Changing Paradigm of Yeast Isolates in HIV-Seropositive Patients with Oropharyngeal Candidiasis (OPC).

Background Oropharyngeal candidiasis (OPC) is a common fungal infection in HIV-seropositive patients. Understanding the spectrum of yeast isolates and their antifungal susceptibility patterns is crucial for effective management. This study aimed to determine the yeast isolates, antifungal susceptibility patterns, and associated factors in HIV-seropositive patients with OPC. Material and methods A prospective observational study was conducted on 350 HIV-seropositive patients attending an Integrated Counselling and Testing Centre (ICTC) at the Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, Bihar. Yeast isolates from oropharyngeal lesions were identified, and their antifungal susceptibility was determined by automated method VITEK 2. Demographic characteristics, highly active antiretroviral therapy (HAART) status, and CD4+ cell count categories were analyzed for associations. Results This study of 350 HIV-seropositive patients revealed that 100 tested positive for Candida, with distinct differences between HAART (n=67) and non-HAART (n=33) groups. HAART patients had a younger age distribution and higher median CD4+ cell counts (350 vs. 250 cells/mm³, U = 175, p < 0.05) compared to non-HAART patients. Candida albicans was the most common species in both groups, but significant variations in species distribution (χ² = 9.23, p < 0.05) and antifungal susceptibility were noted. Specifically, susceptibility differences were significant for flucytosine (χ² = 7.21, p = 0.027) and voriconazole (χ² = 8.64, p = 0.013), emphasizing the influence of HAART on managing immune function and antifungal resistance in HIV patients. Conclusion This study provides insights into the spectrum of yeast isolates and their antifungal susceptibility patterns in HIV-seropositive patients with OPC. The findings emphasize the importance of considering multiple factors, such as Candida species, HAART status, and individual patient characteristics, in treatment decisions. The results will aid in the development of evidence-based management protocols for this vulnerable population. Further research is warranted to explore additional factors influencing antifungal susceptibility and optimize treatment strategies for this patient population.

Evaluation of HIV-1 DNA levels among adolescents living with perinatally acquired HIV-1 in Yaounde, Cameroon: A contribution to paediatric HIV cure research in Sub-Saharan Africa.

Background: With the advent of antiretroviral therapy (ART), most children living with HIV in sub-Saharan Africa (SSA) are growing toward adolescence, with scarcity of evidence on the size of viral reservoirs to enhance paediatric cure research strategies. This study aims to compare HIV-1 proviral DNA levels according to virological response among adolescents living with perinatally acquired HIV-1 (ALPHIV) and identify associated-factors in the Cameroonian context. Methods: In this observational cohort study, HIV-1 RNA viremia and CD4+ T-cell count were assessed through RT-PCR and flow cytometry respectively at three time-points over 18 months of observation. At the third time-point, 80 randomly-selected participants were classified as with viremia (≥50 HIV-1 copies/mL; n = 40) or without viremia (<50 HIV-1 copies/mL; n = 40); immune-competent (≥500 CD4+ T cells/mm3) or immunocompromised (<500 CD4+ T cells/mm3). Among these participants, total HIV-1 DNA load was quantified through droplet digital PCR using Bio-Rad QX200. Results: Of the 80 randomly-selected adolescents, median [IQR] age was 15 (13-17) years, 56.2% were female, duration on ART was 9.3 [5.4-12.2] years. Among the 40 viremic ones (median viremia 7312 [283-71482]) HIV-1 copies/ml, 75.0% (30/40) were in virological failure (≥1000 HIV-1 copies/ml), while median of CD4 T cells were 494 [360-793] cell/mm3 with 48.8% (39/80) immunocompromised. No significant variation in HIV-1 RNA viremia and CD4 T cell count was observed between the three time-points, and 13.7% (11/80) adolescents remained aviremic and immune-competent throughout (stable adolescents). A positive and moderate correlation (r = 0.59; p < 0.001) was found between HIV-1 DNA levels and HIV- 1 RNA viremia. Regarding the CD4 T cell count, a negative and weak correlation (r = -0.28; p = 0.014) was found with HIV-1 DNA loads only among adolescents with viremia. Starting ART within the first year of life, ART for over 9 years and aviremia appear as predictors of low HIV-1 DNA loads. Conclusion: Among ALPHIV, high HIV-1 RNA indicates an elevated viral reservoir size, representing a drawback to cure research. Interestingly, early ART initiation and longer ARTduration lead to sustained viral control and limited HIV-1 reservoir size. As limited size of viral reservoir appears consistent with viral control and immune competence, adolescents with sustained viral control (about 14% of this target population) would be candidates for analytical ART interruptions toward establishing paediatric post-treatment controllers in SSA.

