Adult ; Base Sequence ; Drug Resistance, Multiple, Viral ; Genome, Viral ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; drug therapy ; virology ; Humans ; Male ; Mutation ; Phylogeny

OBJECTIVETo investigate the HIV-1 drug resistance associated mutations and examine the susceptibility of HIV-1 with these mutations to antiretroviral in treatment-naive individuals in Liaoning province from 2004 to 2008.

METHODSRNA was extracted from 20 plasma samples of diagnosed untreated HIV-1-infected treatment-naive patients by drawing method. After the viral loading (VL) test, the protease and nucleoside reverse transcriptase coding regions were amplified by RT-PCR, nested PCR and sequence analysis directly. Levels of resistance and prevalence were evaluated according to the Stanford University HIV Drug Resistance Database's algorithm (http://hivdb.stanford.edu).

RESULTSAmong the 20 plasma samples, 13 got PCR products because of their VL values higher than 1000 copies/ml.Meanwhile, the 13 samples got 65 sequences by using 5 primers each. Polymorphisms in subtype H and circulating recombinant forms (CRFs) CRF10_CD sequences were identified. An overall prevalence of 30.8% (4/13) resistance to NNRTIs, 7.7% (1/13) to PI and no NRTIs mutations were found. The most frequent substitutions (4/13) in the RT region at positions P225H, K238S, V179D, K238T and a major position I54S in PR implied to a multiple drug-resistance. A71V or L10V only, respectively, substitution in PR was found in 3 samples, but no any worse with drug sensitivity.

CONCLUSIONHIV-1 polymorphisms in subtype H and CRFs CRF10_CD sequences were identified circulating in Liaoning. A major mutation position I54S in PR implied that it would be the time to commence a higher level drug regimen.

Anti-HIV Agents ; pharmacology ; China ; Drug Resistance, Multiple ; genetics ; Drug Resistance, Viral ; drug effects ; genetics ; Genotype ; HIV Infections ; drug therapy ; virology ; HIV-1 ; genetics ; Humans ; Mutation ; RNA, Viral ; genetics

OBJECTIVETo investigate HBV mutations in reverse transcriptase (RT) gene and precore/basal core promoter (PC/BCP) regions in a chronic hepatitis B patient and to analyze the link between the mutations and drug resistance or HBeAg sero-conversion.

METHODSEighteen serum samples were collected from a chronic hepatitis B patient during his 14 hospitalizations from June 2002 to September 2007. HBV DNA was extracted and nested PCR was employed for amplification of target gene fragments. Direct sequencing of PCR products was performed followed by analysis with NTI software. The significance of the results was analyzed in combination with the clinical data of the patient.

RESULTSSeveral mutations were identified in succession, including LAM-resistant mutations M204I/V and L180M+M204V, ETV-resistant mutation S202G, and HBeAg nonsense mutation G1896A. The results were in accordance with the disease progression of the patient.

CONCLUSIONSequencing of HBV RT and PC/BCP regions is valuable for comprehensively checking the viral mutations and thus it is helpful in the surveillance of patients in clinics as a way for adopting reasonable antiviral therapy.

Adult ; Antiviral Agents ; pharmacology ; DNA, Viral ; genetics ; Drug Resistance, Multiple, Viral ; genetics ; Genotype ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; virology ; Humans ; Male ; Mutation

