Date of report 22 Jun 2020

Reported case interaction between
Dolutegravir and Valproate

A 50-year old patient with a new HIV infection (CD4 count 10; VL 300.000 copies/ml) was admitted to the hospital for respiratory insufficiency due to PJP and Pasteurella infection. Dolutegravir (DTG) with FTC/TDF was started on 14 November 2019. The patient also received valproate for having a history mental disorders and drug abuse. The valproate-DTG interaction is not considered to be clinically relevant. Valproate reduces total DTG concentrations due to protein binding displacement, free DTG fraction increases, leading to therapeutic free DTG plasma concentrations (Bollen P; 20th International Workshop on Clinical Pharmacology of HIV 2019, abstract 44). Several DTG plasma trough concentrations were measured in this patient – displayed in the table below.

We decided to measure free DTG concentrations, because of the extremely low result at 22 Nov 2019. Free DTG fraction did not increase and was thus considered to be potentially subtherapeutic. DTG was given BID instead of QD to increase plasma concentrations from 29 Nov 2019 onwards. DTG trough concentration increased and the free DTG concentration was above the proposed in vitro EC90 value of unbound dolutegravir (0.9 µg/L). This case suggests that the DDI between valproate and DTG might be clinically relevant in some patients.

DTG concentrations

Viral load data