Viral Load Values Research Articles

Clinical accuracy of OncoPredict HPV Quantitative Typing (QT) assay on self-samples

BackgroundThe VALHUDES initiative was established to assess the clinical accuracy of HPV assays to detect cervical precancers using urine and vaginal self-samples compared to cervical clinician-collected samples. Here, the clinical performance of OncoPredict HPV Quantitative Typing (QT) assay (OncoPredict QT) was evaluated. Methods490 women referred to colposcopy self-collected a urine and a vaginal specimen using Colli-Pee and FLOQSwab, respectively. Subsequently, a colposcopy was performed, and a cervical sample was collected with Cervex-Brush, followed by biopsy if clinically indicated. Vaginal samples were transported dry and resuspended in 5mL of eNAT medium, whilst cervical brushings were immediately transferred in 20mL ThinPrep. ResultsThe clinical sensitivity of OncoPredict HPV QT testing for CIN2+ in urine and vaginal self-samples was similar to cervical samples (ratios of 0.99 [95% CI 0.94-1.05] and 1.00 [95% CI 0.96-1.04]), respectively, when manufacturer's cut-offs were applied. The specificity for <CIN2 on both self-samples was lower than on cervical samples (urine/cervical ratio = 0.91 [95% CI 0.84-0.98]; vaginal/cervical ratio = 0.90 [95 % CI 0.84-0.98]). Cut-off optimisation improved specificity without compromising sensitivity. Median viral load values adjusted for cellularity were significantly higher in cervical samples compared to urine or vaginal self-samples, in general for all 12 high-risk HPV and in particular for HPV16, 18, 31, 33, 35, 45, 51, 58 (p<0.05). No difference was observed in median viral loads between urine and vaginal samples. ConclusionFollowing cut-off optimisation OncoPredict HPV QT assay demonstrated similar accuracy on self-collected versus cervical samples.

Investigation of the relationship between type I (α,β) interferon and viral load in patients with Crimean-Congo haemorrhagic fever (CCHF)

In this study, type I interferon (IFN-α ve IFN-β) levels, viral load levels, the relationship between viral load and interferons, and the relationship between interferon levels and disease severity and mortality in patients with Crimean-Congo Haemorrhagic Fever (CCHF) were investigated. 100 patients diagnosed with CCHF between April-2010 and September-2011 and 74 healthy individuals were selected as control group. IFN-α ve in patient sera was analysed by IFN-β seviyeleri ELISA method and viral load levels were analysed by Real-Time PCR method. Individuals in the patient group were classified as severe (group1) and mild (group2) patients according to the criteria defined by Swanepoel et al. During the follow-up, 25 of the patients in the severe group died. Patients in the severe group who died were classified as group1a and patients who survived were classified as group1b. INF-α ve β düzeyleri CCHF patients in the control group, group1 patients in group2 and control group was found to be significantly higher than the group (p&lt;0.05). When the viral load levels detected in patients in group1 and group2 were compared, the statistical difference was found to be insignificant (p&gt;0.05). Viral load levels in group1a were statistically significant compared to group1b and group2 (p&lt;0.05). In the ROC analysis performed in terms of IFN-α düzeyleri detected in the first blood samples of the patients, the cut off value for predicting mortality was 25042 pg/ml. In this analysis, the area under the curve (AUC) of IFN-α için was 0.713 and statistically significant (p&lt;0.05). IFN-β için values were statistically insignificant (p&gt;0.05). The cut off value for viral load was 8445500 copies/ml, AUC was 0.870 and statistically significant (p&lt;0.05). There was a significant and positive correlation between IFN-α ile and IFN-β arasında in group1a (r=0.551, p&lt;0.05). In conclusion, we found high levels of interferon and viral load in CCHF patients in this study, suggesting that high levels of interferon are released in CCHF patients, but the secreted interferon cannot prevent viral replication adequately. It is likely that the CCHF virus has various evasion mechanisms to avoid the effect of interferon. Further studies are needed to clarify/confirm this situation.

Factors associated with pre-treatment hyperferritinemia in patients with chronic hepatitis C virus infection

Pre-treatment host and viral factors may affect serum ferritin levels in patients with hepatitis C virus (HCV) infection. We delineated pre-treatment factors associated with hyperferritinemia in these patients. 1682 eligible patients underwent pre-treatment assessment for serum ferritin and various host/viral factors. Univariate and multivariate logistic regression analyses were conducted to evaluate factors associated with hyperferritinemia. Multivariate logistic regression analyses revealed that age > 50 years (adjusted odds ratio [OR]: 1.38 (95% confidence interval [CI] 1.09–1.74), p = 0.008), fibrosis stage ≥ F3 (adjusted OR: 1.36 (95% CI 1.04–1.77), p = 0.02), fibrosis index based on four parameters (FIB-4) > 3.25 (adjusted OR: 1.46 (95% CI 1.11–1.92), p = 0.01), presence of metabolic dysfunction-associated steatotic liver disease (MASLD) (adjusted OR: 1.43 (95% CI 1.21–1.76), p = 0.001), and alanine transaminase (ALT) > 2 folds upper limit of normal (ULN) (adjusted OR: 2.87 (95% CI 2.20–3.75), p < 0.001) were associated hyperferritinemia. The log10 value of HBV or HCV viral load was not associated with the log10 value of ferritin level (Spearman’s rank correlation coefficient: − 0.025, p = 0.81 and 0.002, p = 0.92). In conclusion, host factors, rather than viral factors, are associated with hyperferritinemia in patients with HCV.

