Viral Load Group Research Articles

Brief Report: Group-Based Trajectory Modeling to Determine Long-Term HIV Viral Load Trends Among Children With HIV in Kenya.

Identifying determinants of longitudinal HIV viral load (VL) trajectories using group-based trajectory modeling (GBTM) can inform clinical strategies and mechanisms of nonadherence among children. Children under 12 months old who were newly diagnosed with HIV were enrolled in the Optimizing Pediatric HIV therapy cohort (NCT00428116) from 2007 to 2010. Children initiated antiretroviral therapy at enrollment, and VL was assessed every 3 months for 24 months post-antiretroviral therapy and every 6 months thereafter up to 8 years old. VL trajectory groups were defined using GBTM. Fisher's exact and Kruskal-Wallis tests were used to determine the correlates of each trajectory group compared with the sustained-low VL group. Five VL trajectory groups were identified among 89 children with 522 VL visits from 6 to 24 months: sustained-low (63% of children), sustained-very-high (16%), sustained-high (9%), low-to-high (7%), and high-with-periods-of-low (6%). Children in the sustained-high group were more frequently on a first-line protease inhibitor (PI)-based regimen (63% vs 38%; P = 0.03) and had younger caregivers (median: 22 vs 28 years; P = 0.02). Among 54 children with 560 VL visits followed from 48 to 96 months, 5 trajectory groups were identified: sustained-low (74%), mid-range (4%), periods-of-low (7%), high-to-low (7%), and sustained-high (7%). Those in the high-to-low group had younger caregivers (21 vs 29 years; P = 0.01). GBTM identified unique VL patterns among children with unsuppressed VL. Caregiver and regimen-related characteristics were associated with patterns of nonsuppression. Younger caregivers may benefit from tailored counseling to help them support child antiretroviral therapy adherence. Palatable regimens are necessary for viral suppression among children with HIV.

Clinical Efficacy of Microwave Combined with Sophora flavescens Gel in Treating HPV Infection Complicated with Chronic Cervicitis and its Influence on Vaginal Microecology of Patients

Objective: To analyze the effect of microwave combined with Sophora flavescens gel in patients with HPV infection and chronic cervicitis (CC). Methods: From May 2022 to May 2023, 65 patients with HPV infection complicated with CC were randomly selected and divided into group A (31 cases, microwave) and group B (34 cases, microwave + Sophora flavescens gel) by numerical numbering envelope method, and the effects of the two groups were compared. Results: The positive rate of vaginal microenvironment factors, inflammatory factor indexes, immune function indexes, and HPV-DNA viral load in group B were better than those in group A in the following month after treatment (P < 0.05). Conclusion: Combined use of microwave and Sophora flavescens gel in patients with HPV infection and CC can better improve the vaginal microenvironment and inflammatory reaction, boost the body’s immune function, and reduce HPV-DNA viral load.

The effect of intrahepatic cholestasis in pregnancy combined with different stages of hepatitis B virus infection on pregnancy outcomes: a retrospective study.

