Acquired Immunodeficiency Syndrome Research Articles

Predictive value of neutrophil to lymphocyte ratio for the clinical outcomes of acquired immune deficiency syndrome: a systematic review and meta-analysis

ObjectiveThis study aimed to explore the predictive value of the neutrophil-to-lymphocyte ratio (NLR) for outcomes in Acquired Immune Deficiency Syndrome (AIDS) patients.MethodsPubMed, Embase, Cochrane, and Web of Science were conducted to search literature up to May 2024 and cohort and case–control studies were included. The primary outcomes were mortality and progression-free survival (PFS). Pooled odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. We conducted sensitivity analyses to assess result stability, reliability, and subgroup analyses to identify sources of heterogeneity using Review Manager 5.4.1. Egger’s tests were performed with Stata 15.1, and funnel plots were generated using Review Manager 5.4.1. Microsoft Excel was used for the initial data summarization.ResultsFourteen studies involving 30,752 AIDS patients were included. The pooled data showed higher NLR significantly associated with increased mortality (OR: 1.85, 95% CI: 1.43–2.41, p < 0.00001) and shorter progression-free survival (PFS) (HR: 2.46, 95% CI: 1.32–4.59, p = 0.005). Subgroup analyses revealed that NLR’s predictive value was greater in studies with post-ART measurements. Sensitivity analyses show stable and reliable results. Egger’s test and funnel plot analysis revealed no significant publication bias.ConclusionNLR is a key prognostic biomarker for predicting mortality and progression-free survival (PFS) in AIDS patients. Incorporating NLR into predictive models may improve prognostic assessments and guide clinical decision-making.Systematic Review RegistrationPROSPERO (CRD42024532918: https://www.crd.york.ac.uk/PROSPERO).

Dynapenia and Sarcopenia as Risk Factors for Mortality in Interstitial Lung Disease.

Fibrotic interstitial lung disease (ILD) is associated with high morbidity and mortality. Patients often exhibit impaired nutritional status and alterations in body composition, such as dynapenia and sarcopenia, which correlate with poor pulmonary function, reduced exercise tolerance and diminished quality of life. However, the impact of dynapenia and sarcopenia on prognosis has not been examined extensively in ILD patients. We assessed the impact of dynapenia and sarcopenia as risk factors for mortality and their prevalence in ILD. Prospective cohort study. ILD was classified into idiopathic pulmonary fibrosis (IPF), connective tissue disease-related ILD (CTD-ILD) and chronic hypersensitivity pneumonitis (CHP). Patients over 18 years old with a confirmed diagnosis of ILD were included, while those with diagnoses of cancer, human immunodeficiency virus and neurological disease were excluded. Dynapenia and sarcopenia were determined according to EWGSOP2 criteria. Ninety-eight ILD patients were included; 33.66% had IPF, 47.96% had CTD-ILD, and 18.37% had CHP. The mean age was 63.89 ± 12.02 years; 37.76% were male. The risk factors associated with mortality included dynapenia (HR: 2.04, 95% CI: 1.10-3.77, p = 0.022), sarcopenia (HR: 1.88, 95% CI; 1.00-3.33, p = 0.049) and exercise tolerance (HR: 0.99, 95% CI; 0.99-0.99, p = 0.023), adjusted for confounding variables. The prevalence of dynapenia was 45% in ILD; 51% in IPF, 35% in CTD-ILD and 61% in CHP. The prevalence of sarcopenia was 29%; both IPF (39%) and CHP (50%) had a higher prevalence of sarcopenia than CTD-ILD (14%). Sarcopenia and dynapenia are independent risk factors for mortality in ILD.

Examining the Prevalence and Associated Factors of Sexually Transmitted Infections in People Living With HIV/AIDS at a Community Health Center in Bandung City, Indonesia.

This study aims to investigate the prevalence of sexually transmitted infections (STIs) and associated factors among people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) (PLWHA) registered in a community health center (CHC) with HIV/AIDS support and treatment services in Indonesia. A cross-sectional study that included all PLWHA data from medical records registered in a CHC with HIV/AIDS support and treatment services was conducted in Bandung City, Indonesia, between March 2019 and March 2024. This CHC provides comprehensive and continuous HIV/AIDS services, including HIV testing, antiretroviral therapy (ART), and opportunistic infection management. The factors associated with the prevalence of STIs in PLWHA, including sociodemographic factors such as gender, age, education level, marital status, occupation, population group, referral origin, and clinical factors such as length of illness, duration of ART, clinical stage, and comorbidities, were analyzed by using chi-square analysis. Total 156 PLWHA data with STIs from medical records were collected (male, n = 152, 97.4%; female, n = 4, 2.6%). The prevalence of STIs among PLWHA was 32.1%, consisting of syphilis (n = 36; 72%), gonorrhea (n = 11; 22%), genital herpes (n = 2; 4%), and condyloma (n = 1; 2%). The following significant factors associated with the prevalence of STIs were population group men who have sex with men (MSM) (p = 0.046), referral origin from non-government organizations (NGOs) (p = 0.030), duration of disease (p = 0.023) and duration of ART ranging from 12 to 36 months (p = 0.023), and early clinical stage (p = 0.010). STIs affected over one-third of CHC-registered PLWHA, with syphilis being the most common. MSMs and patients referred by NGOs, with illness and treatment durations ranging from 12 to 36 months, as well as the early clinical stage of HIV, are associated with STIs among PLWHA. Intervention strategies to improve STI prevention and control in these populations are urgently needed.