Correlations Between Viro-Immunologic Status of the Newly Diagnosed Patient with HIV Infection and Liver Damage

Abstract Liver damage can be a direct consequence of human immunodeficiency virus infection or indirect mechanisms triggered by human immunodeficiency virus. Hepatic fibrosis may be present in patients newly diagnosed with HIV infection or in those with viro-immunologic failure after initiation of antiretroviral therapy. In the present study we evaluated biologically and viro-immunologically the 351 patients newly diagnosed with HIV infection in the Regional Center Constanta between 01.01.2015 and 31.06.2024, subsequently re- evaluated one year after diagnosis and institution of specific medication. Liver fibrosis stage was assessed using APRI, FIB4 and FORNS scores. The cohort comprised 351 patients, 313 with HIV monoinfection. The mean age at diagnosis was 36.09 years, predominantly male (237 patients). The median CD4+ cell count was 269.5 cells/mm3, and the median HIV-RNA was 164 x103 copies/mL. Most cases were CDC staged A2 (91 cases) and C3 (77 cases). Patients with HIV monoinfection showed a significant association between CD4+ cell level and ALT (p=0.026) and AST (p&lt;0.001), respectively. We observed statistically significant correlation between AST and viral load values (p=0.003 in monoinfection and 0.042 in coinfection). APRI, FIB4 and FORNS scores averaged higher in the coinfected group compared to the HIV monoinfected group. Statistically significant associations were found between APRI, FIB4, FORNS scores and CD4+ cell counts and HIV viral load values, respectively.

TUBERCULOSIS AND ITS ASSOCIATION WITH CD4+T CELL COUNT AND VIRAL LOAD AMONG HIV POSITIVE PATIENTS IN A TERTIARY CARE HOSPITAL

Methods: The present study was a prospective study conducted from April 2022 to March 2023 in 4551 patients. Samples of 238 patients newly diagnosed with HIV attending Integrated Counselling and Testing Centre (ICTC), Visakhapatnam, Andhra Pradesh, India and registered for Antiretroviral Therapy (ART) were taken. 5 ml of blood sample was collected aseptically and tested for HIV. The 238 HIV-positive samples were tested for CD4 counts at presentation and after 6 mo using flow cytometry (Sysmex Partec CyFlow Flow cytometer). They were further subjected to real-time RT-PCR to detect viral load at 6 mo follow-up. Results: Out of 238 HIV-positive cases, predominant gender being males with 140 (58.82%) and the predominant age group was 31-40 y. At 6 mo follow-up, 19 patients (8%) were diagnosed as having TB. The mean CD4 counts at baseline and after 6 mo of antiretroviral therapy (ART)) was 296±229 and 436±271 cells/mm3 (p value of&lt;0.001) for entire study group. The mean baseline CD4 count in patients who were not diagnosed with TB at the time of follow-up and those who were diagnosed as having developed TB was 307±232 cells/mm3 and 167±135 cells/mm3 respectively. At six mo follow-up, 32(14.6%) HIV patients who did not develop TB and 8(42.1%) patients who developed TB still had their CD4 counts&lt;200 cells/mm3. This was statistically significant with a p value=0.019. Significant difference was not found between the two subgroups as the HIV-only group had 192(87.7%) patients and 16(84.2%) patients from newly diagnosed TB patients had their viral loads below detection levels. Conclusion: low CD4 counts at the baseline was a high-risk factor for the development of tuberculosis in HIV patients. The viral load values at 6-month follow-up did not prove to be significantly linked to the development of tuberculosis.

Comparison of Cytomegalovirus Polymerase Chain Reaction Test Results Obtained with Fully Automated Systems: Roche Cobas 6800 and Qiagen NeuMoDx Experience

