The presence of broadly neutralizing anti-SARS-CoV-2 RBD antibodies elicited by primary series and booster dose of COVID-19 vaccine.

Antibody-mediated immunity plays a key role in protection against SARS-CoV-2. We characterized B-cell-derived anti-SARS-CoV-2 RBD antibody repertoires from vaccinated and infected individuals and elucidate the mechanism of action of broadly neutralizing antibodies and dissect antibodies at the epitope level. The breadth and clonality of anti-RBD B cell response varies among individuals. The majority of neutralizing antibody clones lose or exhibit reduced activities against Beta, Delta, and Omicron variants. Nevertheless, a portion of anti-RBD antibody clones that develops after a primary series or booster dose of COVID-19 vaccination exhibit broad neutralization against emerging Omicron BA.2, BA.4, BA.5, BQ.1.1, XBB.1.5 and XBB.1.16 variants. These broadly neutralizing antibodies share genetic features including a conserved usage of the IGHV3-53 and 3-9 genes and recognize three clustered epitopes of the RBD, including epitopes that partially overlap the classically defined set identified early in the pandemic. The Fab-RBD crystal and Fab-Spike complex structures corroborate the epitope grouping of antibodies and reveal the detailed binding mode of broadly neutralizing antibodies. Structure-guided mutagenesis improves binding and neutralization potency of antibody with Omicron variants via a single amino-substitution. Together, these results provide an immunological basis for partial protection against severe COVID-19 by the ancestral strain-based vaccine and indicate guidance for next generation monoclonal antibody development and vaccine design.

Rapid Escherichia coli Cloned DNA Detection in Serum Using an Electrical Double Layer-Gated Field-Effect Transistor-Based DNA Sensor.

In this study, a rapid diagnosis platform was developed for the detection of Escherichia coli O157:H7. An electrical double layer (EDL)-gated field-effect transistor-based biosensor (BioFET) as a point-of-care testing device is demonstrated with its high sensitivity, portability, high selectivity, quick response, and ease of use. The specially designed ssDNA probe was immobilized on the extended gate electrode to bind the target complementary DNA segment of E. coli, resulting in a sharp drain current change within minutes. The limit of detection for target DNA is validated to a concentration of 1 fM in buffer solution and serum. Meanwhile, the results of a Kelvin probe force microscope were shown to have reduced surface potential of the DNA immobilized sensors before and after the cDNA detection, which is consistent with the decreased drain current of the BioFET. A 1.2 kb E. coli duplex DNA synthesized in plasmid was sonicated and detected in serum samples with the sensor array. Gel electrophoresis was used to confirm the efficiency of sonication by elucidating the length of DNA. Those results show that the EDL-gated BioFET system is a promising platform for rapid identification of pathogens for future clinical needs.

Correction: Breadth and function of antibody response to acute SARS-CoV-2 infection in humans.

[This corrects the article DOI: 10.1371/journal.ppat.1009352.].

Breadth and function of antibody response to acute SARS-CoV-2 infection in humans.

Serological and plasmablast responses and plasmablast-derived IgG monoclonal antibodies (MAbs) have been analysed in three COVID-19 patients with different clinical severities. Potent humoral responses were detected within 3 weeks of onset of illness in all patients and the serological titre was elicited soon after or concomitantly with peripheral plasmablast response. An average of 13.7% and 3.5% of plasmablast-derived MAbs were reactive with virus spike glycoprotein or nucleocapsid, respectively. A subset of anti-spike (10 of 32) antibodies cross-reacted with other betacoronaviruses tested and harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection. Fourteen of 32 anti-spike MAbs, including five anti-receptor-binding domain (RBD), three anti-non-RBD S1 and six anti-S2, neutralised wild-type SARS-CoV-2 in independent assays. Anti-RBD MAbs were further grouped into four cross-inhibiting clusters, of which six antibodies from three separate clusters blocked the binding of RBD to ACE2 and five were neutralising. All ACE2-blocking anti-RBD antibodies were isolated from two recovered patients with prolonged fever, which is compatible with substantial ACE2-blocking response in their sera. Finally, the identification of non-competing pairs of neutralising antibodies would offer potential templates for the development of prophylactic and therapeutic agents against SARS-CoV-2.