A Phase-IV Non-interventional Study to Assess Virological Effectiveness, Safety, and Tolerability of DTG-based Antiretroviral Therapy in HIV-1 Infected Indian Persons Living with HIV.

BACKGROUND: Dolutegravir (DTG) is a novel yet preferential first- and -second-line treatment for persons living with HIV (PLH). Owing to its recent introduction, DTG-based regimens have not undergone a comprehensive, systematic evaluation regarding their real-world utilization and safety profile among a sizeable Indian population. OBJECTIVE: This study aimed to assess the 24 week immunovirological outcomes, anthropometric and metabolic changes, tolerability, and adverse events (AEs) of DTG-based antiretroviral (ART) regimens. METHODS: A single-centre phase-IV non-interventional observational study involving 322 ART naïve and treatment-experienced PLH initiating DTG-based-regimens until October 2022 were followed up for outcomes at 24 weeks. RESULTS: At 24 weeks, all PLH (n = 113) in the naïve group, all PLH (n = 67) in the first-line substitution group, 93.9% PLH (n = 46) in the first-line failure group, and 95.7% PLH (n = 89) in the second-line substitution group were virologically suppressed to plasma HIV-RNA <1000 copies/mL. Virological suppression rates to plasma HIV-RNA <200 copies/mL and <50 copies/mL were consistent among PLH who received DTG as first- or second-line ART. The mean-unadjusted weight gain observed was 3.5 kg (SE: 0.330), and it was significantly higher in PLH with poorer health at baseline (either HIV-RNA ≥ 1000 copies/ml or CD4 cell count <350 cells/µL). Overall, 27.3% PLH (n = 88) gained ≥10% of their baseline body weight, corresponding to 3.7% incidence (n = 12) of treatment-emergent clinical obesity. DTG had an overall lipid-neutral effect, with an advantageous effect being observed in PLH switching from non-nucleoside analogue reverse-transcriptase inhibitors (NNRTI) or ritonavir-boosted protease inhibitors (b/PI), especially in dyslipidemic pre-treated PLH (median change in total cholesterol: 28.5 mg/dL and triglycerides: 51 mg/dL), possibly emanating from the withdrawal of the offending ART. The incidence of DTG-specific AEs, including CNS AEs, was low. Two PLH developed proximal myopathy and one developed transaminitis, warranting DTG discontinuation. Asymptomatic serum-CPK elevation and drug-induced transaminitis were seen in 25.2% (n = 27) and 3.2% (n = 10) PLH, respectively. No apparent negative effects on renal function were detected. CONCLUSION: Our results from a large Indian cohort indicate a favourable virological and metabolic response, with good tolerance of DTG-based ART at 24 weeks.

The peripheral immune cell counts and mouth ulcers: A two-sample Mendelian randomization study.

Objective: This study explored the causal association of peripheral immune cell counts with mouth ulcers (MUs) by two-sample Mendelian Randomization. Design: The counts of 12 circulating immune cell types (leukocytes, lymphocytes, monocytes, eosinophils, neutrophils, basophils, CD4+ cells, CD8+ cells, unswitched memory B cells, NK cells, B cells and a derived ratio (CD4+/CD8+)) were determined as the exposure. MUs were the outcome. The analysis was conducted mostly using the inverse-variance weighted (IVW) approach. MR Egger, weighted median, weighted mode and simple mode were used to detect the horizontal pleiotropy. Results: The IVW results for leukocytes and lymphocyte counts were OR = 0.93, 95 % CI = 0.88-0.98, p = 0.0115 and OR = 0.91, 95 % CI: 0.84-0.98, p = 0.0150, respectively. The Wald ratio result for CD4+ cell and CD8+ cell counts were OR = 0.70, 95 % CI: 0.65-0.75, p = 1.05 × 10-20 and OR = 1.25, 95 % CI: 1.19-1.31, p = 9.99 × 10-21, respectively. Conclusions: This study supports a causal effect of peripheral immune cell counts on MUs. Higher leukocyte, lymphocyte and CD4+ cell counts can protect against MUs, but higher CD8+ cell counts enhance the risk of MUs. This finding confirms host immune factors play a crucial role in the aetiology of MUs.

HIV disease metrics and COVID-19 infection severity and outcomes in people living with HIV in central and eastern Europe.