Viral load monitoring is important in identifying patients at risk of developing cytomegalovirus (CMV) related complications after transplantation and for this purpose, quantitative real-time polymerase chain reaction (Rt-qPCR) tests are most commonly used. The main problem in CMV DNA Rt-qPCR tests that make quantitative measurements is that there are significant differences in measurements performed with different kits in different laboratories. Comparability of viral load measurements between laboratories has increased with the introduction of quantitative PCR tests calibrated with the CMV International Quantitation Standard (IQS) developed by the World Health Organization (WHO). However, quantitative agreement between measurements made with different kits has still not been fully achieved. In this study, it was aimed to investigate the quantitative compatibility between measurements made with Cobas 6800 (Roche Diagnostics, Mannheim, Germany) and NeuMoDx (Qiagen, Ann Arbor, USA) CMV DNA Rt-qPCR tests, which are fully automated new generation systems calibrated with the WHO CMV IQS. The results of 214 plasma samples, which were studied simultaneously with Cobas 6800 CMV Rt-qPCR and NeuMoDx CMV Rt-qPCR tests were analyzed. In the tests, the extraction, amplification and detection stages were carried out fully automatically. CMV DNA was detected in 144 (67.28%) samples in both tests and was not detected in 53 (24.76%) samples. Incompatible results were obtained in a total of 17 (7.94%) samples. Good agreement was found between the qualitative results of both tests (kappa= 0.80, p< 0.001). When the quantitative results (n= 129) obtained in the dynamic measurement range of both tests were examined, the median viral load values measured by Cobas 6800 CMV Rt-qPCR and NeuMoDx CMV Rt-qPCR tests were 513 IU/mL (range= 35-37000) and 741 IU/mL (range= 68-48978), respectively. According to the correlation analysis, a very strong correlation was found between the results of both tests (r= 0.94, p< 0.001). According to Bland-Altman analysis; the average difference between the results of the NeuMoDx CMV Rt-qPCR test and the Cobas 6800 CMV Rt-qPCR test was found to be -0.14 log10 [standard deviation (SD)= 0.23] IU/mL and it was determined that the Cobas 6800 CMV Rt-qPCR test had lower measurements than the NeuMoDx CMV Rt-qPCR test. In 120 of 129 samples (93%) whose results were within the dynamic measurement range of both tests, the measurement difference was within ± 0.5 log10 IU/mL and in 9 (7%), it was detected as more than ± 0.5 log10 (median 0.54 log10 IU/ml; range= 0.51-0.81). No measurement difference of more than ± 1.0 log10 was detected in any sample. In this study, quantitative agreement was found in the measurements made in plasma samples with the fully automated Cobas 6800 CMV Rt-qPCR and NeuMoDx CMV Rt-qPCR tests calibrated with the CMV IQS. To the best of our knowledge, a study comparing viral load measurements made with Cobas 6800 and NeuMoDx fully automated systems in the detection of CMV DNA has not yet been conducted, and this is the first study on this subject.

Real-world performance of HIV low viral load values in diagnosing acute HIV infection in a tertiary care hospital in Beijing, China

BackgroundEarly diagnosis of HIV infection decreases the time from HIV diagnosis to viral suppression and reduces further HIV transmission. The Chinese Guidelines for the Diagnosis and Treatment of HIV/AIDS (2021 edition) state that an HIV RNA level > 5,000 copies/mL is the threshold for diagnosing HIV infection. The impact of low viral load values on HIV diagnosis needs to be investigated.MethodsThere were 3455 human immunodeficiency virus (HIV1 + 2) antibody results (immunoblotting method) and 65,129 HIV viral load values at Beijing Youan Hospital from 2019 to 2022. A total of 2434 patients had both antibody confirmatory results and viral load results. The confirmatory antibody results and HIV viral load results of 2434 patients were analyzed to investigate the impact of low viral load values on HIV diagnosis.ResultsOf the 2434 patients who had both confirmatory antibody results and viral load results, the viral load values of 140 patients (5.8%) had viral loads ranging from 40 copies/mL to 5,000 copies/mL before positive confirmatory antibody result, and of these 140 patients, the sample receipt time for the viral load tests of 96 (66.7%) individuals was 1 to 6 days earlier than the corresponding sample receipt time for the confirmatory antibody test. In addition, 34 patients (1.4%) had low viral loads ranging from 40 copies/mL to 1,000 copies/mL before positive confirmatory antibody result.ConclusionThis study revealed that there is a risk of missed diagnosis if a threshold of 5000 copies/mL is used for the diagnosis of HIV infection. These data provide valuable information for the early diagnosis of HIV infection, and our findings have potential benefits for decreasing HIV transmission.

Correlation between the Cycle Threshold Values in Detection of Severe Fever with Thrombocytopenia Syndrome Virus Using PowerChekTM SFTSV Real-Time PCR Kit and Viral Load: Prognostic Implications.

This study aimed to analyze the correlation between the cycle threshold (Ct) values of severe fever with thrombocytopenia syndrome (SFTS) virus small (S) and middle (M) segments and the SFTS viral load, aiming to estimate the initial viral load and predict prognosis in the early clinical course. A retrospective study was conducted with confirmed SFTS patients at Jeju National University Hospital (2016-2022). Patients were categorized into non-fatal and fatal groups. This study included 49 patients with confirmed SFTS (non-fatal group, n = 42; fatal group, n = 7). A significant negative correlation (-0.783) was observed between the log SFTS viral load and Ct values (p < 0.001). This negative correlation was notably stronger in the fatal group (correlation coefficient -0.940) than in the non-fatal group (correlation coefficient -0.345). In this study, we established a correlation between SFTS viral load and Ct values for estimating the initial viral load and early predicting prognosis. These results are expected to offer valuable insights for SFTS patient treatment and prognosis prediction.