BACKGROUND: Most mutations in the reverse transcriptase (RT) gene of the hepatitis B virus (HBV) are related to resistance to antiviral agents. Cross-sectional studies on the mutations of this gene are rare. Thus, we analyzed the mutation patterns of RT genes and their biochemical parameters. METHODS: From 2009 to 2012, 301 blood specimens from patients with chronic hepatitis B at Daegu Catholic University Medical Center were retrospectively analyzed for the RT gene sequence of HBV, ALT, hepatitis B e antigen (HBeAg), and HBV DNA. The mutation patterns of the RT gene were compared with the biochemical parameters. RESULTS: Of the 301 patients, 100 (33.2%) had no RT gene mutations. The remaining showed the following mutation patterns: rtM204I/V (50.2%), rtL180M (39.2%), and rtA181T/V (19.6%). Combined mutations were found in 146 cases (48.5%). Of these, the combination of amino acid changes at rt180+rt204 (49.3%) was most frequently detected, followed by rt181+rt236 (11.0%) and rt173+rt180+rt204 (9.6%). In the mutated group, HBV DNA and HBeAg positive rates were significantly higher (P<0.05 for both). Phenotypic analysis showed that lamivudine resistance was most frequently detected (34.6%), followed by adefovir resistance (15.6%). Multidrug resistance was detected in 48 cases (15.9%). The adefovir-resistant group had a higher proportion of cases with HBV loads greater than 2,000 IU/mL. CONCLUSIONS: We found correlations between the mutation status of the RT domain and biochemical parameters such as HBV DNA and HBeAg positive rate. The presence of RT gene mutations could therefore be utilized to predict clinical status.
Adenine/analogs & derivatives/therapeutic use ; Antiviral Agents/therapeutic use ; DNA, Viral/analysis ; Drug Resistance, Multiple, Viral ; Drug Resistance, Viral ; Hepatitis B e Antigens/blood ; Hepatitis B virus/*enzymology/isolation & purification ; Hepatitis B, Chronic/drug therapy ; Hospitals, University ; Humans ; Lamivudine/therapeutic use ; Mutation ; Organophosphonates/therapeutic use ; Phenotype ; RNA-Directed DNA Polymerase/*genetics ; Republic of Korea ; Retrospective Studies

The combination of atazanavir (ATV) and lopinavir/ritonavir (LPV/RTV) with nucleoside reverse transcriptase inhibitors (NRTI) has been used as a salvage regimen for human immunodeficiency virus (HIV)-positive patients. In this paper, we discuss two cases of HIV-positive patients who had long histories of virological failure following a heavy treatment of antiretroviral drugs, but then achieved virological suppression with double-boosted protease inhibitor (PI) regimens. In patients with multiple genotypic resistance to PIs and NRTIs, virological suppression can be achieved with a combination of ATV plus LPV/RTV with an NRTI backbone. The two cases in this report suggest that a combination of ATV plus LPV/RTV could be a useful salvage regimen for the subset of HIV-positive patients with limited treatment options.
Adult ; Drug Resistance, Multiple, Viral ; Drug Therapy, Combination ; HIV Infections/*drug therapy ; HIV Protease Inhibitors/*administration & dosage ; Humans ; Male ; Oligopeptides/*administration & dosage ; Pyridines/*administration & dosage ; Pyrimidinones/*administration & dosage ; Ritonavir/*administration & dosage

Adult ; Anti-Bacterial Agents/therapeutic use* ; COVID-19/drug therapy* ; Catheter-Related Infections/microbiology* ; China ; Drug Resistance, Multiple, Bacterial ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Intubation, Intratracheal ; Male ; Pneumonia, Viral/drug therapy* ; Prosthesis-Related Infections/microbiology* ; SARS-CoV-2

BACKGROUND/AIMS: Newly developed and potent antiviral agents suffer from the problem of drug resistance. Multidrug resistance is a major impediment in the treatment of patients with chronic hepatitis B (CHB). In line with American Association for the Study of Liver Diseases guidelines, adefovir dipivoxil (ADV) add-on therapy is recommended in the case of lamivudine resistance, while tenofovir disoproxil fumarate (TDF) is recommended for ADV or entecavir (ETV) resistance. TDF is currently not available in Korea. ADV+ETV combination therapy may be a viable alternative to TDF in patients with either ADV or ETV resistance. However, the efficacy of ADV+ETV combination therapy in patients with CHB and multidrug resistance is unclear. This study investigated the efficacy of ADV+ETV combination therapy in patients with multidrug resistance. METHODS: Twenty-five patients were enrolled and were administered ADV+ETV combination therapy for at least 6 months. Blood was drawn at baseline and at 3, 6, 9, and 12 months after commencing treatment, and the following blood parameters were analyzed: alanine transaminase, hepatitis B e-antigen (HBeAg), anti-hepatitis B e-antigen, and hepatitis B virus (HBV) DNA levels. The initial virological response (IVR) was defined as an HBV DNA level of <4 log10 copies/mL after 6 months of combination therapy. RESULTS: The IVR rate was 76%. The proportion of patients with a high viral load (> or =5.0 log) dropped from 76% at baseline to only 5% after 6 months of treatment. The biochemical response rate during the first 6 months was 71%. HBeAg was lost in 2 patients (10%). CONCLUSIONS: ADV+ETV combination therapy induced a good IVR in CHB patients who were refractory to more than 2 antiviral agents. This regimen may be a good alternative to TDF in Korea, where that drug is not available.
Adenine/*analogs & derivatives/therapeutic use ; Adult ; Alanine Transaminase/blood ; Antiviral Agents/*therapeutic use ; DNA, Viral/blood ; Drug Resistance, Multiple, Viral ; Drug Therapy, Combination ; Female ; Genotype ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B Antibodies/blood ; Hepatitis B e Antigens/blood ; Hepatitis B, Chronic/*drug therapy ; Humans ; Male ; Middle Aged ; Nucleosides/therapeutic use ; Phosphonic Acids/*therapeutic use