To investigate the impact of intrahepatic cholestasis of pregnancy (ICP) with hepatitis B virus (HBV) infection on pregnancy outcomes. We selected 512 pregnant women, collected the data including maternal demographics, main adverse pregnancy outcomes and maternal HBV infected markers HBeAg and HBV-DNA loads status, then have a comparative analysis. There were 319 solitary ICP patients without HBV infection (Group I) and 193 ICP patients with HBV infection. Of the latter, there were 118 cases with abnormal liver function(Group II) and 80 cases with normal liver function(Group III). All HBV-infected pregnant women with ICP were divided into hepatitis Be antigen (HBeAg)-positive group (102 cases) and HBeAg-negative group (91 cases), according to the level of the serum HBeAg status; and into high viral load group (92 cases), moderate viral load group (46 cases) and low viral load group (55 cases) according to the maternal HBV-DNA level. Group II had a higher level of serum total bile acids, transaminase, bilirubin as well as a higher percentage of premature delivery, neonatal intensive care unit (NICU) admission and meconium-stained amniotic fluid (MSAF) compared with the other two groups(P < 0.05), but there were no significant differences in the above indicators between the Group I and Group III. Among the HBV-infected patients with ICP, HBeAg-positive group had a higher level of serum transaminase, bilirubin and bile acid as well as earlier gestational weeks of delivery, lower birth weight of new-borns and a higher rate of NICU admission than HBeAg-negative group (P < 0.05). Those with a high viral load (HBV-DNA > 106IU/ml) had a higher level of transaminase, bilirubin, and bile acid as well as shorter gestational weeks of delivery, lower birth weight of new-borns and a higher rate of NICU admission compared with those with a low or moderate viral load (P < 0.05). HBV-infected pregnant women with ICP combined with abnormal liver function have more severe liver damage, a higher percentage of preterm birth and NICU admission. HBeAg-positive status and a high HBV-DNA load will increase the severity of conditions in HBV-infected pregnant women with ICP. HBV-infected patients with ICP who have abnormal liver function, HBeAg-positive or a high viral load should be treated more actively.

Insights into estrogen impact in oral health & microbiome in COVID-19

BackgroundCOVID-19 emerged in late 2019 and has occasioned more than 765 millions cumulative cases and 6.9 millions of deaths globally. Notably, around 70% of patients with severe COVID-19 are men. Therefore, it is to be presumed that women have a hormonal protector factor in inflammation and ACE2 expression. On the other hand, oral health status, and local microbiome can be key factors to respiratory viral infections control. Nevertheless, it has been poorly investigated. In our study 20 premenopausal, 18 postmenopausal and 22 men with COVID-19 were included. Oral health status, viral load, lingual ACE2 expression, as well as microbiome, estrogens and cytokines in saliva were analyzed.ResultsOur results showed a lower expression of ACE2 in tongue cells of postmenopausal compared with premenopausal (p = 0.05), and a strong negative correlation between saliva estrogen and viral load (r = -0.76; p = 0.001). Respect to IFN-γ (p = 0.05), IL-1β, TNF-α, IL-18, and IL-23 levels were increased in postmenopausal. Oral microbiome signature of premenopausal was characterized by Prevotella melaninogenica (Log2 = 26.68; p = 1.34e-10), Haemophilus (Log2 = 23.99; p = 2.96e-9), and Alloprevotella (Log2 = 7.92; p = 0.0001). On the other hand, Leptotrichia (Log2 = -18.74; p = 0.001), Tanerella (Log2 = -17.08; p = 0.004), and Clostridiales (Log2 = -2.88; p = 0.04) represented the poor oral health group compared with the adequate group which was enriched with the commensal microorganism Neisseria perflava (Log2 = 26.70; p = 1.74e-7). Furthermore, the high viral load group was characterized by Prevotella nanceiensis (Log2 = 19.60; p = 6.06e-8), Prevotella melaninogenica (Log2 = 21.45; p = 9.59e-6), Alloprevotella (Log2 = 23.50; p = 2.70e-7) and bacteria from the red complex Porphyromonas endodentalis (Log2 = 21.97; p = 1.38e-7).ConclusionsPostmenopausal and men have a poor oral health status which could be related to a detrimental progression of COVID-19 also linked to a lower expression of ACE2, lower saliva estrogen levels and oral dysbiosis. Nevertheless, functional studies are required for a deeper knowledge.

