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A Population Pharmacokinetic Model Based on HPTN 077 of Long-acting Injectable Cabotegravir for HIV PrEP
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  • Yifan Yu,
  • Kristi Bigos,
  • Mark Marzinke,
  • Raphael Landovitz,
  • Marybeth McCauley,
  • Susan Ford,
  • Craig Hendrix,
  • Robert Bies,
  • Ethel Weld
Yifan Yu
State university of New York at Buffalo

Corresponding Author:[email protected]

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Kristi Bigos
Johns Hopkins University School of Medicine
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Mark Marzinke
Johns Hopkins University School of Medicine
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Raphael Landovitz
UCLA
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Marybeth McCauley
FHI 360
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Susan Ford
GlaxoSmithKline
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Craig Hendrix
John Hopkins University
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Robert Bies
State university of New York at Buffalo
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Ethel Weld
Johns Hopkins University School of Medicine
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Abstract

Background Cabotegravir delivered as a long-acting intramuscular injection has shown superior efficacy to oral tenofovir-emtricitabine as pre-exposure prophylaxis (PrEP) for HIV. Cabotegravir pharmacokinetics (PK), like those of other long-acting depot preparations, exhibit variability between individuals and between injection occasions. Aim To describe the population pharmacokinetics of long-acting cabotegravir (CAB-LA). Methods Using available PK measurements from 133 participants in the HIV Prevention Trials Network (HPTN) 077 trial, we analyzed CAB-LA PK data using nonlinear mixed-effects modeling to develop a population PK model. Results A two-compartment model with first order absorption best described the CAB-LA PK. The analysis identified between-occasional variability (BOV, i.e., differences in PK within one individual from one injection to the next) as a significant covariate affecting the absorption rate. Sex and body weight were identified as significant covariates influencing the absorption rate and apparent clearance of CAB-LA after intramuscular injection at various doses and frequencies. Conclusion The public availability of this model will facilitate and enable a wide variety of future clinically relevant simulations to inform the optimal use of CAB-LA.
Oct 2022Published in British Journal of Clinical Pharmacology volume 88 issue 10 on pages 4623-4632. 10.1111/bcp.15477