2024 updates to the Québec antiretroviral therapeutic drug monitoring guidelines: Key changes over 10 years

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2024 updates to the Québec antiretroviral therapeutic drug monitoring guidelines: Key changes over 10 years

Nancy Sheehan^1,2,3, Myriam Fréchette-Le Bel^1,4, Marie-Eve Dumas^1,4, Rachel Therrien⁵, Claude Fortin^5,6, Isabelle Boucoiran^6,7, Fatima Kakkar^6,7, Benoît Trottier^5,6,8, Jason Szabo^2,9, Xavier Le Guyader¹⁰, Anne-Marie Bérard¹¹ and Jean-Guy Baril^6,8,11

¹Québec Antiretroviral Therapeutic Drug Monitoring Program, McGill University Health Centre; ²Chronic Viral Illness Service, McGill University Health Centre; ³Faculté de pharmacie, Université de Montréal; ⁴Centre hospitalier universitaire de Sherbrooke; ⁵Clinique des infections virales chroniques, Centre hospitalier de l'Université de Montréal; ⁶Faculté de médecine, Université de Montréal; ⁷Centre d'infectiologie mère-enfant, Centre hospitalier universitaire Sainte-Justine; ⁸Clinique de médecine urbaine du Quartier Latin; ⁹Clinique médicale l'Actuel; ¹⁰Programme national de mentorat sur le VIH et les hépatites; ¹¹Direction de la prévention des infections transmissibles sexuellement et par le sang, Ministère de la Santé et des Services Sociaux

Background: Therapeutic drug monitoring (TDM) of antiretrovirals has the potential to improve virologic response and tolerability. In 2013, TDM guidelines in Québec (Canada) were published to assist clinicians. In 2016, an addendum was developed for newer antiretrovirals (dolutegravir, elvitegravir, rilpivirine). From 2018 to 2023, we underwent an update to the guidelines.

Methods: An extensive literature review of published articles and grey literature was conducted using predefined terms. Three waves of literature review were completed (2018, 2020/2021 and 2022). After 1 August 2022, additional articles or conference proceedings were added if judged important. Indications for TDM for each antiretroviral were categorized based on strength of the recommendation (A, strongly recommended; B, moderately recommended; C, optional; D, not recommended) and quality of the evidence (I, prospective TDM trial; II, retrospective or prospective observational data; III, expert opinion or small number of cases ≤10). The rating was determined by two pharmacists by consensus. If consensus was not met, a decision was taken by the working group. Target concentrations were also reviewed. We present key changes, including the percent of recommendations in the current guidelines that were modified compared to the previous recommendations.

Results: Older antiretrovirals (n = 5) were removed and newer agents (n = 6) added to the 2024 guidelines. Overall, 374 references were retained. When comparing indications for antiretroviral TDM in 2013 (including the 2016 addendum) with the 2024 guidelines, for antiretrovirals and indication categories that were present in both guides, there was a total of 288 indication category–antiretroviral pairs. Overall, the quality of the evidence improved for 16.6% (n = 48) and decreased for 4.5% (n = 13) of the recommendations. For the integrase inhibitors, the strength of the recommendations increased in 5.5% (4/72) of cases and decreased in 19.4% (14/72) of cases. For the non-nucleoside reverse transcriptase inhibitors, these values were 14.6% (14/96) and 10.4% (10/96), and for the protease inhibitors 11.5% (11/96) and 12.5% (12/96). For integrase inhibitors, the majority (70.6%) of the cases where the strength of the recommendation dropped was associated with no longer recommending TDM; 50% of these changes were based on new studies with improved quality. Specifically for integrase inhibitors, the 2024 guidelines strongly or moderately recommend TDM for 11.2% and 20.6% of the indication category–antiretroviral pairs, respectively; most commonly for drug interactions, low-level viremia or virologic failure, people with significant viral resistance mutations, pregnancy, severe hepatic impairment, suspected malabsorption and paediatrics. For intramuscular cabotegravir/rilpivirine, we do not recommend routine TDM (D-III). We moderately recommend TDM for this regimen for obese persons who have at least one additional risk factor for virologic failure (B-II). Our target concentrations for virologic efficacy were changed for darunavir, etravirine, nevirapine and rilpivirine and for toxicity for atazanavir, lopinavir, nevirapine and dolutegravir.

Conclusions: Over the last 10 years, the quality of the evidence to support or not antiretroviral TDM has improved. For integrase inhibitors, the strength of the recommendations have decreased for about 20% of the recommendations. Antiretroviral TDM is still moderately to strongly recommended in some situations.