#295 : Comparison of In Vitro Fertilization in Couples with HIV Infection with Negative Viral Load Versus Non-Infected Couples: A Case-Control Study

Background and Aims: The development of Advanced Reproductive Technology (ART) changes many aspects and perspectives towards reproductive health. Current in vitro fertilization (IVF) protocols reduce the risk of Human Immunodeficiency Virus (HIV) transmission to their partners and offspring. This study compares IVF outcome in couples in which at least one partner is HIV positive with negative viral load versus couples in which neither partner is diagnosed with HIV. Method: A total of 100 couples undergoing IVF were categorized into two groups. HIV-positive with negative viral load group in which at least one partner is infected (n = 50) and non-HIV group in which neither partner is diagnosed with HIV (n = 50) are collected from medical record in our center during the same period. The main outcomes were total oocyte retrieved, normal fertilized egg or 2 pronucleus (2PN) one day after fertilization and good quality embryos based on number of embryos that transferred and frozen for IVF procedure. Differences between groups were determined statistically using the Mann-Whitney test. Results: There is a significant difference between HIV-positive with negative viral load groups compared to non-HIV groups in terms of total oocyte retrieved (p = 0,005) and normal fertilized egg one day after fertilization (p = 0.017). There is no significant difference in the number of good quality embryos (p = 0.076) between two groups. Conclusion: The data suggested that couples with HIV-positive women have poorer total oocyte retrieved and normal fertilized egg outcome compared to non-HIV couple. HIV infection might affect success rates of IVF treatments.

Evaluation of Rapid Molecular Viral Load Monitoring with ABBOTT m-PIMATM HIV-1/2 VL

World Health Organization recommends rapid results of Human Immunodeficiency Virus (HIV) viral load by using Point of Care (POC) testing, delivering faster decision-making to prevent transmission and suppress drug resistance and greater likelihood of starting therapy if the clinic provides care and treatment services. The m-PIMATM HIV-1/2VL cartridge is an RT-PCR POC test that detects HIV-1 and HIV-2 RNA viral load, recognizing the conserved-part 5'-UTR of the HIV genome. The standard, Roche Cobas®4800 system HIV-1, targets gag and LTR regions. This study aimed to determine the correlation, sensitivity, and specificity of Abbott m-PIMATM HIV-1/2VL compared to Roche Cobas®4800 system HIV-1. A cross-sectional study at Dharmais Hospital Laboratory. EDTA plasma obtained from 200 HIV patients, consisted of 80 high-viral-load samples (&gt;1000 copies/mL), 80 low-viral-load samples (&lt;1000 copies/mL), and 40 undetectable-viral-load samples (&lt;14.2 copies/mL). Kappa Cohen was used to measure the categorical correlation. Sensitivity and specificity were calculated with diagnostic test. Dharmais Ethic Committee released ethical clearance No.0132/KEPK/IX/2020. The categorical correlation of Abbott m-PIMATM HIV-1/2 VL in determining the group of high or low viral load samples was 0.948 (very strong correlation). The categorical correlation deciding whether the HIV viral load sample was high, low, or undetectable was 0.714 (strong correlation). The categorical sensitivity of Abbott m-PIMATM HIV-1/2 VL compared to Roche Cobas®4800 system HIV-1 in categorizing HIV viral load was 97.5%, specificity of 97.5%. Abbott m-PIMATM HIV-1/2 VL performance in determining HIV RNA viral load group samples has a strong correlation compared to Roche Cobas®4800 system HIV-1. A larger study is required.

Impact of point-of-care HIV viral load and targeted drug resistance mutation testing on viral suppression among Kenyan pregnant and postpartum women: results from a prospective cohort study (Opt4Mamas).