Integrase strand transfer inhibitor resistance mediated by R263K plus E157Q in a patient with HIV infection treated with bictegravir/tenofovir alafenamide/emtricitabine: case report and review of the literature.

The in vivo selection of E157Q plus R263K has not been reported in patients treated with coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). To the best of our knowledge, we hereby report the first case of high-grade INSTI resistance associated with the presence of these aminoacidic substitutions in a treatment-experienced HIV patient treated with BIC/FTC/TAF. Clinical case report and review of the literature. A heavily treatment-experienced patient was switched to BIC/FTC/TAF due to drug-drug interactions after being diagnosed with disseminated Mycobacterium avium-intracellulare disease. He had been treated before with raltegravir with poor adherence. No mutations in the integrase gene were detected 1 year after finishing treatment with raltegravir. Months after being switched to BIC/FTC/TAF, and again with poor adherence documented, virological failure (VF) was detected. The polymorphic substitution E157Q and the resistance mutation R263K in the integrase gene were detected, as well as M184V, among other mutations in the reverse transcriptase gene. The patient is currently being treated with dolutegravir q12h plus boosted darunavir along with directly observed treatment, and for the first time in 20 years, plasmatic viral load values are below 100 copies/mL. This case illustrates that the combination of E157Q and R263K plus M184V can be selected in vivo in a clinical scenario of poor adherence with BIC/FTC/TAF, although it is a very rare phenomenon. Previous VF with first-generation integrase strand transfer inhibitors (INSTIs) should be kept in mind when switching patients to second-generation INSTIs.

Evaluation of SARS-CoV-2 quantification from oropharyngeal swabs, nasopharyngeal swabs, and naso-oropharyngeal swabs: A cross-sectional study

The current naso-oropharyngeal swab for SARS-CoV-2 detection faces several problems, such as waste issues and its use for quantitative studies. This study aimed to evaluate the total RNA and viral loads from different upper respiratory tract swabs types and whether SARS-CoV-2 quantification can use the current internal control for normalization. This cross-sectional study collected positive specimens with single oropharyngeal or nasopharyngeal swabs and naso-oropharyngeal swabs. The samples were extracted, tested with qualitative RT‒PCR, and then tested with quantitative RT‒PCR. The RNA eluate was measured for the total RNA concentration. The total RNA concentration, viral load, and RNaseP Ct values were collected and analysed statistically. The positive results came from 41 oropharyngeal swabs, 34 nasopharyngeal swabs, and 36 naso-oropharyngeal swabs. The total RNA increased significantly from oropharyngeal swabs to nasopharyngeal swabs to naso-oropharyngeal swabs. Significant differences in RNaseP Ct values between groups and their correlations with total RNA were found. In addition, the increase in the total RNA and the RNaseP Ct values were unrelated to the viral load. The physical features in the naso-oropharyngeal area and the swabbing procedures could affect the total RNA but not the viral load. However, since the virus particles could present inside and outside human cells, the increase in collected human cells may not always be followed by the viral load increase. Normalization using the RNaseP Ct value became unnecessary due to the factors mentioned above. Therefore, a careful approach is needed in viral load studies of swab specimens.

On the dynamics and optimal control of a mathematical model of neuroblastoma and its treatment: Insights from a mathematical model

Celyvir is an advanced therapy medicine, consisting of mesenchymal stem cells (MSCs) containing the oncolytic virus ICOVIR 5. This paper sets out a dynamic system which attempts to capture the fundamental relationships between cancer, the immune system and adenoviruses. Two forms of treatment were studied: continuous and periodic, the second being closer to the real situation. In the analysis of the first model, in addition to identifying the critical points, their properties and bifurcation points, a number of numerical simulations were carried out. It has thus been shown that there are bistability regimes in which Celyvir can produce an equilibrium of tumor progression, or even freedom from tumor. A sensitivity analysis was also performed to determine which parameters are most important in the system. Subsequently, an optimal control problem with nonlinear objective functional has been formulated, where the therapeutic goal is not only to minimize the size of the tumor cell population and the total cost of treatment, but also to prevent the tumor from reaching a critical size. It has been shown that the optimal control is bang–bang. With the second model, a threshold value of viral load has been identified at which the success of the treatment could be ensured. It is clear in both models that a low viral load would lead to relapse of the disease. Finally, it is shown that a periodic bang–bang regime should be used to optimize treatment with Celyvir.

