1. LC Assay for a HIV Tablet Containing Emtricitabine, Tenofovir Disoproxil Fumarate and Rilpivirine
Murali Pendela • Getu Weldu Kahsay • Guy Van den Mooter • Lieven Baert. Chromatographia (2011) 73:439–445
It is common practice in HIV treatment to give different drugs to the patient. In order to improve the comfort of the daily intake, manufacturers try to combine several active compounds in one dosage form. In this study, an LC assay method was developed for tablets containing emtricitabine, tenofovir disoproxil fumarate and rilpivirine. Emtricitabine is 5-ﬂuoro-1-(2R,5S)-[(2-hydroxy-methyl)-1,3-oxathiolan-5-yl] cytosine (see Fig. 1a). In the body, emtricitabine is phosphorylated by cellular enzymes to form emtricitabine 5’-triphosphate. It inhibits the activity of the HIV-1 reverse transcriptase. Due to lack of a 3-hydroxyl group, it does not support continued synthesis of the newly made DNA strand and thus terminates or aborts the polymerization process catalyzed by the HIV reverse transcriptase. Emtricitabine is already used in combination with tenofovir disoproxil fumarate in a single tablet to be administered orally once a day. Tenofovir disoproxil fumarate is 9-[(R)-2-[[bis[[(isopropoxycarbonyl)oxy]methoxy]phosphinyl] methoxy]propyl]adenine fumarate (1:1) (see Fig. 1b). It is an acyclic nucleoside phosphonate diester analog of adenosine monophosphate. It requires two phosphorylation steps by cellular kinase to become the active metabolite tenofovir diphosphate.
2. Tenofovir Disoproxil Fumarate for Prevention of Vertical Transmission of Hepatitis B Virus Infection by Highly ViremicPregnant Women: A Case Series
Calvin Q. Pan • Li-Jun Mi • Chalermrat Bunchorntavakul • Jeffrey Karsdon • William M. Huang. Dig Dis Sci (2012) 57:2423–2429
Among the ﬁve United States Food and Drug Administration (FDA) approved oral anti-HBV agents, tenofovir disoproxil fumarate (TDF) and entecavir are the most effective agents in terms of potency and resistance proﬁle, and as such are regarded as ﬁrst-line therapy for HBV. According to the FDA drug category for pregnancy, TDF and telbivudine are classiﬁed as category B (no evidence of risk to humans: either animal ﬁndings indicate risk, but human ﬁndings do not; or, if no adequate human studies have been conducted, animal ﬁndings are negative) for use in pregnancy, whereas lamivudine, entecavir, and adefovir are category C (risk cannot be ruled out: human studies are lacking, and animal studies are either positive for fetal risk, or lacking also. However, potential beneﬁts may justify the potential risk). In addition, TDF has been used in over 600 HIV mono-infected and HIV/HBV co-infected mothers and favorable efﬁcacy and safety proﬁle have been demonstrated. Despite several theoretical advantages of using TDF to prevent VT, to date there have been no studies of the use of TDF in this setting. Therefore, the purpose of this retrospective analysis was to evaluate the efﬁcacy, tolerability, and safety of TDF in preventing VT in highly viremic HBV-infected mothers.
3. Effectiveness and Safety of Tenofovir Disoproxil Fumarate in Chronic Hepatitis B: A 3-Year Prospective Field Practice Study in Germany
Jorg Petersen • Renate Heyne • Stefan Mauss • Jorg Schlaak. Dig Dis Sci
The principal treatment goal in patients with chronic hepatitis B infection (CHB) is to prevent disease progression and therefore disease-related death. The nucleotide analog tenofovir disoproxil fumarate (TDF), a potent inhibitor of HBV polymerase shown to suppress HBV DNA levels effectively, is a ﬁrst-line option for the treatment of CHB in adult and adolescent patients. In Phase 3 clinical trials, TDF had superior antiviral efﬁcacy to adefovir (ADV) in both hepatitis B “e” antigen positive (HBeAg+) and negative (HBeAg-) patients. In these patients, long-term TDF therapy continued to suppress HBV, leading to regression of ﬁbrosis and cirrhosis, without viral resistance being detected. TDF has also been shown to be efﬁcacious with a positive risk/beneﬁt proﬁle in patients with compensated liver disease and prior treatment failure to lamivudine (LAM), ADV, ADV+ LAM, and entecavir (ETV). TDF has also been shown to be effective in the treatment of patients with decompensated liver disease.
4. Circulating Tregs Correlate with Viral Load Reduction in Chronic HBV-Treated Patients with Tenofovir Disoproxil Fumarate
Nirupma TrehanPati & Shyam Kotillil & Syed S. Hissar. J Clin Immunol (2011) 31:509–520
Tenofovir (tenofovir disoproxil fumarate) is a very potent and effective nucleotide analog against HBV. Immunologic mechanisms involved in the control of HBV replication in vivo are not yet completely understood. CD8+ T cells help in the control of HBV replication in vivo and recovery from acute hepatitis B. Recent studies have characterized the Tregs like naturally occurring CD4+ CD25+ Tregs, induced Tregs (IL-10 producing CD4+ type I Tregs (Tr1) and T helper type 3 (Th3) cells) and activated CD4/CD8+ FOXP3 expressing T cells. All these different T cell populations with regulatory function coexist and contribute to immune suppression. T regulatory cell responses may be either beneficial or detrimental in HBV and hepatitis C virus (HCV) patients, by either limiting liver immunopathology or suppressing protective T cell responses. Treg cell subsets in the HBV studies were generally less characterized than in the HCV studies.