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Dolutegravir Troughs Higher With 3TC, Lower With TAF
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International Workshop on Clinical Pharmacology of HIV, Hepatitis and Other Antiviral Drugs, September 20-22, 2021
By Mark Mascolini for NATAP and Virology Education
Dolutegravir trough concentrations in plasma and cells proved higher with lamivudine (3TC) than with a non-3TC combination in an 80-person University of Torino analysis [1]. Dolutegravir troughs were lower when the integrase inhibitor was taken with tenofovir alafenamide (TAF).
Dolutegravir remains a favored antiretroviral when given either with two drugs (TAF/emtricitabine [FTC]) or abacavir [ABC]/3TC), or when given with 3TC alone. To learn more about dolutegravir pharmacokinetics in clinic patients, University of Torino investigators conducted this analysis. They noted that dolutegravir concentrations may determine neuropsychiatric tolerability of this drug.
The study involved 25 people taking 50 mg of dolutegravir with TAF/FTC, 16 taking it with ABC/3TC, and 39 taking it only with 3TC. Sixty-eight of 80 participants (85%) were men, age averaged 49 years (95% confidence interval [CI] 41 to 58) and body mass index 22 kg/m2 (95% CI 19 to 25).
Mean dolutegravir trough concentration (Ctrough) in plasma was significantly lower with TAF/FTC (869.1 ng/mL, 95% CI 590.7 to 1147.5) than with ABC/3TC (1772.2 ng/mL, 95% CI 1405.3 to 2139.0) or 3TC alone (1590.7 ng/mL, 95% CI 1301.4 to 1880.1) (P = 0.001).
The same pattern held true for intracellular dolutegravir Ctrough: 197.4 ng/mL (95% CI 133.2 to 261.7) with TAF/FTC, 389.0 ng/mL (95% CI 170.8 to 607.2) with ABC/3TC, and 398.5 ng/mL (95% CI 312.0 to 485.0) with 3TC alone (P < 0.001 for TAF/FTC vs 3TC alone).
Intracellular/plasma ratio was 0.206 (95% CI 0.160 to 0.253) with TAF/FTC, 0.219 (95% CI 0.156 to 0.282) with ABC/3TC, and 0.250 (95% CI 0.227 to 0.274) with 3TC (P = 0.211, not significant).
Correlations between dolutegravir plasma and intracellular troughs were significant and linear with all 3 regimens (Spearman R = 0.785, P < 0.001). The researchers found a borderline significant linear correlation between dolutegravir plasma Ctrough and age (Spearman R = 0.208, P = 0.064). Neither gender nor body mass index affected dolutegravir troughs.
The Torino team noted that the higher dolutegravir plasma and intracellular troughs with 3TC held true whether 3TC was given alone or with ABC. They called for long-term clinical studies to better appraise the impact of 3TC on dolutegravir pharmacokinetics.
Reference
1. Ferrara M, Salvador E, Di Stefano A, et al. Dolutegravir plasma and intracellular pharmacokinetics according to drug companion in the clinical setting. International Workshop on Clinical Pharmacology of HIV, Hepatitis and Other Antiviral Drugs 2021. September 20-22, 2021. Abstract 17.
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