Antiretroviral treatment for HIV infection and AIDS

Antiretroviral therapy is the cornerstone treatment for people living with human immunodeficiency virus (HIV). Clinical practice guidelines for antiretroviral therapy have been developed.Current Concepts: After the introduction of zidovudine, more than 30 antiretroviral agents have been approved for the treatment of HIV infection. Since a controlled trial proved the efficacy and safety of combination antiretroviral therapy, virologic suppression, immune reconstitution, and long-term survival of people living with HIV have been achievable goals. Early antiretroviral treatment for all people living with HIV is an effective strategy to maintain individual health and prevent the transmission of HIV infection. Selecting an appropriate combination antiretroviral therapy requires careful consideration of various factors, including regimen characteristics, pretreatment viral load and CD4+ cell counts, comorbid conditions, and the anticipated level of compliance. Ongoing advances in antiretroviral treatment, such as the development of long-acting injectables and medications targeting multidrug-resistant HIV, address challenges in the treatment of HIV infection.Discussion and Conclusion: Although cure of HIV infection is impossible with current antiretroviral treatment, HIV infection has become a chronic disease with long-term survival. Hence, clinicians should have knowledge of antiretroviral treatment guidelines.

Extracts from Paeonia lactiflora Pallas, Rehmannia Glutinosa var. Purpurea Makino, Perilla Frutescens var. Acuta Kudo may increase the endometrial receptivity through expression of leukemia inhibitory factor and adhesion molecules.

OBJECTIVE: To find out the combination of the extracts from Paeonia lactiflora Pallas (PL), Reh- mannia Glutinosa var. Purpurea Makino (RG), Perilla Frutescens var. Acuta Kudo (PF) to increase endometrial receptivity. METHODS: Herbal medicines were extracted with boiling water and polysaccharides were removed. We examined the effect of PL, RG, and PF (PRP), a most effective herbal formula deduced from constitutive ingredient herbs of Antai Yin which is composed of PRP, on the leukemia inhibitory factor (LIF) expression and endometrial receptivity. RESULTS: The combination of the extracts from PRP induced the LIF expression in Ishikawa cells and increased the adhesion between Ishikawa and JAr cells. In addition, PRP-induced attachment of JAr cells onto Ishikawa cells and expression of adhesion molecules, ITGAV, ITGB5, CD44s, and L-selectin, are significantly reduced by knock-down of LIF expression. CONCLUSION: Induced by the combination of the PRP extracts, the adhesion between trophoblast and endometrial cells are mediated by expression of LIF and adhesion molecules. Thus, we suggest the combination of the PRP extracts may be a novel therapy for enhancing embryo implantation rate.

Within-Host Evolution of SARS-CoV-2in a B-Cell Depleted Patient With Successful Treatment

Prolonged viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an immunocompromised host is a challenge as the treatment and infection control for chronic coronavirus disease 2019 infection is not well established and there is a potential risk of new variants emerging. A 48-year-old woman who underwent chemotherapy, including rituximab and steroid, had reactivation of SARS-CoV-2 68 days after the virus was first detected. She successfully recovered after receiving convalescent plasma and intravenous immunoglobulin. Genomic analysis demonstrated that viruses collected from the nasopharyngeal specimens at day 0 and day 68 had 18 different nucleotide mutations, implying within-host evolution after in-depth epidemiologic investigation.

Immunogenicity and Safety of Vaccines against Coronavirus Disease in Actively Treated Patients with Solid Tumors: A Prospective Cohort Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We aimed to assess the humoral response to and reactogenicity of coronavirus disease 2019 (COVID-19) vaccination according to the vaccine type and to analyze factors associated with immunogenicity in actively treated solid cancer patients (CPs). @*Materials and Methods@#Prospective cohorts of CPs, undergoing anticancer treatment, and healthcare workers (HCWs) were established. The participants had no history of previous COVID-19 and received either mRNA-based or adenovirus vector–based (AdV) vaccines as the primary series. Blood samples were collected before the first vaccination and after 2 weeks for each dose vaccination. Spike-specific binding antibodies (bAbs) in all participants and neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type, Delta, and Omicron variants in CPs were analyzed and presented as the geometric mean titer. @*Results@#Age-matched 20 HCWs and 118 CPs were included in the analysis. The bAb seroconversion rate and antibody concentrations after the first vaccination were significantly lower in CPs than in HCWs. After the third vaccination, antibody levels in CPs with a primary series of AdV were comparable to those in HCWs, but nAb titers against the Omicron variant did not quantitatively increase in CPs with AdV vaccine as the primary series. The incidence and severity of adverse reactions post-vaccination were similar between CPs and HCWs. @*Conclusion@#CPs displayed delayed humoral immune response after SARS-CoV-2 vaccination. The booster dose elicited comparable bAb concentrations between CPs and HCWs, regardless of the primary vaccine type. Neutralization against the Omicron variant was not robustly elicited following the booster dose in some CPs, implying the need for additional interventions to protect them from COVID-19.

