The Pharmacology of Antiretroviral Nucleoside and Nucleotide Reverse Transcriptase Inhibitors: Implications for Once-Daily Dosing

• Published in: Journal of acquired immune deficiency syndromes (1999) Vol. 39 Suppl 1; no. Supplement 1; pp. S1 - S23
• Main Authors: Back, David J, Burger, David M, Flexner, Charles W, Gerber, John G
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins, Inc 01-08-2005; Lippincott Williams & Wilkins; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Antiretroviral drugs; Attitudes; Biological and medical sciences; Drug Administration Schedule; Drug dosages; Drug Resistance, Multiple, Viral; Drug therapy; Drug Therapy, Combination; Fundamental and applied biological sciences. Psychology; HIV; HIV Infections - drug therapy; HIV-1 - drug effects; HIV-1 - genetics; Human immunodeficiency virus; Human viral diseases; Humans; Infectious diseases; Inhibitor drugs; Medical sciences; Microbiology; Miscellaneous; Mutation; Patient Compliance; Patients; Pharmacology; Reverse Transcriptase Inhibitors - administration & dosage; Reverse Transcriptase Inhibitors - chemistry; Reverse Transcriptase Inhibitors - pharmacokinetics; Viral diseases; Virology; Antiretroviral agent; drug interactions; once-daily dosing; plasma half-life; Microbiology; intracellular half-life; nucleoside reverse transcriptase inhibitor; Virology; Reverse transcriptase inhibitor; pharmacokinetics; Antiviral; Nucleoside; Intracellular
• ISSN: 1525-4135; 1944-7884
• DOI: 10.1097/01.qai.0000168882.67942.3f

The trend toward once-daily dosing in HIV antiretroviral therapy is based on the association between adherence, treatment outcome, and patient preferences. Patients prefer simpler treatments, fewer pills, less frequent dosing, and no food restrictions. When a regimen meets a patientʼs preferences, the patient is more likely to be adherent, and with good adherence, the regimen is more likely to be effective. Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) have been a prime focus for developing once-daily therapies primarily because they form the backbone of most current regimens. Within the NRTI class, however, drugs differ in their pharmacokinetic properties, such as plasma and intracellular half-lives, and thus in their suitability for once-daily dosing. For example, newer NRTIs, such as tenofovir and emtricitabine, combine longer plasma half-lives with longer intracellular half-lives, prolonging exposure and the period of pharmacologic activity. Of equal importance, the clinical impact of systemic and intracellular interactions between concomitant drugs defines which once-daily drugs may be combined in once-daily regimens. To construct simplified and effective therapies for individual patients, clinicians require an understanding of the plasma and intracellular pharmacokinetic properties of NRTIs and how these properties determine a drugʼs appropriateness for once-daily dosing and placement within a once-daily regimen.