A case of newly onset rheumatoid arthritis successfully treated with methotrexate under the anti-retrovirus therapy against HIV infection.

The patient was a 70-year-old woman. In July 2018, she developed pneumocystis pneumonia and was diagnosed with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). Antiretroviral therapy (ART) was continued, the HIV-RNA load was suppressed, and the CD4+cells count was maintained. In 2024, the polyarticular pain and swelling persisted. HIV-associated arthropathy, reactive arthritis, and other diseases were excluded. The patient was diagnosed with rheumatoid arthritis (RA) according to the ACR/EULAR 2010 Rheumatoid Arthritis Classification Criteria. Joint radiography revealed narrowing of the wrist joint, and joint ultrasonography showed synovial thickening and power doppler signals, supporting the diagnosis of RA. Methotrexate was initiated, and remission was achieved and maintained. After starting MTX, HIV-RNA load increased transiently but rapidly decreased after that. CD4+cells count was maintained. Patients with HIV have underlying immune dysfunction, and RA requires treatment with immunosuppressants (DMARDs), which makes treatment challenging. Recently, HIV infection has been considered a factor that makes the diagnosis of RA difficult. When symptoms suggestive of RA are observed in HIV-infected patients, it is important to make a thorough differential diagnosis and determine a treatment plan based on the characteristics of RA complicated by HIV infection.

Gonadal Hormonal Changes in HIV-Positive Individuals Following Anti –retroviral Theraphy at K.R. Hospital, Mysuru, Karnataka, India

Aims: HIV infection and AIDS remain global health challenges, with many individuals suffering from endocrine disorders such as gonadal dysfunction. This study assesses the levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and estradiol in HIV-positive individuals before and after six months of antiretroviral therapy (ART). Study Design: Clinical observational study. Place and Duration of Study: ART Center, K.R. Hospital, Mysuru. Methodology: The clinical–observational study involved seventy patients who were HIV positive, who were recruiting to ART clinic which is located at KR hospital Mysuru. The patients were split into two groups according to their CD4 count (≤200 cells/µL ND >200 cells/µ L). The baseline values were measured for LH, FSH, testosterone and estradiol just prior to ART and the levels of hormones were measured again six months after commencing ART. Results: Our study conducted among 70 patients, 38 were males and 32 were females, average age being around 40 years. These patients were divided into two groups based on CD4 counts (≤200 cells/µL and >200 cells/µL). Gonadal hormone level were checked pre-ART and six months post-ART therapy. After six months of ART therapy, there was significant improvement in testosterone (7.93 pg/mL to 8.94 pg/mL (p < 0.0001)) and LH level noted among male patients, estradiol and FSH levels were not improved significantly. Same degree of improvement in hormone level were not seen in female patients. Hypogonadism improved from 18.57% improved to 69.23% after six-month post-ART therapy. This signifies role of ART therapy in improvement in gonadal dysfunction. Conclusion: Gonadal deficiency or more specifically hypogonadism is common among patients infected with HIV. The improvement in male testosterone and LH levels after ART suggests that hypogonadism may reverse in some cases. However, these observations need long term and larger volume studies to support the hypothesis.

P-1443. Experiences with Human Immunodeficiency Virus (HIV), Dialysis, and Kidney Transplantation

Abstract Background People living with HIV and advanced kidney disease face unique challenges in the kidney transplant evaluation process. Retrospective chart reviews concerning this marginalized patient population portray kidney transplant candidates and the transplant evaluation process through the lens of the provider. We directly solicited patient perspectives to better understand their experiences with HIV, dialysis, and kidney transplantation. Methods We recruited 20 people living with HIV and advanced kidney disease seen at our center to participate in one-on-one interviews guided by a structured questionnaire, audio-recorded, and professionally transcribed. Two physicians coded and reviewed all responses for common themes. A third physician served as the external thematic auditor. Data was collected on demographics, HIV care, and engagement in the transplant evaluation process for each participant. Results All 20 participants (18 Male, 14 Black, Mean Age 54y) were prescribed integrase inhibitor-based regimens and 17 demonstrated suppressed HIV viremia. One was not referred for kidney transplantation, one referred but not yet evaluated, nine undergoing evaluation, three with referrals closed, one listed, and five transplanted. Twenty parent codes were identified, each with 1-10 sub-codes. Seven major themes arose: HIV-associated stigma inside and outside of healthcare; Balance of trust and autonomy in decisions to start therapy for HIV and advanced kidney disease; Effect of health literacy on HIV and advanced kidney disease treatment adherence; Communication failures during the transplant evaluation process; Health and lifestyle changes related to dialysis and transplant listing; Impact of social support on pre- and post-transplantation experiences; and Personal and medical consequences of the perception of the “ideal transplant candidate”. Conclusion Patient perspectives offer valuable insight into the experiences of people living with HIV and advanced kidney disease undergoing dialysis and pursuing transplant evaluation. Attention to common attitudes and beliefs associated with this complex process, as well as its influence on life outside of healthcare, may guide future interventions to increase this vulnerable population’s access to kidney transplantation. Disclosures All Authors: No reported disclosures

