A Dynamic Model for Estimating the Retention Duration of Neutralizing Antibody Titers After Vaccination in a COVID-19 Convalescent Population.

We measured neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a cohort of 235 convalescent patients (representing 384 analytic samples). They were followed for up to 588 days after the first report of onset in Taiwan. A proposed Bayesian approach was used to estimate nAb dynamics in patients postvaccination. This model revealed that the titer reached its peak (1819.70 IU/mL) by 161 days postvaccination and decreased to 154.18 IU/mL by day 360. Thus, the nAb titers declined in 6 months after vaccination. Protection, against variant B.1.1.529 (ie, Omicron) may only occur during the peak period.

Assessment of the performance regarding confirmatory diagnosis and initiation of antiretroviral therapy under a modified national HIV testing algorithm and pay-for-performance program in Taiwan.

BACKGROUND: A pay-for-performance plan for rapid antiretroviral therapy (ART) commencement was initiated in 2018, while a modified testing algorithm offers immunochromatographic test (ICT) to replace Western blot (WB), and simultaneous testing with ICT and Nucleic Acid Amplification Test (NAAT) for HIV-positive sera was adopted in 2019 in Taiwan. METHODS: Serum specimens collected from 1117 suspected or confirmed HIV infection cases in 2016-2019 were reassessed the performance of WB, ICT, and NAAT. We reviewed the medical records of 10,732 individuals diagnosed with HIV in 2015-2021 to determine the time from screening to confirmatory diagnosis, followed by ART commencement. RESULTS: All 860 WB-positives were also positive by ICT and NAAT. The positive detection percentages were 37.0% by ICT and 51.4% by NAAT for 257 WB-indeterminate and -negative sera. The sensitivity for WB and ICT was 93.8% and 95.5%, respectively. In the people living with HIV (PLHIV) cohort, the median time from initial positive to confirmatory diagnosis decreased from 5 to 6 days before 2019 to 1 day in 2021. The median time from initial positive to ART initiation decreased from 37 days in 2015, 14 days in 2018, to 6 days in 2021. Compared to 2015-2017, the time to ART initiation was 91.48 days lower in 2018 (P < 0.001) and 100.66 days lower in 2019-2021 (P < 0.001) by the adjusted linear regression model. CONCLUSION: A significant decrease in the time to ART initiation was observed after initiation of the pay-for-performance program and optimized testing algorithm in Taiwan.

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.

Towards the first 90: impact of the national HIV self-test program on case finding and factors associated with linkage to confirmatory diagnosis in Taiwan.

INTRODUCTION: Being aware of one's HIV-positive status can help reduce unprotected sex and promote early treatment seeking. Therefore, HIV self-test (HIVST) programs may help control the HIV epidemic by case finding. The aims of this study were to determine the effect of HIVST programs on HIV case finding, time to confirmatory diagnosis and factors associated with linkage to confirmatory diagnosis in Taiwan. METHODS: The Centers for Disease Control in Taiwan initiated HIVST programs and imported 78,000 self-test kits in 2017 and 2019. Clients paid 7 US dollars for a self-test kit at facilities, vending machines or online. The programs set up an HIVST logistics management system; each kit had a unique barcode for monitoring the programs because purchases were anonymous. When clients provided their test results with photo barcodes online or at HIV/AIDS-designated hospitals, they received full monetary reimbursement. We conducted a quasi-experimental interrupted time-series (ITS) analysis that covered a period of 60 months from 2015 to 2019. We enrolled a retrospective cohort of reported HIV cases with initial positive results from HIVST programs between March 2017 and July 2020. RESULTS: The ITS analysis included data from 10,976 reported HIV cases from 2015 to 2019. The HIVST-positive cohort included 386 reported HIV cases, of whom 99.7% were males and 97% were men who have sex with men (MSM); the median age was 28 years. The ITS analysis showed a positive slope change in the number of reported HIV cases immediately in the beginning implementation month (coefficient: 51.09 in 2017 and 3.62 in 2019), but there was a significant decrease over time. It was a negative slope change by 9.52 cases per month in 2017 and 5.56 cases per month in 2019. In the HIVST-positive cohort, three of five individuals linked to HIV confirmatory diagnosis within 1 month after a positive self-test result, and an early linkage to confirmatory diagnosis was associated with HIVST disclosure (adjusted OR = 6.5; 95% CI: 3.9-10.6). CONCLUSIONS: HIVST programs were associated with an increase in HIV case finding. Our findings suggest that countries with a high incidence of HIV among MSM populations should offer multichannel HIVST services.

