Adenine ; analogs & derivatives ; therapeutic use ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; Humans ; Lamivudine ; therapeutic use ; Nucleosides ; therapeutic use ; Organophosphonates ; therapeutic use

Adenine ; analogs & derivatives ; therapeutic use ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; Humans ; Lamivudine ; therapeutic use ; Nucleosides ; therapeutic use ; Organophosphonates ; therapeutic use

Besides 36 (28 single-tablets and 8 fixed-dose combinations) used antiretroviral drugs clinically, there are a number of investigational antiretroviral agents currently in phase 2-3 clinical trial. Tenofoviralafenamidefumarate (TAF) is a novel nucleoside analogue reverse transcriptase inhibitor that is potent and less toxicity than tenofovir (TDF). Doravirine is a non-nucleoside analogue reverse transcriptase inhibitor that demonstrates activity against NNRTI-resistant viral strains. GSK744 is an integrase inhibitor with a long acting preparation. In addition, several drugs with new mechanisms are also noted, for example, BMS-663 068 is a small molecule CD4 attachment inhibitors and cenicriviroc is a novel CCR5/CCR2 antagonist with antiretroviral activity and anti-inflammatory effects. Several drug classes that target known pathways in HIV latency have being developed, and leading the list are histone deacetylase inhibitors. Other agents include protein kinase C activators, positive transcription elongation factor activators, DNA methyl-transferase inhibitors and histone methyl-transferase inhibitors and so on. This review is focused on the above-mentioned drug candidates that may be used in clinical in next couple of years and those compounds that can reverse latent HIV infections.
Adenine ; analogs & derivatives ; therapeutic use ; Anti-HIV Agents ; therapeutic use ; HIV Infections ; drug therapy ; Humans ; Organophosphates ; therapeutic use ; Organophosphonates ; therapeutic use ; Piperazines ; therapeutic use ; Pyridones ; therapeutic use ; Reverse Transcriptase Inhibitors ; therapeutic use ; Tenofovir

Adenine ; analogs & derivatives ; pharmacokinetics ; therapeutic use ; toxicity ; Antiviral Agents ; therapeutic use ; Clinical Trials as Topic ; Hepatitis B ; drug therapy ; Humans ; Organophosphonates

During the past decade, major breakthroughs have been achieved in treatment of chronic hepatitis B. Currently, three therapeutic agents are approved for chronic hepatitis B: interferon-alpha, lamivudine and adefovir dipivoxil. In patients with HBeAgpositive chronic hepatitis B, all of these drugs achieve HBeAg loss (24-33%) and anti-HBe seroconversion (12-30%) rates that are superior to those observed in untreated controls. Interferon-alpha has several drawbacks, such as the parenteral administration and the development of frequent and potentially serious side effects. Lamivudine is a safe drug with rare and generally mild side effects. Lamivudine induces an initial virological remission in 70-90% of patients, but only 30-40% of patients remain in remission after the third year due to progressively increasing viral resistance. The main advantage of adefovir dipivoxil is the rare emergence of resistance, which has been identified in less than 2% of patients at 2 yr of treatment. Adefovir is also effective against lamivudine-resistant strains. This review will focus on the natural history and recently gained knowledge on the treatment of chronic hepatitis B.
Adenine/*analogs & derivatives/therapeutic use ; Antiviral Agents/*therapeutic use ; Hepatitis B/*drug therapy ; Humans ; Interferon-alpha/therapeutic use ; Lamivudine/therapeutic use ; Phosphonic Acids/therapeutic use ; Reverse Transcriptase Inhibitors/therapeutic use

Adenine/analogs & derivatives* ; Anti-HIV Agents/therapeutic use* ; Cobicistat/therapeutic use* ; Drug Combinations ; Emtricitabine/therapeutic use* ; HIV ; HIV Infections/drug therapy* ; Humans ; Postoperative Complications ; Quinolones ; Viral Load

Adenine/analogs & derivatives* ; Bridged Bicyclo Compounds, Heterocyclic ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Piperidines ; Pyrazoles/therapeutic use* ; Pyrimidines/therapeutic use* ; Rituximab/therapeutic use* ; Sulfonamides

OBJECTIVETo evaluate antiviral effects of Peg-IFNa-2a in patients with chronic hepatitis B.

METHODS92 chronic hepatitis B patients were enrolled to receive the treatment with Peg-IFNa-2a 180 μg subcutaneous injection once weekly. The patients who did not get early response were divided into 3 groups: group 1, extend the treatment to 72 weeks; group 2, combined with nucleus(s)ide analogue (entecavir or adefovir) treatment; group 3, continue the treatment until 48 weeks. HBV DNA and quantitative HBsAg were assessed at baseline, week 12, 24, 36 and after 24 weeks follow-up.

RESULTSPatients in group 1 had significantly higher SVR rate (78.3%) than patients in group 3 (38.1%, X2=7.33, P<0.05). The mean reduction of HBsAg in group 1 at 24 weeks of post-treatment follow up was higher than that in group 3 (t=2.11, P<0.05). In group 2 the mean reductions of HBV DNA at 24 weeks of post-treatment follow up were (3.9+/-1.1) log10 copy/ml and (3.7+/-1.3) log10 copy/ml respectively with combination of entecavir or adefovir, both of which were significantly higher than that in group 3(t=8.45 and 6.31, P<0.05); the SVR rates in the entecavir group and the adefovir group (83.3% and 85.7%, respectively) were significantly higher than that in group 3 (X2=8.20 and 7.78, P<0.05); the mean reductions of HBsAg in the entecavir group and the adefovir group [(0.8+/-0.5) log10 IU/ml and (0.9+/-0.3) log10 IU/ml, respectively ] were significantly greater than group 3[(0.4+/-0.3) log10 IU/ml, t=3.05 and 4.58, P<0.05]. The level of HBV DNA and C genotype were the main predictors of response.

CONCLUSIONIndividualizing therapy by prolonging the duration of Peg-IFNa-2a treatment to 72 weeks or adding nucleoside analogues such as entecavir and adefovir in patients without early response may substantially increase the SVR rate and lead to the decrease of HBsAg.

Adenine ; analogs & derivatives ; therapeutic use ; Adult ; Antiviral Agents ; therapeutic use ; Female ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Middle Aged ; Organophosphonates ; therapeutic use ; Treatment Outcome

Adenine ; analogs & derivatives ; therapeutic use ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Interferon-alpha ; therapeutic use ; Lamivudine ; therapeutic use ; Nucleosides ; therapeutic use ; Organophosphonates ; therapeutic use

Adenine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Animals ; Antiviral Agents ; therapeutic use ; Drug Therapy, Combination ; Genetic Therapy ; Hepatitis B, Chronic ; drug therapy ; virology ; Humans ; Interferon-alpha ; administration & dosage ; therapeutic use ; Lamivudine ; therapeutic use ; Organophosphonates ; administration & dosage ; therapeutic use ; Phytotherapy