P-455. Post-Transplantation Infection and Rejection Outcomes in Kidney Transplant Recipients Living with Human Immunodeficiency Virus (HIV): A Single-Center Experience Over a Decade of Evolving Practices

Abstract Background The development of integrase inhibitor and injectable antiretroviral therapy (ART), use of lymphocyte-depleting induction, and implementation of the HIV Organ Policy Equity (HOPE) Act have revolutionized kidney transplant eligibility, peri-transplantation management, and post-transplantation outcomes for people living with HIV and advanced kidney disease in the last decade. We describe our experience with HIV-positive recipients over this important period. Methods We conducted a retrospective chart review of all adults living with HIV and advanced kidney disease who underwent kidney transplantation at our center between 2013-2024. Data was collected on demographics, ART and induction regimens, and post-transplantation outcomes: patient/allograft survival, infections, and rejection episodes within the first year. Results Sixteen patients (14 Male, 13 Black, Mean Age 51y) underwent 17 kidney transplantations. Ten transplantations occurred from 2013-2022; seven occurred within 18 months of our center’s implementation of the HOPE Act. HIV-associated nephropathy accounted for all six transplantations from 2013-2017; hypertension and diabetes mellitus accounted for most transplantations in later years. Four patients transplanted prior to 2017 received basiliximab, of whom one experienced rejection within a year; 13 subsequent transplantations were induced with anti-thymocyte globulin (ATG), with three complicated by rejection. Rejection incidence was comparable between recipients of 3 mg/kg and 4.5 mg/kg ATG. Two patients suffered graft loss (rejection, BK nephropathy). Eleven patients had infections within a year, predominantly urinary tract infections and cytomegalovirus viremia. No opportunistic infections were identified. Three out of the four patient deaths in this cohort were due to complications of coronavirus disease 2019. Conclusion Recent advancements in HIV care and solid organ transplantation practices converged to facilitate pre-transplantation optimization, increase opportunities for transplantation, and improve post-transplantation outcomes for people living with HIV and advanced kidney disease. When used with integrase inhibitor-based therapy, ATG can prevent rejection without precipitating opportunistic infections. Disclosures All Authors: No reported disclosures

P-1933. MASTARD-COVID-19: A MAtched-cohort Study of Specific-Treatment-requiring Autoimmune Rheumatic Diseases after COVID-19 Using Japanese Health Insurance Claims Data

Abstract Background Recent database studies indicate an increase in new cases of autoimmune inflammatory rheumatic diseases (AIIRDs) following coronavirus disease 2019 (COVID-19), but these studies have significant limitations. The main issue is the reliance on disease codes like ICD-10 for diagnoses, which does not ensure accuracy. Overcoming the limitation of previous studies, we studied whether a history of COVID-19 infection increases the risk of developing AIIRDs requiring disease-specific treatment.Figure 1.Details of the design of this matched cohort study. Methods This matched cohort study utilized the JMDC Claims Database, sourced from health insurance union receipts from July 2019 to August 2022. Individuals with a history of COVID-19, identified by ICD-10 codes, were placed in Group 1. Group 2 consisted of individuals without a medical history of COVID-19, matched 1:1 with those in Group 1 based on sex, age, risk factors for severe outcomes, and the Charlson Comorbidity Index (Figure 1). We evaluated the incidence of AIIRDs within one year, defined by both diagnosis and the initiation of disease-specific medications (including corticosteroids, immunosuppressants, disease-modifying anti-rheumatic drugs, and biologics, etc.) that two board-certified rheumatologists reviewed. Additionally, we compared the incidences of hospitalization due to AIIRDs between the two groups.Table 1.Demographics and Clinical Characteristics.*One control could have been matched to multiple patients.Abbreviations: AIDS/HIV: acquired immunodeficiency syndrome / human immunodeficiency virus. Results Group 1 and Group 2 included 770,498 individuals in each. The patients' characteristics were presented in Table 1. Within a study period, 0.21% (1,587/766,402) in Group 1 developed AIIRDs required disease-specific treatment, and 0.11% (839/766,402) in Group 2, with a risk difference of 0.10% [95% confidence interval (C.I.): 0.085-0.110], and a risk ratio of 1.9 (95% C.I.: 1.7-2.1). The incidence of more than half of the AIIRD types was statistically significantly higher in Group 1 than in Group 2 (Figure 2). Moreover, Group 1 experienced a notably higher incidence of hospitalization due to AIIRD than Group 2, with a risk difference of 0.027 (95% C.I.: 0.023-0.030), and a risk ratio of 21 (95% C.I.: 11-40).Table 2.Risk differences and risk ratios of the diagnosis of treatment-requiring AIIRDs between each group.Abbreviations: AIIRDs: autoimmune inflammatory rheumatic diseases. Conclusion Compared to the matched group of individuals without a history of COVID-19, the group with a history of COVID-19 showed a higher incidence of a variety of AIIRDs requiring specific treatments and an increased incidence of hospitalizations due to AIIRDs.Figure 2.Risk differences and risk ratios of the diagnosis of AIIRDs requiring specific treatments between each group.* Risk ratios are shown only for those that can be calculated and show a significant difference. Disclosures Ryotaro Tajima, Master of information science, Shionogi & Co., Ltd.: Employee|Shionogi & Co., Ltd.: Stocks/Bonds (Public Company) Shogo Miyazawa, MSc, Shionogi & Co.,Ltd: Stocks/Bonds (Public Company) Takuji Komeda, n/a, Shionogi & Co., Ltd.: Employee|Shionogi & Co., Ltd.: Stocks/Bonds (Public Company)

