BACKGROUND: Hepatitis B surface antigen (HBsAg) clearance is vital for a functional cure of hepatitis B virus (HBV) infection. However, the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus (HIV) remain largely unknown in Guangdong, China. METHODS: Between 2009 and 2019, patients co-infected with HBV/HIV undergoing antiretroviral therapy (ART) in Guangzhou Eighth People's Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31, 2020. The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: A total of 1550 HBV/HIV co-infected patients were included in the study, with the median age of 42 years and 86.0% (1333/1550) males. Further, 98.3% (1524/1550) received ART containing tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC). HBV DNA was examined in 1283 cases at the last follow-up. Over the median 4.7 years of follow-up, 8.1% (126/1550) patients achieved HBsAg seroclearance, among whom 50.8% (64/126) obtained hepatitis B surface antibody, 28.1% (137/488) acquired hepatitis B e antigen seroconversion, and 95.9% (1231/1283) undetectable HBV DNA. Compared with patients who maintained HBsAg positive, cases achieving HBsAg seroclearance showed no differences in age, gender, CD4 + T cell count, alanine aminotransferase (ALT) level, or fibrosis status; however, they presented lower HBV DNA levels, lower HBsAg levels, and higher rates of HBV genotype B at the baseline. Multivariate analysis showed that baseline HBsAg <1500 cutoff index (COI) (adjusted hazard ratio [aHR], 2.74, 95% confidence interval [95% CI]: 1.48-5.09), ALT elevation >2 × upper limit of normal during the first six months after receiving ART (aHR, 2.96, 95% CI: 1.53-5.77), and HBV genotype B (aHR, 3.73, 95% CI: 1.46-9.59) were independent predictors for HBsAg seroclearance (all P <0.01). CONCLUSIONS Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients. Lower baseline HBsAg levels, HBV genotype B, and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.
Male ; Humans ; Adult ; Hepatitis B Surface Antigens ; Hepatitis B virus/genetics* ; HIV Infections/drug therapy* ; HIV ; DNA, Viral ; Incidence ; Coinfection/drug therapy* ; Retrospective Studies ; Tenofovir/therapeutic use* ; Lamivudine/therapeutic use* ; Hepatitis B, Chronic/drug therapy*

BACKGROUND: Dual regimen dolutegravir (DTG) plus lamivudine (3TC) has demonstrated non-inferior efficacy compared to DTG-based three-drug regimens (3DRs), yet directly comparative data regarding the efficacy and safety of DTG + 3TC and bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for therapy-naïve people with human immunodeficiency virus (HIV)-1 (PWH) are still limited. We aimed to assess the antiviral potency and safety profiles of DTG + 3TC vs. B/F/TAF based on antiretroviral therapy (ART)-naïve PWH in China. METHODS: This retrospective multicenter study enrolled PWH initiating ART with DTG + 3TC or B/F/TAF from 2020 to 2022 in Guangdong and Guangxi. We analyzed response rates based on target not detected (TND) status using intention-to-treat (ITT) analysis. Subgroups were formed based on baseline viral load (VL) (<100,000 vs . ≥100,000 copies/mL) and CD4 + cell count (<200 vs . ≥200 cell/µL). Median time to TND VL was assessed by Kaplan-Meier method. We also measured changes from baseline in CD4 + cell counts, CD4/CD8 ratio, lipid parameters, weight, creatinine (Cr), estimated glomerular filtration rate (eGFR), and drug-related adverse effects (DRAEs). RESULTS: We enrolled 280 participants, including 137 (48.9%) on DTG + 3TC and 143 (51.1%) on B/F/TAF. At week 48, 96.4% (132/137) on DTG+3TC and 100% (143/143) on B/F/TAF achieved TND ( P = 0.064). At week 12, TND responses were higher with B/F/TAF (78.3% [112/143]) than DTG+3TC (30.7% [42/137]) ( P <0.001). This trend held across subgroups. B/F/TAF achieved TND faster (12 weeks) than DTG+3TC (24 weeks) ( P <0.001). No differences were seen in CD4 + cell count and CD4/CD8 ratio, except in the high-VL subgroup, where B/F/TAF showed better recovery. DRAEs were significantly lower with B/F/TAF (4.9% [7/143]) than with DTG + 3TC (13.1% [18/137]) ( P = 0.016). Lipid parameters, body weight, and Cr increased in both groups over 48 weeks, with DTG+3TC showing a more favorable effect on triglycerides, high-density lipoprotein (HDL) cholesterol, and weight gain. CONCLUSIONS In this real-life study, B/F/TAF led to a faster viral decline and fewer DRAEs compared to DTG+3TC. No significant difference was observed in the TND rate at week 48, regardless of baseline VL and CD4 + cell count. CD4 + recovery was superior for B/F/TAF in participants with high VL. The DTG + 3TC regimen had less impact on metabolic changes than B/F/TAF.
Adult ; Humans ; Anti-HIV Agents/therapeutic use* ; China ; Emtricitabine/pharmacology* ; HIV Infections/drug therapy* ; HIV-1 ; Lamivudine/pharmacology* ; Lipids ; Retrospective Studies