Clevudine is a nucleoside analog of the unnatural beta-L configuration which has potent antiviral activity against hepatitis B virus (HBV). Clevudine is expected to have similar pattern of resistance profile as lamivudine. However, there was no report on the mutation associated with clevudine resistance in patients with chronic hepatitis B. We report a case of young male patient with chronic hepatitis B who presented with clevudine resistance. The patient had received lamivudine therapy for 5 months with reduced serum HBV DNA levels. Then, lamivudine was switched to clevudine monotherapy. After the 6 months of clevudine therapy, the patient developed virologic breakthrough (>1.0x10(8) copies/mL) as well as biochemical breakthrough, which was associated with the presence of rtM204I plus rtL80I mutant. After switching from clevudine to adefovir, the viral load decreased with biochemical improvement.
Adenine/analogs & derivatives/therapeutic use ; Adult ; Amino Acid Substitution ; Antiviral Agents/*therapeutic use ; Arabinofuranosyluracil/*analogs & derivatives/therapeutic use ; Base Sequence ; DNA, Viral/blood ; Drug Resistance, Multiple, Viral ; Hepatitis B e Antigens/metabolism ; Hepatitis B, Chronic/*drug therapy/genetics ; Humans ; Lamivudine/*therapeutic use ; Male ; Phosphonic Acids/therapeutic use ; Reverse Transcriptase Inhibitors/*therapeutic use

Substantial progress has been made in the treatment of chronic hepatitis B during the past decade. Nucleos(t)ide analogues are now widely used due to their convenience, less side effects, and considerable response rates. However, development of antiviral resistance is a major problem being considered as the most important factor for the treatment failure. Viral breakthrough associated with selection of antiviral-resistant hepatitis B virus (HBV) is usually followed by biochemical breakthrough, clinical deterioration, and even progressive liver failure. Therefore, appropriate management of antiviral resistance is critical for improving treatment outcomes. Strategies for the management of antiviral-resistant chronic HBV infection are described herein considering recently published guidelines. Lamivudine/telbivudine resistance can be managed by adding adefovir. Switching to adefovir or entecavir is also a viable option. However, careful follow-up of viral load is mandatory to detect any primary or secondary treatment failure in case of sequential monotherapy. Interferon or peg-interferon therapy can also be considered in case of young patients with compensated liver disease. For adefovir resistance, lamivudine can be added, but adding or switching to entecavir is a more reasonable option. Likewise, adding or switching to adefovir can be considered for entecavir resistance. Adding or switching to tenofovir needs to be considered upon availability. Experiences for clevudine resistance are still lacking, and need to be studied further upon the isolation of clinically resistant strains. To avoid emergence of resistant mutations, antiviral therapy should be initiated after careful balance of risk and benefit, and the most potent antiviral agent with the lowest resistance rate should be selected.
Adenine/analogs & derivatives/therapeutic use ; Antiviral Agents/therapeutic use ; Arabinofuranosyluracil/analogs & derivatives/therapeutic use ; *Drug Resistance, Multiple, Viral ; Guanine/analogs & derivatives/therapeutic use ; Hepatitis B virus/*drug effects/isolation & purification ; Hepatitis B, Chronic/*drug therapy ; Humans ; Lamivudine/therapeutic use ; Mutation ; Nucleosides/therapeutic use ; Phosphonic Acids/therapeutic use ; Practice Guidelines as Topic ; Pyrimidinones/therapeutic use ; Treatment Outcome

DNA, Viral ; analysis ; Drug Resistance, Viral ; Hepatitis B ; drug therapy ; immunology ; virology ; Humans ; Viral Load