Safety, Tolerability, Pharmacokinetics, and Acceptability of Oral and Long-Acting Cabotegravir in HIV-Negative Chinese Men

• Published in: Antimicrobial agents and chemotherapy Vol. 66; no. 3; p. e0205721
• Main Authors: Han, Kelong, Wannamaker, Paul, Lu, Hongzhou, Zhu, Biao, Wang, Meixia, Paff, Melanie, Spreen, William R, Ford, Susan L
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 15.03.2022
• Subjects: Adult; Anti-HIV Agents - adverse effects; Antiviral Agents; Diketopiperazines; HIV Infections - drug therapy; HIV Infections - prevention & control; Humans; Injections, Intramuscular; Male; Pyridones - therapeutic use; Virology; pharmacokinetics; Chinese; HIV; preexposure prophylaxis; cabotegravir; long-acting
• ISSN: 0066-4804; 1098-6596; 1098-6596
• DOI: 10.1128/aac.02057-21

Long-acting (LA) cabotegravir demonstrated superior efficacy versus daily oral standard-of-care for HIV-1 preexposure prophylaxis. This phase 1 study assessed safety, tolerability, pharmacokinetics, and acceptability of cabotegravir in 47 HIV-negative adult Chinese men at low risk of acquiring HIV-1. Participants received once-daily oral cabotegravir 30 mg for 4 weeks and, after a 1-week washout, five 600-mg (3-mL) intramuscular cabotegravir LA injections at weeks 5, 9, 17, 25, and 33. Pharmacokinetic plasma samples were intensively collected on day 27 (  = 17) and sparsely collected before each injection until 56 weeks after final injection (  = 47). Cabotegravir LA injections were acceptable and well tolerated. Common adverse events included injection site pain, injection site swelling, and upper respiratory tract infection. No drug-related serious adverse events or deaths occurred. Mean cabotegravir concentration remained above 1.33 μg/mL (8× protein-adjusted concentration for 90% of the maximum inhibition of viral growth [PA-IC ]) before each injection and above 0.166 μg/mL (PA-IC ) for >32 weeks after final injection. Trough concentrations remained above PA-IC in nearly all participants and showed minimal accumulation. Noncompartmental pharmacokinetic analysis was performed. Geometric mean of terminal half-life was 1.89 and 47 days after oral and LA dosing, respectively. Cabotegravir concentrations were estimated to remain quantifiable for 48.7 weeks after final injection. Steady-state area under the concentration-time curve (AUC), peak concentration, trough concentration, terminal half-life, time to peak concentration, and apparent clearance after cabotegravir oral and LA dosing were similar to those estimated in non-Asian men in historical studies. These results support further clinical development of cabotegravir LA in China. (This study has been registered at ClinicalTrials.gov under registration no. NCT03422172.).