Achievements of COVID-19 vaccination programs: Taiwanese perspective.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health crisis. The specific characteristics of aerosol transmission in the latent period and the contagiousness of SARS-CoV-2 lead to rapid spread of infection in the community. Vaccination is the most effective method for preventing infection and severe outcomes. As of December 1, 2022, 88% of the Taiwanese population had received at least two doses of COVID-19 vaccines. Heterologous vaccination with ChAdOx1-mRNA-based or ChAdOx1-protein-based vaccines has been found to elicit higher immunogenicity than homologous vaccination with ChAdOx1-ChAdOx1 vaccines. A longitudinal cohort study revealed that 8-12-week intervals between the two heterologous vaccine doses of the primary series led to good immunogenicity and that the vaccines were safe. A third booster dose of mRNA vaccine is being encouraged to evoke effective immune responses against variants of concern. A novel domestic recombinant protein subunit vaccine (MVC-COV1901) was manufactured and authorized for emergency use in Taiwan. It has shown a good safety profile, with promising neutralizing antibody titers against SARS-CoV-2. Given the global pandemic due to emerging novel variants of SARS-CoV-2, booster COVID-19 vaccines and appropriate intervals between booster doses need to be investigated.

Serological responses to COVID-19 vaccination in patients with chronic liver diseases.

Longitudinal analysis of antibody responses following three-dose COVID-19 vaccination in patients with chronic liver disease (CLD) has been limited. From August 2021 to February 2023, sequential anti-SARS-CoV-2 spike IgG titers were determined in 45 patients with CLD who received two or three doses of COVID-19 vaccine. The geometric mean of anti-spike IgG at four weeks after the second and third doses were 1313.16 BAU/mL and 3042.29 BAU/mL, respectively, and it decreased significantly from four to 24 weeks after the second (1313.16 vs. 198.42 BAU/mL, p = 0.002) and the third (3042.29 vs. 636.71 BAU/mL, p < 0.001) dose. The anti-spike IgG titers in participants receiving prime-boost homologous mRNA vaccines (BNT162b2 or mRNA-1273) were comparable between participants with and those without significant liver fibrosis at each follow-up time point. This study demonstrated a notable decrease in anti-spike IgG after completion of the vaccination schedule in patients with CLD, highlighting the importance of additional booster doses.

Higher serologic responses of early syphilis to single-dose benzathine penicillin G plus doxycycline versus single-dose benzathine penicillin G alone among people with HIV.

BACKGROUND: Single-dose benzathine penicillin G (BPG) is the preferred therapy for early syphilis, but poorer serologic responses have been observed among people with HIV (PWH). No enhanced regimen has previously been shown to improve serologic outcomes of early syphilis. METHODS: We conducted a retrospective study to compare the treatment responses to single-dose BPG combined with 7-day doxycycline versus BPG alone in PWH who presented with early syphilis. Rapid plasma reagin (RPR) titers were determined every 3-6 months for all included PWH. Serologic response was defined as at least a fourfold decline in RPR titers at month 12. RESULTS: During January 2018 to March 2022, 223 PWH with 307 episodes of early syphilis received single-dose BPG plus doxycycline and 347 PWH with 391 episodes received BPG alone. The median age was 36 years and baseline CD4 count was 600 cells/mm3. In the intention-to-treat with last-observation-carried-forward analysis, PWH receiving BPG plus doxycycline had a significantly higher serologic response rate at 12 months of treatment than those receiving BPG alone (79.5% vs 70.3%, respectively; P= .006). The factors associated with 12-month serologic response were RPR titer (per 1-log2 increase, adjusted odds ratio [AOR], 1.25; 95% CI, 1.15-1.35) and receipt of BPG plus doxycycline (AOR, 1.71; 95% CI, 1.20-2.46). In the subgroup analyses, BPG plus doxycycline was consistently associated with a better serologic response than BPG alone at month 12. CONCLUSIONS: Among PWH with early syphilis, single-dose BPG plus doxycycline achieved higher serologic responses than BPG alone during a 12-month follow-up period.

A Randomized Clinical Trial of 1-Dose vs Accelerated 2-Dose Schedule for Hepatitis A Virus (HAV) Revaccination Among People With Human Immunodeficiency Virus Who Were Nonresponders or Had Seroreversion After Primary HAV Vaccination.