Estimating HIV incidence, prevalence, and percent of undiagnosed infections in Taiwan using CD4 data.

BACKGROUND/PURPOSE: Estimation of the human immunodeficiency virus (HIV) epidemic trend and percent of undiagnosed infections is an important measure for the assessment of HIV control programs. In this study, we aimed to investigate and estimate the HIV incidence, HIV prevalence, and percent of undiagnosed HIV infections in Taiwan using the CD4 depletion model. METHODS: Data on newly reported HIV diagnoses during 2012-2019 were obtained from the National HIV/AIDS reporting and case management system. We used an Asian-adjusted CD4 depletion model to determine diagnosis delays and then used this distribution and HIV case surveillance data to estimate the incidence, prevalence and percent of undiagnosed infections. RESULTS: The estimated HIV incidence rate decreased after 2012, from 9.4 per 100,000 people (95% confidence interval [CI]: 8.7 to 10.2) to 7.1 per 100,000 people (95% CI: 5.7 to 8.5) in 2019. The prevalence rate increased from 111 per 100,000 people (95% CI: 107 to 116) in 2012 to 158 per 100,000 people (95% CI: 146 to 169) in 2019, whereas the undiagnosed rate decreased from 21.5% (95% CI: 18.2%-24.8%) in 2012 to 12.1% (95% CI: 8.9%-15.2%) in 2019. In addition, the undiagnosed percentage in the population of men who have sex with men (MSM) also decreased from 28.8% to 13.6% during this period. CONCLUSION: We found decreases in the HIV incidence and undiagnosed percentage from 2012 to 2019 in Taiwan. These findings highlight the importance of intensified HIV testing efforts to achieve the global 95-95-95 goals by 2030.

An outbreak of HIV infection among people who inject drugs linked to injection of propofol in Taiwan.

INTRODUCTION: The aim of this study was to report an HIV outbreak related to propofol-injection and the impact of regulating propofol on the HIV epidemic among people who inject drugs (PWID). METHODS: A retrospective cohort study of 252 PWID who were diagnosed with an HIV infection between 2014 and 2017 in Taiwan. The propofol information was collected by routine epidemic surveillance and interviews. We linked several national databases to collect other related factors, including methadone maintenance treatment (MMT) attendance and incarceration. The serums were tested for recent infection by the LAg-avidity EIA assay and relationship of the trains by the Phylogenetic tree analysis. Analyses were conducted using the R Surveillance package for retrospective modeling for outbreak detection. A multiple logistic regression was used to evaluate the association between propofol-injection and other related factors. RESULTS: There were 28 cases reported with propofol-injection, all of which were reported in Central Taiwan. A total of 11 (50%) cases among 22 propofol-injectors with serums were recent infections, which were higher than that 33 (23.4%) of non-propofol group. The phylogenetic tree indicated that 6 propofol-injectors were grouped together with the same cluster in circular. The HIV epidemic curve among PWID revealed an outbreak of 82 in 2015, which then decreased to 43 in 2016 after propofol began to be regulated as a Schedule 4 controlled drug in August 2015. In a multiple logistic regression, attendance at methadone clinics was associated with a significantly higher risk for propofol-injection (adjusted OR = 2.43, 95% CI = 0.98-5.98), and HIV reported in the year 2015 was associated with an increased risk of propofol-injection (adjusted OR = 4, 95% CI = 1.08-14.86). CONCLUSIONS: Our data indicate that the government regulation of propofol as a controlled drug strategy was associated with significant reduction in the spread of HIV among PWID.

Changes in HIV incidence among people who inject drugs in Taiwan following introduction of a harm reduction program: a study of two cohorts.