BACKGROUND: To date there remains much ambiguity in the literature regarding the immunological interplay between SARS-CoV-2 and HIV and the true risk posed to coinfected individuals. There has been little conclusive data regarding the use of CD4 cell count and HIV viral load stratification as predictors of COVID-19 severity in this cohort. METHODS: We performed a retrospective, observational cohort study on people living with HIV (PLWH) who contracted COVID-19 in central and eastern Europe. We enrolled 536 patients from 16 countries using an online survey. We evaluated patient demographics, HIV characteristics and COVID-19 presentation and outcomes. Statistical analysis was performed using SPSS 20.1. RESULTS: The majority of the study cohort were male (76.4%) and 152 (28.3%) had a significant medical comorbidity. Median CD4 cell count at COVID-19 diagnosis was 605 cells/µL [interquartile range (IQR) 409-824]. The majority of patients on antiretroviral therapy (ART) were virally suppressed (92%). In univariate analysis, CD4 cell count <350 cells/µL was associated with higher rates of hospitalization (p < 0.0001) and respiratory failure (p < 0.0001). Univariate and multivariate analyses found that an undetectable HIV VL was associated with a lower rate of hospitalization (p < 0.0001), respiratory failure (p < 0.0001), ICU admission or death (p < 0.0001), and with a higher chance of full recovery (p < 0.0001). CONCLUSION: We can conclude that detectable HIV viral load was an independent risk factor for severe COVID-19 illness and can be used as a prognostic indicator in this cohort.

Predictors associated with CD4 cell count changes over time among HIV-infected children on anti-retroviral therapy follow-up in Mekelle General Hospital, Northern Ethiopia, 2019: a retrospective longitudinal study.

INTRODUCTION: AIDS continues to be a serious global public health issue. It targets CD4 cells and immunological cells, which are in charge of the body's resistance against pathogenic pathogens. In situations with limited resources, CD4 cell measurement is essential for assessing treatment responses and clinical judgments in HIV-infected children receiving Anti-Retroviral Therapy (ART). The volatility of CD4 cells during ART follow-up is still largely uncharacterized, and there are few new datasets on CD4 cell changes over time. Therefore, the purpose of this analysis was to identify the factors that were predictive of CD4 cell count changes over time in children who started ART at Mekelle General Hospital in northern Ethiopia. METHODS: A retrospective follow-up study was done. 437 patients in Mekelle general hospital, northern Ethiopia, from 2014-2016 were involved. All patients who have started anti-retrieval treatment (ART) and measured their CD4 cell count at least twice, including the baseline and those who initiated ART treatment, were included in the study population. An exploratory data analysis and linear mixed model analysis were used to explore the predictors of CD4 cell count change in patients and consider variability within and between patients. RESULTS: This study found the correlation variation explained in cells accounted for between patients was 61.3%, and the remaining 38.7% variation existed within. This indicates that there is a substantial change in random slope and intercept between and within patients. WHO clinical stage IV (ß = -1.30, 95% CI: -2.37, -0.23), co-infection HIV/TB (ß = -1.78, 95% CI: -2.58, -0.98), children aged 2-5 (ß = -0.43; 95% CI: -0.82, -0.04), and 6-14 years (ß = -1.02; 95% CI: -1.47, -0.56), non-opportunistic infection (ß = 1.33, 95% CI: 0.51, 2.14), and bedridden functional status (ß = -1.74, 95% CI: -2.81, -0.68) were predictors of cell changes over time. CONCLUSIONS: This study found that patients receiving ART experienced a significant change in CD4 cells over time. Because 61.3% of the variation in CD4 cells explained between patients and the remaining 38.7% within patients, such nested data structures are often strong correlation evidence. Co-infection of HIV/TB, functional status, age category of children, WHO clinical stage, and opportunistic infections are potential predictors of CD4 cells count change. Hence, special guidance and attention is also required, especially for those patients who have an opportunistic infections, higher WHO clinical stages, co-infections with HIV and TB, and bedridden functional status.

Predictors for CD4 cell count and hemoglobin level with survival time to default for HIV positive adults under ART treatment at University of Gondar Comprehensive and Specialized Hospital, Ethiopia.