P-648. Shorter vs Standard-Duration Antibiotic Therapy for Nocardiosis: A Multicenter Retrospective Cohort Study

Abstract Background The recommendation to treat nocardiosis for long durations (usually 6-12 months) relies on small case series published decades ago. We implemented real-world data to assess the association between treatment duration and outcomes in nocardiosis.Table 1.Clinical characteristics and outcomes of individuals diagnosed with nocardiosis, according to treatment duration rangea Calculated for the three treatment groups using Chi-square test or Fisher’s exact test (⸙) and one-way ANOVA for categorical and continuous variables, respectively; b Average daily prednisone dosage (in milligrams), during the 90 days prior to presentation. Whenever dexamethasone was used, dosage was converted to the equivalent prednisone dosage; c Individuals with active malignancy, primary immune deficiency, autoimmune diseases, and chronic corticosteroid therapy (≥5 and <20 mg per day); d Solid organ transplant recipients, hematopoietic stem cell transplant recipients, and individuals with acquired immunodeficiency syndrome (AIDS) or on chronic corticosteroid therapy (≥20 mg per day); e Identification to the species level was available for 95/176 (54%) of the cohort. IV = intravenous; NA = not applicable; SMX-TMP = sulfamethoxazole-trimethoprim. Methods A multicenter retrospective cohort study comprising individuals with nocardiosis during 2007-2022, excluding those who died within 90 days from diagnosis. Patients were classified into three groups according to treatment duration: short (≤90 days), intermediate (91-180 days), and long ( >180 days). We compared overall mortality, relapse rates, and antibiotic-related adverse events at 1-year. Treatment duration was cross tabulated with immune status and nocardiosis syndrome, considering that clinical judgment has led physicians to deviate from recommended long durations in appropriate cases.Figure 1.Study flow diagram Results A total of 176 individuals were diagnosed with nocardiosis during the study period, 43 (24%) of whom died within 90 days and were excluded (Figure 1). Of the remaining 133 individuals, 45 (34%) were apparently immunocompetent, 26 (19%) and 62 (47%) had mild-moderate and substantial immune suppression, respectively. Patients received short (N=37, 28%), intermediate (N=40, 30%) and long (N=56, 42%) treatment durations. Longer treatment duration was positively associated with systemic corticosteroid use (p=0.009), immune suppression (p=0.014), and nocardiosis syndrome (longer durations for dissemination, p=0.001; Table, Figure 2). By 1-year, 20 (15%) individuals died and 2 (1.5%) relapsed. Treatment duration was not associated with mortality (p=0.977; Figure 3) or nocardiosis relapse (p=0.509). Of those with solitary pulmonary nocardiosis (N=73), none of the 20 immunocompetent individuals died by 1-year, while 5/16 (31%), and 6/37 (17%) of those with mild-moderate and substantial immune suppression, respectively, died, regardless of treatment duration. Adverse events rate did not differ significantly between duration groups.Figure 2.Distribution of treatment duration groups according to nocardiosis clinical syndrome and immune status For each color, shades signify immune status (apparently immunocompetent individuals, and those with mild-moderate or substantial immune suppression): darker shades signify diminished immunity. Conclusion With clinically guided case-by-case patient selection nocardiosis can be safely treated for durations significantly shorter than traditionally recommended.Figure 3.Survival curves of the entire cohort, according to treatment group The entire cohort is presented as a single curve up to 90 days, then divided into 3 treatment groups, according to the total treatment duration. p value calculated using Log-rank test. Disclosures All Authors: No reported disclosures

