Median Viral Load Research Articles

Limited utility of Epstein-Barr virus (EBV) surveillance for predicting post-transplant lymphoproliferative disorders in adult EBV seropositive lung transplant recipients.

EBV DNAemia surveillance, with reduction of immunosuppression at certain viral load (VL) thresholds, is a common practice for mitigating progression from EBV DNAemia to post-transplant lymphoproliferative disorder (PTLD) in lung transplant recipients (LTRs). The utility of EBV surveillance in adult EBV seropositive LTRs is unknown. We performed a retrospective cohort study of EBV seropositive adult LTRs who underwent lung transplant between 1/1/19 and 12/31/20 and received whole blood (WB) EBV PCR surveillance. We compared peak WB EBV VLs among 3 groups: 1) asymptomatic LTRs who developed PTLD, before PTLD was clinically suspected, 2) LTRs who developed PTLD, after PTLD was clinically suspected, and 3) LTRs who did not develop PTLD. We calculated the positive predictive value (PPV) of moderate-grade DNAemia (2840 to 11,360 IU/mL) and high-grade DNAemia (≥ 11,360 IU/mL) for identifying active or future PTLD. Six (2.6 %) of 229 LTRs developed PTLD. Among LTRs who developed PTLD, median peak EBV VL was significantly higher after PTLD was suspected than before clinical signs of PTLD were present (16,004 IU/mL vs. ≤568 IU/mL, p = 0.016). Median peak EBV VLs were similar between asymptomatic LTRs who later developed PTLD and LTRs who did not develop PTLD (median peak EBV VL ≤568 IU/mL vs. ≤568 IU/mL, p = 0.62). The PPVs for moderate- and high-grade DNAemia were 14.7 % and 33.3 %, respectively. EBV surveillance did not accurately identify EBV seropositive LTRs at risk for progressing to PTLD. EBV PCR testing in asymptomatic EBV seropositive transplant recipients may represent an opportunity for diagnostic stewardship.

Real-Life Efficacy and Safety of Glecaprevir/Pibrentasvir Pediatric Formulation for Chronic Hepatitis C Infection in Children Aged 3 to 12 Years: A Case Series of 6 Patients.

Glecaprevir/pibrentasvir (GLE/PIB) has been approved by the European Medicines Agency and by US Food and Drug Administration for the treatment of children and adolescents aged 3 to 12 years with chronic hepatitis C (CHC) virus infection. The aim of this study was to confirm the real-world effectiveness and safety of GLE/PIB pediatric formulations in children aged 3 to 12 years with CHC. This case series describes a pediatric population (3 to ≤12 years of age) treated with a weight-based dose of GLE/PIB pediatric formulation once daily for 8 weeks. The effectiveness end point was a sustained virologic response 12 weeks after the end of treatment. Safety was assessed on adverse events and clinical/laboratory data. Six patients (median age 6 years; interquartile range, 3 years) were enrolled and treated between March 2023 and December 2023. Genotype distribution was as follows: 4 of 6 genotype 1 (60%), 1 of 6 genotype 2 (20%), and 1 of 6 genotype 3 (20%). Median viral load at baseline was 541,000 IU/mL (interquartile range, 641,000 IU/mL). All (100%) patients completed treatment. Sustained virologic response (SVR) 12 weeks after the end of treatment was 100%. No virologic relapse or breakthrough was observed. No adverse events occurred. This study confirmed the real-life effectiveness and safety profile of an 8-week treatment with GLE/PIB for CHC in children aged 3 to 12 years.

P-703. Manifestations of parainfluenza type 4 infections and viral loads in children

Abstract Background Although parainfluenza virus type 4 (PIV-4) typically causes mild respiratory illnesses in children, it can cause severe diseases occasionally. It is not known Whether viral load of PIV-4 could correlate with severity. This study aimed to assess the relationship between PIV-4 viral load and disease’s severity in children. Viral load and severity This figure shows the relationship between severity of illness and viral load.There was no correlation between viral load and severity. Methods A retrospective study at Tokyo Metropolitan Children's Medical Center from April to October 2023 screened hospitalized children using multiplex PCR. PIV-4 positive samples were assayed for viral load of all detected viruses using real-time PCR. Cases with PIV-4 were included if PIV-4 was only detected or the viral load of PIV-4 was higher than other co-detected viruses. Demographic data, underlying diseases, laboratory, co-infections, diagnoses, and outcomes were collected from electrical charts. Cases with PIV-4 were categorized into mild cases with no oxygen demand, moderate cases with low-flow oxygen demand and severe cases with high flow nasal cannula oxygen or non-invasive/invasive mechanical ventilation or PICU admission.The viral loads of PIV-4 and number of co-infected virus were compared among severity groups. Characteristics, Symptoms and Laboratory Data of PIV-4 positive patients Results Nasal swab samples were collected from 2884 cases. PIV-4 was detected in 185 samples. As 108 cases were excluded for higher viral loads of other viruses, 77 cases were included for analysis. The severity of PIV-4 comprised 37 mild, 24 moderate, and 16 severe cases. The rate of lower respiratory tract infections in mild, moderate and severe cases were 8%, 96%, and 75%, respectively. There was only one PIV-4-related mortality at 28 days. Co-detection with rhinovirus/enterovirus was the most frequent. Median viral loads (log10 copies/mL) in mild, moderate and severe cases were 5.98 (IQR 3.58-6.89), 6.09 (IQR 4.93-6.66) and 5.98 (IQR 3.57-7.03), respectively. No significant correlation was found between viral load and severity, but severity correlated with the number of viral co-infections. Treatment and Outcome of PIV-4 positive patients Conclusion Moderate or severe Pediatric PIV-4 infections primarily show as lower respiratory tract infections, with no relation between viral load and illness severity, though the number of co-infected virus may play a role. Severity and co-infection viruses Disclosures All Authors: No reported disclosures