Lack of viral suppression (VS) among pregnant and breastfeeding women living with HIV poses challenges for maternal and infant health, and viral load (VL) monitoring via centralized laboratory systems faces many barriers. We aimed to determine the impact of point-of-care (POC) VL and targeted drug resistance mutation (DRM) testing in improving VS among pregnant and postpartum women on antiretroviral therapy. We conducted a pre/post-intervention prospective cohort study among 820 pregnant women accessing HIV care at five public-sector facilities in western Kenya from 2019 to 2022. The pre-intervention or "control" group consisted of standard-of-care (SOC) centralized VL testing every 6 months and the post-intervention or "intervention" group consisted of a combined strategy of POC VL every 3 months, targeted DRM testing, and clinical management support. The primary outcome was VS (VL ≤1000 copies/ml) at 6 months postpartum; secondary outcomes included uptake and turnaround times for VL testing and sustained VS. At 6 months postpartum, 321/328 (98%) of participants in the intervention group and 339/347 (98%) in the control group achieved VS (aRR 1.00, 95% confidence interval [CI] 0.98, 1.02). When assessing VS using a threshold of <40 copies/ml, VS proportions were lower overall (90-91%) but remained similar between groups. Among women with viraemia (VL>1000 copies/ml) who underwent successful DRM testing in the intervention group, all (46/46, 100%) had some DRMs and 20 (43%) had major DRMs (of which 80% were nucleos(t)ide reverse transcriptase inhibitor mutations). POC VL testing uptake was high (>89%) throughout pregnancy, delivery, and postpartum periods, with a median turnaround time of 1 day (IQR 1, 4) for POC VL in the intervention group and 7 days (IQR 5, 9) for SOC VL in the control group. Sustained VS throughout follow-up was similar between groups with either POC or SOC VL testing (90-91% for <1000 copies/ml, 62-70% for <40 copies/ml). Our combined strategy markedly decreased turnaround time but did not increase VS rates, which were already very high, or sustained VS among pregnant and postpartum women living with HIV. Further research on how best to utilize POC VL and DRM testing is needed to optimize sustained VS among this population.

Pulmonary Function in HIV-Infected Children at a Tertiary Care Hospital in North India: A Prospective Cross-Sectional Study.

Background The global burden of HIV remains significant, particularly in India. Antiretroviral therapy (ART) has improved outcomes for children with HIV, yet understanding the virus's impact on respiratory health is essential. Pulmonary complications, common in HIV-infected adults, are poorly understood in children. Despite India's high HIV prevalence, data on pediatric lung function are lacking. This study aims to evaluate spirometry-based pulmonary function in perinatally HIV-infected children, exploring associations with disease severity, immune status, and other factors. Methods This prospective cross-sectional study conducted in a North Indian tertiary care hospital aimed to assess pulmonary function using spirometry in children (6-18 years) with HIV infection. Ethical approval and informed consent were secured. Data on demographics, clinical history, CD4+ T-cell counts, and viral load were collected. Certified respiratory therapists performed spirometry using standardized protocols. Descriptive statistics were computed, and differences in pulmonary function based on CD4+ T-cell counts, viral load, and opportunistic infection were analyzed. The study adhered to ethical guidelines and maintained participants' confidentiality. Results This cross-sectional study enrolled 57 children (mean age 13.6±3.2 years) with HIV infection. Age distribution was <9 years (24.6%), 9-11 years (28.1%), and >11 years (47.4%). Males constituted 56.1%. The mean BMI was 15.92±2.78 kg/m². HIV viral load (87.23±56.28 copies/μL) and CD4 count (1146.32±103.98 cells/mm³) were recorded. ART duration averaged 6.21±1.36 years. Viral load groups were <1 (52.6%), 1-1000 (26.3%), and >1000 copies/μL (21.1%). CD4 categories were >500 cells/mm³ (47.4%), 200-499 (42.1%), and <200 cells/mm³ (10.5%). Spirometry showed 71.9% normal and 28.1% abnormal (mild/moderate obstruction: 18.8%, mild/moderate restriction: 81.3%). No significant spirometric differences were observed among CD4 or viral load groups (p>0.05), nor with opportunistic infections (p>0.05). Conclusion This study reveals complex associations between spirometric parameters and CD4 count, viral load, and opportunistic infections in children with HIV. Further research, including longitudinal studies, is needed to unravel the intricate interplay and improve management strategies for this population.

The IPTA Nashville Consensus Conference on Post-Transplant lymphoproliferative disorders after solid organ transplantation in children: III - Consensus guidelines for Epstein-Barr virus load and other biomarker monitoring.