P-544. Whole Food Plant-Based Diet for HIV-Associated Reduction in Cardiovascular Risk: A Pilot Randomized Clinical Trial (PLANT-HART)

Abstract Background Globally, 39 million people are affected by HIV, most of whom are on antiretroviral therapy (ART), which increases cardiovascular risks. Guidelines lack specific dietary recommendations for this population, though plant-based diets may reduce these risks. This pilot study (NCT05796882), to our knowledge, is the first to explore the effects of a plant-based diet on cardiovascular risk in HIV-positive individuals.Table 1.Differences in variables for both groups combined and their statistical significance. Paired sample analysis. Methods This randomized controlled pilot clinical trial, conducted in Mexico, involved HIV-positive adults on stable ART, aged 30-60, with a body mass index > 25 and ≥ 1 cardiovascular risk factor. Exclusion criteria included: acquired immunodeficiency syndrome, major cardiovascular events, substance abuse, and ART non-adherence. Of 150 invited, 21 consented and 10 completed the 8-week intervention. Outcomes were analyzed using non-parametric tests (Wilcoxon Sign-rank and Mann-Whitney U). The ethics committee approved; all participants provided informed consent. Results Ten male participants (mean age 40.3 ± 8.2) were divided into a plant-based diet (PBD, n=4) and a nutritional standard care (NSC, n=6) group. After 8 weeks, reductions in cardiovascular risk were observed; the NSC group experienced a -0.9% in Framingham Hard Coronary Risk (p=0.2) and the PBD group a -0.1% (p=0.1). Blood pressure decreased significantly in both groups: systolic blood pressure decreased by 15.2 mmHg (p=0.01) and diastolic blood pressure by -7.3 mmHg (p=0.02) (Table 1). The PBD group also showed reductions in weight (-700g, p=0.7), body fat percentage (-0.9%, p=1.0), tricipital fold (-3mm, p=0.06), total cholesterol (-32.0 mg/dL, p=0.1) and LDL cholesterol (-39.7 mg/dL, p=0.2), though not statistically significant. Conclusion This pilot study suggests that a plant-based diet may reduce cardiovascular risks in HIV-positive individuals. Both groups were significant for reducing systolic and diastolic blood pressure. The plant-based diet can potentially be beneficial for weight and cholesterol management. Despite a small sample size and adherence challenges, regular follow-ups and dietary self-reports enhanced compliance, underscoring the need for larger, comprehensive studies to confirm these findings. Disclosures All Authors: No reported disclosures

P-1451. Missed Opportunities for HIV Diagnosis in Mexico City: Unveiling the Gender Gap

Abstract Background Women in Mexico are not considered a key population for acquiring HIV, consequently, neither the patients nor their physicians are aware of this risk. This lack of recognition may contribute to late diagnoses and unfavorable clinical outcomes. This study aims to determine the frequency of missed opportunities for HIV diagnosis (MOHD) in a tertiary care center in Mexico City. Methods A questionnaire for newly enrolled healthcare patients was routinely applied since 2013 to look for MOHD, at the HIV Clinic of a tertiary care center in Mexico City. MOHD was defined as a healthcare encounter in which a) HIV diagnosis was not made, b) was prompted by a clinical manifestation related to HIV, and c) occurred at least 30 days before the HIV diagnosis was confirmed. Frequency and proportion of MOHD by sex were reported, we described demographics, presence of AIDS at enrollment and compared the proportion of MOHD and AIDS defining events by gender. Results A total of 1,143 questionaries were applied from January 1st 2013, to December 31st 2023; 107 (9.4%) respondents were female and 1036 (90.6%) were male. A total of 486 (42.5%) patients reported experiencing symptoms related to HIV before their diagnosis, with 36 (7.4%) being women. 466 of 486 sought medical attention for their symptoms: 403 patients had data to establish MOHD, 27 were women and 376 men. MOHD was considered in 18/27 (66%) women and in 155/376 (41%) men (p=0.03). Among the patients with MOHD, 10/18 (56%) of the women and 52/155 (34%) of men had AIDS at enrollment in HIV care (p=0.02). In the MOHD group, women's mean age was 43 years (SD=12.2) vs 35 in men (SD=12.2, p=0.01), 39% were married (7/18) vs. 11% of the men (17/155) (p< 0.01), and years of education were similar: 12.2 (SD= 4.6) vs. 13.2 (SD=4.2), respectively (p=0.51). Conclusion This study reveals a higher proportion of missed opportunities for HIV diagnosis and AIDS in women compared to men. Women with MOHD were older and married in a higher proportion than men. Our results underscore the urgent need of strategies for increasing awareness of HIV risk in Mexican women. Disclosures All Authors: No reported disclosures

P-1866. Polymorphonuclear Myeloid-Derived Suppressor Cells regulates immune reconstitution during HIV infection through PD-L1 and TGF-β signaling

