A clinical review of HIV integrase strand transfer inhibitors (INSTIs) for the prevention and treatment of HIV-1 infection.

Autor: Zhao AV; Department of Pharmacy Practice and Translational Research, University of Houston, 4849 Calhoun Road Rm 3044, Houston, TX, 77204-5039, USA. avyain@central.uh.edu., Crutchley RD; Department of Pharmacotherapy, Washington State University College of Pharmacy and Pharmaceutical Sciences, 3110 Inspiration Dr, Yakima, WA, 98901, USA., Guduru RC; GSK Medical Information Center of Excellence, 410 Blackwell Street, Durham, NC, 27701, USA., Ton K; Department of Pharmacy Services, UC Davis Health, 2315 Stockton Blvd, Sacramento, CA, 95817, USA., Lam T; PharmD Candidate, University of Houston College of Pharmacy, 4849 Calhoun Rd Rm 3044, Houston, TX, 77204-5039, USA., Min AC; Department of Pharmacy Practice, Temple University School of Pharmacy, 3401 N. Broad St, Philadelphia, PA, 19140, USA.
Jazyk: angličtina
Zdroj: Retrovirology [Retrovirology] 2022 Oct 22; Vol. 19 (1), pp. 22. Date of Electronic Publication: 2022 Oct 22.
DOI: 10.1186/s12977-022-00608-1
Abstrakt: Integrase strand transfer inhibitors (INSTIs) have improved the treatment of human immunodeficiency virus (HIV). There are currently four approved for use in treatment-naïve individuals living with HIV; these include first generation raltegravir, elvitegravir, and second generation dolutegravir and bictegravir. The most recent INSTI, cabotegravir, is approved for (1) treatment of HIV infection in adults to replace current antiretroviral therapy in individuals who maintain virologic suppression on a stable antiretroviral regimen without history of treatment failure and no known resistance to its components and (2) pre-exposure prophylaxis in individuals at risk of acquiring HIV-1 infection. Cabotegravir can be administered intramuscularly as a monthly or bi-monthly injection depending on the indication. This long-acting combination has been associated with treatment satisfaction in clinical studies and may be helpful for individuals who have difficulty taking daily oral medications. Worldwide, second generation INSTIs are preferred for treatment-naïve individuals. Advantages of these INSTIs include their high genetic barrier to resistance, limited drug-drug interactions, excellent rates of virologic suppression, and favorable tolerability. Few INSTI resistance-associated mutations have been reported in clinical trials involving dolutegravir, bictegravir and cabotegravir. Other advantages of specific INSTIs include their use in various populations such as infants and children, acute HIV infection, and individuals of childbearing potential. The most common adverse events observed in clinical studies involving INSTIs included diarrhea, nausea, insomnia, fatigue, and headache, with very low rates of treatment discontinuation versus comparator groups. The long-term clinical implications of weight gain associated with second generation INSTIs dolutegravir and bictegravir warrants further study. This review summarizes key clinical considerations of INSTIs in terms of clinical pharmacology, drug-drug interactions, resistance, and provides perspective on clinical decision-making. Additionally, we summarize major clinical trials evaluating the efficacy and safety of INSTIs in treatment-naïve patients living with HIV as well as individuals at risk of acquiring HIV infection.
(© 2022. The Author(s).)
Databáze: MEDLINE
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