Steady-state pharmacokinetics of lamivudine in end-stage kidney failure persons with detectable and undetectable HIV-1 RNA in peritoneal dialysis effluent

TL;DR

This study examines how lamivudine behaves in the blood and dialysis fluid of HIV patients with kidney failure, finding that drug levels are therapeutic even when HIV is detectable in dialysis fluid.

Contribution

The study shows that HIV shedding in dialysis fluid is not due to poor lamivudine absorption or dosing.

Findings

Lamivudine exposure in blood was higher than in dialysis fluid across all doses.

Therapeutic drug levels were maintained in serum despite detectable HIV in dialysis fluid for some patients.

Higher lamivudine doses did not consistently prevent HIV shedding into dialysis fluid.

Abstract

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.

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 spectrometer. Pharmacokinetic measures were obtained through non-compartmental analysis.

Twenty-eight participants were recruited with a median antiretroviral (ARV) drug duration of 8 (IQR,4.5–10.5) years and a CAPD duration of 13.3 (IQR,3.3–31.9) months. 14.3% (4/28) had detectable unsuppressed HIV-1 viral load in CAPD effluents. The majority (78,6%,22/28) of participants received a 50 mg dose, 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, 66.7% (2/3) and 33.3% (1/3) 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 h, 651.3 ng/mL; 75 mg-AUC0-24 h, 677.84 ng/mL; 300 mg-AUC0-24 h, 3135.89 ng/mL) compared to CAPD effluents (50 mg-AUC0-24 h, 384.91 ng/mL; 75 mg-AUC0-24 h, 383.24 ng/mL; 300 mg-AUC0-24 h, 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.

Steady-state lamivudine pharmacokinetic measures were variable among the entire study population. However, the total lamivudine exposure was within the therapeutic levels.

What was known: steady-state lamivudine pharmacokinetics in persons living with HIV (PLHIV) and managed with peritoneal dialysis (PD).This study adds: HIV-1 shedding into CAPD effluents is not necessarily contributed by reduced lamivudine dosages pharmacokinetics.Potential impact: Renally adjusted lamivudine dosages are effective even in patients shedding HIV-1 into CAPD effluents.

What was known: steady-state lamivudine pharmacokinetics in persons living with HIV (PLHIV) and managed with peritoneal dialysis (PD).

This study adds: HIV-1 shedding into CAPD effluents is not necessarily contributed by reduced lamivudine dosages pharmacokinetics.

Potential impact: Renally adjusted lamivudine dosages are effective even in patients shedding HIV-1 into CAPD effluents.

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