Abstract
A major challenge in the management of antiretroviral therapy (ART) is to improve the patient’s adherence, reducing the burden caused by the high number of drugs that compose the treatment regimens for human immunodeficiency virus positive (HIV+) patients. Selection of the most appropriate treatment regimen is responsible for therapeutic success and aims to reduce viremia, increase the immune system response capacity, and reduce the incidence rate and intensity of adverse reactions. In general, protease inhibitor (PI) is one of the pillars of regimens, and darunavir (DRV), in particular, is frequently recommended, along with low doses of enzyme inhibitors as cobicistat (COBI) or ritonavir (RTV), by the international guidelines. The potential of clinically significant drug interactions in patients taking COBI or RTV is high due to the potent inhibitory effect on cytochrome CYP 450, which attracts significant changes in the pharmacokinetics of PIs. Regardless of the patient or type of virus, the combined regimens of DRV/COBI or DRV/RTV are available to clinicians, proving their effectiveness, with a major impact on HIV mortality/morbidity. This study presents current information on the pharmacokinetics, pharmacology, drug interactions, and adverse reactions of DRV; it not only compares the bioavailability, pharmacokinetic parameters, immunological and virological responses, but also the efficacy, advantages, and therapeutic disadvantages of DRV/COBI or DRV/RTV combinations.
Highlights
The human immunodeficiency virus (HIV), responsible for the development of acquired human immunodeficiency syndrome (AIDS), is today one of the most serious public health challenges that humanity has to deal with [1]
This study aims to provide the main information on the topic related to antiretroviral treatment/therapy (ART) usage in HIV-infected patients, especially regarding those in whose regimen a protease inhibitor (PI)—namely darunavir (DRV)—is introduced in combination with an enzyme inhibitor, which increases the ARV effect of PI
To minimize the metabolism of these enzymes, pharmacokinetic enhancers (PK enhancers) like RTV and COBI are used as ART due to their ability to inhibit CYP3A4, CYP3A5, and CYP2C9; this reduces the dose and frequency of PI administration [71,72]
Summary
The human immunodeficiency virus (HIV), responsible for the development of acquired human immunodeficiency syndrome (AIDS), is today one of the most serious public health challenges that humanity has to deal with [1]. This study aims to provide the main information on the topic related to ART usage in HIV-infected patients, especially regarding those in whose regimen a protease inhibitor (PI)—namely darunavir (DRV)—is introduced in combination with an enzyme inhibitor (a booster), which increases the ARV effect of PI. COBI is a newly introduced pharmacological enhancer that has inhibitory activity against several drug metabolizing enzymes in addition to CYP 3A4 including CYP 2D6 and the P-glycoprotein (P-gp) transporter, making it an important agent It is used in therapy when the increase in active substance levels of agents metabolized by the cytochrome P450 system is desired, being available as 150 mg tablets [14]. PIs represent the largest class of drugs used in the fight against HIV These substances block the activity of HIV protease, an enzyme that the virus uses to break down high-mass polyproteins into smaller units needed to assemble new viral particles [15]. HIV PIs approved by the Food and Drug Administration (FDA) have some structural similarities and a similar binding pattern, which may be responsible for some of the common side effects of the regimens containing them
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