Abstract Background Although myeloid-derived suppressor cells (MDSCs) are widely recognized for their immunoinhibitory effect in a variety of pathological conditions, their function during human immunodeficiency virus (HIV) infection and the onset of inadequate immune reconstitution remains elusive. PMN-MDSCs inhibit autologous CD4+ T-cell proliferation and cytokines (IL-2, TNF-α, and IFN-γ) production in HIV INRs. Methods We conducted a cross-sectional study in which 30 healthy controls (HC) and 62 HIV-1-infected subjects [31 immunological non-responders (INRs) and 31 immunological responders (IRs)] were selected. After two years of antiretroviral therapy, INRs and IRs were designated as patients with CD4+ T-cell counts < 350 cells/μL and >500 cells/μL, respectively. The proportion of MDSCs was measured and their relationship with HIV disease progression was studied. Specifically, using flow cytometry and real-time PCR, immune regulatory molecules (including programmed death-ligand 1 [PD-L1], arginase 1, inducible nitric oxide synthase, interleukin 10, transforming growth factor beta [TGF-β], and indoleamine 2,3-dioxygenase) that are relevant for MDSCs activity were quantified. Furthermore, we investigated the impact of the blockade of PD-L1 and/or TGF-β signaling on MDSCs and their effects on CD4+ T cells using in vitro functional experiments. PD-L1 and TGF-β mediate the suppressive effect of PMN-MDSCs on CD4+ T-cells response. Results We found that polymorphonuclear MDSCs (PMN-MDSCs) are more abundant and negatively correlated with CD4+ T-cell counts in HIV-infected individuals. PMN-MDSCs suppress CD4+ T-cell proliferation and interferon-γ (IFN-γ) production in INRs. Furthermore, correlations were found between PD-L1 expression on PMN-MDSCs and PD-1+ CD4+ T-cells. TGF-β expression on PMN-MDSCs was likewise enhanced in INRs. Importantly, inhibiting both PD-L1 and TGF-β signaling had a synergistic impact on restoring CD4+ T-cell activity in vitro. Conclusion Our findings reveal that the expansion of PMN-MDSCs decreased CD4+ T-cell proliferation and IFN-γ secretion in HIV infection through PD-L1 and TGF-β mediated pathways. Interventions that target both PD-L1 and TGF-β pathways may be novel strategies for enhancing immune reconstitution in INRs. Disclosures All Authors: No reported disclosures

Roles of mobile teams in tracing lost to follow–up clients: evidence from the optimization of COVID-19 vaccination uptake and routine immunization in Ekiti State

BackgroundEvidence from literature has established that tracing lost to follow-up clients is an effective strategy for complementing other mechanisms for infectious disease control like human immunodeficiency virus (HIV), tuberculosis, and other diseases such as Ebola. As a long-standing successful public health method of optimizing acceptance and/or adherence to infectious disease treatment tracing lost to follow-up clients is usually carried out by manually investigating individuals who absconded or are absent from treatments designed to manage and/or promote their health status. This study seeks to explore the role of mobile teams in tracing clients lost to follow-up for immunization.MethodsThis study was premised on a qualitative research approach to elicit information from purposively selected populations across 9 local government areas (LGA) in Ekiti state, Nigeria. Focus group discussions, in-depth interviews, and key informant interviews were the selected methods of data collection on the roles of mobile teams in tracing lost to follow–up clients for the optimization of COVID-19 and routine immunization in Ekiti state.ResultsA total of 107 healthcare workers across Ekiti state were selected to participate in this study. Our study found tracing lost to follow-up clients resulted in two major successes for health workers. These are increased awareness of COVID-19 vaccination and routine immunization, and improved vaccination coverage for both categories of vaccinees. Distance between communities, and transportation, were interdependent issues reported by health workers as challenges in the course of their duties.ConclusionOur study emphasizes the importance of onboarding and/or training health workers across all categories that are involved in the implementation of a public health program, irrespective of the existing knowledge that they may have on the concept. This study recommends that health workers across all levels, in collaboration with key players and stakeholders employ human-centered designed approaches to improve the sensitization of caregivers, and community populace on the values, benefits, and significance of the COVID-19 vaccination and routine immunization uptake.

Seroprevalence and Associated Outcomes of Parvovirus B19 Infection in Human Immunodeficiency Virus Patients: A Systematic Review