Detection of SARS-CoV-2 variants distributed from March 2020 to May 2022 and their effect on the infection severity in Iraqi population

New SARS-CoV-2 variants appeared in late December 2020 as Mutations accumulated in the original virus. This study aimed to provide a local database about variants of COVID-19 circulating in the Iraqi population from 2020 to 2022 and the time of emergence of new strains each month since very few local studies have documented its existence in the country. Real-time reverse transcriptase polymerase chain reaction (rRT-PCR) assays were employed to 319 collected and analyzed nasal swabs to determine whether an infection had occurred. A sophisticated diagnostic kit that sorted the distinctive mutations was implemented to evaluate the variants. Results showed Younger patients were more likely to be infected with the Alpha variant (66 patients) than older people (43 patients). Additionally, patients with wild-type infestations had more robust viral load and lower Ct threshold values, culminating in an increase in severity during infection with wild-type virus 26/32 (81.250). Meanwhile, 65/109(59.63%) of patients infected with the Alpha variant developed severe and critical illness and 51/84(60.71%)were infected with Delta or Delta plus variants. In conclusion, the Alpha variant had the highest infection percentage of 109(46.6%), followed by Delta or Delta plus variant 84(26.33%), Beta or Gamma variants 47(20.1%), Omicron variant 46(19.6%), and finally wild-type virus of 32(13.7%). February 2020 witnessed a preliminary finding of the wild-type, while the Alpha variant emerged in December 2020, Beta/Gamma variances were recognized in December 2020, Delta/Delta plus variances began in April 2021, and the Omicron variant debuted in March 2022. Keywords: SARS-CoV-2, Mutation, rRT-PCR, Coronavirus disease 2019, TaqPath, cycle threshold (Ct) value

Detection of SARS-CoV-2 variants distributed from March 2020 to May 2022 and their effect on the infection severity in Iraqi population

New SARS-CoV-2 variants appeared in late December 2020 as Mutations accumulated in the original virus. This study aimed to provide a local database about variants of COVID-19 circulating in the Iraqi population from 2020 to 2022 and the time of emergence of new strains each month since very few local studies have documented its existence in the country. Real-time reverse transcriptase polymerase chain reaction (rRT-PCR) assays were employed to 319 collected and analyzed nasal swabs to determine whether an infection had occurred. A sophisticated diagnostic kit that sorted the distinctive mutations was implemented to evaluate the variants. Results showed Younger patients were more likely to be infected with the Alpha variant (66 patients) than older people (43 patients). Additionally, patients with wild-type infestations had more robust viral load and lower Ct threshold values, culminating in an increase in severity during infection with wild-type virus 26/32 (81.250). Meanwhile, 65/109(59.63%) of patients infected with the Alpha variant developed severe and critical illness and 51/84(60.71%)were infected with Delta or Delta plus variants. In conclusion, the Alpha variant had the highest infection percentage of 109(46.6%), followed by Delta or Delta plus variant 84(26.33%), Beta or Gamma variants 47(20.1%), Omicron variant 46(19.6%), and finally wild-type virus of 32(13.7%). February 2020 witnessed a preliminary finding of the wild-type, while the Alpha variant emerged in December 2020, Beta/Gamma variances were recognized in December 2020, Delta/Delta plus variances began in April 2021, and the Omicron variant debuted in March 2022. Keywords: SARS-CoV-2, Mutation, rRT-PCR, Coronavirus disease 2019, TaqPath, cycle threshold (Ct) value

Polymorphisms of CCR5, IL-6, IFN-γ and IL-10 genes in Cuban HIV/AIDS patients

IntroductionGenetic studies have shown associations of several single nucleotide polymorphisms (SNP) with different rates of progression and variation in susceptibility to HIV infection. This study aimed to estimate the frequency of ccr5Δ32, IL-6-174G/C, IFN-γ+874T/A and IL-10-1082A/G polymorphisms in Cuban HIV-infected patients and a group of sero-discordant couples to assess their influence on risk and disease progression. MethodsA cross-sectional study was carried out on 120 subjects registered at the Institute of Tropical Medicine «Pedro Kour» (IPK) and the Ameijeiras Hospital from June 2018 until December 2019. The amplification of fragments of the ccr5, IL-6, IFN-γ and IL-10 genes was performed by polymerase chain reaction followed by identification of polymorphisms using the restriction fragment length polymorphism analysis for IL-6 with the restriction enzymes Nla III. Amplification Refractory Mutation System was used for IFN-γ and IL-10 genes. ResultsThe allelic and genotypic distributions of the genes ccr5, IL-6, IFN-γ and IL-10 did not differ significantly between the two groups. Cell counts and plasma viral load values did not differ significantly between genotypes of the ccr5, IL-6, IFN-γ and IL-10 genes. Only the IL-6 GC genotype was associated with higher viral load values. The combination of alleles of the four considered SNPs showed a highly significant increase in the risk of HIV infection for one of them, but with a very low frequency (<1%). ConclusionThis study contributes to evaluating the frequency of these polymorphisms and their influence on biomarkers of the progression of HIV infection in the Cuban HIV-population.

Impact of prophylaxis with rituximab on EBV-related complications after allogeneic hematopoietic cell transplantation in children.