Sudden Hearing Loss in Patients With COVID-19: Case Series and Analysis of the Literature / 대한이비인후과학회지

This study reports on patients with severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) presenting with sudden sensorineural hearing loss (SSNHL) during the coronavirus disease 2019 (COVID-19) pandemic. The study included four adult patients who presented with the complaint of unilateral SSNHL after testing positive for SARS-CoV-2 by RT-PCR from January to April 2022. Of the four patients, only one young adult recovered his hearing following a combination of oral and intratympanic steroid therapy. It is a challenge to confirm evidence of association between COVID-19 and SSNHL. Nevertheless, the early screening and diagnosis for SSNHL following COVID-19 enables prompt treatment with steroids, which offers the best chance of hearing recovery.

Cost-Benefit Analysis of Tafenoquine for Radical Cure of Plasmodium vivax Malaria in Korea

Background@#Plasmodium vivax malaria has a persistent liver stage that causes relapse, and introducing tafenoquine to suppress relapse could aid in disease eradication. Therefore, we assessed the impact of tafenoquine introduction on P. vivax malaria incidence and performed a cost-benefit analysis from the payer’s perspective. @*Methods@#We expanded the previously developed P. vivax malaria dynamic transmission model and calibrated it to weekly civilian malaria incidences in 2014–2018. Primaquine and tafenoquine scenarios were considered by assuming different relapse probabilities, and relapse and total P. vivax malaria cases were predicted over the next decade for each scenario. We then estimated the number of cases prevented by replacing primaquine with tafenoquine. The cost and benefit of introducing tafenoquine were obtained using medical expenditure from a nationwide database, and a cost-benefit analysis was conducted. A probabilistic sensitivity analysis was performed to assess the economic feasibility robustness of tafenoquine introduction under uncertainties of model parameters, costs, and benefits. @*Results@#Under 0.04 primaquine relapse probability, the introduction of tafenoquine with relapse probability of 0.01 prevented 129 (12.27%) and 35 (77.78%) total and relapse cases, respectively, over the next decade. However, under the same relapse probability as primaquine, introducing tafenoquine had no additional preventative effect. The 14-day primaquine treatment cost was $3.71. The tafenoquine and the glucose-6-phosphate dehydrogenase rapid diagnostic testing cost $57.37 and $7.76, totaling $65.13. The average medical expenditure per malaria patient was estimated at $1444.79. The cost-benefit analysis results provided an incremental benefit-cost ratio (IBCR) from 0 to 3.21 as the tafenoquine relapse probability decreased from 0.04 to 0.01. The probabilistic sensitivity analysis showed an IBCR > 1, indicating that tafenoquine is beneficial, with a probability of 69.1%. @*Conclusion@#Tafenoquine could reduce P. vivax malaria incidence and medical costs and bring greater benefits than primaquine.