The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders after solid organ transplantation in children. In this report from the Viral Load and Biomarker Monitoring Working Group, we reviewed the existing literature regarding the role of Epstein-Barr viral load and other biomarkers in peripheral blood for predicting the development of PTLD, for PTLD diagnosis, and for monitoring of response to treatment. Key recommendations from the group highlighted the strong recommendation for use of the term EBV DNAemia instead of "viremia" to describe EBV DNA levels in peripheral blood as well as concerns with comparison of EBV DNAemia measurement results performed at different institutions even when tests are calibrated using the WHO international standard. The working group concluded that either whole blood or plasma could be used as matrices for EBV DNA measurement; optimal specimen type may be clinical context dependent. Whole blood testing has some advantages for surveillance to inform pre-emptive interventions while plasma testing may be preferred in the setting of clinical symptoms and treatment monitoring. However, EBV DNAemia testing alone was not recommended for PTLD diagnosis. Quantitative EBV DNAemia surveillance to identify patients at risk for PTLD and to inform pre-emptive interventions in patients who are EBV seronegative pre-transplant was recommended. In contrast, with the exception of intestinal transplant recipients or those with recent primary EBV infection prior to SOT, surveillance was not recommended in pediatric SOT recipients EBV seropositive pre-transplant. Implications of viral load kinetic parameters including peak load and viral set point on pre-emptive PTLD prevention monitoring algorithms were discussed. Use of additional markers, including measurements of EBV specific cell mediated immunity was discussed but not recommended though the importance of obtaining additional data from prospective multicenter studies was highlighted as a key research priority.

Association of CD4 cell counts and viral load with cystatin C level in children with human immunodeficiency virus (HIV) infection

Background The ease of access to antiretroviral therapy (ART) has improved both survival rate and comorbidities in patients with human immunodeficiency virus (HIV) infection. Impaired kidney function is one of the most common comorbidities of HIV. CD4 and viral load can be used to monitor HIV progression and to determine the effectiveness of ART. The most commonly used estimated-glomerular filtration rate (e-GFR) technique is to use serum creatinine but often causes late detection of kidney dysfunction while serum cystatin increases at the beginning of the GFR decrease. This supports cystatin C serum as an early diagnostic tool to detect kidney function or biomarker early kidney disorders.&#x0D; Objective To evaluate a possible association between serum cystatin C as a marker of kidney function and HIV progression through CD4 levels and viral load.&#x0D; Methods This cross-sectional study was conducted through evaluation of secondary data from medical and laboratory records of pediatric patients who had routine visits to the HIV Clinic at Dr. Hasan Sadikin General Hospital, Bandung, West Java, in January-February 2020.&#x0D; Results Sixty subjects were reviewed in the study. Median cystatin C-based eGFR was 28.1mL/minute/1.73m2. Subjects were categorized by viral load result into &lt;40 and ?40 copies/mL. The median serum cystatin C was significantly higher [3.7 (range 2.61–6.55) mg/L] in the &gt;40 copies/mL viral load group than the &lt;40 copies/mL group [2.4 (range 0.26–13.61) mg/L]. The median absolute CD4 count, CD4 percentage, and cystatin C were 776 (range 7–1644) cells/mm3, 27.5 (range 1.6–57.4) %, and 3 (range 0.26–13.61) mg/L, respectively. There were no significant correlations (r=-0.2; P=0.1) between CD4 and serum cystatin C&#x0D; Conclusion Higher viral load associates with higher cystatin C level, while CD4 shows no correlation to cystatin C. However, patients with low CD4 tend to have increased cystatin C level.&#x0D;

Correlation of Viral Load With the Biochemical and Hematological Profiles of COVID-19 Patients in Al Buraimi Hospital, Sultanate of Oman: A Cross-Sectional Study.