Objective: This article investigated the clinical characteristics and distribution of drug resistance mutation sites in HBV RT region of hepatitis B infected patients. Methods: Retrospective analysis was made on 1 948 patients with HBV infection, who had been tested for NAs resistance mutation and had a medical history of NAs in the Laboratory Department of the Fifth Medical Center of the PLA General Hospital from January 2020 to December 2021. Basic clinical information and drug resistance related mutation information were recorded. Meanwhile, the serological index data of hepatitis B were collected. Drug resistance gene mutant group and non-mutated group were grouped according to whether the drug resistance genes had a mutation in HBV RT region, and the clinical characteristics and genotype distribution of the two groups were statistically analyzed. The pattern of drug resistance gene mutation, number of mutation sites, drug resistance type and mutation of NAs resistance-related sites were analyzed in 917 patients with drug resistance gene mutation in HBV RT region. χ² Inspection was used for counting data. Meanwhile, two independent samples t-test and Wilcoxon rank sum test were used for measurement data. Results: Among the 1 948 patients with chronic HBV infection, 917 patients had drug resistance gene mutation in RT region (47.07%). The proportion of patients with acute hepatitis B and CHB in HBV RT resistance gene mutant group was lower than that in the non-mutated group, while the proportion of patients with HBV-related cirrhosis was higher than that in the non-mutated group, these differences were statistically significant. Compared with the non-mutated group in HBV RT region, the age, the positive rates of HBeAg and HBV DNA, and HBV DNA load of these patients were increased in drug resistance gene mutant group, these differences were statistically significant. Genotypes of patients in both groups were dominated by C, followed by B and D. The proportion of patients with genotype C in HBV RT drug resistance gene mutant group was higher than that of non-mutated group, the difference was statistically significant. There were 53 gene mutation patterns in 917 patients with drug resistance gene mutation in HBV RT region, and the main pattern was rtL180M+rtM204V+rtS202G (9.70%). The mutation sites were dominated by 3 (20.74%). There were 5 types of drug resistance, LAM+Ldt (21.25%) was the most. Among the 18 sites that were clearly associated with LAM, ADV, ETV and Ldt resistance in the HBV RT region, 14 sites were mutated, and the most common mutation sites were rtL180M, rtM204V, rtM204 and rtS202G. what's more, the proportion of patients with NAs drug resistance was LAM>Ldt>ETV>ADV. Conclusion: In order to prevent adverse consequences of this study such as disease recurrence or disease progression caused by HBV drug resistance, HBV infected patients, who have long-term use of NAs antiviral therapy, should monitor the level of HBV DNA and drug resistance genes in HBV RT region in order to optimize the treatment plan in time or guide individualized treatment.
Humans ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic ; Antiviral Agents/therapeutic use* ; DNA, Viral/therapeutic use* ; Retrospective Studies ; Mutation ; Drug Resistance, Viral/genetics* ; Lamivudine/therapeutic use*

