline comorbidities, those receiving concomitant medications, and ART-naïve participants, relative to their counterparts. Notably, no progressive increase in ADR incidence was observed during prolonged use > 2 years. Plasma HIV RNA levels demonstrated sustained improvements from baseline in both ART-naïve and ART-experienced participants. By 12 months after administration, the proportion of participants achieving plasma HIV RNA levels < 50 copies/ml was about 90% in ART-naïve participants and about 96% in ART-experienced participants. Additionally, CD4+ T cell counts also demonstrated sustained improvement from baseline in both ART-naïve and ART-experienced participants. This 10-year post-marketing surveillance confirms the long-term safety and effectiveness of single-agent DTG and DTG/ABC/3TC in Japanese PLHIV. No new safety concerns emerged over the 10-year surveillance period, further supporting their established safety profiles and reinforcing their continued role as key therapeutic options in routine clinical practice. Dolutegravir is a commonly used drug for the initial treatment for HIV infection or AIDS worldwide. In Japan, approved dolutegravir-containing products include tablets containing dolutegravir only (Tivicay® tablets) and combination tablets containing dolutegravir, abacavir sulfate, and lamivudine (Triumeq® combination tablets). Although these products are widely used globally, data on Japanese people living with HIV/AIDS (PLHIV) remain limited. This 10-year post-marketing survey followed Japanese PLHIV who were taking these two dolutegravir-containing products to evaluate their long-term safety and effectiveness. The data for this survey were jointly collected by Japanese pharmaceutical companies that market HIV medication, and this survey analyzed data from 2345 participants who used the two dolutegravir-containing products. Side effects were reported in 652 participants (27.80%). The most common side effects were higher creatinine levels in the blood (4.78%), liver function problems (2.43%), and nausea (2.30%). Participants with comorbidities, those receiving additional medications, and those who had never had therapy for HIV/AIDS before tended to experience side effects more often than those without these characteristics. The number of participants with side effects did not increase during long-term use for > 2 years. Sustainably suppressed plasma HIV RNA (viral load) and improved numbers of CD4+ T cells suggested the long-term effectiveness of these two dolutegravir-containing products. These findings indicate that long-term use of these two dolutegravir-containing products in Japanese PLHIV showed no new safety issues and maintained effectiveness, supporting their use for Japanese PLHIV in real-world care.