Immune response and safety of heterologous ChAdOx1-nCoV-19/mRNA-1273 vaccination compared with homologous ChAdOx1-nCoV-19 or homologous mRNA-1273 vaccination.

BACKGROUND/PURPOSE: Efficacy and safety data of heterologous prime-boost vaccination against SARS-CoV-2 remains limited. METHODS: We recruited adult volunteers for homologous or heterologous prime-boost vaccinations with adenoviral (ChAdOx1, AstraZeneca) and/or mRNA (mRNA-1273, Moderna) vaccines. Four groups of prime-boost vaccination schedules were designed: Group 1, ChAdOx1/ChAdOx1 8 weeks apart; Group 2, ChAdOx1/mRNA-1273 8 weeks apart; Group 3, ChAdOx1/mRNA-1273 4 weeks apart; and Group 4, mRNA-1273/mRNA-1273 4 weeks apart. The primary outcome was serum anti-SARS-CoV-2 IgG titers and neutralizing antibody titers against B.1.1.7 (alpha) and B.1.617.2 (delta) variants on day 28 after the second dose. Adverse events were recorded up until 84 days after the second dose. RESULTS: We enrolled 399 participants with a median age of 41 years and 75% were female. On day 28 after the second dose, the anti-SARS-CoV-2 IgG titers of both heterologous vaccinations (Group 2 and Group 3) were significantly higher than that of homologous ChAdOx1 vaccination (Group 1), and comparable with homologous mRNA-1273 vaccination (Group 4). The heterologous vaccination group had better neutralizing antibody responses against the alpha and delta variant as compared to the homologous ChAdOx1 group. Most of the adverse events (AEs) were mild and transient. AEs were less frequent when heterologous boosting was done at 8 weeks rather than at 4 weeks. CONCLUSION: Heterologous ChAdOx1/mRNA-1273 vaccination provided higher immunogenicity than homologous ChAdOx1 vaccination and comparable immunogenicity with the homologous mRNA-1273 vaccination. Our results support the safety and efficacy of heterologous prime-boost vaccination using the ChAdOx1 and mRNA-1273 COVID-19 vaccines. (ClinicalTrials.gov number, NCT05074368).

National Surveillance of Antimicrobial Susceptibility of Bacteremic Gram-Negative Bacteria with Emphasis on Community-Acquired Resistant Isolates: Report from the 2019 Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART).

A multicenter collection of bacteremic isolates of Escherichia coli (n = 423), Klebsiella pneumoniae (n = 372), Pseudomonas aeruginosa (n = 300), and Acinetobacter baumannii complex (n = 199) was analyzed for susceptibility. Xpert Carba-R assay and sequencing for mcr genes were performed for carbapenem- or colistin-resistant isolates. Nineteen (67.8%) carbapenem-resistant K. pneumoniae (n = 28) and one (20%) carbapenem-resistant E. coli (n = 5) isolate harbored blaKPC (n = 17), blaOXA-48 (n = 2), and blaVIM (n = 1) genes.

Early Seroreversion After 2 Doses of Hepatitis A Vaccination in Human Immunodeficiency Virus-Positive Patients: Incidence and Associated Factors.