BACKGROUND: For people with human immunodeficiency virus (PWH) who have no serological responses to their primary hepatitis A virus (HAV) vaccination or have seroreversion after successful primary vaccination, the optimal revaccination strategy remains unclear. METHODS: In this open-label, randomized clinical trial, PWH who tested negative for anti-HAV antibodies after receiving a standard 2-dose series of primary HAV vaccination were enrolled and assigned in a 1:1 ratio to receive either 1 dose (the 1-dose group) or 2 doses of HAV vaccine administered 4 weeks apart (the 2-dose group). Serological response rates and anti-HAV antibody titers were compared at weeks 24 and 48. RESULTS: Of the 153 participants (77 in the 1-dose group and 76 in the 2-dose group), the overall serological response rates at week 48 after revaccination were similar between the 2 groups (2- vs 1-dose, 80.2% vs 71.4%, P = .20). However, anti-HAV antibody titers were consistently higher in the 2-dose group than in the 1-dose group. In subgroup analysis, PWH who were nonresponders to primary HAV vaccination were significantly more likely to mount a serological response after 2-dose HAV revaccination (68.4% vs 44.1%, P = .038). No severe adverse events were reported throughout the study. CONCLUSIONS: Two-dose HAV revaccination administered 4 weeks apart yielded similar serological responses as 1-dose revaccination among PWH who were nonresponders or had seroreversion after primary HAV vaccination. The 2-dose revaccination schedule generated significantly higher anti-HAV antibody titers and was more likely to elicit serological responses at week 48 among PWH who were nonresponders to primary HAV vaccination. Clinical Trials Registration. NCT03855176.

Immunogenicity and safety of heterologous mRNA-1273/MVC-COV1901 vaccination versus homologous mRNA1273 vaccination: A randomized, double-blind controlled study.

BACKGROUND/PURPOSE: MVC-COV1901 is a protein vaccine based on the same SARS-CoV-2 strain used in mRNA vaccine mRNA-1273. Data are lacking on immunogenicity and safety of MVC-COV1901 as heterologous boost for people already received one dose of mRNA-1273. METHODS: This is a randomized, double-blind trial that recruited adults aged 20-70 years who previously received a single dose of mRNA-1273 vaccine and were randomly assigned in a 1:1 ratio to receive a second dose with the homologous vaccine or protein-based MVC-COV1901 8-12 weeks after the first dose. The primary outcome was neutralizing antibody titers in terms of the geometric mean titer (GMT) 14 days after the second dose. Safety was assessed in all participants who received a dose of the study vaccine. The study is registered with ClinicalTrials.gov (NCT05079633). RESULTS: From September 30 to November 5, 2021, 144 participants were enrolled and randomly assigned to the MVC-COV1901 boost group (n = 72) or the mRNA-1273 boost group (n = 72). The neutralizing antibodies on Day 15 and the anti-SARS-CoV-2 IgG titers on Day 15 and 29 of homologous mRNA-1273 were significantly higher than those of heterologous mRNA-1273/MVC-COV1901. Cellular immune responses were comparable in both groups. However, adverse events were much more frequent after the mRNA-1273 boost than after the MVC-COV1901 boost. CONCLUSION: Our results show that heterologous boost with MVC-COV1901 yielded an inferior immunogenicity but significantly fewer adverse events, compared with homologous boost with mRNA-1273. In people experienced severe adverse events after prime dose of mRNA-1273, as well as in periods when the supply of mRNA-1273 is limited, MVC-COV1901 could serve as an acceptable alternative heterologous boost.

Evolution of Hepatitis B Virus (HBV) Serologic Markers Among Antiretroviral-Naive Young People Living With Human Immunodeficiency Virus Who Had Undergone Neonatal HBV Vaccination and Initiated Antiretroviral Therapy.