BACKGROUND: Lipid abnormalities are prevalent among people living with human immunodeficiency virus (HIV) (PLWH) and contribute to increasing risk of cardiovascular events. This study aims to investigate the incidence of dyslipidemia and its risk factors in PLWH after receiving different first-line free antiretroviral regimens. METHODS: PLWH who sought care at the Third People's Hospital of Shenzhen from January 2014 to December 2018 were included, and the baseline characteristics and clinical data during the follow-up were collected, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). The risk factors of dyslipidemia after antiretroviral therapy were analyzed with the generalized estimating equation model. RESULTS: Among the 7623 PLWH included, the mean levels of TC, HDL-C and LDL-C were 4.23 ± 0.85 mmol/L, 1.27 ± 0.29 mmol/L and 2.54 ± 0.65 mmol/L, respectively, and the median TG was 1.17 (IQR: 0.85-1.68) mmol/L. Compared with that in PLWH receiving tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) + ritonavir-boosted lopinavir (LPV/r), zidovudine (AZT) + 3TC + efavirenz (EFV), and AZT + 3TC + LPV/r, the incidence of dyslipidemia was lower in PLWH receiving TDF + 3TC + EFV. In multivariate analysis, we found that the risks of elevations of TG, TC, and LDL-C were higher with TDF + 3TC + LPV/r (TG: odds ratio [OR] = 2.82, 95% confidence interval [CI]: 2.55-3.11, P < 0.001; TC: OR = 1.24, 95% CI: 1.14-1.35, P < 0.001; LDL: OR = 1.06, 95% CI: 1.00-1.12, P = 0.041), AZT + 3TC + EFV (TG: OR = 1.41, 95% CI: 1.28-1.55, P < 0.001; TC: OR = 1.43, 95% CI: 1.31-1.56, P < 0.001; LDL: OR = 1.18, 95% CI: 1.12-1.25, P < 0.001), and AZT + 3TC + LPV/r (TG: OR = 3.08, 95% CI: 2.65-3.59, P < 0.001; TC: OR = 2.40, 95% CI: 1.96-2.94, P < 0.001; LDL: OR = 1.52, 95% CI: 1.37-1.69, P < 0.001) than with TDF + 3TC + EFV, while treatment with TDF + 3TC + LPV/r was less likely to restore HDL-C levels compared with TDF + 3TC + EFV (OR = 0.95, 95% CI: 0.92-0.97, P < 0.001). In addition to antiretroviral regimens, antiretroviral therapy duration, older age, overweight, obesity and other traditional factors were also important risk factors for dyslipidemia. CONCLUSION The incidence of dyslipidemia varies with different antiretroviral regimens, with TDF + 3TC + EFV having lower risk for dyslipidemia than the other first-line free antiretroviral regimens in China.
Aged ; Anti-HIV Agents/adverse effects* ; China/epidemiology* ; Dyslipidemias/epidemiology* ; HIV ; HIV Infections/drug therapy* ; Humans ; Lamivudine/therapeutic use* ; Lipids ; Risk Factors

Despite all these exciting developments, there remain some unmet needs in the management for patients with chronic hepatitis B (CHB). As majority of CHB patients are going to use oral nucleos(t)ide analogues (NAs) for decades, Safety profile of NAs is of no doubt an important issue. The newest nucleotide analogue tenofovir alafenamide is potent in terms of viral suppression, together with favourable renal and bone safety profile. Biochemical response as reflected by alanine aminotransferase (ALT) normalization is recently found to be prognostically important. Patients who achieved ALT normalization have reduced the risk of hepatic events by 49%. Functional cure as reflected by hepatitis B surface antigen seroclearance not only implies patients may stop NA treatment, it also confers to a reduced risk of hepatocellular carcinoma and other hepatic events. Hence functional cure should be the ultimate treatment goal in CHB patients. Preemptive antiviral treatment may reduce mother-to-child transmission of hepatitis B virus, especially if birth dose of vaccination cannot be given in the first two hours after delivery. Lastly, despite the currently first-line NAs have high-genetic barrier to drug resistance mutations, there are still are many patients who were previously treated with low barrier of resistance including lamivudine, telbivudine or adefovir dipivoxil which could lead to antiviral resistance and affecting the choice of NAs.
Alanine Transaminase ; Carcinoma, Hepatocellular ; Drug Resistance ; Fibrosis ; Hepatitis B ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Lamivudine ; Mortality ; Parturition ; Tenofovir ; Vaccination