Serological responses (Seroresponse) and durability of hepatitis A virus (HAV) vaccination are reduced among human immunodeficiency virus (HIV)-positive patients. Incidence of and associated factors with early seroreversion (loss of seroresponse) among HIV-positive patients who have achieved seroresponses after two doses of HAV vaccination remain unclear. In this multicenter study, we followed HIV-positive adults who had mounted seroresponses after completing two doses of HAV vaccination during a recent outbreak of acute hepatitis A between 2015 and 2017, a 1:4 case-control study was conducted to identify factors associated with seroreversion. Case patients were those with seroreversion, and controls were those with similar follow-up durations who were able to maintain seroresponses. During the study period, 49 of the 1,256 patients (3.9%) seroreverted after a median follow-up of 611 days. In a case-control study, seroreversion was more likely to occur in patients with a higher weight (adjusted odds ratio [aOR], 1.703; 95% confidence interval [CI], 1.292-2.323, per 10-kg increment) and HIV viremia at the time of vaccination (aOR, 2.922; 95% CI, 1.067-7.924), whereas positive seroresponse at 6 months of HAV vaccination and higher CD4 lymphocyte counts at vaccination were inversely associated with early seroreversion with an aOR of 0.059 (95% CI, 0.020-0.154) and 0.837 (95% CI, 0.704-0.979, per 100-cell/mm3 increment), respectively, in multivariable analyses. Conclusion: During an outbreak setting, early seroreversion following two-dose HAV vaccination occurred in 3.9% of HIV-positive patients. Lower and delayed seroresponses to HAV vaccination, a higher weight, and HIV viremia and lower CD4 lymphocyte counts at the time of HAV vaccination were associated with early seroreversion. Regular monitoring of seroresponse and booster vaccination might be warranted, especially in HIV-positive adults with predictors of early seroreversion.

Tenofovir disoproxil fumarate-associated hypophosphatemia as determined by fractional excretion of filtered phosphate in HIV-infected patients.

INTRODUCTION: Tenofovir disoproxil fumarate (TDF) -containing regimens have been associated with nephrotoxicity and hypophosphatemia in HIV-infected patients. The objective of this study was to assess the possible risk factors for hypophosphatemia and evaluate the relationship between fractional excretion of filtered phosphate (FePi) and hypophosphatemia in TDF users. PATIENT AND METHODS: Patients were enrolled in a prospective cohort study between January 2011 and December 2014. We classified experienced HIV-infected patients (individuals maintained on antiretroviral therapy (ART) for 6 months or more) and naïve patients into 3 treatment groups: TDF-containing ART (group 1), non-TDF-containing ART (never received TDF or had not received TDF in the past 6 months; group 2) and naive to antiretroviral therapy (group 3). Specimens from each individual were assessed for serum phosphate, serum creatinine, urine phosphate, and urine creatinine. Multivariable logistic regression was performed to control for the following variables measured at baseline: eGFR, age, sex, sexual orientation, injection drug use (IDUs), HIV-RNA viral load, and CD4 cell count. RESULTS: The frequency of hypophosphatemia in groups 1, 2, and 3 was 20.2%, 7.2%, and 14.6%, respectively (P = 0.002). FePi above 10% also was significantly associated with hypophosphatemia (P = 0.003; adjusted odds ratio = 2.54). Patients with elevated CD4 cell counts (>500 cells/µL) exhibited a lower risk of hypophosphatemia (P = 0.002; adjusted odds ratio = 0.35). CONCLUSIONS: Hypophosphatemia is a multifactorial etiology; FePi was confirmed as a suggested method to predict the risk of hypophosphatemia in TDF users. Clinical Trial Number: TYGH103011.

Oncogenic human papillomavirus is not helpful for cytology screening of the precursor lesions of anal cancers in Taiwanese men who are infected with human immunodeficiency virus.