BACKGROUND: Harm reduction strategies for combating HIV epidemics among people who inject drugs (PWID) have been implemented in several countries. However, large-scale studies using sensitive measurements of HIV incidence and intervention exposures in defined cohorts are rare. The aim of this study was to determine the association between harm reduction programs and HIV incidence among PWID. METHODS AND FINDINGS: The study included two populations. For 3,851 PWID who entered prison between 2004 and 2010 and tested HIV positive upon incarceration, we tested their sera using a BED HIV-1 capture enzyme immunoassay to estimate HIV incidence. Also, we enrolled in a prospective study a cohort of 4,357 individuals who were released from prison via an amnesty on July 16, 2007. We followed them with interviews at intervals of 6-12 mo and by linking several databases. A total of 2,473 participants who were HIV negative in January 2006 had interviews between then and 2010 to evaluate the association between use of harm reduction programs and HIV incidence. We used survival methods with attendance at methadone clinics as a time-varying covariate to measure the association with HIV incidence. We used a Poisson regression model and calculated the HIV incidence rate to evaluate the association between needle/syringe program use and HIV incidence. Among the population of PWID who were imprisoned, the implementation of comprehensive harm reduction programs and a lower mean community HIV viral load were associated with a reduced HIV incidence among PWID. The HIV incidence in this population of PWID decreased from 18.2% in 2005 to 0.3% in 2010. In an individual-level analysis of the amnesty cohort, attendance at methadone clinics was associated with a significantly lower HIV incidence (adjusted hazard ratio: 0.20, 95% CI: 0.06-0.67), and frequent users of needle/syringe program services had lower HIV incidence (0% in high NSP users, 0.5% in non NSP users). In addition, no HIV seroconversions were detected among prison inmates. CONCLUSIONS: Although our data are affected by participation bias, they strongly suggest that comprehensive harm- reduction services and free treatment were associated with reversal of a rapidly emerging epidemic of HIV among PWID. Please see later in the article for the Editors' Summary.

Higher methadone doses are associated with lower mortality in patients of opioid dependence in Taiwan.

Optimal methadone dosage and service profile is challenging in treatment of opioid dependence. This study explores the impact of methadone dosage on the mortality of opioid-dependent patients in methadone maintenance therapy by using a large-scale and continual supervised dosing registry information system. Database of nationwide enrolled opioid-dependent patients at methadone clinics in Taiwan during 2006-2008 was assessed. The relative risk of age, sex, marital status, HIV infection and methadone dosage were analyzed by Cox regression analysis. Among all of the 33,549 recruited patients, the crude mortality rate was 134.78/10,000 person-years, and the standardized mortality ratio was 4.68. A dose-response relationship of higher- vs. lower-dosage groups on the risk of mortality risk was observed (adjusted HR = 0.68, P = 0.016). In further sub-grouping analysis, this trend was more significant in HIV positive patients, in subgroup of patients who continuously staying in MMT, and in subgroup of patients who re-enter MMT. This dosage effect is not significantly seen in patients receiving MMT more than 365 days. Further exploration of other treatment-related factors may be important for understanding the long-term treatment outcome of opioid addiction patients.

Syphilis among men who have sex with men (MSM) in Taiwan: its association with HIV prevalence, awareness of HIV status, and use of antiretroviral therapy.

To understand how awareness of HIV-positivity and the use of antiretroviral therapy associated with syphilis infection, 361 MSM attending 16 Hong-Pa (drug-and-sex parties) in Taiwan were studied. The syphilis rate of individuals within their first 2 years after HIV diagnosis (awareness) was lower than that in individuals who had not been diagnosed HIV infection prior to Hong-Pa (unawareness) (Adj OR = 0.24, P < 0.05). Notably, there was a decrease in the beneficial effect of HIV-positive status awareness on syphilis prevention with an increase in time since notification. Moreover, antiretroviral therapy was not associated with a lower incidence of syphilis, and syphilis infection peaked during the treatment dropout period. In conclusion, the duration of a protective effect of knowing one's HIV-positivity against syphilis infection was short, and the highest risk of syphilis infection was observed when patients discontinued antiretroviral therapy. Future research should examine the behavioral mechanisms involved in this prevention failure.

