| Sung Soon Kim | 10 Articles |
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<title>Objectives</title>
<p>Vaccinations against diphtheria and tetanus are essential in providing immunity against these bacterial infections. The potency of diphtheria and tetanus toxoid vaccines can be measured using the in vivo toxin neutralization assay. The limit of potency of this assay was determined only for children. Therefore, we assessed the potency of adult vaccines using this assay to identify the feasibility of limit for adult vaccines.</p></sec>
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<title>Methods</title>
<p>Fifteen lots of tetanus-reduced diphtheria and tetanus-diphtheria-acellular pertussis vaccines were used. In vivo toxin neutralization and lethal challenge assays were conducted on each vaccine to calculate the potencies of the toxoids. National reference standards for toxins and antitoxins were used for in vivo toxin neutralization assay.</p></sec>
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<title>Results</title>
<p>All 15 lots satisfied the limits of potency for lethal challenge assay. The potency of diphtheria and tetanus toxoids exceeded 1 and 8 units/mL, respectively, for in vivo toxin neutralization assay.</p></sec>
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<title>Conclusion</title>
<p>Although additional studies are required for new assays and limits, the current level of potency for adult vaccines as determined by in vivo toxin neutralization assay, was demonstrated in this study. Such efforts to improve assays are expected to promote the development of diphtheria and tetanus vaccines for adults and to contribute to vaccine self-sufficiency.</p></sec>
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Objectives
To estimate human immunodeficiency virus (HIV) incidence using HIV avidity assays in Korea, we established a serological testing method to differentiate recent HIV infections from long-standing ones. Methods We adopted two incidence assays, the BED HIV-1 incidence test (Calypte Biomedical) and an HIV avidity assay (using Abbott AxSYM HIV Antigen/Antibody Combo), and performed them on Korean HIV samples obtained from 81 HIV seroconverters (<i>n</i> = 193), 135 HIV-positive samples, and three HIV commercial incidence panels (PRB965, PRB933, and PRB601 from SeaCare). To determine the most optimal concentration of the chaotropic agent (Guanidine) and the cutoff value for the avidity assay, we evaluated the sensitivity and specificity of the assay at different concentration levels. Results We determined that the concentration of Guanidine to be used in the avidity assay was 1.5M. The cutoff value of the avidity index (AI) was 0.8, and the sensitivity and specificity were 90.2% and 83.8%, respectively, under this condition. The gray zone for the avidity assay was 0.75–0.85 AI. The mean of coefficient of variation was low, at 5.43%. Conclusion An optimized avidity assay for the diagnosis of recent HIV infections using Korean samples was established. This assay will be applied to investigate the level of recent infection and will provide basic data to the HIV prevention policy in Korea. Citations
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Objectives
Measurement of the incidence of the human immunodeficiency virus (HIV) is very important for epidemiological studies. Here, we determined the recency period with the AxSYM avidity assay and the BED-capture enzyme immunoassay (BED-CEIA) in Korean seroconverters. Methods Two hundred longitudinal specimens from 81 seroconverters with incident HIV infections that had been collected at the Korea National Institute of Health were subjected to the AxSYM avidity assay (cutoff = 0.8) and BED-CEIA (cutoff = 0.8). The statistical method used to estimate the recency period in recent HIV infections was nonparametric survival analyses. Sensitivity and specificity were calculated for 10-day increments from 120 days to 230 days to determine the recency period. Results The mean recency period of the avidity assay and BED-CEIA using a survival method was 158 days [95% confidence interval (CI), 135–181 days] and 189 days (95% CI, 170–208 days), respectively. Based on the use of sensitivity and specificity, the mean recency period for the avidity assay and BED-CEIA was 150 days and 200 days, respectively. Conclusion We determined the recency period to estimate HIV incidence in Korea. These data showed that the nonparametric survival analysis often led to shorter recency periods than analysis of sensitivity and specificity as a new method. These findings suggest that more data from seroconverters and other methodologies are needed to determine the recency period for estimating HIV incidence. Citations