P-573. Analysis of Cabotegravir-Rilpivirine Use in HIV Patients at MedStar Washington Hospital Center

Abstract Background Intramuscular cabotegravir-rilpivirine (CAB-RPV) is a long-acting antiretroviral for the treatment of HIV which can be administered every 1-2 months. Registration trials demonstrated the non-inferiority of CAB-RPV versus oral antiretroviral therapy, but data on the ‘real world’ performance of CAB-RPV is sparse. In addition, these trials required HIV virologic suppression (viral load (VL) < 50 copies/mL) with oral medications before transitioning to CAB-RPV. Small studies have reported success when CAB-RPV was started in patients with detectable viremia, and our study sought to build on those findings. Methods Descriptive, retrospective study based on patients who began treatment with CAB-RPV between May 2022-Nov 2023. Virologic undetectability (VL < 50 copies/mL), suppression (VL 51-200 copies/mL) and virologic failure (VL > 201 copies/mL) at last measurement are described among patients with a VL < 50 copies/mL, 51-200 copies/mL or >201 copies/mL at baseline. Results 42 patients are included in the analysis with a median age of 42 (range 27-80). The cohort was 93% African American, 60% male and 81% received Medicare/Medicaid or both as their primary insurer. Median CD4 count was 861 (range 15-1827) and median viral load was 40 copies/mL (range < 20-294,000). Among 38 patients with a baseline VL of < 50, 34 maintained viral undetectability, 1 become virally suppressed (VL=60) and 3 did not have results available due to recently starting CAB-RPV. One patient with baseline viral suppression (VL=90) became virally undetectable. Two patients with baseline virologic failure (VL 1,210 and 7,200) became virologically undetectable. One patient with baseline virological failure (VL=294,000) developed resistance shortly after starting therapy. Conclusion Similar to data in registration trials, CAB-RPV maintained viral suppression in 100% of patients who were at least virally suppressed at baseline. Two patients with virological failure at baseline achieved virological suppression, adding to data that CAB-RPV may be beneficial in patients who are unable to adhere to oral antivirals. One patient with baseline virological failure and high viral load quickly developed resistance after starting therapy, supporting data that CAB-RPV needs to be used carefully in certain populations. Disclosures All Authors: No reported disclosures

HIV-1 resistance mutations and genetic diversity among children failing antiretroviral treatment in five healthcare facilities in Benin, West Africa.

Antiretroviral treatment increases the risk of accumulation of resistance mutations that negatively impact the possibilities of future treatment. This study aimed to present the frequency of HIV-1 antiretroviral resistance mutations and the genetic diversity among children with virological failure in five pediatric care facilities in Benin. A cross-sectional study was carried out from November 20, 2020, to November 30, 2022, in children under 15 years of age who failed ongoing antiretroviral treatment at five facilities care in Benin (VL > 3log10 on two consecutive realizations three months apart). Viral loads were measured using the m2000 RealTime Abbott platform. Genotyping was carried out with the commercial Viroseq kit. Sequences were read on the ABI 3500 sequencer and then edited with ViroSeqHIVv3.0 software. The HIV drug resistance database at Stanford University was used to identify mutations and viral subtypes were assigned by phylogenetic analyses. The HIV-1 pol gene was sequenced in 47 participants with virological failure of antiretroviral treatment. The median age was 120 [Interquartile Range 90-144] months. The prevalent treatment was EFV base regimen (22/47; 46.8%). Median viral load was 4.39 log10 [IQR 3.81-4.86 log10] respectively. Resistance testing was successful among (37/47; 78.72%) children, resistance mutations were detected in (32/37; 86.48%) children, and (29/32; 90.62%) had at least one surveillance drug resistance mutation. Respectively (25/32; 78.12%), (28/32; 87.5%), (4/32; 12.90%), (22/32; 68.75%) had at least one resistance mutation associated with NRTIs, NNRTIs, PIs and NNRTIs+NRTIs. (12/32; 37.5%) of children carried mutations related to TAMs. the most frequently NRTIs identified were M184V (21/62; 33.9%) followed by TAMs (20/62; 32.2%) and T69G/D (2/62; 3.2%)s. Among mutations associated with NNRTIs K103N represented (18/64; 28.1%) followed by P225H (7/64; 10.9%). The I54V (3/6; 50%) mutation is the major PI observed. Genetic diversity is characterized by a preponderance of CRF02_AG (72%, 23/32), followed by unique recombinant forms (URFs) (25%, 8/32) and one subtype G. A high rate of mutations has been observed in children. These data underline the importance of implementing routine genotypic testing in the biological monitoring of infected children to anticipate the accumulation of resistance mutations and thus compromise the treatment options available in Benin.

