Long-term tolerability and effectiveness of raltegravir in Japanese patients: Results from post-marketing surveillance

• Published in: PloS one Vol. 14; no. 1; p. e0210384
• Main Authors: Kuroishi, Naho, Watananbe, Asuka, Sakuma, Ryuta, Ruzicka, Daniel J, Hara, Mitsuyoshi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09-01-2019; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adolescent; Adult; Aged; AIDS; Analysis; Antiretroviral agents; Antiretroviral drugs; Biology and Life Sciences; CD4 antigen; CD4 Lymphocyte Count; Clinical medicine; Clinical trials; Dosage and administration; Drug therapy; FDA approval; Female; HIV; HIV infections; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; HIV Integrase Inhibitors - adverse effects; HIV Integrase Inhibitors - therapeutic use; HIV-1; Human immunodeficiency virus; Humans; Hyperlipidemia; Infections; Integrase; Japan; Male; Marketing; Medicine and Health Sciences; Middle Aged; Patients; People and Places; Pharmaceutical industry; Product Surveillance, Postmarketing; Raltegravir; Raltegravir Potassium - adverse effects; Raltegravir Potassium - therapeutic use; Review boards; Ribonucleic acid; RNA; RNA, Viral - blood; Safety; Substance abuse treatment; Surveillance; Time Factors; Treatment Outcome; Viral Load - drug effects; Viruses; Young Adult; Japan; Uganda; United States > US; Senegal
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0210384

Antiretroviral agents are approved in Japan based on non-clinical and clinical data reported from overseas. Neither the long-term tolerability nor the effectiveness of raltegravir or other integrase strand transfer inhibitors in Japan is known. This study reports on the long-term tolerability and effectiveness of raltegravir in Japanese clinical practice using data collected through approximately 9 years of post-marketing surveillance. This observational survey used data on human immunodeficiency virus (HIV) infected patients initiated treatment with raltegravir between 2008 and 2017 in the HIV-related drug (HRD) cooperative survey to assess the safety and effectiveness of raltegravir in real world clinical practice. There were totally 1,303 patients prescribed raltegravir across 30 institutions; 1,293 patients and 1,178 patients were included for the safety and effectiveness analyses, respectively. The overall risk of adverse drug reaction was 17.25%, with abnormal hepatic function and hyperlipidaemia (<1.5%) having the highest proportion. Median HIV-1 RNA viral loads rapidly decreased below 40 copies/mL after 3 months of raltegravir use in treatment-naïve patients, and consistently sustained below 40 copies/mL after the start of raltegravir use in treatment-experienced patients. Among the patients who were treated for 7 years, 92.00% (95% CI: 73.97-99.02) maintained HIV-1 RNA viral load below 50 copies/mL. Additionally, CD4+ cell counts exceeded >500 cells/μL in treatment-naïve and treatment-experienced patients after 3 years and 4 years of treatment, respectively. In Japanese HIV patients, long-term treatment with raltegravir is well-tolerated and effective at viral suppression as measured by HIV-1 RNA levels and subsequent change in CD4+ cell counts. Such benefits can be expected for not only treatment-naïve but also treatment-experienced patients.