BACKGROUND: Homosexual men infected with human immunodeficiency virus (HIV) are at increased risk of developing anal cancer. The aim of this study was to assess the clinical sensitivity of anal cytology analysis and oncogenic human papillomavirus (HPV) detection for predicting histological anal intraepithelial neoplasia. METHODS: Between March 2011 and December 2013, we enrolled 196 HIV-positive men in Taoyuan General Hospital, Taiwan. We analyzed the results of thin-preparation anal Pap smears, HPV genotyping, and histology of anoscopic biopsy samples. RESULTS: The mean age (±standard deviation) was 31.43 (±8.74) years. The proportion (95 % confidence interval) with abnormal thin-preparation anal cytology was 36.2 % (29.8-43.2 %): 16.8 % (12.2-22.7 %) atypical squamous cells of undetermined significance, 14.8 % (10.5-20.4 %) low-grade squamous intraepithelial lesions, and 4.6 % (2.4-8.5 %) high-grade squamous intraepithelial lesions. At least one HPV genotype was detected in 90.8 % of subjects, and the mean number of HPV infection types was 4.41 (±3.24).The frequency of histological high-grade anal intraepithelial lesions was 7.14 % (95 % confidence interval 4.3-11.6 %). Anal cytology yielding atypical squamous cells of undetermined significance or higher grades resulted in a sensitivity of 64.3 %, specificity of 65.9 %, positive predictive value of 12.7 %, and negative predictive value of 96 %. Using both oncogenic HPV and cytology did not provide better performance. CONCLUSIONS: Anal cytology yielding atypical squamous cells of undetermined significance or higher grades could detect two-thirds of high-grade anal intraepithelial neoplasias in HIV-infected men and should be promoted for anal cancer prevention.

Screening and risk factors for anal cancer precursors in men infected with HIV in Taiwan.

Homosexual men infected with human immunodeficiency virus (HIV) are at a greater risk of developing anal cancer. Men who are infected with HIV and visited the outpatient clinics in Taoyuan General Hospital were enrolled to this study. During March to December 2011, thin preparation anal Pap smear and human papillomavirus (HPV) genotyping were performed in 230 subjects, of which 69 subjects underwent anoscopic biopsy. Their mean age was 32.9 ± 8.1 years, and 181 (78.6%) men were homosexual. The proportion and 95% confidence interval (CI) of subjects with anal dysplasia in cytology was 23.0% (17.56-28.44), including 13.4% (9.26-18.14) with atypical squamous cells of undetermined significance, 7.0% (3.70-10.30) with low-grade squamous intraepithelial lesions, and 2.6% (0.54-4.66) with high-grade squamous intraepithelial lesions. For participants having atypical squamous cells of undetermined significance or higher grades, multivariate logistic regression models yielded adjusted odds ratios (95% CI) of 12.61 (1.63-97.56) for homosexuality, 1.62 (1.31-2.00) for number of oncogenic HPV types, and 1.01 (1.00-1.02) for number of lifetime sexual partners. For detection of histological grade II or III anal intraepithelial neoplasm in anoscopic biopsies, the sensitivity of sequential tests for oncogenic HPV and cytology with atypical squamous cells of undetermined significance or higher grades was 100%. The positive likelihood ratio was 3.09 (P = 0.05). It is important to consider anal cancer precursors among homosexual men who are infected with HIV. Anal cytology and oncogenic HPV genotyping testing are effective screening methods.

The impact of HAART initiation timing on HIV-TB co-infected patients, a retrospective cohort study.