P-452. Factors Associated with Liver Fibrosis Development in HIV-Monoinfected Patients Within the Modern ART Era

Abstract Background Liver fibrosis (LF) is a significant contributor to morbidity and mortality in people living with HIV (PLWH). Using data from the US Military HIV Natural History Study (NHS), we examined prevalence and risk factors of LF in the era of fixed dose combination antiretroviral therapy (ART).Table 1.Pertinent Participant Characteristics Categorized by the Presence or Absence of Liver Fibrosis: Methods The NHS is comprised of military beneficiaries with HIV, who are often diagnosed and treated early due to mandatory screening and guideline-based initiation of ART. We included ART-treated NHS participants, diagnosed after 2006, without active hepatitis B or C infection. LF was defined as a FIB-4 Index >2.67, a validated, non-proprietary, readily available marker of LF based on age, platelets, and liver-associated enzymes. Risk factors examined included demographic, HIV-specific, and other recognized associations with LF, see Table 1 footnote for details. Participants characteristics were analyzed with either the Kruskal Wallis or Chi2 test. Cox proportional hazard models, adjusted for baseline and time-updated variables, were used to assess risk factors for developing LF.Table 2.Unadjusted and adjusted HR on liver fibrosis Results Among 1209 participants, followed for a median of 5.4 years, 60 (5.0%) met the criteria for LF. Overall, the median time to ART initiation was 2.4 months. The median time to LF was 2.5 years. At LF diagnosis the median age, CD4 count and viral load were 36 years, 526 cells/uL and 20 copies/mL respectively. Those with LF were older, had lower CD4 count and high VL at HIV diagnosis and more likely to initiate NNRTI based ART, table 1. In an adjusted model, LF was associated with female gender, hypertension, obesity, at risk drinking, and higher VL, while African American race, integrase strand transfer inhibitor (INSTI) use, and higher CD4 counts were protective, table 2. Conclusion In the contemporary ART era, in this young and promptly treated cohort, the prevalence of LF was 5%, suggesting liver-related morbidity remains an important concern. Our results underscore the protective effect of immune preservation (by timely initiation and continuation of ART) against LF; however, the observed protective association with INSTI-based regimens will need further study to determine long-term benefit. As observed previously, hypertension, at risk drinking, and obesity are modifiable risk factors that should be addressed. Disclosures All Authors: No reported disclosures

Mortality and immunological indicators of men who have sex with men living with HIV on antiretroviral therapy: a 10-year retrospective cohort study in Southern China

BackgroundThe proportion of people living with HIV (PLHIV) in Guangxi who are men who have sex with men (MSM) increased rapidly to nearly 10% in 2023; notably, over 95% of this particular population is currently receiving antiretroviral therapy (ART). This study aimed to describe the survival of MSM PLHIV, depict the characteristics and trends of changes in CD4+ T cell counts, CD4+/CD8+ T cell ratio, and viral load, and explore immunological indicators that may be related to mortality during different stages of treatment.MethodsImmunological indicators of MSM PLHIV receiving ART were extracted and categorized into baseline, mid-treatment, and last values. These were then incorporated into the Cox models in the form of repeated measurements to evaluate the associations (Adjusted-hazard ratios, aHRs) and 95% confidence intervals (95% CIs) of these immunological indicators with mortality at different stages.ResultsA total of 5,642 patients who met the criteria were enrolled in the study, and 160 died, representing a mortality of 2.8%. The first, median, and last values of the CD4+ count and the CD4+/CD8+ ratio in surviving patients were significantly greater than the corresponding values in nonsurviving patients (P < 0.001). Except for the first viral load (P = 0.379), the median and last viral loads of the former were significantly lower than those of the latter (P < 0.001). In Cox model, with 2,144 cases, immunological indicators of increased mortality risk included a baseline CD4+ count below 200 cells/µL (aHR: 4.58, 95% CI: 2.28–9.19), a median (aHR: 8.46, 95% CI: 3.05–23.46), and a final (aHR: 4.43, 95% CI: 1.06–18.45) ratio below 0.7 and a median (aHR: 9.47, 95% CI: 4.02–22.35) and final (aHR: 14.46, 95% CI: 4.50–46.50) viral load 100,000 copies/mL and above.ConclusionsMortality among MSM PLHIV on ART in Guangxi is relatively low, and both high viral loads and low CD4+/CD8+ T cell ratios during treatment and at recent follow-up are strongly predictive of a serious prognosis and should be closely monitored.