BACKGROUND: With initiation of antiretroviral therapy (ART) containing nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) with anti-hepatitis B virus (HBV) activity, the evolution of HBV serologic markers among people living with human immunodeficiency virus (PLWH) who were born in the era of nationwide neonatal HBV vaccination is rarely investigated. METHODS: This retrospective cohort study evaluated the changes of HBV serologic markers (hepatitis B surface antigen [HBsAg], antibody to hepatitis B surface antigen [anti-HBs], and antibody to hepatitis B core antigen [anti-HBc]) of PLWH who had undergone neonatal HBV vaccination. Clinical characteristics were analyzed and the incidences of evolution of HBV serologic markers were estimated. RESULTS: Between 2004 and 2020, 608 PLWH (mean age, 24 years) were included and 62.0% initiated tenofovir-containing ART: 13 (2.1%) were HBsAg-positive, 312 (51.3%) tested triple-negative, 209 (34.4%) had vaccine-induced seroprotection against HBV, and 74 (12.2%) tested positive for anti-HBc with or without anti-HBs. Among 492 PLWH who received a median follow-up of 2.8 years, 4 cases of incident HBV infection occurred (0.59 per 100 person-years of follow-up [PYFU]) in PLWH testing triple-negative at baseline despite ART containing NRTIs with anti-HBV activity. Of PLWH with seroprotection against HBV at baseline, 38 subsequently lost anti-HBs (4.46 per 100 PYFU) and 4 cases of incident HBV infection occurred (0.47 per 100 PYFU). PLWH with an anti-HBs antibody titer ≥100 mIU/mL at baseline (adjusted hazard ratio [aHR], 0.10 [95% confidence interval {CI}: .02-.42]) and CD4 ≥500 cells/µL during follow-up (aHR, 0.51 [95% CI: .30-1.00]) were less likely to lose HBV seroprotection. CONCLUSIONS: Among young PLWH who had undergone neonatal HBV vaccination, evolution of HBV serologic markers and incident infections occurred despite ART containing NRTIs with anti-HBV activity.

Evolution of estimated glomerular filtration rate in human immunodeficiency virus and hepatitis C virus-coinfected patients receiving sofosbuvir-based direct-acting antivirals and antiretroviral therapy.

The nephrotoxicity of sofosbuvir (SOF) on human immunodeficiency virus and hepatitis C virus (HIV/HCV)-coinfected patients receiving antiretroviral therapy (ART) remains controversial. We prospectively compared the estimated glomerular filtration rate (eGFR) changes in 167 patients receiving SOF-based direct-acting antivirals (DAAs) who also received tenofovir disoproxil fumarate (TFV)-based (n = 116) and TFV-free ART (n = 51). The eGFR was assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, and the eGFR changes between ART regimens were compared by the generalized estimated equation. During DAA treatment, participants on TFV-based ART had a higher eGFR decline than those on TFV-free ART (slope coefficient difference: -0.82 ml/min/1.73 m2 /month [95% CI: -1.21 to -0.43]; p < 0.001), whereas the eGFR changes did not differ between groups (slope coefficient difference: 0.13 ml/min/1.73 m2 /month [95% CI: -0.32 to 0.58]; p = 0.42) after discontinuing DAAs. Participants on TFV TDF-based ART had a higher eGFR decline than those on TFV alafenamide fumarate (TAF)-based ART (slope coefficient difference: -0.31 ml/min/1.73 m2 /month [95% CI: -0.50 to -0.12]; p = 0.01). After discontinuing DAAs, the eGFR changes did not differ between groups (slope coefficient difference: 0.06 ml/min/1.73 m2 /month [95% CI: -0.98 to 1.10]; p = 0.91). In conclusion, HIV/HCV-coinfected patients on TFV-based ART had a slight eGFR decline compared to those on TFV-free ART during SOF-based DAA therapy. A similar trend between TDF-based and TAF-based ART was also observed. Because the differences of eGFR changes are limited, the physicians should not discourage the use of SOF-based DAAs in HIV-positive patients on TFV-based ART.

Healthcare-associated carbapenem-resistant Klebsiella pneumoniae bloodstream infections: Risk factors, mortality, and antimicrobial susceptibility, 2017-2019.