Evaluation of Intervention Policies for the COVID-19Epidemic in the Seoul/Gyeonggi Region through a Model Simulation

Purpose@#To evaluate the efficacy of intervention policies on coronavirus disease-19 (COVID-19) dissemination. @*Materials and Methods@#An age-structured compartmental model for the COVID-19 outbreak was proposed to predict the impact of control measures in the Seoul/Gyeonggi region. The model was calibrated based on actual data and realistic situations, including daily vaccine doses, proportion of delta variant cases, and confirmed cases by age. We simulated different scenarios for non-pharmaceutical interventions by varying social distancing and school attendance strategies. @*Results@#Two-step mitigation of social distancing without in-person classes would result in a rapid increase in confirmed cases up to 10000 but would keep severe cases within the manageable range of the health care system. The overall impact of taking down the distancing level by one step with twice the increase in contacts at school was comparable to the above scenario. Implementation of two-step mitigation of social distancing along with a two-fold increase in contacts among the school-age group would dramatically increase confirmed and severe cases by over 80000 and 100, respectively, as early as the beginning of December. This policy would cause the situation to spiral out of control, considering the scale of the response and time to prepare. On the other hand, the burden on the current healthcare system caused by two-step mitigation of social distancing and 40% increased contacts in the school-age group was manageable if prepared. @*Conclusion@#A compromise between social distancing and school attendance policy and timely preparations for the spread of COVID-19 are required.

Implementation of Procalcitonin in Antibiotic Stewardship: Derivation of a Consensus Algorithm for Procalcitonin Use in Clinical Practice / 감염과화학요법

Reducing antibiotics overuse is essential to minimize antibiotics related side effects and to prevent the emergence of multidrug-resistant bacteria. Procalcitonin (PCT) guided antibiotics therapy has been reported to be safe in patients with acute respiratory infections and sepsis, improving clinical outcomes as well as reducing the duration of antibiotics use.However, there is still no universal agreement on clinical guidelines in Korea for optimal PCT applications. Through this expert consensus meeting, clinical research findings in the PCT-guided antibiotics treatment interventions and real-world clinical applications were discussed. From the perspective of antibiotic stewardship, PCT application target groups, cut-offs, and testing cycles were discussed to reach a consensus on the PCT-guided antibiotics treatment algorithm for application in Korea. Combining clinical assessment for patients with an appropriate PCT-guided antibiotics treatment algorithm could improve the diagnosis and treatment of acute respiratory infections and sepsis. In addition, continuous education and regular feedback would improve the effectiveness of antibiotic stewardship.

Implementation of a Nurse-Delivered Cognitive Behavioral Therapy for Adherence and Depression of People Living with HIV in Korea / 감염과화학요법

Background@#Cognitive behavioral therapy for adherence and depression (CBT-AD) performed by clinical psychologists is an effective treatment for improving the depression in people living with HIV (PLWH). However, because access to clinical psychologists is limited in most clinics, CBT-AD is rarely performed for PLWH in Korea. This pilot study evaluates whether CBT-AD can be effectively performed by a nurse trained and supervised by a clinical psychologist, with a view to the wider provision of CBT-AD. @*Materials and Methods@#One clinical psychologist developed manuals, educated and supervised one nurse. PLWH with depression or adherence to self-reported antiretroviral therapy <90% were enrolled, and CBT-AD was conducted once weekly for 12 sessions. PLWH were assessed for adherence by visual analog scale, Beck depression inventory (BDI) for depression, PozQoL for quality of life, and Berger’s 40-item stigma scale for stigma at baseline, after the 6th, 12th session, at 4-, and 8-months after CBT-AD. Acceptability for PLWH and feasibility for providers were evaluated through surveys. @*Results@#Five male PLWH have completed the study protocols (mean age 29.2 years). All study participants showed improving depression (mean BDI at baseline 33.0 ± 7.0, and after the 12th session 13.4 ± 3.5), and the effect was maintained at the 8-month follow-up (BDI 15.4 ± 6.4). Quality of life showed a tendency to improve (mean PozQoL at baseline 28.0 ± 7.7, after 12th session 36.8 ± 4.4, and at the 8-month follow-up 38.2 ± 7.9), but stigma did not show clear improvement (Berger’s 40-item stigma scale at baseline 121.0 ± 3.9, after 12th session 107.6 ± 8.8. and at the 8-month follow-up 107.6 ± 5.0). All study participants received great help from CBT-AD and expressed their desire to continue. All providers agreed that nursedelivered CBT-AD could be implemented in routine clinical practice. @*Conclusion@#Our findings suggest that a nurse-delivered CBT-AD could be feasible and acceptable for PLWH through structured interventions. It has been shown to have the potential to help PLWH, especially for their depression and quality of life.

