Viread

The name of Antonín Holý has become synonymous for the era of acyclic nucleoside phosphonates (ANPs), which started with (S)-HPMPA as the prototype and (S)-HPMPC (cidofovir) as the first marketed compound. It has now evolved to a number of compounds clinically used in the treatment of HIV and hepatitis B virus infections, either as such [tenofovir disoproxil fumarate (TDF, Viread®)] or in combination [Truvada®, Atripla®, Complera®, Stribild®]. Truvada has also been approved for the prevention of HIV infections...

BACKGROUND AND OBJECTIVE: Tenofovir dipivoxil fumarate (9-[(R)-2-[[bis (pivaloyloxymethoxy) phosphinoyl] methoxy] propyl] adenine fumarate) is a novel ester prodrug of tenofovir. It has been developed as an anti-hepatitis B virus clinical candidate. The purpose of this study was to determine the pharmacokinetic parameters of tenofovir dipivoxil fumarate (test) and the commercially available tenofovir disoproxil fumarate (Viread®, reference). In addition, the bioavailability of tenofovir dipivoxil fumarate was evaluated in healthy male fasted subjects after a single comparatively equivalent dose...

The pre-exposure chemoprophylaxis (now commonly referred to as PrEP) of HIV infection has gained increased momentum, concomitantly with the successful use of combination drug regimens for the treatment of AIDS. A pivotal component in the current drug combination regimens for the treatment of AIDS as well as the ongoing PrEP trials is tenofovir disoproxil fumarate (TDF, Viread®) and its combination with emtricitabine (FTC). The combination of TDF with FTC has been marketed as Truvada®. TDF and TDF/FTC has proven effective, if orally administered daily or intermittently, in the prevention of rectal simian human immunodeficiency virus (SHIV) infection in macaques...

CMX157 is a lipid (1-0-hexadecyloxypropyl) conjugate of the acyclic nucleotide analog tenofovir (TFV) with activity against both wild-type and antiretroviral drug-resistant HIV strains, including multidrug nucleoside/nucleotide analog-resistant viruses. CMX157 was consistently >300-fold more active than tenofovir against multiple viruses in several different cell systems. CMX157 was active against all major subtypes of HIV-1 and HIV-2 in fresh human peripheral blood mononuclear cells (PBMCs) and against all HIV-1 strains evaluated in monocyte-derived macrophages, with 50% effective concentrations (EC(50)s) ranging between 0...

INTRODUCTION: Tenofovir disoproxil fumarate (Viread((R))) is the only nucleotide reverse transcriptase inhibitor currently approved for the treatment of HIV. It is frequently prescribed not only for its efficacy but also for its decreased side effect profile compared with other nucleotide analogs. In addition, it is now increasingly recognized as a cause of acquired Fanconi's syndrome in individuals with HIV. CASE PRESENTATION: We describe a 48-year-old woman infected with HIV, with chronic renal insufficiency, who developed Fanconi's syndrome after inclusion of tenofovir disoproxil fumarate in her antiretroviral therapy...

Many developing countries have enacted intellectual property laws allowing patents on pharmaceutical products. These countries now must figure out how to provide legitimate protection of innovative discoveries while avoiding drug patents that do not conform to their laws. Using case-study examples, including the antiretroviral tenofovir disoproxil fumarate (TDF, or Viread), we demonstrate the importance of having outside experts participate in the review of drug patents. Vibrant patent review systems require sharing information among developing countries and active consultation with local public health authorities...

OBJECTIVES: Zidovudine (ZDV) has been the cornerstone of antiretroviral (ARV) therapy for pregnant women infected with HIV-1 in the prevention of mother-to-child transmission (MTCT) and remains the only licensed ARV for use in pregnancy. We explored the current and future roles of tenofovir disoproxil fumarate (TDF) in the prevention of MTCT of HIV-1. METHODS: We reviewed the published literature by conducting database searches of in vitro, animal and clinical studies, reported in journals and at conferences, using the search terms Tenofovir/gs4331/viread, pregnant/pregnancy, lactate, lactation, natal, reproduce/reproduction, placenta/placental, malformation, and teratogenicity/teratogenic...

