tenofovir

tenofovir
Drug name	Tenofovir
Routes of administration	Oral, Intravenous, Topical
Legal status	Rx-only

tenofovir Tenofovir is an antiviral nucleotide analogue used in the treatment and prevention of chronic viral infections. It is prescribed as part of antiretroviral therapy and as pre-exposure prophylaxis, and appears in treatment guidelines from major organizations. Clinical use and research involve collaboration among institutions and investigators worldwide.

Medical uses

Tenofovir is indicated for the treatment of human immunodeficiency virus infections in combination with other antiretrovirals endorsed by World Health Organization, Centers for Disease Control and Prevention, European AIDS Clinical Society, United States Department of Health and Human Services, British HIV Association. It is also used for chronic hepatitis B virus infection following recommendations from American Association for the Study of Liver Diseases, European Association for the Study of the Liver, Asian Pacific Association for the Study of the Liver, Infectious Diseases Society of America, World Hepatitis Alliance. As pre-exposure prophylaxis, tenofovir-containing regimens are recommended by Joint United Nations Programme on HIV/AIDS, Public Health England, Australia Department of Health, New York State Department of Health. Clinical trials and cohort studies have been conducted at centers such as National Institutes of Health, University College London, Imperial College London, Johns Hopkins University, University of California, San Francisco.

Mechanism of action

Tenofovir acts as a nucleotide reverse transcriptase inhibitor, blocking the activity of reverse transcriptase enzymes characterized in studies at Cold Spring Harbor Laboratory, Max Planck Institute for Infection Biology, Pasteur Institute, National Institute for Communicable Diseases. It is incorporated into viral DNA and causes chain termination, a mechanism elucidated in structural studies at Scripps Research, Stanford University School of Medicine, Harvard Medical School, Massachusetts Institute of Technology. Resistance mutations mapped in surveillance programs run by European Centre for Disease Prevention and Control, WHO Global Influenza Programme, US Food and Drug Administration involve reverse transcriptase loci identified by researchers at Fred Hutchinson Cancer Research Center and Dana-Farber Cancer Institute.

Pharmacology

Pharmacokinetic and pharmacodynamic profiling has been performed by researchers at University of Liverpool, Karolinska Institutet, University of Copenhagen, University of Toronto, McGill University. Absorption, distribution, metabolism, and excretion data are cited in monographs by British Pharmacopoeia Committee and regulatory summaries from European Medicines Agency and Food and Drug Administration. Drug–drug interaction studies have been conducted with agents produced by Gilead Sciences, GlaxoSmithKline, Roche, Merck & Co., Bristol-Myers Squibb and monitored by pharmacovigilance networks such as World Health Organization Global Individual Case Safety Reports (VigiBase). Therapeutic drug monitoring protocols referenced by International Society of Pharmacovigilance and clinical guidance from American Society of Clinical Oncology inform dosing adjustments in populations treated at Mayo Clinic, Cleveland Clinic, Mount Sinai Hospital.

Adverse effects

Adverse effect profiles, including renal toxicity and bone mineral density changes, have been reported in multicenter trials coordinated by National Institute of Allergy and Infectious Diseases, European AIDS Treatment Group, International AIDS Society, Bill & Melinda Gates Foundation-funded studies. Case series and Pharmacovigilance reports have appeared in journals affiliated with American Medical Association, New England Journal of Medicine, The Lancet, The BMJ, often involving clinical sites such as Royal Free Hospital, St Thomas' Hospital, Bellevue Hospital, Toronto General Hospital. Management guidelines have been issued by Kidney Disease: Improving Global Outcomes, Endocrine Society, International Osteoporosis Foundation for monitoring kidney function and bone health during therapy.

Formulations and dosing

Formulations include prodrugs and fixed-dose combinations developed and marketed by pharmaceutical companies including Gilead Sciences, ViiV Healthcare, Merck & Co., and generic manufacturers following approvals from European Medicines Agency and United States Food and Drug Administration. Dosing regimens and pediatric formulations have been evaluated in trials run by Pediatrics Research in Office Settings Network, International Maternal Pediatric Adolescent AIDS Clinical Trials Network and implemented in clinics like Boston Children's Hospital, Great Ormond Street Hospital, Red Cross War Memorial Children's Hospital. Implementation programs in public health systems in South Africa, Brazil, India, Thailand, Kenya have used tenofovir-containing products in national formularies.

History and development

The compound was discovered and developed through research collaborations involving academic laboratories and biotechnology firms, with clinical development sponsored by companies such as Gilead Sciences and studied in trials coordinated by National Institutes of Health and networks like Cooperative Clinical Trials Group. Regulatory submissions referenced data from Phase I–III trials conducted at institutions including Mayo Clinic, University of California, San Diego, Vanderbilt University Medical Center, University of Washington. Historical overviews and reviews have been published by authors associated with Johns Hopkins Bloomberg School of Public Health, London School of Hygiene & Tropical Medicine, Columbia University Mailman School of Public Health.

Regulatory status and availability

Approvals and labeling decisions have been issued by Food and Drug Administration, European Medicines Agency, Health Canada, Therapeutic Goods Administration (Australia), Japan Pharmaceuticals and Medical Devices Agency, with procurement through Global Fund to Fight AIDS, Tuberculosis and Malaria, United States President's Emergency Plan for AIDS Relief, UNICEF. Availability in national health systems has been reported in policy documents from Ministry of Health (South Africa), National Health Service (England), Brazilian Ministry of Health, Indian Council of Medical Research and distribution efforts coordinated with NGOs such as Médecins Sans Frontières, Clinton Health Access Initiative, Results UK.

Category:Antiviral drugs