HIV-1 Integrase Inhibitors: A Comparative Review of Efficacy and Safety
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REVIEW ARTICLE
HIV‑1 Integrase Inhibitors: A Comparative Review of Efficacy and Safety Kimberly K. Scarsi1,2 · Joshua P. Havens1,2 · Anthony T. Podany1 · Sean N. Avedissian1 · Courtney V. Fletcher1,2
© Springer Nature Switzerland AG 2020
Abstract The newest class of antiretrovirals for all persons living with HIV are the integrase strand transfer inhibitors (INSTIs). Since 2007, five INSTIs have been introduced: raltegravir, elvitegravir, dolutegravir, bictegravir, and cabotegravir. The INSTIs have favorable pharmacokinetic and pharmacodynamic properties, which contribute to both their effectiveness and their ease of use. With the exception of cabotegravir, each INSTI is US Food and Drug Administration approved for treatment-naïve individuals initiating antiretroviral therapy. All of the INSTIs, except raltegravir, are approved for antiretroviral treatment simplification for virologically suppressed patients without INSTI resistance. Data also support the use of dolutegravir and raltegravir in individuals with antiretroviral resistance as part of an optimized antiretroviral regimen. INSTIs are generally well tolerated by people living with HIV compared with older classes of antiretrovirals, but emerging data suggest that some INSTIs contribute to weight gain. Due to their efficacy, safety, and ease of use, HIV treatment guidelines recommend oral INSTIs as preferred components of antiretroviral therapy for individuals initiating therapy. The newest INSTI, cabotegravir, represents an alternative to oral administration of life-long antiretroviral therapy with the availability of a long-acting injectable formulation. This review summarizes the current use of INSTIs in adults living with HIV, highlighting the similarities and differences within the class related to pharmacodynamics, pharmacokinetics, safety, dosing, and administration that contribute to their role in modern antiretroviral therapy.
1 Introduction For the nearly 40 million persons living with HIV (PLWH), effective antiretroviral therapy (ART) reduces morbidity and mortality, leading to a life expectancy expected to be similar to age-matched peers [1, 2]. Randomized, clinical trials have demonstrated health benefits associated with early initiation of ART beyond the reduction in HIV-associated morbidity and mortality [3, 4]. Furthermore, effective ART offers a significant public health benefit by preventing transmission of HIV [5–7]. Based on these combined benefits, together with improvements in available antiretroviral options, ART is now recommended for all PLWH [8–10]. * Kimberly K. Scarsi [email protected] 1
Antiviral Pharmacology Laboratory, College of Pharmacy, University of Nebraska Medical Center, 986145 Nebraska Medical Center, Omaha, NE 68198‑6145, USA
Division of Infectious Diseases, Department of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
2
Key Points Bictegravir and dolutegravir are both co-formulated as a single-tablet regimen, and the choice of agent may be driven based on the preferred nucleosid
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