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From the introduction of HIV into the Republic of Korea in 1985 through 2012, 9,410 HIV-infected Koreans have been identified. Since 2000, there has been a sharp increase in newly diagnosed HIV-infected Koreans. It is necessary to estimate the changes in HIV infection to plan budgets and to modify HIV/AIDS prevention policy. We constructed autoregressive integrated moving average (ARIMA) models to forecast the number of HIV infections from 2013 to 2017. Methods HIV infection data from 1985 to 2012 were used to fit ARIMA models. Akaike Information Criterion and Schwartz Bayesian Criterion statistics were used to evaluate the constructed models. Estimation was via the maximum likelihood method. To assess the validity of the proposed models, the mean absolute percentage error (MAPE) between the number of observed and fitted HIV infections from 1985 to 2012 was calculated. Finally, the fitted ARIMA models were used to forecast the number of HIV infections from 2013 to 2017. Results The fitted number of HIV infections was calculated by optimum ARIMA (2,2,1) model from 1985–2012. The fitted number was similar to the observed number of HIV infections, with a MAPE of 13.7%. The forecasted number of new HIV infections in 2013 was 962 (95% confidence interval (CI): 889–1,036) and in 2017 was 1,111 (95% CI: 805–1,418). The forecasted cumulative number of HIV infections in 2013 was 10,372 (95% CI: 10,308–10,437) and in 2017 was14,724 (95% CI: 13,893–15,555) by ARIMA (1,2,3). Conclusion Based on the forecast of the number of newly diagnosed HIV infections and the current cumulative number of HIV infections, the cumulative number of HIV-infected Koreans in 2017 would reach about 15,000. Citations
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Objectives
The Korea HIV/AIDS cohort was constructed with 18 hospitals that care for HIV-infected individuals in 2006. We compared the epidemiological and immunological characteristics of the cohort registrants with those of the HIVinfected population at the time of HIV diagnosis. Methods This study was conducted on 5717 people living with HIV/AIDS from 1985 to 2009, of which 789 individuals registered with the Korea HIV/AIDS cohort study. Individuals who had data from initial CD4+ T-cell counts measured within 6 months following HIV diagnosis were selected as study participants to predict the status of disease progression at the time of HIV diagnosis. A total of 2886 patients (50%) were selected from people living with HIV/AIDS, of whom 424 individuals (54%) were cohort registrants. The χ<sup>2</sup> test and Wilcoxon rank sum test were used for analysis. Results The distributions of age, marital status, diagnosed regions, reason for HIV testing, and screening site were similar between the HIV-infected population and the cohort registrants. In 1985–2004, the male ratio for the cohort registrants (94.3%) was significantly higher than that measured for the HIV-infected population (89.5%) (<i>p</i> = 0.0339). With regard to transmission route, homosexual contact of cohort registrants (46.6%) was higher than that of the HIV-infected population (40.1%) (<i>p</i> = 0.022) in 2005–2009. No statistical difference in CD4+ T-cell counts at the time of HIV diagnosis was found between the HIVinfected population and cohort registrants (<i>p</i> = 0.2195). Conclusion The Korea HIV/AIDS cohort registrants represent the HIV-infected population, and the data collected from this cohort could be used as a foundation for national statistics. Citations
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HIV is able to continuously adapt to and evade the evolving neutralizing antibody responses of the host. We investigated the ability of HIV variants to evade neutralizing antibodies in order to understand the distinct characteristics of HIV-1 Korean clade B. Methods Three drug-naive subjects were enrolled in this study who were infected with HIV-1 Korean clade B. Neutralizations were performed using autologous plasma and pseudovirion-based assays in order to analyze and compare changes in the <i>env</i> gene. Results In the early phase of infection, neutralizing activities against autologous virus variants gradually increased, which was followed by a decline in the humoral immune response against the subsequent viral escape variants. The amino acids lengths and number of potential N-linked glycosylation sites (PNGS) in HIV-1 <i>env</i> gene was positively correlated with neutralized antibody responses during the early stages of infection. Conclusion This study suggests that change within the <i>env</i> domains over the course of infection influences reactivities to neutralized antibodies and may also have an impact on host immune responses. This is the first longitudinal study of HIV-1 humoral immunity that took place over the entire course of HIV-1 Korean clade B infection. Citations