BACKGROUND: In Taiwan, carbapenem-resistant Klebsiella pneumoniae (CRKP) now became a leading cause of difficult-to-treat healthcare-associated infection, for which there are a lack of recent hospital epidemiological studies on risk factors, mortality, and antimicrobial susceptibility. METHODS: We prospectively enrolled patients with healthcare-associated CRKP monomicrobial bloodstream infection (mBSI) and matched patients with carbapenem susceptible K. pneumoniae (CSKP) mBSI at National Taiwan University Hospital (Taipei, Taiwan) from October 2017 through December 2019 in a 1:2 ratio. Multivariable logistic regression and Kaplan-Meier analyses were applied to identify factors associated with CRKP mBSI and to compare the 14-day survival curves, respectively. We detected the presence of blaKPC and blaNDM gene among the included CRKP strains, and performed antimicrobial susceptibility testing (including susceptibility to colistin, aminoglycoside, tigecycline, and ceftazidime/avibactam). RESULTS: A total of 36 CRKP cases and 72 CSKP controls were enrolled. Patients with CRKP mBSI were more likely to have liver cirrhosis (adjusted odds ratio [aOR], 5.61; P = 0.024), length of hospital stay over the previous 14 days (aOR, 1.23; P = 0.001) and prior use of carbapenems in the previous 14 days (aOR, 6.07; P = 0.004) than patients with CSKP mBSI. The 14-day survival was significantly worse for patients with CRKP mBSI than those with CSKP mBSI (all CRKP cases: 50.0% vs. 87.5%; P < 0.001; CRKP cases treated with colistin as an appropriate backbone antibiotic: 58.3% vs. 87.5%; P = 0.007). Compared with the CSKP isolates, CRKP isolates were significantly less susceptible to colistin, amikacin, and tigecycline. Of the 36 CRKP isolates, none harbor blaNDM gene and 35 (97%) had low minimum inhibitory concentrations (≤8/4 µg/ml) of ceftazidime/avibactam by the E test method. CONCLUSION: Prior exposure to carbapenems, longer hospital stay, and the presence of liver cirrhosis predicted CRKP instead of CSKP mBSI. Even with colistin therapy, CRKP mBSIs was still associated with a very high risk of mortality within 14 days. Ceftazidime/avibactam is a potentially useful therapeutic choice for cases caused by in vitro susceptible CRKP strains.

A cross-sectional seroprevalence for COVID-19 among healthcare workers in a tertially care hospital in Taiwan.

BACKGROUND: Healthcare workers (HCWs) are at the frontline during the pandemic of COVID-19 globally. According to the WHO situation report at April 17, there were 22, 073 HCWs contracted the infection. Whether the infection control policy and practice in the hospital setting can protect the HCWs is an important issue. METHODS: We performed a cross-sectional serology study in a tertiary care hospital in Taiwan to explore the sero-prevalence rate among HCWs. The participants are enrolled on a voluntary basis. A structured questionnaire was collected to gather the epidemiology character and risk factors for potential exposure. ELISA tests as Architect SARS-CoV-2 IgG (Abbott) and Elecsys Anti-SARS-CoV-2 assay (Roche) were used to detect antibody responses. If any of the tests was positive, a western blot assay was used for confirmation. RESULTS: There were 194 HCWs participated during July 1 to Aug. 31, 2020. The mean age was 36.3 ± 10.4. More than half of the participants had possible hospital associated risk for COVID-19 exposure (110/192, 57.3%) and 64 had possible community risk for COVID-19 exposure (64/194, 33.0%). There was only one participant had positive test by Architect IgG test and confirmed to be negative for seasonal coronavirus and SARS-CoV-2 antibody. (Mikrogen Diagnostik, Germany). CONCLUSION: The cross-sectional serology study in a tertiary care hospital in Taiwan revealed no HCWs had positive serology response to SARS-CoV-2. We believe that the infection control policy and practice in the hospital and in the community are both important to prevent the disease transmission.

Evolution of SARS-CoV-2 neutralizing antibody in an HIV-positive patient with COVID-19.

We presented the clinical course and immune responses of a well-controlled HIV-positive patient with COVID-19. The clinical presentation and antibody production to SARS-CoV-2 were similar to other COVID-19 patients without HIV infection. Neutralizing antibody reached a plateau from 26th to 47th day onset but decreased on 157th day after symptoms.

Effect of a Hepatitis A Vaccination Campaign During a Hepatitis A Outbreak in Taiwan, 2015-2017: A Modeling Study.