BACKGROUND: HIV/AIDS is the most known powerful risk factor for morbidity and mortality in the world. The greatest biological markers in HIV patients are CD4 cell count and hemoglobin level, as they are independent predictors of survival of HIV patients. The objective of this study was to investigate the common socio-demographic, clinical, and behavioral Predictor's affecting the CD4 cell count, and hemoglobin level with survival time to default from ART treatment among HIV positive adults under ART treatment at university of Gondar comprehensive and specialized hospital, North-west Ethiopia. METHOD: This study was conducted at University of Gondar comprehensive specialized hospital by using a retrospective cohort follow up study design. The source of data in this study was secondary data obtained from patients chart. Bayesian joint models were employed to get wide-ranging information about HIV/AIDS progression. RESULT: From a total of 403 HIV positive adults, about 44.2% were defaulted from therapy and the rest were actively followed ART treatment. The estimate of the association parameter for the current true value of CD4 cell count ([Formula: see text]), and hemoglobin level ([Formula: see text]), trend of CD4 cell count ([Formula: see text]) and hemoglobin level ([Formula: see text]) is positive. Positive values indicating that the higher CD4 cell count and hemoglobin level is related with the higher time of defaulting from ART. Predictor's hematocrit, weight, platelet cell count, lymphocyte count, sex, adherence, and WHO clinical stage were joint determinate risk factors affecting CD4 cell count, hemoglobin level and time to default at 5% level of significance. CONCLUSION: Current study results revealed that hematocrit, weight, BMI, platelet cell count, lymphocyte count, sex (female), and good treatment adherence were significantly associated with higher CD4 cell count, hemoglobin level and time to default while having advanced WHO clinical stage-IV had significantly decreased CD4 cell, hemoglobin level, and time to default from treatment. Patients with HIV should be given special attention based on these important factors to improve their health and prolong their lives.

Real-World Effectiveness of COVID-19 Vaccine and Identification of SARS-CoV-2 Variants among People Living with HIV on Highly Active Antiretroviral Therapy in Central Kerala of India-An Ambi-Directional Cohort Study.

BACKGROUND: Vaccine effectiveness for first-generation coronavirus disease (COVID-19) vaccines among People Living with HIV (PLHIV) in India remains unexplored. This study entails the estimation of the real-world effectiveness of COVID-19 vaccines (AZD1222/Covishield, BBV152/Covaxin) among PLHIV and the identification of variants of SARS-CoV-2 among those infected with COVID-19. METHODS: An ambi-directional cohort study was conducted among 925 PLHIV above 18 years of age in two districts of central Kerala, India, from February 2022 to March 2023. Selected PLHIV were recruited as Participant Liaison Officers (PLOs) for the follow-up on the study participants. At enrolment, basic details, baseline CD4 count, and a Nasopharyngeal (NP) swab for RT-PCR were collected. In the follow-up phase, NP swabs were collected from subjects with COVID-19 symptoms. Positive subjects had a CD4 count and genomic sequencing performed. RESULTS: The mean age of the participants was 46.93 ± 11.00 years. The majority, 819 (93.6%), of participants had received at least one dose of any vaccine, while 56 (6.4%) were unvaccinated. A total of 649 (79.24%) participants were vaccinated with Covishield and 169 (20.63%) with Covaxin. In the vaccinated group, 158 (19.3%) reported COVID-19 infection. Vaccine Effectiveness (VE) for one dose of any vaccine was 43.2% (95% CI: 11.8-64.5), p = 0.015. The effectiveness of full vaccination with Covishied was 63.8% (95% CI: 39.3-79.2), p < 0.001, and Covaxin was 73.4% (95% CI: 44.3-87.3). VE was highest, at 60.7% (95% CI: 23.6-81.3), when the two doses of the vaccine were given at an interval of less than 6 weeks. Participants with a baseline CD4 count > 350 had greater protection from COVID-19, at 53.4% (95% CI: 19.6-75.3) p = 0.004. The incident cases were sub-variants of Omicron (BA.2, BA.2.38, BA.2.10). CONCLUSIONS: Full vaccination with Covishield and Covaxin was effective against COVID-19 infection among PLHIV on treatment; albeit, that of Covaxin was higher. A gap of 4 to 6 weeks between the two doses of COVID-19 vaccine was found to have higher VE among PLHIV.

Real-Life Experience With Bictegravir/Emtricitabine/Tenofovir Alafenamide in Turkey.