Serological and Molecular Characterization of the Hepatitis B Virus in Blood Donors in Maputo City, Mozambique.

Hepatitis B virus (HBV) is a major public health concern responsible for hepatitis and hepatocellular carcinoma (HCC) worldwide. In Mozambique, HBsAg prevalence is high and endemic, and despite the strategies to mitigate the spread of the disease, the HCC incidence is still high and one of the highest in the world. There is still limited data on the serological profile and molecular epidemiology of HBV in Mozambique given the burden of this disease. In this study, we aimed to describe the serological and molecular characterization of HBV among blood donors. We conducted a cross-sectional survey from November 2014 to October 2015 at the Blood Bank of the Hospital Central de Maputo. Serological testing and molecular testing were performed. The frequency of HBV infection was estimated at 4.4% and was higher among males (79.1%), individuals aged 25-39 years (55.2%), and replacement donors (89.6%). The median viral load of HBV-positive blood donors was 1288.5 IU/mL, and 43.8% had a viral load higher than 2000 IU/mL. Most of the sequenced samples (94.3%) belonged to subgenotype A1. These findings underscore the importance of ongoing surveillance to inform effective HBV control strategies and present evidence about the burden of HBV among blood donors, which definitely requires attention, and clinical blood banks in Mozambique and in similar settings.

Major role of dolutegravir in the emergence of the S147G integrase resistance mutation.

The S147G mutation is associated with high-level resistance to the integrase strand transfer inhibitor (INSTI) elvitegravir. In several poorly documented cases, it was also selected in patients on dolutegravir. Given the widespread use of dolutegravir, further studies of S147G are required. We consulted the HIV-1 resistance databases of French laboratories to identify all cases of S147G emergence. We collected immunological and virological parameters, history of treatment and INSTI resistance mutations. Mann-Whitney and Fisher's exact tests were performed. We retrospectively identified 88 cases of S147G selection, from 2015 to 2022, in 22 laboratories. The most frequent HIV-1 subtypes were Clade B (55.7%) and CRF02_AG (21.6%). At the time of resistance genotyping, the median viral load was 5860 copies/mL (IQR 1011-24 525) and the median CD4 cell count was 412 cells/mm3 (228-560). S147G emerged on dolutegravir (48%), elvitegravir (36%) and raltegravir (10%) treatments. S147G was associated with a larger median number of other INSTI mutations on dolutegravir than on elvitegravir [3.0 (2.0-4.0) versus 2.0 (1.0-2.0); P = 0.0002] and was never observed with G148H or G118R. On dolutegravir, S147G was associated principally with T97A (62%), N155H (59%), E138K (50%), L74I/M (38%) and Q148R (33%). In this French study, S147G emerged principally in patients on dolutegravir regimens, in association with up to five other INSTI resistance mutations. This accumulation of mutations suggests a replicative advantage on HIV strains under dolutegravir selection pressure, suggesting that caution is required when interpreting dolutegravir resistance in the presence of such S147G resistance patterns, even in patients prescribed dolutegravir twice daily.

Detection of Severe Acute Respiratory Syndrome Coronavirus 2 in Pregnant Women Treated with Nirmatrelvir/Ritonavir (Paxlovid) Using Salivary Polymerase Chain Reaction: A Prospective Cohort Study.

We aim to study the relative viral load using salivary polymerase chain reaction among pregnant women treated with Paxlovid. Pregnant women with coronavirus disease 2019 were allocated to two groups: those receiving Paxlovid and those receiving no antiviral agents. We compared the nasopharyngeal and salivary relative viral loads and their changes in saliva specimens. Among the thirty-seven pregnant women, seventeen received Paxlovid, and twenty received no antiviral agents. The viral cycle threshold value of saliva was significantly higher than that from nasopharynx, with a median ± interquartile range of 26.44 ± 7.68 versus 17.6 ± 9.6 in the Paxlovid group (p = 0.005). Following treatment, the median salivary viral load decreased by 13.40 cycle threshold values in the Paxlovid group (from a median of [Day 0 Ct] to [Day 4/5 Ct]), compared to a change of -1.59 cycle threshold values in the no-antiviral group (from a median of [Day 0 Ct] to [Day 4/5 Ct]) (p = 0.021). The detection rate of coronavirus disease 2019 using salivary polymerase chain reaction was 83.8% (31/37). This study showed that saliva is a useful diagnostic tool for coronavirus disease 2019 in pregnant women, and a significant decrease in the relative viral load of saliva was observed in those treated with Paxlovid.