BACKGROUND: Optimal timing for initiating highly active antiretroviral therapy (HAART) in HIV-TB coinfected patients is challenging for clinicians. We aim to evaluate the impact of different timing of HAART initiation on TB outcome of HIV-infected adults in Taiwan. METHODS: A population-based retrospective cohort study was conducted through linking the HIV and TB registries of Taiwan Centers for Disease Control (CDC) during 1997 to 2006. Clinical data of HIV-TB co-infected patients, including the presence of immune reconstitution inflammatory syndrome (IRIS), was collected through medical records review. The outcome of interest was all-cause mortality within 1 year following TB diagnosis. The Cox proportional hazard model was used to explore the probability of death and IRIS after TB diagnosis by adjusting for confounding factors and factors of interest. The probability of survival and TB IRIS were calculated by the Kaplan-Meier method and compared between different HAART initiation timing groups by the log-rank test. RESULTS: There were 229 HIV-TB co-infected patients included for analysis and 60 cases (26.2%) died within one year. Besides decreasing age and increasing CD4 lymphocyte count, having started HAART during TB treatment was significantly associated with better survival (adjusted Hazard Ratio was 0.11, 95% CI 0.06-0.21). As to the timing of HAART initiation, there was only non-significant benefit on survival among cases initiating HAART within 15 days, at 16-30 days and at 31-60 days of TB treatment than initiating after 60 days. Cases with HAART initiated after 30 days had lower risk in developing IRIS than cases with HAART initiated earlier. Cases with IRIS had significantly higher rate of re-hospitalization (49% vs. 4%, p < 0.001) and prolonged hospitalization (28 days vs. 18.5 days, p < 0.01). CONCLUSION: The present study found that starting HAART during TB treatment is associated with better one-year survival, although earlier initiation within 60 days of TB treatment did not show statistical differences in survival than later initiation. Initiation of HAART within 30 days appeared to increase the risk of IRIS. Deferring HAART to 31-60 days of TB treatment might be optimal after considering the risks and benefits.

Skin rash related to once-daily boosted darunavir-containing antiretroviral therapy in HIV-infected Taiwanese: incidence and associated factor.

OBJECTIVES: The study aimed to investigate the incidence of and associated factors with skin rashes among HIV-infected Taiwanese patients who received once-daily darunavir (DRV) boosted by ritonavir (RTV) (800/100 mg) plus 2 nucleoside reverse-transcriptase inhibitors (NRTIs). METHODS: We reviewed the medical records of HIV-infected patients who switched to once-daily DRV/RTV-containing regimens between January 2012 and November 2013. Patients who switched from 2 NRTIs plus non-NRTI (nNRTI) or other protease inhibitor (PI) to 2 NRTIs plus PIs other than DRV were chosen as comparators. RESULTS: During the study period, 238 patients who switched to once-daily DRV/RTV-containing regimens (Group A) and 178 patients who switched from 2 NRTIs plus nNRTI or other PI to 2 NRTIs plus PI other than DRV/RTV (Group B) were included. There were no differences between Groups A and B in most of the baseline characteristics. Compared with Group B in which 7 (3.9%) developed rashes after switch to PI other than DRV, 26 patients (10.9%) in Group A developed rashes after a median interval of 14 days of starting DRV/RTV-containing regimens (P = 0.009). In multivariate analysis, patients with a history of rashes related to the previous nNRTI-containing regimens before starting DRV/RTV-containing regimens were more likely to develop rashes with an adjusted odds ratio of 3.53 (95% confidence interval, 1.45-8.62). CONCLUSIONS: Once-daily regimens containing DRV/RTV is associated with a higher rate of adverse cutaneous reactions than other PI-containing regimens in HIV-infected Taiwanese, especially in those who have a history of rashes to nNRTI-containing regimens before switch to DRV/RTV-containing regimens.

Comparable clinical outcomes with same-day versus rapid initiation of antiretroviral therapy in Taiwan.

OBJECTIVES: WHO has recommended same-day antiretroviral therapy (SDART) initiation since 2017; however, higher attrition rates were noted in developing countries. METHODS: We included newly diagnosed people with HIV (PWH) from 2018 to 2022 at 18 hospitals around Taiwan. SDART initiation was defined as starting ART on the same day of HIV diagnosis and rapid initiation as starting ART within 14 days of diagnosis. A composite unfavorable outcome was defined as death after 30 days of diagnosis, loss to follow-up (LTFU), or virologic failure or rebound at 12 months. RESULTS: At 12 months, PWH on SDART initiation and those on rapid ART initiation showed similar rates of engagement in care with plasma HIV-1 RNA <50 copies/mL (87.5% vs 87.7%) and composite unfavorable outcome (7.7% vs 7.7%). PWH aged >30 years were less likely to have LTFU (aHR 0.44, 95% CI 0.28-0.70). PWH aged >30 years (aHR 0.59, 95% CI 0.41-0.85) and gay, bisexual, and men who have sex with men (GBMSM) (aHR 0.50, 95% CI 0.32-0.79) were less likely to have composite unfavorable outcomes. CONCLUSIONS: SDART and rapid ART initiation resulted in comparable clinical outcomes and viral suppression rates. PWH aged >30 years and GBMSM were less likely to have unfavorable outcomes.