BACKGROUND/AIMS: Direct sequencing is the gold standard for the detection of drug-resistance mutations in hepatitis B virus (HBV); however, this procedure is time-consuming, labor-intensive, and difficult to adapt to high-throughput screening. In this study, we aimed to develop a dendron-modified DNA microarray for the detection of genotypic resistance mutations and evaluate its efficiency. METHODS: The specificity, sensitivity, and selectivity of dendron-modified slides for the detection of representative drug-resistance mutations were evaluated and compared to those of conventional slides. The diagnostic accuracy was validated using sera obtained from 13 patients who developed viral breakthrough during lamivudine, adefovir, or entecavir therapy and compared with the accuracy of restriction fragment mass polymorphism and direct sequencing data. RESULTS: The dendron-modified slides significantly outperformed the conventional microarray slides and were able to detect HBV DNA at a very low level (1 copy/μL). Notably, HBV mutants could be detected in the chronic hepatitis B patient sera without virus purification. The validation of our data revealed that this technique is fully compatible with sequencing data of drug-resistant HBV. CONCLUSIONS: We developed a novel diagnostic technique for the simultaneous detection of several drug-resistance mutations using a dendron-modified DNA microarray. This technique can be directly applied to sera from chronic hepatitis B patients who show resistance to several nucleos(t)ide analogues.
DNA ; Drug Resistance ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis B, Chronic ; Hepatitis* ; Humans ; Lamivudine ; Mass Screening ; Oligonucleotide Array Sequence Analysis ; Sensitivity and Specificity

BACKGROUND: The purpose was to compare the efficacy between tenofovir disoproxil fumarate (TDF) and lamivudine (LMV) in children with nucleos(t)ide-naive chronic hepatitis B (CHB) infection. Patients with CHB were treated with TDF in the immune-reactive phase and compared with a historical control group of patients treated with LMV before the TDF era. METHODS: Hepatitis B virus (HBV) DNA titer decrements (> 3 log₁₀ IU/mL) were monitored after treatment initiation. The treatment duration for HBV DNA clearance (< 357 IU/mL) and complete response (HBeAg loss and HBV DNA clearance) were analyzed. The follow-up period was 96 weeks. RESULTS: Sixteen patients were treated with TDF and compared with a historical control group of 24 patients treated with LMV. HBV DNA decrement (> 3 log₁₀ IU/mL) was achieved in 100% (16/16) of the TDF group but in only 62.5% (15/24) of the LMV group (P = 0.005) at 48 weeks. The HBV DNA clearance (< 357 IU/mL) in the TDF and LMV groups was, respectively, as follows: 62.5% (10/16) and 25.0% (6/24) at 12 weeks (P = 0.018), 81.3% (13/16) and 37.5% (9/24) at 24 weeks (P = 0.006), 93.8% (15/16) and 50.0% (12/24) at 48 weeks (P = 0.004), and 100% (16/16) and 54.2% (13/24) at 96 weeks (P = 0.001). Complete response occurred in 41.7% (5/12) of HBeAg-positive patients in the TDF group and 28.6% (6/21) of the LMV group at 96 weeks (P = 0.443). CONCLUSION: TDF monotherapy for 96 weeks produced a significantly more effective virologic response than LMV monotherapy in children with nucleos(t)ide-naive CHB.
Child ; DNA ; Follow-Up Studies ; Hepatitis B virus ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Lamivudine ; Tenofovir

BACKGROUND: The aim of this study was to compare the long-term efficacy of entecavir (ETV) and lamivudine (LAM) therapy in children with chronic hepatitis B (CHB) who had not received nucleoside analogue treatment. METHODS: In this multicenter, retrospective study, we included pediatric CHB patients younger than 20 years who received ETV or LAM treatment for at least 12 months and had no concomitant diseases. All of the patients were followed up every 1 to 3 months. At each visit, the patients underwent clinical evaluation and biochemical testing. RESULTS: Eight (53.3%), 14 (93.3%), and 2 (15.4%) of the ETV-treated patients achieved virologic suppression, alanine aminotransferase (ALT) normalization and hepatitis B e antigen (HBeAg) seroconversion, respectively, at 1 year. In the ETV group, the cumulative rate of virologic suppression at 3 years was 91.7%, which was significantly higher than that in the LAM group (P < 0.001). The mean duration of treatment before virologic suppression was shorter in the ETV group than in the LAM group (P = 0.040). The cumulative rate of seroconversion in the ETV group at 3 years was 39.4%, which was not significantly different from that in the LAM group (P = 0.439). The ETV group showed lower cumulate rates of virologic breakthrough (33.3% at 6 years) and genotypic mutation than the LAM group (P = 0.033 and P = 0.011, respectively). CONCLUSION: ETV is superior to LAM in pediatric CHB treatment because of its higher virologic suppression rate and lower cumulative rates of virologic breakthrough and genotypic mutation.
Alanine Transaminase ; Child ; Hepatitis B ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Lamivudine ; Retrospective Studies ; Seroconversion