Children undergoing allo-HCT are at high risk of EBV-related complications. The objective of the study was to analyze the impact of prophylactic post-transplant rituximab on EBV infection and EBV-PTLD in children after allo-HCT, to determine the risk factors for the development of EBV infection and EBV-PTLD and to determine their outcomes. Additionally, the impact of EBV-driven complications on transplant outcomes was analyzed. Single center retrospective analysis of EBV-related complications in pediatric population undergoing allo-HCT, based on strategy of prophylaxis with rituximab. Overall 276 consecutive children, including 122 on prophylaxis, were analyzed for EBV-driven complications and transplant outcomes. Prophylaxis with rituximab resulted in significant reduction of EBV infection (from 35.1% to 20.5%; HR=2.7; p<0.0001), and EBV-PTLD (from 13.0% to 3.3%; HR=0.23; p=0.0045). A trend for improved survival was also observed (HR=0.66; p=0.068), while non-relapse mortality was comparable in both cohorts. The peak value of viral load was a risk factor in the development of EBV-PTLD: 10-fold higher peak viral load in comparison to the baseline 104 copies/mL, caused a 3-fold (HR=3.36; p<0.001) increase in the risk of EBV-PTLD. Rituximab treatment was effective as a preemptive therapy in 91.1%, and in 70.9% in EBV-PTLD. Patients who developed PTLD had dismal 5-year overall survival (29% vs 60%; p<0.001), and an increased risk of relapse (72% vs 35%; p=0.024). Rituximab for prophylaxis of EBV infection and EBV-PTLD was highly effective in pediatric population. Treatment of EBV-PTLD was successful in 70%, however the occurrence of EBV-PTLD was associated with an increased risk of relapse of primary malignant disease.

Influenza A infections: predictors of disease severity.

Influenza affects approximately 10% of the world's population annually. It is associated with high morbidity and mortality rates due to its propensity to progress to severe acute respiratory infection, leading to 10-40% of hospitalized patients needing intensive care. Characterizing the multifactorial predictors of poor prognosis is essential for developing strategies against this disease. This study aimed to identify predictors of disease severity in influenza A-infected (IFA-infected) patients and to propose a prognostic score. A retrospective cross-sectional study was conducted with 142 IFA-infected out- and inpatients treated at a tertiary hospital between 2010 and 2018. The viral subtypes, hemagglutinin mutations, viral load, IL-28B SNPs, and clinical risk factors were evaluated according to the patient's ICU admission. Multivariate analysis identified the following risk factors for disease severity: neuromuscular diseases (OR = 7.02; 95% CI = 1.18-41.75; p = 0.032), cardiovascular diseases (OR = 5.47; 95% CI = 1.96-15.27; p = 0.001), subtype (H1N1) pdm09 infection (OR = 2.29; 95% CI = 1.02-5.15; p = 0.046), and viral load (OR = 1.43; 95% CI = 1.09-1.88; p = 0.009). The prognosis score for ICU admission is based on these predictors of severity presented and ROC curve AUC = 0.812 (p < 0.0001). Our results identified viral and host predictors of disease severity in IFA-infected patients, yielding a prognostic score that had a high performance in predicting the IFA patients' ICU admission and better results than a viral load value alone. However, its implementation in health services needs to be validated in a broader population.

512. Interim Results of a Prospective Cohort Study to Monitor the Emergence of Resistance in Immunocompromised Non-Hospitalized Patients With COVID-19 Who Were Treated with Sotrovimab in Great Britain: LUNAR Study