INTRODUCTION: Single-tablet regimens (STRs) can increase treatment success and even improve the quality of life of human immunodeficiency virus (HIV) patients. In this study, we aim to analyze the real-life efficacy and tolerability data of people living with HIV (PLWH) initiated on or switched to bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) as first-line treatment. MATERIALS AND METHODS: This retrospective analysis was performed in HIV-1-positive patients who were initiated BIC/FTC/TAF in the HIV clinic between June 2020 and June 2022. Patients who received BIC/FTC/TAF for at least 12 months were included in this study. Virological suppression, laboratory parameters, side effects, and immunological response were analyzed at one, three, six, nine, and 12 months. RESULTS: A total of 116 patients, 66 (56.9%) treatment-experienced and 50 (43.1%) naive, were evaluated within the scope of the study. In the naive patient group, baseline HIV-RNA, CD4+ and CD8+ T cell counts, CD4/CD8 ratio, and estimated glomerular filtration rate (eGFR) values were significantly different in different follow-up months. The number of patients with HIV-1 RNA levels below 50 copies/mL was 55.9% in the first month, 73.7% in the third month, 90.2% in the sixth month, and 100% in the ninth and 12th months. CONCLUSION: In our real-life observational study, BIC/FTC/TAF treatment achieved rapid viral suppression, maintained viral suppression in virally suppressed patients, and was effective for immunological recovery in both treatment-experienced and naive HIV patients. No serious side effects were observed. Our study has proved the potential of BIC/FTC/TAF as an important option in the treatment of HIV patients.

Leveraging CD4 Cell Count at Entry Into Care to Monitor Success of Human Immunodeficiency Virus Prevention, Treatment, and Public Health Programming in the Greater St Louis Area Between 2017 and 2020.

CD4 cell count at entry into human immunodeficiency virus (HIV) care is a useful indicator of success of multiple steps in HIV public health programming. We demonstrate that CD4 cell count at care initiation was stable in St Louis between 2017 and 2019 but declined in 2020. Missouri efforts in the Ending the HIV Epidemic plan should focus on rapidly identifying individuals with undiagnosed HIV infection.

Treatment Outcomes of Dolutegravir- Versus Efavirenz-Based Highly Active Antiretroviral Therapy Regimens Among Treatment-Naive People Living With HIV.

BACKGROUND: In India, following the implementation of the dolutegravir (DTG) based regimen, only a few studies compared the outcomes of DTG and efavirenz (EFV) based regimens. Therefore, this study aimed to assess virological suppression and gain in CD4+ counts of DTG and EFV-based antiretroviral therapy (ART) regimens. METHODS:  A retrospective study was conducted and the entire sample (n=140) was divided into two major classes as DTG group (n=70) and EFV group (n=70) further classified as tenofovir/lamivudine/dolutegravir (TLD) and tenofovir/lamivudine/efavirenz (TLE) regimen. Data was collected on socio-demographic characteristics, laboratory measures, and clinical and drug-related variables. For quantitative and qualitative data analysis, respectively, the T-tests and Chi-square tests were applied. RESULTS:  The mean CD4+ gain was comparable in both regimens after six months of ART but significant after 12 months of ART in the TLD group. Viral load suppression was achieved in 55.71% of clients in the TLE group after six months of ART while in the TLD group, 88.57% of clients achieved virologic suppression which was highly significant. Clients who remained on the DTG-based regimen gained significantly more weight at 12 months (mean +6.15 kg) as compared to the EFV-based regimen (mean +1.85 kg). After 12 months of ART, the majority of laboratory variables were unaffected by either regimen with the exception of serum creatinine and random blood sugar (RBS) in the TLD group. CONCLUSIONS:  Our study provides real-life evidence of better outcomes of therapy with DTG over EFV in terms of viral load suppression but immunologic recovery is equivalent in EFV-based regimens after six months of treatment. We recommend the use of DTG only in clients with a high baseline viral load as it costs approximately twice as much as EFV when cost-effectiveness is taken into account.

Comparative Assessment of Serum Selenium Status in HIV-Infected and Non-infected Children: A Pilot Study in a Tertiary Hospital in Nigeria.