Recent literature is reviewed about treatment of chronic hepatitis B virus (CHB), focusing on tenofovir disoproxil fumarate (TDF; Viread((R))), among the nucleotide and nucleoside analogs. TDF pharmacokinetics and pharmacodynamics, activity in respect of hepatitis B virus (HBV) multi-drug-resistant mutations, efficacy in treatment-naïve and treatment-experienced patients, and side effects are described. The most predictive response factors to TDF therapy are discussed and all available combination therapies to optimize clinical outcome in the various patient profiles are analyzed, such as compensated and/or decompensated cirrhotic patients...

Standard antiretroviral therapy (ART) consists of a combination of three active drugs. The selection of these drugs varies considerably according to the clinical scenario. The "gold standard" in patients initiating ART is tenofovir (TDF)/emtricitabine (FTC)/efavirenz. TDF/FTC is also considered a combination of choice when, for various reasons, ART is initiated with a boosted protease inhibitor. Abacavir and lamivudine (ABC/3TC) is also considered a combination of choice in most clinical practice guidelines...

The ten stories told here deal with (i) ribavirin as an inhibitor of IMP dehydrogenase and (ii) ribavirin, in combination with pegylated interferon, as the present "standard of care" for hepatitis C; (iii) S-adenosylhomocysteine hydrolase inhibitors as antiviral agents; (iv) new adamantadine derivatives for the treatment of influenza A virus infections; (v) 5-substituted 2'-deoxyuridines (i.e. IDU, TFT) for the treatment of herpes simplex virus (HSV) infections; (vi) acyclic guanosine analogues (e...

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9-R-[2-(Phosphonomethoxy)propyl]-adenine (tenofovir) is an acyclic nucleoside phosphonate with antiviral activity against human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV). Tenofovir is not orally bioavailable but becomes orally active against HIV-1 infection as the disoproxil ester (tenofovir disoproxil fumarate [Viread]). We have developed an alternative strategy for promoting the oral availability of nucleoside phosphonate analogs which involves esterification with a lipid to form a lysolecithin mimic...

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Three acyclic nucleoside phosphonates are currently approved for clinical use against infections caused by cytomegalovirus (Vistide), hepatitis B virus (Hepsera), and human immunodeficiency virus type 1 (Viread). This important antiviral class inhibits viral polymerases after cellular uptake and conversion to their diphosphates, bypassing the first phosphorylation, which is required for conventional nucleoside antivirals. Small chemical alterations in the acyclic side chain lead to marked differences in antiviral activity and the spectrum of activity of acyclic nucleoside phosphonates against various classes of viral agents...

The collaboration between Antonín Holý [Institute of Organic Chemistry and Biochemistry (IOCB, Prague, Czech Republic)] and Erik De Clercq (Rega Institute for Medical Research, K.U. Leuven, Belgium) started exactly 30 years ago. It led to the discovery of a (rather small) series of acyclic nucleoside analogues (prototype: DHPA), followed by the discovery of a large number of nucleotide analogues [acyclic nucleoside phosphonates (ANPs)] (prototype: HPMPA). From HPMPA originated three compounds, which have been approved by regulatory agencies worldwide for clinical use: (i) HPMPC [cidofovir (Vistide)] for the treatment of cytomegalovirus (CMV) retinitis in AIDS patients, and "off label" for the treatment of polyoma-, papilloma-, adeno-, herpes- and poxvirus infections; (ii) PMEA [adefovir (in its oral prodrug form, adefovir dipivoxil (Hepsera)] for the treatment of chronic HBV (hepatitis B virus) infections, and (iii) PMPA [tenofovir (in its oral prodrug form, tenofovir disoproxil fumarate (Viread)] for the treatment of HIV infections (AIDS)...

Acyclic nucleoside analogues bearing phosphonomethoxy residues in the side chain (ANP) attract much attention due to a very beneficial combination of biological properties. Intensive work of organic chemists during the last two decades resulted in a large panel of new compounds that were evaluated as potential antiviral drugs. Herein, we present an overview of major chemical structures within the group of acyclic nucleoside analogues containing phosphonomethoxy side fragments and describe main aspects of their synthesis and antiviral potential...

BACKGROUND: Long-term antiretroviral therapy, while dramatically reducing HIV-related morbidity and mortality, is associated with metabolic and morphological changes. Peripheral fat loss, lipoatrophy, appears most associated with prolonged therapy with thymidine nucleoside analogues. METHODS: A randomized, open-label, comparative study of switching from a thymidine nucleoside analogue to either tenofovir disoproxil fumarate (DF) or abacavir in 105 individuals on successful antiretroviral therapy with clinically evident moderate to severe lipoatrophy...