AbstractSeveral case reports have highlighted the presence of serious clinical outcomes in patients with human immunodeficiency virus (HIV) related to parvovirus B19 (PVB19). However, epidemiological studies have produced inconsistent and varying results regarding the prevalence of PVB19 and its associated clinical outcomes in this population. These inconsistencies highlight the need for a thorough summary and analysis of present data to better understand burden and impact of PVB19 on HIV patients. This review aims to provide an overview of current evidence and identify areas for further research.Following the Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines, a comprehensive search was conducted across Medline/PubMed, Google Scholar, and World Health Organization Virtual Health Library Regional Portal. The pooled prevalence with the corresponding 95% confidence interval (CI) was measured using Comprehensive Meta-Analysis Software version 3.3. Publication bias was estimated based on Begg's test, Egger's test, and examination of the funnel plots.A total of 16 studies, with 2,122 HIV patients, were included in the meta-analysis. The pooled prevalence of detecting anti-PVB19 immunoglobulin G, anti-PVB19 immunoglobulin M, and PVB19 DNA particles among HIV patients was 43.6% (95% CI: 23.5–66.1%), 5.10% (95% CI: 2.10–12.10%), and 6.40% (95% CI: 4.10–9.90%), respectively. In the overall population of HIV patients, most of the included studies did not establish a statistically significant association between PVB19 infection and the occurrence of anemia.PVB19 infection is commonly detected in individuals with HIV. However, anemia due to PVB19 is not common in this population. Findings from a few studies suggest that PVB19 infection may contribute to anemia in individuals with advanced HIV disease or significant immunosuppression. Additional research is needed to confirm and clarify these relationships in individuals with HIV, particularly those with compromised immune systems.

Anti-HIV Treatment: History, Current Advances and Targets

Human Immunodeficiency Virus (HIV) is a retrovirus that is well known to be the causative agent for acquired immunodeficiency syndrome. In this review, we discussed the HIV virus, its transmission, events that lead to AIDS, the historical aspect of its emer-gence, current prospects in antiretroviral drugs, and its evolution up until current treatment strategies. We have also discussed the recent research related to new molecules, which showed potent anti-HIV activity and have the potential to become a key targetfor drugde-velopment. New studies have explored novel drug target sites and the benefits of using ar-tificial intelligence and machine learning in drug discovery and design, leading to better results and advancements in treatment.

Bayesian Analysis of Censored Linear Mixed-Effects Models for Heavy-Tailed Irregularly Observed Repeated Measures.

The use of mixed-effect models to understand the evolution of the human immunodeficiency virus (HIV) and the progression of acquired immune deficiency syndrome (AIDS) has been the cornerstone of longitudinal data analysis in recent years. However, data from HIV/AIDS clinical trials have several complexities. Some of the most common recurrences are related to the situation where the HIV viral load can be undetectable, and the measures of the patient can be registered irregularly due to some problems in the data collection. Although censored mixed-effects models assuming conditionally independent normal random errors are commonly used to analyze this data type, this model may need to be more appropriate for accommodating outlying observations and responses recorded at irregular intervals. Consequently, in this paper, we propose a Bayesian analysis of censored linear mixed-effects models that replace Gaussian assumptions with a flexible class of distributions, such as the scale mixture of normal family distributions, considering a damped exponential correlation structure that was employed to account for within-subject autocorrelation among irregularly observed measures. For this complex structure, Stan's default No-U-Turn sampler is utilized to obtain posterior simulations. The feasibility of the proposed methods was demonstrated through several simulation studies and their application to two AIDS case studies.

Factors associated with having a steady homosexual partner among men who have sex with men, based on internet recruitment.

This study analyzed the status and factors associated with having a steady homosexual partner (HP) among men who have sex with men (MSM) to provide a scientific basis for developing prevention and control strategies for acquired immunodeficiency syndrome in this population. A questionnaire survey was conducted among study participants who were MSM recruited online by a non-governmental organization in May 2024. The participants were divided into two groups based on whether they had a steady HP. Univariate and multivariate logistic regression analyses were used to evaluate the factors influencing whether the participants had a steady HP. We surveyed 604 participants;211 (34.93%) had a current steady HP. Multivariate logistic regression analysis showed that older participants having a steady HP (adjusted odds ratio [aOR]: 1.04; 95% confidence interval [CI]: 1.01-1.07)was associated with an average monthly income >6,000 Chinese yuan (aOR: 1.47; 95% CI: 1.01-2.16), a belief that using enhancers such as Rush Popper increases the human immunodeficiency virus (HIV) infection risk (aOR: 1.56; 95% CI: 1.02-2.41), identification as purely homosexual (aOR: 2.02; 95% CI: 1.37-2.99), having engaged in anal sex with a HP in the previous 6 months (aOR: 4.13; 95% CI:2.51-6.90), and knowing the HIV status of their HP (aOR: 1.88; 95% CI: 1.17-3.06). Participants less likely to have a steady HP had used condoms consistently during anal sex with a HP in the prior 6 months (aOR: 0.56; 95% CI: 0.35-0.90) and engaged in one-night stands with HPs (aOR: 0.44; 95% CI: 0.29-0.65). A low proportion of participants had steady HPs (34.93%). Therefore, public education for MSM should be promoted to encourage individuals to improve their awareness of HIV infection risks. Sexual responsibility, including correct use and risks of enhancers like Rush Popper, and avoiding high-risk behaviors, such as one-night stands, is crucial to reducing the risks of HIV and sexually transmitted infections.