Incidence and risk factors of anemia among newly reported HIV/AIDS patients in Jiangsu Province in 2021

To investigate the incidence of anemia and evaluate the immune status among newly reported HIV/AIDS patients in Jiangsu Province in 2021, and to identify the risk factors of anemia among patients living with HIV infections. Newly reported HIV/AIDS patients in Jiangsu Province from January 1 to December 31, 2021 that were registered in China's National AIDS Comprehensive Control Information Management System were enrolled. Subjects' fresh whole blood samples were collected, and hemoglobin levels, CD4 and CD8 cell counts and HIV viral loads were measured. Anemia was defined according to hemoglobin levels, and the immunological parameters and HIV viral loads were compared between HIV-infected patients with and without anemia. The risk factors of anemia were identified among individuals living with HIV infections using univariate analysis and multivariate logistic regression analysis. In addition, subjects' CD4 cell counts one year following antiretroviral therapy (ART) were retrieved from China's National AIDS Comprehensive Control Information Management System, and compared between subjects with and without anemia. A total of 635 newly diagnosed HIV/AIDS patients were reported in Jiangsu Province in 2021, including 544 males (85.67%) and 91 females (14.33%), and with ages of 15 to 83 years, and the overall incidence of anemia was 5.51% (35/635) among the study subjects. Men, individuals at ages of 45 years and lower and workers had relatively higher hemoglobin levels, with median hemoglobin levels of 156 (interquartile range, 22), 154 (interquartile range, 23) g/L and 162 (interquartile range, 19) g/L, respectively. The median baseline HIV viral load was 40 500.00 (interquartile range, 119 735.00) copies/mL among HIV-infected individuals with anemia and 29 754.00 (69 183.00) copies/mL among those without anemia (Z = -0.91, P = 0.31), and the median baseline CD4 and CD8 cell counts were significantly lower among HIV-infected individuals with anemia [166 (interquartile range, 143) cells/μL and 755 (653) cells/μL] than those without anemia [308 (253) cells/μL and 892 (638) cells/μL] (Z = -4.36 and -2.37, both P values < 0.05). The median CD4 cell counts remained lower among HIV-infected individuals with anemia than those without anemia [296 (interquartile range, 229) cells/μL vs. 457 (interquartile range, 313) cells/μL; Z = -3.71, P < 0.05] one year following ART, and the proportions of moderate and severe immunosuppression were significantly higher among HIV-infected individuals with anemia (40.00% and 17.14%) than those without anemia (21.00% and 9.33%) (χ2 = 10.37 and 8.79, both P values < 0.01). Univariate analysis showed a higher detection rate of anemia among female HIV-infected individuals than among males [odds ratio (OR) = 4.528, 95% confidence interval (CI): (3.811, 5.245), P < 0.001], a higher rate among HIV-infected individuals at ages of 45 to < 60 years [OR = 3.415, 95% CI: (1.191, 9.788), P = 0.022] and 60 years and older [OR = 5.820, 95% CI: (2.013, 16.826), P < 0.001] than among those at ages of 15 to < 30 years, a higher rate among HIV-infected individuals through heterosexual transmission than among those through homogeneous transmission [OR = 3.015, 95% CI: (1.423, 6.387), P = 0.004], a lower rate among HIV-infected individuals with an educational level of college and above than among those with an educational level of primary school [OR = 0.103, 95% CI: (0.028, 0.386), P < 0.001], a higher rate among HIV-infected individuals with baseline CD4 cell counts of < 200 cells/μL than among those with baseline CD4 cell counts of 200 cells/μL and higher [OR = 4.340, 95% CI: (2.165, 8.702), P < 0.001], and lower detection rates among HIV-infected individuals with CD4/CD8 cell ratios of 0.208 to < 0.326 [OR = 0.232, 95% CI: (0.076, 0.711), P = 0.011] and 0.516 and higher [OR = 0.292, 95% CI: (0.104, 0.818), P = 0.019] than among those with CD4/CD8 cell ratios of < 0.208. Multivariate logistic regression analysis identified woman [OR = 4.945, 95% CI: (3.944, 5.946), P = 0.002], and CD4 cell counts of < 200 cells/μL [OR = 3.597, 95% CI: (1.448, 8.937), P = 0.006] as risk factors of anemia among newly reported HIV/AIDS patients. The incidence of anemia was low among newly reported HIV/AIDS patients in Jiangsu Province in 2021, and the immune status was poorer among HIV-infected individuals with anemia than those without anemia at baseline and one year following ART. Female and CD4 cell counts of < 200 cells/μL are risk factors of anemia among individuals living with HIV infections, and intensified surveillance, follow-up and precision interventions are recommended targeting female HIV-infected individuals and HIV-infected individuals with low CD4 cell counts.