BACKGROUND: Beginning from 2015-2016, unprecedented large outbreaks of acute hepatitis A that predominantly affected men who have sex with men (MSM) reemerged across the continents. We assessed the impact of an early initiated hepatitis A virus (HAV) vaccination campaign that targeted MSM living with human immunodeficiency virus (HIV) during the 2015-2017 hepatitis A outbreak in Taiwan. METHODS: First, we ascertained the effectiveness of HAV vaccination for MSM living with HIV using a nested case-control study of 1470 persons living with HIV who were initially HAV-seronegative. We then fitted a model of HAV transmission among MSM, risk-structured by HIV status, to the actual epidemic curve of reported acute hepatitis A cases in Taiwan during 2015-2017. RESULTS: Fifty-five cases of acute hepatitis A were matched to 220 controls. Single-dose and 2-dose HAV vaccination provided protection rates of 96.1% and 97.8% among recipient MSM living with HIV, respectively. Model fitting yielded basic reproductive number estimates of 7.26 (MSM living with HIV) and 3.04 (MSM not living with HIV). In a counterfactual scenario without an HAV vaccination campaign, the outbreak would have involved 7153 hepatitis A cases during 2015-2017 in contrast to the 1352 that were observed. We therefore estimated that the HAV vaccination campaign averted 80.7% (sensitivity analysis, 48.8%-92.7%) of acute hepatitis A cases that would otherwise have occurred by the end of 2017. CONCLUSIONS: The early initiated HAV vaccination campaign, which targeted MSM living with HIV, very effectively curtailed the 2015-2017 hepatitis A outbreak in Taiwan.

Glecaprevir/pibrentasvir for patients with chronic hepatitis C virus infection: Real-world effectiveness and safety in Taiwan.

BACKGROUND & AIMS: Large-scale data regarding the real-world effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) for patients with chronic hepatitis C virus (HCV) infection were limited in East Asia. We aimed to evaluate the clinical performance of GLE/PIB in different HCV populations in Taiwan. METHODS: A total of 658 chronic HCV patients with compensated liver diseases receiving GLE/PIB for 8 (n = 549), 12 (n = 103) or 16 (n = 6) weeks were retrospectively enrolled. The effectiveness was determined by sustained virologic response at off-therapy 12 weeks (SVR12 ). Patient characteristics potentially related to SVR12 and the safety profiles were also assessed. RESULTS: By evaluable population (EP) and per-protocol (PP) analyses, the overall SVR12 rate was 98.2% (95% confidence interval (CI): 96.8%-99.0%) and 99.4% (95% CI: 98.4%-99.8%). The SVR12 rates were 98.9% (95% CI: 97.6%-99.5%), 94.2% (95% CI: 87.9%-97.3%) and 100% (95% CI: 60.1%-100%) in patients receiving 8, 12 and 16 weeks of treatment respectively. A total of 656 (99.7%) patients completed the scheduled treatment. The SVR12 rates were comparable regardless of baseline characteristics or week 4 viral decline. Twenty (3.0%) patients had serious adverse events (AEs), but none were not related to GLE/PIB. The two most common AEs were pruritus (7.8%) and fatigue (5.5%). Two (0.3%) and no patients had ≥3-fold upper limit of normal (ULN) for total bilirubin and alanine aminotransferase (ALT) levels. CONCLUSIONS: GLE/PIB for 8-16 weeks is effective and well-tolerated for patients with chronic HCV infection in Taiwan.

10-year outcome of temporary structured treatment interruption (STI) among HIV-1-infected patients: An observational study in a single medical center.

BACKGROUND: Lifelong antiretroviral therapy (ART) is recommended for HIV-1 infected patients but may lead to intolerance or poor adherence. Structured treatment interruption (STI) is a strategy for drug holiday or to boost HIV-specific immunity. But the long-term outcome of STI was never reported in literature. METHODS: This is a single-center observational study. We followed the HIV-infected patients who already had a stable viral suppression and voluntarily started temporary STI with a fixed 12-week interval after counseling, evaluation and education. HIV-1-specific T cell response was also measured in some patients. RESULTS: Totally 34 HIV-infected patients received temporary STI since July, 2006. 18 patients completed 10-year follow-up. All patients received protease inhibitors (PI)-based ART before and during temporary STI. The patients received temporary STI with a period of 36-85 weeks. All of them reached viral suppression after 12 weeks of restarting continuous ART. No viral rebound or opportunistic disease was recorded during follow-up. No adverse event or comorbidity was attributed to STI. The plasma viral load (PVL) at the end of STI was significantly lower than baseline PVL in patients with a longer duration of STI (≤36 weeks vs. >36 weeks, P = 0.005). The T cell response study revealed that cyclically increased HIV-1-specific T cell response after starting STI in patients with baseline CD4+ count >350/µL. CONCLUSION: Temporary STI may not lead to worse long-term outcome among highly selected patients. The policy may partially control viral replication through reminding the HIV-1 specific T cell immunity.

