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

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

Nucleoside reverse transcriptase inhibitors which act as a major component of highly active antiretroviral therapy regimens are widely used in treatment of Acquired Immune Deficiency Syndrome. However, the emergence of drug-resistant variants of HIV-1 severely limits the effectiveness of these drugs. Many drug resistance mutations confer a fitness cost, which can be partially overcome by compensatory mutations or other molecular mechanisms. This review focuses on the impacts of resistance mutations emerging during treatment with nucleoside reverse transcriptase inhibitors on viral fitness, and inter actions between these mutations.
Animals ; Drug Resistance, Viral ; HIV Infections ; drug therapy ; virology ; HIV Reverse Transcriptase ; antagonists & inhibitors ; genetics ; metabolism ; HIV-1 ; drug effects ; enzymology ; genetics ; physiology ; Humans ; Mutation ; Nucleosides ; therapeutic use ; Reverse Transcriptase Inhibitors ; therapeutic use

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

OBJECTIVESTo study the effect of using lamivudine to prevent fulminant hepatic failure (FHF) in patients with chronic hepatitis B.

METHODS164 patients were randomly put into a conventional supporting treatment control group and a lamivudine treatment group. In the latter, 82 patients were given lamivudine orally at a dose of 100 mg every day besides the support care which was also given to the control group.

RESULTSThe rate of deterioration to chronic severe hepatitis in the lamivudine treatment group was significantly lower than that of the control group (23.2% vs. 46.3%, P < 0.01). 52.6% (20/38) with chronic severe hepatitis in the control group died. Only 26.3% (5/19) in the lamivudine treatment group succumbed to terminal liver disease (P < 0.01). There was a significant difference between the two groups in regards to the complication incidence of gastrointestinal bleeding, infections, hepatic coma, and kidney failure (P < 0.05). In addition, the recovery of liver function and liver fibrosis, and the rates of HBeAg loss and seroconversion in the lamivudine treatment group were better than those in the control group. Furthermore, the serum HBV DNA levels decreased more rapidly and continued to be substantially suppressed in the lamivudine treatment group.

CONCLUSIONSOur results suggest that lamivudine administration with improved support care not only is likely to prevent chronic severe hepatitis occurrence in patients with chronic viral hepatitis B of a severe degree, but also shows some efficacy in preventing FHF.

Adult ; Female ; Hepatitis B, Chronic ; drug therapy ; Humans ; Lamivudine ; therapeutic use ; Liver Failure, Acute ; prevention & control ; Male ; Middle Aged ; Reverse Transcriptase Inhibitors ; therapeutic use

Adult ; Female ; Hepatitis B ; drug therapy ; Humans ; Lamivudine ; adverse effects ; therapeutic use ; Pregnancy ; Pregnancy Complications, Infectious ; drug therapy ; Reverse Transcriptase Inhibitors ; adverse effects ; therapeutic use

OBJECTIVE: To assess the quality of life of 3 types of chronic hepatitis B before and after the treatment of lamivudine, and to find an ideal way of medical treatment for chronic hepatitis B. METHODS: One hundred and fifty patients with chronic hepatitis B were investigated in this study, among whom 5 1 were in mild state illness, 53 were middle-range and the other 46 were severe. The quality of life of the patients was assessed by the quality of life questionnaire (SF-36). The marks of questionnaire were compared before and after the use of lamivudine to assess its comprehensive curative effect on chronic hepatitis B. RESULTS: The total score of SF-36, score of physical function, role-physical, mental health, social function, bodily pain and vitality were significant different before and after the treatment. Statistically significant differences were found among the 3 types of chronic hepatitis B before and after the treatment. CONCLUSION The quality of life of patients with chronic hepatitis B can be improved by using lamivudine. Assessment of quality of life may be taken as an important index in treating chronic hepatitis B.
Female ; Hepatitis B, Chronic ; drug therapy ; psychology ; Humans ; Lamivudine ; therapeutic use ; Male ; Quality of Life ; Reverse Transcriptase Inhibitors ; therapeutic use ; Surveys and Questionnaires