Abstract Background Immunocompromised (IC) patients are at risk of adverse COVID-19 outcomes. The risk of treatment emergent resistance may be high in this population. This study investigated clinical and virological outcomes in sotrovimab-treated IC patients in Great Britain while the Omicron variant was predominant. Methods IC, non-hospitalized patients aged ≥ 18 years who were infected with SARS-CoV-2 and received early treatment with sotrovimab 500 mg IV for COVID-19 as per standard of care were included in this multicenter, single arm, observational prospective cohort study. Nasal/oropharyngeal samples were collected at baseline, Day (D) 7, 14, and 28 (+/-2 days) for viral load and sequencing analyses. Clinical (hospitalization, respiratory support, intensive care unit [ICU] admission and death) and safety outcomes were assessed through D28. This interim analysis included patients enrolled from 1 July 2022–31 January 2023. Results Among 195 patients (median age: 58 years), 56% were female, 86% were white, and 98.5% had ≥ 1 COVID-19 vaccine dose prior to enrollment. All patients received sotrovimab within 8 (median: 2) days of diagnosis. Absolute median viral load declined from 7.46 log10 copies/mL at baseline to 0.55 log10 copies/mL at D28 (Table 1). Of 189 patients with spike consensus sequencing data, all harbored the Omicron variant, with 32 sublineages identified. Omicron BA.4, BQ.1, BE.9, BA.5.1.18, and BN.1 were most common in this data cut. We also plan to present interim data on treatment emergent substitutions. No patients were hospitalized due to COVID-19. Six (1.3%) patients had all-cause hospitalizations; none were admitted to ICU. One patient (0.5%; infected with Omicron CH.1.1) with progressive neuromuscular disease needed high flow oxygen/non-invasive mechanical intervention and died on D18 (death deemed not COVID-19 related by investigator) (Table 2). Three mild sotrovimab-related adverse events were reported.Table 1:Summary of absolute viral load (log10 copies/mL) through Day 28, as measured by qRT-PCR from nasal/oropharyngeal swabsNote: Baseline log10 viral load was defined as the non-missing assessment taken at Day 0, excluding the negative viral load results. The post-baseline viral load values with Ct value &amp;gt; 38 were imputed as half the lower limit of detection (i.e. 453 copies/mL*0.5=226.5). Negative viral loads were defined as Ct ≥ 45 and were imputed as 3.57 copies/mL. These imputed values were used to derive log10 viral loads. Ct, cycle threshold; IV, intravenous; qRT-PCR, quantitative real-time reverse transcriptase polymerase chain reactionTable 2:Summary of clinical outcomes through Day 28Notes: N = Number of participants in Completer population (defined as all participants who were enrolled, exposed to study intervention [sotrovimab], and who had been followed for 30 days or discontinued from the study early); n = Number of participants with data available. ECMO, extracorporeal membrane oxygenation; ICU, intensive care unit; IV, intravenous Conclusion Sotrovimab-treated patients had reduced viral load by D7 which further decreased through D28, despite being IC and infected with Omicron subvariants (reduced in vitro neutralization has been reported for some of the subvariants). Few severe clinical outcomes were reported (all unrelated to COVID-19). Disclosures Judith Breuer, MD, GSK: Funding to conduct study|MRC/UKRI: Grant/Research Support|National Institutes of Health: Grant/Research Support|NIHR: Senior investigator|UKNIHR: Grant/Research Support|Vir Biotechnology, Inc: Funding to conduct study|Wellcome Trust: Grant/Research Support Myriam Drysdale, PhD, GSK: Employee|GSK: Stocks/Bonds Jill Walker, PhD, GSK: Employee|GSK: Stocks/Bonds Jennifer Han, MD, GSK: Employment|GSK: Stocks/Bonds Magdalena Gorczycka, MSc, GSK: Employee|GSK: Stocks/Bonds Alicia Aylott, MSc, GSK: Employee|GSK: Stocks/Bonds Melissa K. Van Dyke, PhD, GSK: Employee|GSK: Stocks/Bonds Helen Birch, PhD, GSK: Employee|GSK: Stocks/Bonds Elizabeth McKie, PhD, GSK: Employee|GSK: Stocks/Bonds David M. Lowe, FRCP, PhD, Biotest: Speaker fees|Blood Cancer UK: Grant/Research Support|Bristol Myers Squibb: Grant/Research Support|British Society of Antimicrobial Chemotherapy: Grant/Research Support|Gilead: Speaker fees (educational video)|GSK: Funding to conduct study|Langland: Speaker fees|LifeArc: Grant/Research Support|Merck: Personal fees for a round-table discussion|National Institute of Health Research: Grant/Research Support|Octapharma: Travel, accommodation and conference fees|UK Medical Research Council: Grant/Research Support|Vir Biotechnology, Inc: Funding to conduct study

Molecular Evaluation of HIV-1 HAART Efficacy, Comparison of TDF+3TC+EFV and AZT+3TC+NVP Regimens

Context: The UNAIDS goal of ending the HIV epidemic by 2030 will be achieved primarily through the success of the three &amp;ldquo;95s&amp;rdquo; by 2030, and in particular the third &amp;ldquo;95 &amp;raquo;, which consists of achieving an undetectable viral load thanks to effective antiretroviral treatment. Achieving and maintaining viral suppression is the goal of ART and a good knowledge of the effectiveness of triple ARV therapies can help national HIV programs. Thus, the objective of this study was to evaluate and compare the effectiveness of the two ARTs, Tenovofir + Lamivudine +Efavirenz (TDF+3TC+EFV) and Zidovudine+Lamivudine+ Efavirenz (AZT+3TC+NVP) in their abilities to make the plasma viral load of HIV+ patients under treatment undetectable. &#x0D; &#x0D; Material and method: This is a retrospective study of the management of HIV-1 seropositive patients, followed at the Military Hospital of Ouakam (HMO) Molecular Biology laboratory from 2014 to 2021. The main criterion for evaluating the effectiveness of the treatment was the proportions of patients whose Viral load values were undetectable, VL&amp;lt; 50 copies/ml depending on duration of antiretroviral therapy (ART). Plasma viral load tests were carried out on Abbott Real Time HIV-1&amp;reg; (m2000sp/rt) and COBAS&amp;reg;AmpliPrep/COBAS&amp;reg;TaqMan&amp;reg; (Roche) version 2.0. Variables with p&amp;lt;0.05 were considered statistically significant for all comparisons between groups.&#x0D; &#x0D; Results: 3,335 patients met the inclusion criteria, including 2,078 on TDF+3TC+EFV, 445 on AZT+3TC+NVP and 812 were excluded due to death, transfer or loss to follow-up. At 6 months of ART, VL was undetectable in 7.3% of patients on TDF+3TC+EFV and 6.7% of patients on AZT+3TC+NVP (P=0.67). 78.2% versus 73.4% of patients had an undetectable VL respectively for TDF+3TC+EFV and AZT+3TC+NVP at 12 months of ART (p=0.03). TDF+3TC+EFV had significantly higher virological success rates than AZT+3TC+NVP (85.7% versus 80.2%) and virological failure (VL&amp;gt;1000 copies/ml) was significantly greater in patients taking AZT+3TC+NVP (13% versus 7.2%) after 18 months (P=0.001). Gender and age had a significant relationship in treatment success.&#x0D; &#x0D; Conclusion: TDF+3TC+EFV was superior in terms of virological suppression at the end of the study period. These results support the WHO recommendation to use TDF+3TD+EFV as an alternative first-line regimen.