Treatment of Human Immunodeficiency Virus-Associated Facial Lipoatrophy With Hyaluronic Acid Filler Mixed With Micronized Cross-Linked Acellular Dermal Matrix

Background@#Human immunodeficiency virus (HIV)-associated facial lipoatrophy (FLA) is a stigmatizing side effect associated with the use of highly active antiretroviral therapy. We sought to evaluate the safety and efficacy of the hyaluronic acid filler mixed with micronized cross-linked acellular dermal matrix (HA/MADM) in HIV-associated FLA. @*Methods@#We conducted an open-label safety and efficacy study in patients with HIVassociated FLA. Fourteen patients received single injection of the HA/MADM, and 13 patients completed the 24-week follow-up evaluation. Treatment efficacy, safety, and patient and physician satisfaction were evaluated. Repeated measure analysis of variance with post-hoc analysis with the Wilcoxon signed rank test was performed to compare and incorporate parameters at each time point. @*Results@#All 13 patients maintained a significant improvement of the Carruthers Lipoatrophy Severity Scale grade throughout the study period, along with improvement of the depressed volume due to lipoatrophy measured using a three-dimensional camera system. More than 80% of patients and physicians were satisfied with the treatment, and no treatment-related adverse events were reported, except for one case of transient subcutaneous nodule formation. @*Conclusion@#Our study findings suggest that injectable HA/MADM is a potentially effective and safe treatment option for treating HIV-positive patients with FLA.

The Incidence and Risk Factors of Renal Insufficiency among Korean HIV infected Patients: The Korea HIV/AIDS Cohort Study / 감염과화학요법

Renal insufficiency is one of the common issues in people living with human immunodeficiency virus (PLHIV). We studied the incidence and risk factors for renal insufficiency in male PLHIV using the Korea HIV/acquired immunodeficiency syndrome (AIDS) Cohort Study. Among the 830 enrolled patients, 32 (3.9%) cases of renal insufficiency occurred over 9576 patient-years of follow-up. The incidence of renal insufficiency in HIVinfected men in this study was 3.3 per 1000 patient-years. Diabetes mellitus, dyslipidemia, tenofovir or non-nucleoside reverse transcriptase inhibitor exposure for >1 year, and AIDSdefining illness were risk factors for renal insufficiency.

Comparison of Three Cardiovascular Risk Scores among HIV-Infected Patients in Korea: The Korea HIV/AIDS Cohort Study / 감염과화학요법

Background@#We investigated cardiovascular disease (CVD), risk factors for CVD, and applicability of the three known CVD risk equations in the Korean human immunodeficiency virus/ Acquired Immune Deficiency Syndrome (HIV/AIDS) cohort. @*Materials and Methods@#The study parcitipants were HIV-infected patients in a Korean HIV/ AIDS cohort enrolled from 19 hospitals between 2006 and 2017. Data collected at entry to the cohort were analyzed. The 5-year CVD risk in each participant was calculated using three CVD risk equations: reduced CVD prediction model of HIV-specific data collection on adverse effects of anti-HIV drugs (R-DAD), Framingham general CVD risk score (FRS), and Korean Coronary Heart Disease Risk Score (KRS). @*Results@#CVD events were observed in 11 of 586 HIV-infected patients during a 5-year (median) follow-up period. The incidence of CVD was 4.11 per 1,000 person-years. Older age (64 vs. 41 years, P = 0.005) and diabetes mellitus (45.5% vs. 6.4%, P <0.001) were more frequent in patients with CVD. Using R-DAD, FRS, and KRS, 1.9%, 2.4%, and 0.7% of patients, respectively, were considered to have a very high risk (≥10%) of 5-year CVD. The discriminatory capacities of the three prediction models were good, with c-statistic values of 0.829 (P <0.001) for R-DAD, 0.824 (P <0.001) for FRS, and 0.850 (P = 0.001) for KRS. @*Conclusion@#The FRS, R-DAD, and KRS performed well in the Korean HIV/AIDS cohort. A larger cohort and a longer period of follow-up may be necessary to demonstrate the risk factors and develop an independent CVD risk prediction model specific to Korean patients with HIV.

