#3017 Renal-friendly lamivudine dosages are unlikely to contribute to HIV-1 shedding into PD effluents—an open label non-randomized pharmacokinetics study

Abstract

Abstract Background and Aims Renally adjusted lamivudine dosages are effective. However, some of the kidney failure patients managed with lamivudine-containing regimens are failing to suppress HIV in peritoneal dialysis (CAPD) effluent. The steady-state lamivudine pharmacokinetics among these patients was evaluated. Method This overnight open-label pharmacokinetic study enrolled participants living with HIV and managed with CAPD. Lamivudine levels in blood serum and CAPD effluent samples were quantified using liquid chromatography coupled with a mass spectrometry. Pharmacokinetic measures were obtained through non-compartmental analysis. Results Twenty-eight participants were recruited with a median ARV duration of 8 (IQR, 4.5-10.5) years and a CAPD duration of 13.3 (IQR, 3.3-31.9) months. The majority, 78.6% (22/20) of participants received a 50 mg dose and 25% (1/4) had a detectable HIV viral load (HIV-VL) in CAPD, while 10.7% (3/28), and another 10.7% (3/28) received 75 mg and 300 mg dosages, respectively. Among those treated with 75 and 300 mg, 50% (2/4) and 25% (1/4) had detectable HIV-VL in CAPD, respectively. The peritoneal membrane characteristics and CAPD system strengths were variable across the entire study population. Lamivudine exposure was increased in blood serum (50 mg-AUC0-24 hours, 651.3 ng/mL; 75 mg-AUC0-24 hours, 677.84 ng/mL; 300 mg-AUC0-24 hours, 3135.89 ng/mL) compared to CAPD effluents (50 mg-AUC0-24 hours, 384.91 ng/mL; 75 mg-AUC0-24 hours, 383.24 ng/mL; 300 mg-AUC0-24 hours, 2001.60 ng/mL) among the entire study population. The Cmax (50 mg, 41.5 ng/mL; 75 mg, 53.2 ng/mL; 300 mg, 199.1 ng/mL) and Cmin (50 mg, 17.8 ng/mL; 75 mg, 16.4 ng/mL; 300 mg, 76.4 ng/mL) measured in serum were within the therapeutic levels. Conclusion Steady-state lamivudine pharmacokinetic measures were variable among the entire study population; however, the total lamivudine exposure was within the therapeutic levels.