Background Selenium is an essential micronutrient that plays a crucial role in a wide range of physiological processes, including immune responses. Selenium deficiency has been recognized as an associated factor in the progression of HIV to advanced HIV disease and/or mortality. Although selenium supplementation has been shown to reduce hospitalizations and improve cellular immunity, the evidence remains mixed. This study aimed to determine the prevalence of selenium deficiency and its relationship with HIV disease markers in HIV-infected children at the Lagos University Teaching Hospital. Methodology This is a cross-sectional, comparative, pilot study of plasma concentrations of selenium in HIV-infected (n = 30) and non-infected (n = 20) children enrolled in the pediatric HIV clinic of the Lagos University Teaching Hospital, Lagos, Nigeria, from May 2019 to May 2021. HIV-infected children were on stable antiretroviral therapy (ART) with an undetectable viral load. The serum concentration of selenium was measured using the automated atomic absorption spectrophotometer (hydride generation method). Logistic regression was used to study the effect of selenium status on the levels of HIV disease markers (CD4 count, viral load, weight, opportunistic infections) in the study participants. Results The median age of all participants was nine (4-12) years, with 74% being boys. The mean selenium concentrations were lower in HIV-infected children (91.1 ± 12.0 µg/L) compared to the comparison group without HIV (147.8 ± 4.9 µg/L) (p = 0.001). After controlling for age, ART duration, markers of HIV infection, and other potentially confounding variables, participants with selenium deficiency had approximately 11-fold odds of increased hospital admissions (adjusted odds ratio = 10.57, 95% confidence interval = 1.58 to 70.99; p = 0.015). Conclusions In this study, selenium concentrations were significantly lower in HIV-infected children than in the HIV-negative comparison group. Lower serum selenium concentrations were associated with increased hospitalizations. Although our findings suggest the potential need for selenium supplementation for children living with HIV in Nigeria, further studies are warranted to determine the safety and efficacy of selenium supplementation in this key population.

Quality of Life and Associated Factors of HIV Patients Under Treatment with First Line Regimens in Public Hospitals in Amhara Region, North-West Ethiopia.

Background: The availability of medication related to HIV treatment in the world is one of the substantial improvements for reaching USAID's 90-90 targets. Among the 90% of patients who have awareness about their disease, 90% are accessing their treatment and patients who received appropriate treatment have a suppressed viral load and improved CD4 cell count. Therefore, the main objective of the current study was to investigate the quality of life and associated factors of people living with HIV receiving first-line regimens at public hospitals in the Amhara region, Ethiopia. Methods: A retrospective cohort study was conducted on 700 adult HIV-infected patients under treatment with first-line regimens, who were followed-up in 17 public hospitals in the Amhara region. A multivariate linear regression analysis was used for the current study. Results: Of the 700 patients included in the current analyses, 59.5% (n=358) reported no impairment in self-care, while 63.1% (n=380) were extremely anxious/depressed. The overall expected EQ-5D utility score and visual analog scale (EQ-VAS) scores were 0.388 0.41 and 66.20 17.22 respectively. The current study indicated that the covariates sex, age of patient, level of education, appointment frequency, disclosure status of the disease, and substance use significantly affected the quality of life of people living with HIV and under treatment with first-line regimens. Hence, higher CD4 cell count and less detectable viral load lead to good quality of life of people living with HIV. Conclusion: This study indicates that certain covariates have been identified as statistically significant predictors of the study variable "quality of life" of HIV-positive people. The findings obtained in the current investigation can help policy-makers to revise the current directives. The result obtained in this study can also help health staff to conduct health-related education during the treatment of HIV patients.

Autoantigen-selected B cells are bystanders in spontaneous T cell-driven experimental autoimmune hepatitis.

Autoreactive B cells are considered pathogenic drivers in many autoimmune diseases; however, it is not clear whether autoimmune B cells are invariably pathogenic or whether they can also arise as bystanders of T cell-driven autoimmune pathology. Here, we studied the B cell response in an autoantigen- and CD4+ T cell-driven model of autoimmune hepatitis (AIH), the Alb-iGP_Smarta mouse in which expression of a viral model antigen (GP) in hepatocytes and its recognition by GP-specific CD4+ T cells causes spontaneous AIH-like disease. T cell-driven AIH in Alb-iGP_Smarta mice was marked by autoantibodies and hepatic infiltration of plasma cells and B cells, particularly of isotype-switched memory B cells, indicating antigen-driven selection and activation. Immunosequencing of B cell receptor repertoires confirmed B cell expansion selectively in the liver, which was most likely driven by the hepatic GP model antigen, as indicated by branched networks of connected sequences and elevated levels of IgG antibodies to GP. However, intrahepatic B cells did not produce increased levels of cytokines and their depletion with anti-CD20 antibody did not alter the CD4+ T cell response in Alb-iGP_Smarta mice. Moreover, B cell depletion did not prevent spontaneous liver inflammation and AIH-like disease in Alb-iGP_Smarta mice. In conclusion, selection and isotype-switch of liver-infiltrating B cells was dependent on the presence of CD4+ T cells recognizing liver antigen. However, recognition of hepatic antigen by CD4+ T cells and CD4+ T cell-mediated hepatitis was not dependent on B cells. Thus, autoreactive B cells can be bystanders and need not be drivers of liver inflammation in AIH.