Therapeutic drug monitoring of the teicoplanin trough level after the loading doses in patients receiving venoarterial extracorporeal membrane oxygenation.

BACKGROUND: The optimal loading dose of teicoplanin in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) has never been determined by therapeutic drug monitoring. This study investigated the appropriateness of proposed loading dose regimens of teicoplanin when administered to patients receiving VA-ECMO by using a previously proposed loading dosage and measuring the teicoplanin trough concentration (Ctrough). METHODS: Patients who initiated teicoplanin therapy while receiving VA-ECMO were enrolled. Every included patient received four loading doses of teicoplanin at a dose of 12 mg/kg. The first three doses were administered 12 h apart, and the fourth dose was administered 24 h after the third dose. Blood samples were collected before administering the maintenance dose (i.e., the fifth dose), and the teicoplanin Ctrough was measured. Serum teicoplanin levels were determined using an Agilent 1290 ultra-high performance liquid chromatography system. RESULTS: The teicoplanin Ctrough was successfully tested in 11 patients. Their median age was 68.2 years, and 81.8% of them were men. The median of each loading dose was 11.6 (range, 10.7-12.8) mg/kg. The median teicoplanin Ctrough was 22.01 (range, 14.85-44.84) mg/L. All patients had a Ctrough of more than 10 mg/L, whereas 90.9% (10/11) of the patients achieved a Ctrough of more than 15 mg/L. CONCLUSION: The loading dosage consisting of four doses of teicoplanin administered within the first 72 h at a dose of 12 mg/kg/dose could achieve an adequate therapeutic Ctrough of teicoplanin in patients receiving VA-ECMO.

Serologic responses and effectiveness of hepatitis A vaccination among human immunodeficiency virus-positive individuals during the outbreak of acute hepatitis A.

Outbreaks of hepatitis A virus (HAV) infection have been occurring among men who have sex with men in the Asia-Pacific region, the United States, and several European countries since June 2015 and recently among persons who are homeless and use illicit drugs in the United States. We evaluated the serologic responses and effectiveness of HAV vaccination in human immunodeficiency virus (HIV)-positive individuals during the outbreak in Taiwan. From June 1, 2015, to September 30, 2016, anti-HAV immunoglobulin G was prospectively determined among all HIV-positive individuals. We prospectively observed 1,533 HAV-seronegative, HIV-positive individuals (94.1% being men who have sex with men with a median cluster of differentiation 4 (CD4) count of 550 cells/µL) who were advised to receive two doses of HAV vaccine administered 6 months apart. Of them, 1,001 individuals (65.3%) received at least one dose of HAV vaccine during the study period and 532 (34.7%) declined to receive vaccine. The primary endpoints were serologic response at weeks 28-36 and acquisition of HAV infection during follow-up. The incidence rate of acute HAV infection was 3.7 and 99.3 per 1,000 person-years of follow-up in the vaccinated and unvaccinated groups, respectively, resulting in a vaccine effectiveness of 96.3%. At weeks 28-36, the seroconversion rates were 63.8% and 93.7% in the intention-to-treat and per-protocol analyses, respectively. The factors associated with seroconversion at weeks 28-36 were younger age (per 1-year decrease, adjusted odds ratio, 1.08; 95% confidence interval, 1.02-1.12) and undetectable plasma HIV RNA load (adjusted odds ratio, 3.19; 95% confidence interval, 1.32-7.68). CONCLUSION: During the outbreak of acute hepatitis A, two-dose HAV vaccination is effective at preventing HAV infection among HIV-positive individuals receiving combination antiretroviral therapy; our data highlight the importance of HAV serologic screening and vaccination to prevent outbreaks of acute hepatitis A in at-risk populations. (Hepatology 2018;68:22-31).