Mortality among a cohort of drug users after their release from prison: an evaluation of the effectiveness of a harm reduction program in Taiwan.

AIMS: To determine the effect of methadone maintenance therapy (MMT) on mortality among injection drug users. DESIGN: A cohort of prisoners with a history of injecting opiates who were followed after their release from prison in July 2007. Mortality between July 2007 and December 2008 was determined by linking the National Death Registry with the Methadone Maintenance Treatment (MMT) database. SETTING: Taiwan. PARTICIPANTS: A total of 4357 amnestied prisoners with a history of opiate injection. MEASUREMENTS: The total mortality rates (MR) among the cohort were calculated based on their person-time contribution to methadone attendance and re-incarceration during follow-up. We used survival methods with MMT and re-incarceration as time-varying covariates adjusted for length of follow-up in the community. RESULTS: A total of 142 deaths occurred: 13 in the 1st week after release [MR = 13.7/100 person-years (pyrs)], which was greater than that in the next 4 weeks [MR = 3.2/100 pyrs, relative rate (RR) = 4.3, P < 0.001]. Overall, 1982 (46%) subjects enrolled in MMT; however, 1282 of them discontinued MMT after enrolling. FINDINGS: The mortality among those who continued in MMT attendance was lower (MR = 0.24/100 pyrs) than those who never enrolled in MMT (MR = 2.6/100 pyrs) or those who enrolled but dropped out of MMT (MR = 7.0/100 pyrs) after adjusting for age, gender and human immunodeficiency virus status at amnesty (RR = 0.07). CONCLUSIONS: In ex-prisoners in Taiwan with a history of opiate injecting, enrollment and continued participation in methadone maintenance treatment is associated with substantially lower mortality.

An uncommon case of HIV-1 transmission due to a knife fight.

This article describes a case of human immunodeficiency virus type 1 (HIV-1) infection transmission caused by a bloody knife fight in a robbery. The victim was a 69-year-old man who was not infected with HIV-1, and his wife was HIV-antibody negative. A robber, a 42-year-old man, was HIV antibody-positive since December 2005 and had not taken antiretroviral therapy. The BED IgG Capture incidence EIA (BED-CEIA assay) data showed that the specimens from the victim were compatible with a recent seroconversion. Phylogenetic analysis of fragments of pol, encompassing protease and a portion of reverse transcriptase, and of env genes isolated from the victim, the robber, and a local population samples of HIV-1 positive individuals showed that the victim's HIV-1 sequences were most closely related to and nested within a lineage comprised of the robber's HIV-1 sequences. We provide HIV-1 seroconversion data and phylogenetic analysis as evidence that the HIV-1 transmission likely occurred from contact during the robbery.

Update and projection on HIV/AIDS in Taiwan.

The HIV/AIDS epidemic in Taiwan started in 1986, with 5,221 cases of HIV infections, 1,596 cases of AIDS, and 911 deaths reported through 2003. National surveillance data indicate that men who have sex with men accounted for 48.2% of HIV infections, followed by heterosexual men (33.8%) and heterosexual women (6.1%). Only 353 (6.8%) of all HIV cases are females. The average age of HIV-infected persons, AIDS cases, and deaths was 31.2, 36.2, and 39.0 years, respectively. The incidence of HIV infection has increased by approximately 15% every year since 1997. The continuing epidemic will likely burden the national health care system and may result in an estimated socioeconomic loss of U.S. dollars 1.6 billion in 2010, as 15,125 HIV infections and 1,420 deaths from AIDS are projected. To respond to the HIV/AIDS epidemic in Taiwan, the government has been working with nongovernmental organizations to promote HIV testing, conduct various education programs, and reach out to high-risk groups. HIV/AIDS patients are linked to medical care and provided with free highly active antiretroviral treatment. The main challenge is to reduce HIV-related stigma. Prevention focused on preventing further transmission of HIV by seropositive persons to others is urgently needed in fighting the HIV/AIDS epidemic.