HIV and AIDS remain as the crucial global health concern, therefore, research and development of novel anti-HIV-1 chemical therapeutics is still of paramount significance, which may be illuminated by cases of successful marketed drugs. Herein, we document the discovery and biological profile of new anti-HIV-1 drugs approved by FDA between 2005 and 2008 and some drug candidates are also discussed.
Acquired Immunodeficiency Syndrome ; drug therapy ; Anti-HIV Agents ; chemistry ; pharmacology ; therapeutic use ; HIV Fusion Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV Infections ; drug therapy ; HIV Integrase Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV Protease Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV-1 ; drug effects ; Humans ; Molecular Structure ; Reverse Transcriptase Inhibitors ; chemistry ; pharmacology ; therapeutic use

Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immunodeficiency disease syndrome (AIDS). After over 26 years of efforts, there is still not a therapeutic cure or an effective vaccine against HIV/AIDS. The clinical management of HIV-1 infected people largely relies on antiretroviral therapy (ART). Although highly active antiretroviral therapy (HAART) has provided an effective way to treat AIDS patients, the huge burden of ART in developing countries, together with the increasing incidence of drug resistant viruses among treated people, calls for continuous efforts for the development of anti-HIV-1 drugs. Currently, four classes of over 30 licensed antiretrovirals (ARVs) and combination regimens of these ARVs are in use clinically including: reverse transcriptase inhibitors (RTIs) (e.g. nucleoside reverse transcriptase inhibitors, NRTIs; and non-nucleoside reverse transcriptase inhibitors, NNRTIs), protease inhibitors (PIs), integrase inhibitors and entry inhibitors (e.g. fusion inhibitors and CCR5 antagonists). Here, we intend to provide updated information of currently available antiretroviral drugs for ART to promote the development of novel anti-HIV-1 drugs.
Acquired Immunodeficiency Syndrome ; drug therapy ; Anti-HIV Agents ; chemistry ; pharmacology ; therapeutic use ; HIV Fusion Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV Infections ; drug therapy ; HIV Integrase Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV Protease Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV-1 ; drug effects ; Humans ; Molecular Structure ; Reverse Transcriptase Inhibitors ; chemistry ; pharmacology ; therapeutic use

OBJECTIVETo collect background information on drug-resistant HIV-1 strains in various regions before the start of nation-wide antiretroviral therapy in China.

METHODSTwenty percent of the 2,000 blood samples from antiretroviral therapy naive patients collected for the 2nd national HIV molecular epidemiology survey (NHMES) in 2002 were randomly sampled for this study. The entire protease gene and 20-230 amino acids of the reverse transcriptase gene were amplified by PCR from provirus DNA and sequenced. The results were analyzed with HIV db-Drug Resistance Algorithm and genotypic resistance mutations were determined to particular anti-HIV drugs.

RESULTSTotally 164 protease gene sequences and 138 reverse transcriptase gene sequences were obtained from patients; 0.61% of 164 sequences displayed primary resistance mutations in the protease gene, whereas 99.39% carried 1 or more secondary mutations. Genotypic resistance to at least one nucleoside reverse transcriptase inhibitors (NRTI) was present in 5.80%,and resistance to at least one non-nucleo side reverse transcriptase inhibitors (NNRTI) was present in 1.45% of samples.

CONCLUSIONThe prevalence of genotypic drug resistance is very low in drug-naive HIV infected patients from 21 provinces of China tested in this study. Laboratories participated in the NHMES have organized a network to provide drug resistance monitoring service in the current nation-wide antiviral treatment program in China.

Anti-HIV Agents ; therapeutic use ; China ; epidemiology ; Drug Resistance, Viral ; Genotype ; HIV Infections ; drug therapy ; epidemiology ; virology ; HIV Protease ; genetics ; HIV Protease Inhibitors ; therapeutic use ; HIV Reverse Transcriptase ; genetics ; HIV-1 ; genetics ; Humans ; Mutation ; Reverse Transcriptase Inhibitors ; therapeutic use ; Sentinel Surveillance