A Case of African Tick-Bite Fever in a Returning Traveler from Southern Africa / 감염과화학요법

African tick-bite fever (ATBF), caused by Rickettsia africae, is the second most frequent cause of fever after malaria in travelers returning from Southern Africa. As the Korean outbound travelers are increasing every year, tick-borne rickettsial diseases as a cause of febrile illness are likely to increase. We describe a febrile Korean returning traveler who showed two eschars after visiting the rural field in Manzini, Swaziland. We performed nested polymerase chain reaction using the eschar and diagnosed the patient with ATBF. He was treated with oral doxycycline for 7 days, and recovered without any complications. We believe that the present case is the first ATBF case diagnosed in a Korean traveler.

Development of the Korean Standardized Antimicrobial Administration Ratio as a Tool for Benchmarking Antimicrobial Use in Each Hospital

Background@#The Korea National Antimicrobial Use Analysis System (KONAS), a benchmarking system for antimicrobial use in hospitals, provides Korean Standardized Antimicrobial Administration Ratio (K-SAAR) for benchmarking. This article describes K-SAAR predictive models to enhance the understanding of K-SAAR, an important benchmarking strategy for antimicrobial usage in KONAS. @*Methods@#We obtained medical insurance claims data for all hospitalized patients aged ≥ 28 days in all secondary and tertiary care hospitals in South Korea (n = 347) from January 2019 to December 2019 from the Health Insurance Review & Assessment Service. Modeling was performed to derive a prediction value for antimicrobial use in each institution, which corresponded to the denominator value for calculating K-SAAR. The prediction values of antimicrobial use were modeled separately for each category, for all inpatients and adult patients (aged ≥ 15 years), using stepwise negative binomial regression. @*Results@#The final models for each antimicrobial category were adjusted for different significant risk factors. In the K-SAAR models of all aged patients as well as adult patients, most antimicrobial categories included the number of hospital beds and the number of operations as significant factors, while some antimicrobial categories included mean age for inpatients, hospital type, and the number of patients transferred from other hospitals as significant factors. @*Conclusion@#We developed a model to predict antimicrobial use rates in Korean hospitals, and the model was used as the denominator of the K-SAAR.

Surveillance of Close Contacts and Implications of Pediatric Patients with COVID-19–Experiences from a Single Residential Treatment Center

Residential treatment centers (RTCs) are successful in isolating and closely monitoring adults confirmed with coronavirus disease 2019 (COVID-19), but there are concerns for children who need care. This study was conducted as a retrospective analysis of the surveillance of guardians who entered an RTC with infected pediatric patients to identify the secondary attack rate of COVID-19 to close contacts in a single RTC and to provide directions for developing guidelines for caregivers who co-isolate with infected children. When caregivers were admitted to this RTC, aside from negative confirmation before discharge, tests were additionally performed one or two times. There were 57 index children and adolescent patients who entered the RTC with their parents as caregivers. The secondary attack rate by pediatric patients to close contacts outside their households was 25% (95% confidence interval, 10.0 to 40.0) (8 out of 32 contacts). The transmissibility of SARS-CoV-2 in children was close to zero at 6 days after the confirmation tests. It is reasonable to test the close contacts of pediatric patients after 7 days of isolation to identify infections among caregivers.

Development of a Roadmap for the Antimicrobial Usage Monitoring System for Medical Institutions in Korea: a Delphi Study / 감염과화학요법

Background@#It is necessary to develop a roadmap for antimicrobial usage monitoring in order to perform monitoring of antimicrobial use at the national level properly. Therefore, this study aimed to develop a roadmap for establishing surveillance and monitoring of antimicrobial use in medical institutions at the national level. @*Materials and Methods@#A modified Delphi study was conducted, including 3 rounds of an online survey and a virtual meeting with 16 expert panels. The survey items were developed based on a literature review of the surveillance systems for antimicrobial use in 12 countries and interviews with experts. The questionnaire was designed to include both the surveillance and benchmarking systems. @*Results@#Regarding the scope of target institutions to be included in the surveillance system, medical institutions for sentinel surveillance had the highest proportion of agreement among the panels (75.0%, 9/12). For the benchmarking system, “tertiary- and secondarycare hospitals” were accepted as the scope of target institutions at the current moment.Furthermore, the National Health Insurance claims and prescription data of individual hospitals were considered appropriate data sources for the surveillance system. As for the measures to promote the participation of hospitals in the benchmarking system, “compensation through the establishment of antimicrobial management fees” and “set the participation in the program as a quality evaluation or accreditation index for hospital evaluation” were accepted. @*Conclusion@#This study provides a roadmap for establishing an antimicrobial use monitoring and benchmarking system for medical institutions at a national level in Korea.