Does COVID-19 Vaccination with BNT162b2 Influence HIV-Related Immunological and Virological Markers? Data from 235 Persons Living with HIV at Cotugno Hospital, Naples, Italy: Immune Response After Second and Third Doses, and Influence on Immunovirological Markers.

Few data are available on the impact of COVID-19 vaccination on CD4 counts and HIV-RNA in persons living with HIV (PLWH). We present the data of 235 PLWH who were vaccinated with BNT162b2 in March 2021-February 2022 at the "Cotugno" hospital in Naples. PLWH treated at the "Cotugno" hospital, who were vaccinated at the hospital vaccination center, without prior COVID-19 and for whom immunological/virological data were available in the last 12 months and in the 6 months after vaccination were included. Antispike Ab were available for 187 and 64 PLWH after the second and third doses: PLWH with antispikes >33 binding antibodies units (BAU)/mL increased from 91% to 98%. Antinucleocapsid Ab performed in 147 and 56 patients identified 19 (13%) asymptomatic/paucisymptomatic COVID-19 infections after the second dose and an additional 15 (27%) after the third dose. Immunological/virological data were collected before vaccination (T0), after the second dose (T1), and after the third dose (T2). The absolute number of CD4 increased after the third dose (median 663, 657, and 707 at T0, T1, and T2; p < 0.000 T0 vs. T2). The proportion of patients with HIV-RNA <50 copies/mL increases significantly after the second dose (73%; 85.7%; 87.7%; p < 0.000 T0 vs. T2). The presence of COVID-19 asymptomatic/paucisymptomatic infections (demonstrated by the presence of antinucleocapsid Ab) significantly increases SARS-CoV-2 antispike Ab after second dose, but not after third dose. Asymptomatic/paucisymptomatic COVID-19 infections do not have influence on CD4 cell number and HIV-RNA level. Similarly, the presence of not-controlled HIV-RNA (HIV-RNA >50 copies/mL) does not influence antispike Ab response. According to our data, the response to SARS-CoV2 vaccination is effective in people living with HIV. Vaccination against COVID-19 appears to positively affect immunological and virological levels in people living with HIV.

Subdividing ART patients and analyzing the medical burden by modeling of CD4 cell count.

Objective: To subdivide the antiretroviral therapy (ART) human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) patients by modeling the CD4 cell count variable, with an aim to reduce the medical burden from lifelong ART. Materials and Methods: The data of outpatients at the research unit between August 2009 and December 2020 were exported and mined. A recency-frequency (RF) model was established for data subdivision, and data of non-churn ART patients were preserved. Common factor analysis (CFA) was conducted on the three indicators of the baseline/mean/last CD4 cell counts to obtain critical variables; then, k-means modeling was used to subdivide ART patients and their medical burden was analyzed. Results: A total of 12,106 samples of non-churn ART patients were preserved by RF modeling. The baseline/mean/last CD4 cell counts served as important variables employed for modeling. The patients were divided into 15 types, including two types with poor compliance and poor immune reconstitution, two types with good compliance but poor immune reconstitution, four types with poor compliance but good immune reconstitution, and seven types with good compliance and good immune reconstitution. The frequency of visits was 5.25-9.95 visits/person/year, and the percentage of examination fees was 44.24%-59.05%, with a medical burden of 4114.24-12,676.66 yuan/person/year, of which 42.62%-70.09% was reduced. Conclusion: The CD4 cell count is not only an important indicator for judging post-ART immune recovery, but also a major modeling variable in subdividing ART patients with varying medical burdens. Poor compliance and poor immune reconstitution lead to excessive visits and frequent examinations, which were the leading causes of the heavy medical burden of ART.

The Effect of HIV Treatment Interruption on Subsequent Immunological Response.