Outcomes after a virological failure to first-line second-generation INSTI-based therapy in a real-life setting.

Virological failures of first-line second-generation (SG) INSTI-based regimens are rare, usually characterized by low viremia and absence of drug resistance mutations. To explore the efficacy of rescue regimens introduced after virological failure (VF) to a first-line SG-INSTI therapy. This was a retrospective study on people living with HIV (PWH) failing a first-line SG-INSTI regimen [DTG/3TC, BIC/FTC/TAF, DTG-based three-drug regimen (DTG-3DR)] between 24 March 2016 and 31 December 2021. Follow-up accrued from the second viral load (VL) ≥ 50 copies/mL under SG-INSTI regimen (baseline) until virological success (VS, achievement of at least one VL < 50 copies/mL after baseline) or last visit. Cumulative probabilities of VS were estimated by Kaplan-Meier curves and compared using a log-rank test. Overall, of 521 naïve PWH who started a first-line SG-INSTI regimen, 45 (8.6%) had VF after a median of 14.9 (IQR = 6.9-25.9) months: 33/395 (8.4%) individuals failed a DTG-3DR, 11/102 (10.8%) a BIC/FTC/TAF and 1/24 (4.2%) failed a DTG/3TC.At baseline, 12/45 (27%) PWH changed antiretroviral therapy [median baseline VL 134 (IQR = 81-233) copies/mL], while 33 (73%) maintained their failing regimen [median baseline VL 75 (IQR = 60-145) copies/mL].During a median follow-up of 5.13 (IQR = 3.8-7.1) months, 34 (75.6%) PWH achieved VS: 25/33 (75.8%) maintaining their failing regimen, 9/12 (75%) switched regimen; the estimated 6- and 12-months probabilities of VS were 59% and 84%, respectively.There was no difference in VS curves between PWH who maintained their failing regimen and those who switched therapy. Most individuals remained on their failing regimen, achieving spontaneous virological suppression in most cases. These data help to understand a real-life VF scenario in the context of the current SG-INSTI era.

Clinical, Histological, and HPV-Related Factors Associated to Diffuse Presentation of Exophytic Nasal Papillomas.

Background: Sinonasal exophytic papillomas (SNEP) are benign tumours arising from nasal mucosa. Human papillomavirus (HPV) infection seems to be related to the aetiology of a fraction of SNEP cases. SNEP presentation can be focal (FSNEP) or diffuse (DSNEP), but factors related to focal or diffuse presentation have not yet been well ascertained. This study aimed to analyse clinical, histological, and HPV-related differences between FSNEP and DSNEP. Methods: A retrospective cohort of 18 patients with SNEP from our centre were evaluated. Demographic, clinical and follow-up data were collected. All samples were subject to histopathological evaluation, DNA quality control, HPV-DNA detection, and viral load assessment. Univariate analyses were performed to evaluate differences between FSNEP and DSNEP. Results: Twelve SNEP patients were included in the final analysis. Seven patients had a diffuse nasal presentation, being younger than patients affected with FSNEP (42.7 years vs. 65.2 years, p = 0.019). The nasal septum was significantly more affected in DSNEP than in FSNEP (85.7% vs. 20%, p = 0.029). HPV-DNA was detected more frequently (100%) in DSNEP (HPV11 in six cases, HPV6 in one case) than in FSNEP (40%, p = 0.045, HPV6 in two cases). The median viral load among HPV6-positive samples was 626.8 virus/cell for FSNEP and 80.2 for DSNEP, and among HPV11-positive samples was 1673.7 for DSNEP. Recurrences were more frequent in the diffuse than in the focal group (85.7% vs. 20%, p = 0.029). Conclusions: The diffuse presentation of SNEP seems to be related to younger patients, nasal septum involvement, HPV infection, mostly HPV11, and a higher risk of recurrence.

Epidemiological and virological characteristics of people living with HIV on antiretroviral treatment for more than 6 months in virological failure in Brazzaville, Republic of Congo.

Introduction. Virological failure is one of the main causes of failing to treat, and better management of HIV infection requires understanding and controlling the factors that contribute to this phenomenon. The main objective was to characterize the patients of the active file of the Brazzaville Outpatient Treatment Center in virological failure to identify predictive factors leading to virological failure. Methods. Conducted between June and December 2020, this was a cross-sectional study. Patients enrolled were HIV-1-infected patients from the Brazzaville Outpatient Treatment Center receiving a potent combination therapy for at least 6 months but experiencing virological failure. Viral load was measured using the automated Abbott Real-time HIV-1 m2000rt System. Sociodemographic and clinical data were collected from a computerized patient record software called Santia. For the identification of the independent predictors of virological failure, statistical analysis was performed. Results. A total of 109 patients with virological failure were recruited. The median age of the patients was 45 years (interquartile range: 37-52 years) and women were more represented (74%). More than half of the patients had World Health Organization stage IV HIV and the median duration of antiretroviral treatment was 96 months. The most followed treatment regimen was AZT+3TC+EFV (or nevirapine) with 48%, while the median viral load was 12985 copies ml-1. Conclusion. In our study, we did not identify any sociodemographic or clinical variables predictive of virological failure. However, we felt that it would be desirable to carry out a study with temporal follow-up and the possibility of sequencing in order to identify the different circulating genotypes and resistance mutations.