Clinical assessment of SARS-CoV-2 infectivity by rapid antigen test compared with virus isolation.

Although real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) remains as a golden standard for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, it can not be easily expanded to large-scaled screening during outbreaks, and the positive results do not necessarily correlate with infectious status of the identified subjects. In this study, the performance of Vstrip® RV2 COVID-19 Antigen Rapid Test (RAT) and its correlation with virus infectivity was examined by virus culture using 163 sequential respiratory specimens collected from 26 SARS-CoV-2 infected patients. When the presence of cytopathic effects (CPE) in cell culture was used as a reference method for virus infectivity, the sensitivity, specificity and accuracy of Vstrip® RV2 COVID-19 Antigen Rapid Test was 96.43%, 89.63%, and 90.8%, respectively. The highest Ct value was 27.7 for RdRp gene and 25.79 for E gene within CPE-positive samples, and the highest Ct value was 31.9 for RdRp gene and 29.1 for E gene within RAT positive samples. When the Ct values of specimens were below 25, the CPE and RAT results had high degree of consistency. We concluded that the RAT could be a great alternative method for determining the infectious potential of individuals with high viral load.

Week 96 Results of Switching from Tenofovir Disoproxil Fumarate-Based Antiretroviral Therapy to Coformulated Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide among HIV/Hepatitis B Virus-Coinfected Patients.

Data regarding the durability of tenofovir alafenamide (TAF)-containing antiretroviral therapy (ART) in maintaining hepatitis B virus (HBV) viral suppression among HIV/HBV-coinfected patients are limited. Between February and October 2018, 274 HIV/HBV-coinfected participants who had achieved HIV RNA of <50 copies/mL with tenofovir disoproxil fumarate (TDF)-containing ART and switched to elvitegravir/cobicistat/emtricitabine/TAF were prospectively enrolled. Serial plasma HIV and HBV viral loads, HBV and hepatitis D virus (HDV) serology, renal parameters, metabolic profiles, and bone mineral density (BMD) were assessed through 96 weeks. At baseline and weeks 48, 72, and 96, 5.8%, 5.1%, 5.8%, and 5.1% of the participants had plasma HBV DNA of ≥20 IU/mL, and 0%, 0.7%, 1.5%, and 2.2% had HIV RNA of ≥50 copies/mL, respectively. Hepatitis B surface antigen (HBsAg) loss occurred in 1.5% of 274 participants, and hepatitis B e-antigen (HBeAg) loss or seroconversion occurred in 14.3% of 35 HBeAg-positive participants. Compared with baseline, the median urine protein-to-creatinine ratio (79 versus 63 mg/g, P < 0.001) and ß2-microglobulin-to-creatinine ratio (165 versus 83 µg/g, P < 0.001) continued to decrease at week 96. BMD of the spine and hip slightly increased (mean change, +0.9% and +0.5%, respectively). The median triglycerides, total cholesterol, low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein (HDL)-cholesterol increased from baseline to week 96 (116 versus 141, 166 versus 190, 99 versus 117, and 42 versus 47 mg/dL, respectively; all P < 0.001), and most of the increases occurred in the first 48 weeks of the switch. Our study showed that switching from TDF-containing ART to elvitegravir/cobicistat/emtricitabine/TAF maintained HBV and HIV viral suppression through 96 weeks among HIV/HBV-coinfected patients. Proteinuria continued to improve, while fasting lipids increased and BMD stabilized at 96 weeks after the switch. IMPORTANCE Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide as a maintenance therapy showed durable and high rates of viral suppression for HIV/HBV-coinfected patients, with only 5.1% and 2.2% of patients having HBV DNA of ≥20 IU/mL and HIV RNA of ≥50 copies/mL, respectively, at 96 weeks. Our study fills the data gap on the long-term clinical effectiveness of tenofovir alafenamide-containing antiretroviral therapy in people living with HIV who have HBV coinfection.