Recovery of CD4-positive T lymphocyte count after initiation of antiretroviral therapy (ART) has been thoroughly examined among people with human immunodeficiency virus infection. However, immunological response after restart of ART following care interruption is less well studied. We compared CD4 cell-count trends before disengagement from care and after ART reinitiation. Data were obtained from the East Africa International Epidemiology Databases to Evaluate AIDS (IeDEA) Collaboration (2001-2011; n = 62,534). CD4 cell-count trends before disengagement, during disengagement, and after ART reinitiation were simultaneously estimated through a linear mixed model with 2 subject-specific knots placed at the times of disengagement and treatment reinitiation. We also estimated CD4 trends conditional on the baseline CD4 value. A total of 10,961 patients returned to care after disengagement from care, with the median gap in care being 2.7 (interquartile range, 2.1-5.4) months. Our model showed that CD4 cell-count increases after ART reinitiation were much slower than those before disengagement. Assuming that disengagement from care occurred 12 months after ART initiation and a 3-month treatment gap, CD4 counts measured at 3 years since ART initiation would be lower by 36.5 cells/µL than those obtained under no disengagement. Given that poorer CD4 restoration is associated with increased mortality/morbidity, specific interventions targeted at better retention in care are urgently required.

Temporal Trends of Clinical Characteristics and Treatments in People Living with HIV at the Initiation of Antiretroviral Therapy - Beijing Municipality, China, 2010-2020.

What is already known about this topic?: Antiretroviral therapy (ART) eligibility criteria and treatment regimens were updated in national guidelines. However, whether treatment was timely and followed guidelines was under-assessed. What is added by this report?: Among 22,591 people living with human immunodeficiency virus (PLWH) who initiated ART in Beijing between 2010 and 2020, the time from diagnosis to initiating ART decreased, the clinical condition of PLWH improved, and ART regimens changed in accordance with guidelines. What are the implications for public health practice?: Over the past decade, improvements in clinical status have been observed among PLWH; however, a proportion of PLWH remain who started ART late. Early linkage to human immunodeficiency virus (HIV) care should be further improved.

Serum biomarkers of liver fibrosis identify globus pallidus vulnerability.

The CNS manifestation of chronic liver disease can include magnetic resonance (MR) signal hyperintensities in basal ganglia structures. Here, relations between liver (serum-derived fibrosis scores) and brain (regional T1-weighted signal intensities and volumes) integrity were evaluated in a sample of 457 individuals including those with alcohol use disorders (AUD), people living with human immunodeficiency virus (HIV), those comorbid for AUD and HIV, and healthy controls. Liver fibrosis was identified from cutoff scores as follows: aspartate aminotransferase to platelet ratio index (APRI) > 0.7 in 9.4% (n = 43) of the cohort; fibrosis score (FIB4) > 1.5 in 28.0% (n = 128) of the cohort; and non-alcoholic fatty liver disease fibrosis score (NFS) > -1.4 in 30.2% (n = 138) of the cohort. Presence of serum-derived liver fibrosis was associated with high signal intensities selective to basal ganglia (i.e., caudate, putamen, and pallidum) structures. High signal intensities in the pallidum, however, explained a significant portion of the variance in APRI (25.0%) and FIB4 (23.6%) cutoff scores. Further, among the regions evaluated, only the globus pallidus showed a correlation between greater signal intensity and smaller volume (r = -0.44, p <.0001). Finally, higher pallidal signal intensity correlated worse ataxia (eyes open ρ = -0.23, p =.0002; eyes closed ρ = -0.21, p =.0005). This study suggests that clinically relevant serum biomarkers of liver fibrosis such as the APRI may identify individuals vulnerable to globus pallidus pathology and contribute to problems with postural balance.

Contribution of Low CD4 Cell Counts and High Human Immunodeficiency Virus (HIV) Viral Load to the Efficacy of Preferred First-Line Antiretroviral Regimens for Treating HIV Infection: A Systematic Review and Meta-Analysis.

We assessed whether low CD4 count and high viral load (VL) affect the response to currently preferred ART. We performed a systematic review of randomized, controlled clinical trials that analyzed preferred first-line ART and a subgroup analysis by CD4 count (≤ or >200 CD4/µL) or VL (≤ or >100 000 copies/mL). We computed the odds ratio (OR) of treatment failure (TF) for each subgroup and individual treatment arm. Patients with ≤200 CD4 cells or VL ≥100 000 copies/mL showed an increased likelihood of TF at 48 weeks: OR, 1.94; 95% confidence interval (CI): 1.45-2.61 and OR, 1.75; 95% CI: 1.30-2.35, respectively. A similar increase in the risk of TF was observed at 96 weeks. There was no significant heterogeneity regarding integrase strand transfer inhibitor or nucleoside reverse transcriptase inhibitor backbone. Our results show that CD4 <200 cells/µL and VL ≥100,000 copies/mL impair ART efficacy in all preferred regimens.