Incidence of Epstein-Barr Virus Reactivation and Its Risk Factors in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

Epstein-Barr virus (EBV) reactivation in allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients can lead to significant complications including post-transplant lymphoproliferative disease. Despite progress in managing EBV reactivation in allo-HCT recipients, data on clinical characteristics and prognostic implications of EBV viral load remain limited. Here, we aim to evaluate the prevalence, identify risk factors, and assess the clinical implications of EBV-DNA positivity in allo-HCT recipients. A retrospective audit of laboratory records for EBV load monitoring in allo-HCT recipients during the period from 2021 to 2023 was performed. EBV viral load was assessed using quantitative PCR. The medical records were reviewed for clinical features, identifying risk factors, and prognostic impact of EBV-DNA positivity. A total of 40 patients with a median age of 20.5 years were included. Patients were divided into two groups based on presence (>600 copies/mL) and absence of EBV-DNA. We observed EBV-DNA positivity in 16 (40%) patients with a median EBV viral load of 12,400 copies/ml. Patients with EBV-DNA positivity exhibited a higher incidence of acute graft versus host disease (p=0.039). Patients with EBV-DNA positivity tended to have poorer 1-year overall survival and disease-free survival, although the results did not reach statistical significance. Our data highlights the importance of monitoring EBV viral load in predicting the outcome in terms of overall survival in allo-HCT recipients. The development of GVHD has also surfaced as a significant element increasing the likelihood of EBV-DNA positivity. It is imperative to conduct further research and establish comprehensive protocols for the routine monitoring and management of EBV post-allo-HCT.

Early Mortality and Health Care Costs in Patients Recently Diagnosed With Kaposi Sarcoma at the National Cancer Institute, Mexico City.

Kaposi sarcoma (KS) is a marker of advanced HIV disease; it is still the most frequent AIDS-associated malignancy in Mexico despite universal access to antiretroviral therapy, reflecting a gap in early HIV diagnosis. The objectives of the study were to describe people with HIV with KS who died within 30 days of admission at INCan (National Cancer Institute) and to quantify resources and years of life lost (YLL). We collected demographic data, HIV-related variables, all diagnostic and therapeutic procedures, hospitalizations, and estimated YLL and disability-adjusted life years. Eighteen (6.7%) people with HIV with KS from 270 patients admitted at INCan from 2014 to 2021 were included. The median age was 31 years (IQR 27-36), and the median days from admission to death and from HIV diagnosis to death were 15 (IQR, 6-24) and 73 (IQR, 30-857), respectively. Upon admission, the median HIV viral load was 314 476 copies/mL (IQR, 140 709-695 613); CD4+ T cells, 93 cells/mL (IQR 35-124); and CD4/CD8 ratio, 0.08 (IQR, 0.06-0.12). Coinfections were diagnosed in 14 (77.7%) patients. The average expenditure per patient was US $7685.99 USD, and the total YLL was 737.4 with a median 42 years (IQR, 37.7-47) per patient. The total care cost was US $183 947.48, equivalent to a screening program in key populations, which would have allowed the early detection of 1227 cases and saved 8410 disability-adjusted life years. Reinforcement of early HIV infection detection in key population programs should be prioritized to reduce KS-associated deaths and YLL and for rational use of health budgets.

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

The 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. 490 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 5 mL of eNAT medium, whilst cervical brushings were immediately transferred in 20 mL ThinPrep. The 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. Following cut-off optimisation OncoPredict HPV QT assay demonstrated similar accuracy on self-collected versus cervical samples.