SARS-CoV-2 Variants of Concern

Since the COVID-19 pandemic first began in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has continuously evolved with many variants emerging across the world. These variants are categorized as the variant of interest (VOI), variant of concern (VOC), and variant under monitoring (VUM). As of September 15, 2021, there are four SARS-CoV-2 lineages designated as the VOC (alpha, beta, gamma, and delta variants). VOCs have increased transmissibility compared to the original virus, and have the potential for increasing disease severity. In addition, VOCs exhibit decreased susceptibility to vaccineinduced and infection-induced immune responses, and thus possess the ability to reinfect previously infected and recovered individuals. Given their ability to evade immune responses, VOC are less susceptible to monoclonal antibody treatments. VOCs can also impact the effectiveness of mRNA and adenovirus vector vaccines, although the currently authorized COVID-19 vaccines are still effective in preventing infection and severe disease. Current measures to reduce transmission as well as efforts to monitor and understand the impact of variants should be continued. Here, we review the molecular features, epidemiology, impact on transmissibility, disease severity, and vaccine effectiveness of VOCs.

A Case of Blue Nevus of the Nasal Septum

Blue nevus (BN) is a blue- or black-colored benign melanocytic proliferation that commonly occurs on the dorsal surface of the hands and feet or in the head and neck region. However, BN arising from the sinonasal mucosa is extremely rare. BN is usually asymptomatic and small in size. Based on the pigmentation of BN, sinonasal malignant melanoma should be considered in the differential diagnosis of BNs in this region. We herein report a case of BN of the nasal septum. Histopathologic examination revealed the presence of heavily pigmented, spindle-shaped melanocytic cells within the stromal tissue. On immunohistochemical analysis, BN cells were positive for S-100 and HMB-45. Due to the few reported cases of sinonasal BN and challenging location, complete resection, biopsy, and adequate follow-up are recommended.

SARS-CoV-2 Variants of Concern

Since the COVID-19 pandemic first began in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has continuously evolved with many variants emerging across the world. These variants are categorized as the variant of interest (VOI), variant of concern (VOC), and variant under monitoring (VUM). As of September 15, 2021, there are four SARS-CoV-2 lineages designated as the VOC (alpha, beta, gamma, and delta variants). VOCs have increased transmissibility compared to the original virus, and have the potential for increasing disease severity. In addition, VOCs exhibit decreased susceptibility to vaccineinduced and infection-induced immune responses, and thus possess the ability to reinfect previously infected and recovered individuals. Given their ability to evade immune responses, VOC are less susceptible to monoclonal antibody treatments. VOCs can also impact the effectiveness of mRNA and adenovirus vector vaccines, although the currently authorized COVID-19 vaccines are still effective in preventing infection and severe disease. Current measures to reduce transmission as well as efforts to monitor and understand the impact of variants should be continued. Here, we review the molecular features, epidemiology, impact on transmissibility, disease severity, and vaccine effectiveness of VOCs.

A Case of Blue Nevus of the Nasal Septum

Blue nevus (BN) is a blue- or black-colored benign melanocytic proliferation that commonly occurs on the dorsal surface of the hands and feet or in the head and neck region. However, BN arising from the sinonasal mucosa is extremely rare. BN is usually asymptomatic and small in size. Based on the pigmentation of BN, sinonasal malignant melanoma should be considered in the differential diagnosis of BNs in this region. We herein report a case of BN of the nasal septum. Histopathologic examination revealed the presence of heavily pigmented, spindle-shaped melanocytic cells within the stromal tissue. On immunohistochemical analysis, BN cells were positive for S-100 and HMB-45. Due to the few reported cases of sinonasal BN and challenging location, complete resection, biopsy, and adequate follow-up are recommended.