Longitudinal neutralizing antibody responses after SARS-CoV-2 infection: A convalescent cohort study in Taiwan.

BACKGROUND: Understanding the neutralizing antibody (NAb) titer against COVID-19 over time is important to provide information for vaccine implementation. The longitudinal NAb titer over one year after SARS-CoV-2 infection is still unclear. The purposes of this study are to evaluate the duration of the neutralizing NAb titers in COVID-19 convalescents and factors associated with the titer positive duration. METHODS: A cohort study followed COVID-19 individuals diagnosed between 2020 and 2021 May 15th from the COVID-19 database from the Taiwan Centers for Disease Control. We analyzed NAb titers from convalescent SARS-CoV-2 individuals. We used generalized estimating equations (GEE) and a Cox regression model to summarize the factors associated with NAb titers against COVID-19 decaying in the vaccine-free population. RESULTS: A total of 203 convalescent subjects with 297 analytic samples were followed for a period of up to 588 days. Our study suggests that convalescent COVID-19 in individuals after more than a year and four months pertains to only 25% of positive titers. The GEE model indicates that longer follow-up duration was associated with a significantly lower NAb titer. The Cox regression model indicated the disease severity with advanced condition was associated with maintaining NAb titers (adjusted hazard ratio: 2.01, 95% CI: 1.11-3.63) and that smoking was also associated with higher risk of negative NAb titers (adjusted hazard ratio: 0.55, 95% CI: 0.33-0.92). CONCLUSIONS: Neutralizing antibody titers diminished after more than a year. The antibody titer response against SARS-CoV-2 in naturally convalescent individuals provides a reference for vaccinations.

Optimal Frequency of Hepatitis C Virus (HCV) RNA Testing for Detection of Acute HCV Infection Among At-risk People With Human Immunodeficiency Virus: A Multicenter Study.

Using 3-stage pooled-plasma hepatitis C virus (HCV) RNA testing performed quarterly among at-risk people with human immunodeficiency virus (PWH), we found that if testing had been performed every 6 or 12 months, 58.6%-91.7% of PWH who recently acquired HCV would be delayed for diagnosis and might contribute to onward HCV transmission with longer durations.

Influence of age and CD4+ T cell counts on the prevalence of genital human papillomavirus infection among HIV-seropositive men who have sex with men in Taiwan.

This study aimed to examine the baseline prevalence of genital human papillomavirus (HPV) infection among human immunodeficiency virus (HIV)-seropositive men who have sex with men in Taiwan and to determine the association of age and CD4+ T cell counts with HPV infection. In 2010, 305 men who have sex with men infected with HIV and 100 HIV-seronegative men who have sex with men were recruited. Genital swabs were collected and 37 HPV genotypes were detected using linear array HPV genotyping. HPV infection was present in 45.3% of the patients infected with HIV and in 18% of the HIV-negative subjects (P < 0.001). HPV types 52, 51, and 16 were the most commonly identified oncogenic types. Oncogenic HPV types were identified in 31.2% of the patients infected with HIV and in 13% of the seronegative subjects (P < 0.001). Adjusted odd ratios (ORs) for the detection of any HPV type were 2.9 (95% confidence interval [CI], 1.4-5.9) for men who have sex with men aged 30-34 and 2.1 (95% CI, 1.1-4.3) for those aged >35 compared with that for those aged <25. ORs were 2.8 (95% CI, 1.0-7.4) for a CD4+ T cell count of 200-350 cells/µl and 8.5 (95% CI, 2.9-24.5) for a CD4+ T cell count of <200 cells/µl compared with that for seronegative subjects. In conclusion, this novel HPV study, carried out in Northern Taiwan on men who have sex with men, revealed that age and immune state were associated significantly and independently with HPV infection.