THE EFFECTS OF VALACYCLOVIR ON POLYOMAVIRUS INFECTION (BKV) IN KIDNEY TRANSPLANT RECIPIENTS

Abstract Polyomavirus-associatednephropathy(PVAN) is one of the most serious infectious complications in allograft recipients, with the BK virus (BKV) being the primary etiologic agent. This study was conducted to investigate the efficacy of valacyclovir on BK virus (BKV) infection and viremia control in infected patients in Iran. This quasi-experimental study involved 21Iranian patients. All kidney transplant recipients with a confirmed diagnosis of BKV infection based on renal biopsy and PCR were administered standard therapy (reduced doses of immunosuppressive drugs) with or without valacyclovir at a one-gram dose twice daily for one month. After collecting the data, the data was analyzed using SPSS 23. The K-S test confirmed the normality of the quantitative data. Chi-square for trend, independent-t, and Fisher's exact tests were used to examine group homogeneity in terms of socio-demographic characteristics. Before the intervention, a t-test was used to compare mean scores among the groups; and repeated measures independent sample test, pair sample test, chi square test and ANOVA. The significance level of P 0.05 was considered for all tests. The mean creatinine level, mean GFR(Glomerular Filtration Rate) level, and median viral load in the serum were not significantly different between the two groups at the time of graft rejection diagnosis. One month after treatment, the serum viral load decreased in 90.9% of patients in the intervention group and 50% of patients in the control group, with the difference being statistically significant(p=0.038). Also, in the two-month review, the results showed that the reduction of the virus serum load level was observed in 81.8% of patients in the intervention group and 40% of patients in the control group, and this difference was statistically significant (p=0.049). Mean age, body mass index, and transplant duration were comparable between the two groups. Neither creatinine nor GFR levels differed significantly between the two groups after the intervention(P=0.557 and P=0.387). Valacyclovir can effectively reduce the serum viral load in BKV-infected kidney transplant recipients. This reduction, however, is not accompanied by an improvement in renal function or prevention of rejection.

SARS-CoV-2 RNAemia as a reliable predictor of long-term mortality among older adults hospitalized in pulmonary intermediate care units: a prospective cohort study

BackgroundSARS-CoV-2 viremia is associated with disease severity and high risk for in-hospital mortality. However, the impact of SARS-CoV-2 viremia on long-term outcomes in hospitalized patients with COVID-19 is poorly understood.MethodsWe conducted a prospective cohort study and recruited a group of older adult patients with COVID-19 admitted to pulmonary intermediate care units of Peking University Third Hospital during December 2022 and January 2023. The plasma level of SARS-CoV-2 RNA was determined by a standardized RT-PCR technique, and SARS-CoV-2 RNAemia was defined as a plasma viral load ≥ 50 copies/ml. In-hospital and follow-up (180-day) outcome data were collected.ResultsA total of 101 patients with an average of 80.4 years were recruited, and 63.4% of them were severe or very severe cases. Twenty-eight patients (27.7%) had SARS-CoV-2 RNAemia, with a median viral RNA load of 422.1 [261.3, 1085.6] copies/ml. Patients with SARS-CoV-2 RNAemia were more likely to develop critical cases and had a higher incidence of sepsis. Accordingly, they had a higher 180-day mortality (57.1% vs. 19.7%, P < 0.001), as well as in-hospital mortality (50.0% vs. 13.7%, P < 0.001), independent of age, disease severity, sepsis, lymphocyte count and C-Reactive protein. In addition, the risk for 180-day mortality increased with the SARS-CoV-2 RNA load in plasma. Plasma cytokines, including IL-6, IL-8 and IL-10, were higher in patients with SARS-CoV-2 RNAemia.ConclusionsOur study indicates that SARS-CoV-2 RNAemia serves as a useful biomarker for predicting mortality, especially long-term mortality, in older adult patients hospitalized in pulmonary intermediate care units.Trial registrationChinese Clinical Trial Registry website (No. ChiCTR2300067434).

Exploring atypical manifestations and multisystem involvement of Epstein-Barr virus infection in hospitalized pediatric patients from Mexico: insights from a tertiary hospital (2012-2022).

Epstein-Barr virus (EBV) infection, with a global prevalence exceeding 95%, typically manifests in children as infectious mononucleosis. However, clinical practice frequently encounters diverse atypical presentations characterized by multisystem involvement, often resulting in an unfavorable clinical course. Our objective is to describe the clinical manifestations and results of EBV infection in a tertiary pediatric hospital in Mexico. An observational, transversal, retrospective, and descriptive study that included a systematic review of medical records (2012-2022) of patients under 18 years of age with detectable EBV particles in peripheral blood. The study included 26 patients with a median age of 5 years and a male predominance of 53.8%. Predominant symptoms were fever (85%) and lymphadenopathy (35%). Sixty-five percent had severe and atypical manifestations, including pneumonia and hepatic, hematologic-oncologic, and autoimmune diseases. Anemia, thrombocytopenia and leukopenia were common, with lymphocytosis in 19% of cases. The median EBV viral load was 2816 copies/mL (range: 555-355,500 copies/mL). Four deaths related to EBV infection were reported. Viral load in these cases also varied widely from 594 to 121,000 copies/mL. Supportive care was administered to 85% of patients, while others received antiviral treatment, steroids, and rituximab. Atypical manifestations were common, especially in children with multisystem involvement. EBV should be considered as a potential contributor to a diverse spectrum of clinical presentations, emphasizing the need for comprehensive evaluation and awareness in clinical diagnosis.