A Flexible Regression Modeling Approach Applied to Observational Laboratory Virological Data Suggests That SARS-CoV-2 Load in Upper Respiratory Tract Samples Changes with COVID-19 Epidemiology.

(1) Background. Exploring the evolution of SARS-CoV-2 load and clearance from the upper respiratory tract samples is important to improving COVID-19 control. Data were collected retrospectively from a laboratory dataset on SARS-CoV-2 load quantified in leftover nasal pharyngeal swabs (NPSs) collected from symptomatic/asymptomatic individuals who tested positive to SARS-CoV-2 RNA detection in the framework of testing activities for diagnostic/screening purpose during the 2020 and 2021 winter epidemic waves. (2) Methods. A Statistical approach (quantile regression and survival models for interval-censored data), novel for this kind of data, was applied. We included in the analysis SARS-CoV-2-positive adults >18 years old for whom at least two serial NPSs were collected. A total of 262 SARS-CoV-2-positive individuals and 784 NPSs were included: 193 (593 NPSs) during the 2020 winter wave (before COVID-19 vaccine introduction) and 69 (191 NPSs) during the 2021 winter wave (all COVID-19 vaccinated). We estimated the trend of the median value, as well as the 25th and 75th centiles of the viral load, from the index episode (i.e., first SARS-CoV-2-positive test) until the sixth week (2020 wave) and the third week (2021 wave). Interval censoring methods were used to evaluate the time to SARS-CoV-2 clearance (defined as Ct < 35). (3) Results. At the index episode, the median value of viral load in the 2021 winter wave was 6.25 log copies/mL (95% CI: 5.50-6.70), and the median value in the 2020 winter wave was 5.42 log copies/mL (95% CI: 4.95-5.90). In contrast, 14 days after the index episode, the median value of viral load was 3.40 log copies/mL (95% CI: 3.26-3.54) for individuals during the 2020 winter wave and 2.93 Log copies/mL (95% CI: 2.80-3.19) for those of the 2021 winter wave. A significant difference in viral load shapes was observed among age classes (p = 0.0302) and between symptomatic and asymptomatic participants (p = 0.0187) for the first wave only; the median viral load value is higher at the day of episode index for the youngest (18-39 years) as compared to the older (40-64 years and >64 years) individuals. In the 2021 epidemic, the estimated proportion of individuals who can be considered infectious (Ct < 35) was approximately half that of the 2020 wave. (4) Conclusions. In case of the emergence of new SARS-CoV-2 variants, the application of these statistical methods to the analysis of virological laboratory data may provide evidence with which to inform and promptly support public health decision-makers in the modification of COVID-19 control measures.

Molecular Evaluation of the Efficacy of the TDF+3TC+EFV Therapeutic Regimen in the Treatment of HIV-1 Patients

Background: Antiretroviral therapy (ART) has played an important role in the response to HIV infection and has significantly reduced morbidity and mortality worldwide. It allows control of plasma viral load (CV) to an undetectable level CV&lt;50 copies/ml, an indicator of successful treatment. Assessing the effectiveness of ART makes it possible to make recommendations to limit failures in the treatment of HIV. Thus, the objective of this study is to evaluate the efficacy of the TDF+3TC+EFV therapeutic regimen in the treatment of HIV-1 infection. Materials and methods: This is a retrospective study of the treatment of HIV-1 seropositive patients, at the Molecular Biology Laboratory of HMO in Dakar, Senegal, from 2014 to 2021. The main criterion for evaluating the effectiveness of the treatment was the proportion of patients whose viral load value was undetectable (CV&lt;50 copies/ml) according to the duration of ART. Plasma viral load tests were performed on Abbott Real Time HIV-1® (m2000sp/rt) and COBAS®AmpliPrep/COBAS®TaqMan®(Roche) version 2.0. Variables with p&lt;0.05 were considered statistically significant for all comparisons between groups. Results: Of a cohort of 2,704 HIV+ patients, 2,078 met the inclusion criteria and 626 were excluded due to death, transfer or loss to follow-up. The median age was 38 years, women represented 71% patients. At 6 months of treatment, viral suppression was achieved in 8.9% of men and 6.5% of women (P=0.04) and it was significantly greater in young patients aged 0 to 25 years, 11.4% of patients. 79% of women and 75.2% of men had an undetectable viral load at 12 months of ART (P=0.01). Significantly the suppression was better in men in the first 6 months of treatment, they had more virological success, while women responded better to treatment for a duration of 12 months (P=0.01). At the end of the 18-month study period, 85.5% of patients had a suppressed viral load, 5.3% had a decrease in viral load levels and 7.2% of patients had ...