PURPOSE: This prospective study aimed to investigate the therapeutic efficacy of lamivudine in children with chronic hepatitis B virus (HBV) infection. METHODS: During July 2003 through October 2015, children with chronic hepatitis B who visited our institution were included in this study. Fifty-five patients, who received first-line treatment of lamivudine (3 mg/kg, 100 mg maximum) for over three months, were enrolled. After initiating lamivudine, alanine aminotransferase (ALT), HBV-DNA, and HBV markers were followed up at 1 month, 3 months, and every 3 months, thereafter. The treatment endpoint was determined as 1) normalization of ALT, 2) HBeAg seroconversion, and 3) anti-HBe positivity for twelve consecutive months. RESULTS: Thirty-one male (56.4%) and 24 female (43.6%) patients were included. The mean age at treatment initiation was 8.1 years. The mean duration of treatment was 23.4 months. ALT normalization was found in 98.2% (54 of 55). Anti-HBe seroconversion was found in 70.6% (36/51). Loss of HBsAg was found in 10.9% (6/55). All biochemical responses occurred under age seven. The rate of virologic response (defined as HBV-DNA <2,000 IU/mL) at six months after treatment initiation was 78.7% (37/47). At twelve months after reaching treatment endpoint, 87.2% (34/39) maintained their virologic response. Resistance to lamivudine was found in 16.4% (9/55). CONCLUSIONS: Lamivudine treatment in Korean pediatric patients with chronic hepatitis B showed better outcomes compared with other studies that implemented similar protocols in foreign populations. Further studies are needed to investigate the efficacy of newly recommended antiviral drugs on the Korean pediatric population.
Adolescent ; Alanine Transaminase ; Antiviral Agents ; Child ; Female ; Hepatitis B e Antigens ; Hepatitis B Surface Antigens ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Lamivudine ; Male ; Prospective Studies ; Seroconversion

PURPOSE: This study examined 2-year outcome of consecutive therapy using entecavir (ETV) followed by telbivudine (LdT) in subjects with undetectable hepatitis B virus (HBV) DNA level and normal alanine aminotransferase level after the initial 6 months of ETV treatment. MATERIALS AND METHODS: Sixty subjects were randomized to continue with ETV or switch to LdT. Significant difference in baseline characteristics was not found between the two groups. Persistent HBV DNA level of 20–60 IU/mL in three consecutive samples collected three months apart or singly measured HBV DNA level of >60 IU/mL was defined as virological rebound. RESULTS: During 96 weeks of follow-up, all subjects of the ETV-only group (n=30) resulted in undetectable HBV DNA level. On the other hand, 83.3% (n=25) of the LdT-switched group showed treatment success. Virological rebound time varied from week 24 to 84 after switching to LdT. HBV DNA level was 180 to 2940 IU/mL at rebound time. All subjects with virological rebound (n=5) showed drug-resistant mutation: three had mutation rtM204I, and two had mutation rtM204V. Consecutive treatment using ETV followed by LdT showed virological rebound in 16.7% of subjects during 96 weeks of follow-up. HBV DNA negativity during initial ETV therapy could not be achieved in patients who switched to LdT. CONCLUSION: Consecutive treatment using ETV followed by lamivudine was ineffective for treating chronic hepatitis B. LdT was found as a more potent antiviral agent than lamivudine. However, this conclusion requires larger-scale, long-term prospective reviews of the treatment effects of ETV-LdT switch therapy.
Alanine Transaminase ; DNA ; DNA, Viral* ; Follow-Up Studies ; Hand ; Hepatitis B virus ; Hepatitis B* ; Hepatitis B, Chronic ; Hepatitis* ; Humans ; Lamivudine ; Prospective Studies