Sensitivity Pattern of the Candida Species Separated from the Blood and Urine of the Patients with Malignancy in Hospital

Background: Infection with Candida species has been increased globally during the past decade. This can be due to the increase in the number of patients with immunodeficiency problems like cancer, HIV AIDs, organ transplantation and hospitalization in ICUs. We aimed to investigate the prevalence rate of the fungal colonization and related species in chemotherapy-subjected children with malignancy. Methods: Present analytical-applied research was conducted on 128 chemotherapy-subjected children with malignancy. Blood and urine samples were collected from all the patients; afterwards, the urine samples were cultivated on Saborrads Dextrose Agar and the blood samples in ordinary culture bottles (monophasic culture method and blood culturing). Then, the developed fungi were separated from the culture medium and subjected to identification tests. Results: There was no significant relationship between the age group and infection with fungus (P=0.998) but there was a significant relationship between gender and fungus infection (P=0.049) in such a way that fungus infection was found more prevalent amongst the females. Overall, 28 individuals (58.33%) were found infected with C. albicans; 9 (18.75%) with C. tropicalis; 5 (10.42%) with C. glabrata; 3 (6.25%) with C. kefir; 2 (4.116%) with C. krusei and 1 (2.09%) with C. parapsilosis. Conclusion: C. albicans is the most common species in this geographical area. The best treatment for these infectious diseases is voriconazole.

Structure of the Kaposi's sarcoma-associated herpesvirus gB in post-fusion conformation.

Discovered in 1994 in lesions of an AIDS patient, Kaposi's sarcoma-associated herpesvirus (KSHV) is a member of the gammaherpesvirus subfamily of the Herpesviridae family, which contains a total of nine that infect humans. These viruses all contain a large envelope glycoprotein, glycoprotein B (gB), that is required for viral fusion with host cell membrane to initial infection. Although the atomic structures of five other human herpesviruses in their postfusion conformation and one in its prefusion conformation are known, the atomic structure of KSHV gB has not been reported. Here, we report the first structure of the KSHV gB ectodomain determined by single-particle cryogenic electron microscopy (cryoEM). Despite a similar global fold between herpesvirus gB, KSHV gB possesses local differences not shared by its relatives in other herpesviruses. The glycosylation sites of gB are arranged in belts down the symmetry axis with distinct localization compared to that of other herpesviruses, which occludes certain antibody binding sites. An extended glycan chain observed in domain I (DI), located proximal to the host membrane, may suggest its possible role in host cell attachment. Local flexibility of domain IV (DIV) governed by molecular hinges at its interdomain junctions identifies a means for enabling conformational change. A mutation in the domain III (DIII) central helix disrupts incorporation of gB into KSHV virions despite adoption of a canonical fold in vitro. Taken together, this study reveals mechanisms of structural variability of herpesvirus fusion protein gB and informs its folding and immunogenicity.IMPORTANCEIn 1994, a cancer-causing virus was discovered in lesions of AIDS patients, which was later named Kaposi's sarcoma-associated herpesvirus (KSHV). As the latest discovered human herpesvirus, KSHV has been classified into the gammaherpesvirus subfamily of the Herpesviridae. In this study, we have expressed KSHV gB and employed cryogenic electron microscopy (cryoEM) to determine its first structure. Importantly, our structure resolves some glycans beyond the first sugar moiety. These glycans are arranged in a pattern unique to KSHV, which impacts the antigenicity of KSHV gB. Our structure also reveals conformational flexibility caused by molecular hinges between domains that provide clues into the mechanism behind the drastic change between prefusion and postfusion states.

Disease burden of communicable diseases among children and adolescents aged under 20 years in China from 1990 to 2021

To investigate the epidemiological characteristics and changing trends of communicable diseases among children and adolescents in China from 1990 to 2021. Based on the Global Burden of Disease Database, epidemiological indicators for communicable diseases among the population aged under 20 years in China from 1990 to 2021 were selected to analyze the burden of communicable diseases in this population, and a comparative analysis was performed with global data as well as data from Western Europe and North America. In 1990-2021, the overall burden of communicable diseases tended to decrease among children and adolescents in China. In 2021, the prevalence rate of communicable diseases in China was lower than the global prevalence rate and was higher than that in Western Europe and North America. There was a significant reduction in the mortality rate of communicable diseases, and the gap with Western Europe and North America gradually narrowed year by year. The overall incidence rate, mortality rate, and disability-adjusted life year rate of communicable diseases in males were higher than those in females, and respiratory infections and intestinal infections were more common in children aged <5 years, while the incidence rate of sexually transmitted diseases was higher in adolescents. From 1990 to 2021, the disease burden of communicable diseases among the population under 20 years old in China has significantly decreased. However, there is still a certain gap compared to developed regions. Strengthening the prevention and control of diseases such as respiratory infections and acquired immunodeficiency syndrome, as well as enhancing health interventions for children under 5 years old, will help improve the overall health level of children and adolescents in China.