Impact of antiretroviral therapy containing tenofovir disoproxil fumarate on the survival of patients with HBV and HIV coinfection.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is active against both HBV and HIV. Whether the introduction of TDF-containing combination antiretroviral therapy (cART) has improved the outcome of HIV/HBV-coinfected patients remains unclear in areas of higher HBV endemicity. METHODS: We retrospectively reviewed medical records of newly diagnosed antiretroviral-naïve HIV-infected patients between 2007 and 2015. Four groups of patients were defined, according to the HBV status and availability of TDF for HIV treatment in Taiwan in 2011. The primary outcome was all-cause mortality. RESULTS: During the 9-year study period, 1,723 HIV-infected patients were included, with a median age of 31 years and baseline CD4 count of 273 cells per µL. The HBV seroprevalence had declined from 18.1% (125/692) in the pre-TDF era to 10.1% (104/1031) in the post-TDF era. The respective mortality rate for HIV/HBV-coinfected and HIV-monoinfected patients in the pre-TDF era was 23.2 (95% CI, 12.5-43.1) and 9.6 (95% CI, 6.1-15.0) deaths per 1000 person-years of follow-up [PYFU], and the respective mortality rate in the post-TDF era was 15.7 (95% CI, 7.0-34.8) and 8.0 (95% CI, 5.5-11.6) deaths per 1000 PYFU. The adjusted hazard ratio for mortality in multivariate Cox proportional-hazards regression analysis among HIV/HBV-coinfected patients compared to HIV-monoinfected patients was 2.79 (95% CI, 1.25-6.22) in pre-TDF era and 1.11 (95% CI, 0.45-2.72) in post-TDF era. CONCLUSIONS: In this country of high HBV endemicity, the adverse impact of chronic HBV infection on the survival observed in the pre-TDF era has significantly diminished among HIV/HBV-coinfected patients compared to HIV-monoinfected patients in the era of TDF-containing cART.

Comparable Serologic Responses to 2 Different Combinations of Inactivated Hepatitis A Virus Vaccines in HIV-Positive Patients During an Acute Hepatitis A Outbreak in Taiwan.

We evaluated the serologic responses to different 2-dose combinations of the inactivated hepatitis A virus (HAV) vaccines Havrix and Vaqta among human immunodeficiency virus-positive individuals during an acute hepatitis A outbreak in Taiwan. In this 16-month retrospective study, one group received 1 dose of Havrix followed by 1 dose of Vaqta, and another group received 2 doses of Vaqta. The Havrix-Vaqta and Vaqta-Vaqta groups achieved similar seroconversion rates at weeks 28-36 (82.3% and 80.9%, respectively; absolute difference, 1.3% [95% confidence interval {CI}, -6.3%-3.7%]) and week 48 (94.7% and 94.4%, respectively; absolute difference, 0.3% [95% CI, -2.6%-3.2%]), suggesting the interchangeability of different combinations of HAV vaccines. The significantly higher seroconversion rate after the first dose of Vaqta, compared with the dose of Havrix (53.0% vs 32.4%) may provide potential benefits in preventing HAV infection during the outbreak.

Serological responses to revaccination with hepatitis A virus (HAV) vaccines among HIV-positive individuals whose anti-HAV antibody waned after primary vaccination.