Safety and Immunogenicity of a Heterologous Booster of Protein Subunit Vaccine MVC-COV1901 after Two Doses of Adenoviral Vector Vaccine AZD1222.

We report the safety and immunogenicity results in participants administrated with a booster dose of protein subunit vaccine MVC-COV1901 at 12 (Group A) or 24 (Group B) weeks after two doses of AZD1222 (ChAdOx1 nCoV-19). The administration of the MVC-COV1901 vaccine as a booster dose in both groups was generally safe. There were no serious adverse events related to the intervention as adverse events reported were "mild" or "moderate" in nature. In subjects fully vaccinated with two doses of AZD1222, waning antibody immunity was apparent within six months of the second dose of AZD1222. At one month after the MVC-COV1901 booster dose, those who were vaccinated within 12 weeks after the last AZD1222 dose (Group A) had anti-SARS-CoV-2 spike IgG antibody titers and neutralizing antibody titers which were 14- and 6.5-fold increased, respectively, when compared to the titer levels on the day of the booster dose. On the other hand, fold-increase a month post-booster in people who had a booster 24 weeks after the last AZD1222 dose (Group B) were 19.5 and 14.0 times for anti-SARS-CoV-2 spike IgG antibody titers and neutralizing antibody titers, respectively. Among those who were vaccinated within 12 weeks after the last AZD1222 dose, we also observed 5.2- and 5.6-fold increases in neutralizing titer levels against ancestral strain and Omicron variant pseudovirus after the booster dose, respectively. These results support the use of MVC-COV1901 as a heterologous booster for individuals vaccinated with AZD1222. Furthermore, regardless of the dosing schedule, the combination of AZD1222 primary series and MVC-COV1901 booster can be cost-effective and suitably applied to low- and middle-income countries (LMIC).

Incidence and Risk Factors of Reinfection with HCV after Treatment in People Living with HIV.

Infection with hepatitis C virus (HCV) does not induce protective immunity, and re-exposure to HCV can reinfect the population engaging in high-risk behavior. An increasing incidence of acute hepatitis C infection in people living with HIV (PLWH) has been described in recent years. This retrospective cohort study was conducted in PLWH who completed HCV therapy between June 2009 and June 2020 at an HIV care hospital, to analyze their basic characteristics and risky behavior. Of 2419 patients, 639 were diagnosed with HCV infection and 516 completed the HCV therapy with a sustained virologic response. In total, 59 patients (11.4%) were reinfected with acute hepatitis C, and the median time to reinfection was 85.3 weeks (IQR: 57-150). The incidence of reinfection was 6.7 cases/100 person-years. The factors associated with reinfection were being male (AHR, 8.02; 95% CI 1.08-59.49), DAA (direct-acting antiviral) treatment (AHR, 2.23; 95% CI 1.04-4.79), liver cirrhosis (AHR, 3.94; 95% CI 1.09-14.22), heroin dependency (AHR: 7.41; 95% CI 3.37-14.3), and HIV viral loads <50 copies/mL at the follow-up (AHR: 0.47, 95% CI 0.24-0.93) in the subgroup of people who inject drugs (PWID). Amphetamine abuse (AHR: 20.17; 95% CI 2.36-172.52) was the dominant factor in the subgroup of men who have sex with men (MSM). Our study suggests that education and behavioral interventions are needed in this population to prevent reinfection.