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Many natural compounds have been investigated as drug candidates to prevent human immunodeficiency virus (HIV) with low cytotoxicity. We tested whether ingenol from <i>Euphorbia ingens</i> exerts anti-HIV effects in human T cell lines. Methods and Results Ingenol effectively maintained high cell viability (CD<sub>50</sub>, >1 mM) in H9 and MT4 T cells. The efficacy of ingenol to inhibit HIV-1 infection was dose dependent. ED<sub>50</sub> for 100 and 200 TCID<sub>50</sub> of HIV-1 was 5.06 and 16.87 μM, respectively. Gag p24 antigen production in ingenol-treated MT4 cells was reduced by 24.5% on day 6 post-infection. While p24 antigen was reduced in ingenol-treated cells, levels of cytokines such as TNF-α and IL-6 and chemokines such as RANTES and MCP-1 were increased. dUTP level related to late apoptotic events was increased on day 2 post-infection of HIV by ingenol treatment, whereas expression of annexin V was unchanged. Reduced levels of iNOS and ZAP-70 after HIV infection were recovered by ingenol treatment. Conclusion Ingenol helps T cells to survive longer against viremia after HIV-1 infection, without exerting cytotoxic effects. Ingenol can be considered a safe and efficacious candidate for immune-boosting therapy for AIDS patients. Citations
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The incidence of anal disease is higher among persons with human immunodeficiency virus (HIV) infection than among the general population. We surveyed the status of seroprevalence in colorectal hospitals in Korea. Methods The survey was conducted in colorectal hospitals in Korea from November to December 2008. The questionnaire was comprised of six topics about the status of HIV testing in colorectal hospitals. We gathered the data by website (<ext-link ext-link-type="uri" xlink:href="http://hivqa.nih.go.kr/risk">http://hivqa.nih.go.kr/risk</ext-link>) or fax. Results Among 774 colorectal hospitals contacted, 109 (14%) hospitals participated in the survey. Among these, 48 hospitals (44%) performed HIV tests in their own hospitals and 11 (23%) took HIV testing by rapid method. The main reason for recommending an HIV test was surgical operation (54%) followed by endoscope (11%) and health checkup (9%). The annual number of HIV tests increased from 58,647 (at 21 hospitals) in 2002 to 246,709 (at 58 hospitals) in 2007. HIV seroprevalence was >3.0 per 10,000 individuals during 2002–2005, decreased to 2.2 per 10,000 individuals in 2006 and rose to 2.8 per 10,000 individuals in 2007. Conclusions HIV seroprevalence of colorectal hospitals was more than twice that of general hospitals in Korea. HIV surveillance systems based on colorectal hospitals for HIV/AIDS transmission prevention by early HIV diagnosis are needed. Citations
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In this study, the viral fitness of pseudo-viruses with a drug-resistant site in the reverse transcriptase (RT) region of the genome was investigated. The pseudo-viruses were derived from highly active antiretroviral therapy (HAART)-experienced HIV/AIDS patients. Methods HIV-1 RNA was extracted from the plasma of HAART-experienced (KRB9149, KRB7021, KRC1097) and HAART-naïve (KRC5180, KRC5123) HIV-1 patients. The RT gene from the extracted viral RNA was amplified and the polymerase chain reaction product was cloned from the pHXB2Δ2-261 RT vector. C8166 and TZM-bl cell lines were used as the HIV-1 replication capacity measurement system. To quantify the infectivity of homologous recombinant HIV-1, the infectivity derived from each pseudo-virus was compared with the infectivity of the reference strain HXB2. Results Patient-derived HIV-1 was cotransfected into C8166 cells and the expression level of the p24 antigen was measured. The expression was high in the HIV-1 isolates from patients KRC5180 and KRB9149 and low in patients KRB7021, KRC5123, and KRC1097, when compared with the reference strain. The infectivity of the pseudo-virus measured in TZM-bl cells decreased in the order, reference strain HXB2 > KRC5180 > KRC5123 > KRB9149 > KRB7021 > KRC1097. Conclusion In this study, HIV-1 infectivity of the drug-resistant strain isolated from HAART-experienced patients with HIV/AIDS was found to be lower than the infectivity of the reference strain HXB2. This study provides useful data for the phenotypic susceptibility assay in HAART-experienced patients infected with HIV-1. Citations
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