BACKGROUND: Among HIV-positive individuals, seroprotection for hepatitis A virus (HAV) following primary vaccination may wane with time. However, seroresponses to HAV revaccination are rarely investigated among HIV-positive patients who have lost protective antibodies after primary vaccination. METHODS: During the outbreak of acute hepatitis A in Taiwan after June 2015, HAV-seronegative, HIV-positive individuals were advised to receive two doses of HAV vaccines at 24 weeks apart. A retrospective 1:2 matched case-control study was conducted to compare the seroresponses at weeks 4, 24, 28 and 48 of HAV vaccination between those who underwent revaccination after having lost protective antibodies (case patients) and those who underwent primary vaccination (controls). RESULTS: Seventy-five case patients and 150 matched controls were included. The serological response rates were consistently higher among the case patients than controls: 88.1% vs 10.5% at week 4 following the first dose of HAV vaccination (P < .001); 93.3% vs 46.0% at week 24 (immediately before the second dose; P < .001); 98.7% vs 62.7% at week 28 (4 weeks after the second dose; P < .001) and 98.7% vs 92.7% at week 48 (P = .06). The anti-HAV antibody titres as reflected by the semi-quantitative assay for the case patients were also significantly higher than the controls at weeks 24, 28 and 48 following HAV vaccination. CONCLUSIONS: We demonstrated faster and better serological responses to HAV revaccination among the HIV-positive individuals who had lost their anti-HAV antibodies after primary vaccination. Single dose of HAV revaccination may provide rapid and sufficient seroresponses for HAV during the outbreak of acute hepatitis A.

Incidence of acute hepatitis A among HIV-positive patients during an outbreak among MSM in Taiwan: Impact of HAV vaccination.

BACKGROUND: An unprecedented outbreak of acute hepatitis A has occurred among MSM in Taiwan since June 2015. We aimed to describe the seroepidemiology of HAV infection and to investigate the relationship between HAV vaccination and the incidence of acute hepatitis A among HIV-positive patients at the largest designated hospital for HIV care during the outbreak. METHODS: Between 2012 and 2016, the HAV serostatus, vaccination history and clinical characteristics of HIV-positive patients were retrospectively reviewed. A case-control study was performed to identify the factors associated with acute hepatitis A. The trends of HAV vaccination rate and incidence of acute hepatitis A among HAV-seronegative patients were examined during the outbreak. RESULTS: During the 4.5-year period, 2088 HIV-positive patients with a mean age of 37.7 years and 90.2% being MSM were included. The overall HAV seroprevalence was 34.3%, which was significantly higher in older and non-MSM patients. The estimated incidence rate of acute hepatitis A was 52.6 cases per 1000 person-years of follow-up during the outbreak. The associated factors with acquiring acute hepatitis A were recent syphilis and having not received HAV vaccines. The HAV vaccination rate during the outbreak increased from 4.7% to 70.6% and the incidence rate of acute hepatitis A declined when up to 65% of the patients were immunized or tested positive for HAV. CONCLUSIONS: The seroprevalence of HAV infection was low in the younger HIV-positive individuals. Prevention of acute hepatitis A was achieved among HIV-positive, HAV-seronegative patients through HAV vaccination and increased herd immunity during the ongoing outbreak.

Serological responses to revaccination against HBV in HIV-positive patients born in the era of nationwide neonatal HBV vaccination.

BACKGROUND: Serological responses to revaccination against hepatitis B virus (HBV) are unclear in HIV-positive adults who had undergone neonatal HBV vaccination and whose antibodies against HBV had waned in the era of combination antiretroviral therapy (cART). METHODS: Between 2000 and 2017, 666 HIV-positive men who have sex with men (MSM) who were born after 1986, when nationwide neonatal HBV vaccination programme was implemented in Taiwan, were included for analyses. A serological response was defined when a hepatitis B surface antibody (anti-HBs) titre ≥10 mIU/mL was measured 4-24 weeks after the third dose of HBV vaccination. RESULTS: During the study period, 295 (48.7%) HIV-positive MSM (mean age, 23.2 years) who had lost HBV seroprotection were eligible for revaccination; 171 (58.0%) received at least 1 dose (20-µg) of HBV vaccine and 116 (39.3%) completed the 3-dose schedule. The serological response rate to 3 doses of HBV revaccination was 74.0% and the rate of high-titre response (anti-HBs titre ≥100 mIU/mL) was 46.0%. The CD4 count before the first dose (per 50-cell/µL increment, adjusted odds ratio, 1.14; 95% confidence interval, 1.01-1.29) was positively associated with the serological response. The incident rate of HBV infection was 9.2 per 1000 person-years of follow-up among the patients who were non-responders after revaccination. CONCLUSIONS: Despite HBV vaccination in the neonatal period, the serological response rate to HBV revaccination in HIV-positive MSM was modest and could wane rapidly. Regular testing of anti-HBs should be integrated into the HIV care despite cART containing HBV-active agents.