Background Rapid identification of COVID-19 is crucial during the pandemic for the treatment and management of patients. Thus, early diagnosis of the disease using laboratory parameters can help in the rapid management of infected patients. This study aimed to investigate the correlation of viral load with hematological and biochemical parameters. This will ultimately help physicians to better understand the dynamics of this novel virus and aid in the management of patients. Methodology Laboratory confirmation of SARS-CoV-2 was performed by reverse transcription-polymerase chain reaction (RT-PCR) at the Al-Buraimi Hospital Laboratory Department using oropharyngeal and nasopharyngeal swabs. Positive cases were collected from July 2020 to January 2021 to be enrolled in this study. Results In this study, 264 confirmed positive patients were included initially and divided into three groups according to their cycle threshold (Ct) values obtained by PCR. Out of the total 264 patients, 174 (65.9%) were male, while 90 (34.1%) were female. However, the final sample was only 253 patients who met the inclusion criteria. With regard to Ct values, the study population was divided into the following three groups: Group 1 with Ct values of 9-20 (n = 87; 34.4%), group 2 with Ct values of 21-30 (n = 122; 47.8%), and group 3 with Ct values of 31-42 (n = 44; 17.4%). Conclusions We found that the proportion of male patients infected with COVID-19 was higher compared to females.In addition, the highest incidence was among patients in the age group of 51-70 years.The ferritin and alanine transaminase levels were highest in the initial stage of the infection (group 1) and decreased at the recovery stage. However, neutrophil, lymphocyte, alkaline phosphatase, and C-reactive protein showed an increasing trend from high viral load groups to low viral load groups. The values of the rest of the parameters, such as albumin, total bilirubin, lactate dehydrogenase, and D-dimer, were slightly higher in the initial stage of the infection but the decreasing trend was low; therefore, they were not considered helpful in predicting the disease severity reflected by their Ct value in the three different groups.

Molecular analysis of human adenoviral keratoconjunctivitis cases: Results of a 2-year survey

Objective: This study aimed to determine the adenovirus genotypes and their epidemiological features between January 2018 and&#x0D; November 2019, in Istanbul, Turkey.&#x0D; Material and Methods: Conjunctival swab samples were obtained from patients who were clinically diagnosed with keratoconjunctivitis.&#x0D; Samples were screened with an Adeno Detector kit (Rapid Pathogen Screening, RPS Inc., South Williamsport, PA). Nucleic acid&#x0D; extraction and amplification were performed with the ADENOVIRUS ELITe MGB® kit in the ELITe In Genius instrument (Elitech&#x0D; Group, Torino, Italy). For subtyping of the strains, sequencing primers targeted the ‘Hypervariable Region 7’ (HVR-7) of the hexon&#x0D; gene were used. DNA sequence analysis (n:72) was performed with ABI PRISM® 3100 Genetic Analyzer (Applied Biosystems, USA),&#x0D; and subtyping was done by BLAST analysis.&#x0D; Results: The median viral load in the samples (n: 77) was 7 log10 copies/mL (IQR: 4.5-7.4 log10 copies/mL). The clinical finding score&#x0D; was found to be significantly higher in the high viral load group (Adenovirus DNA≥6 Log 10 copies/mL) than in the low viral load&#x0D; group (Adenovirus DNA

Plasma IL-33 levels and immune activation in HIV-TB coinfection: a cross-sectional study in Yaoundé, Cameroon.

HIV-1 and Mtb are characterized by immune activation and unbalances production of cytokines, but the expression of IL33 in HIV/TB coinfection remain understudied. This study aimed to evaluate the level of IL-33 in plasma of HIV and M. tuberculosis (HIV/TB) coinfected patients compared to patients with respective mono infections in Yaoundé. a cross-sectional study was conducted among patients attending the pneumology service and HIV treatment center of the Yaoundé Jamot Hospital. Plasma samples of 157 HIV/TB coinfected patients (n =26, 50% males and 50% females, mean age 39), HIV-1 monoinfected patients (n = 41, 41% males and 59% females, mean age 35), TB monoinfected patients (n = 48, 56% males and 44% females, mean age 37) and healthy controls (n = 42, 29% males and 71% females, mean age 32) were examined by enzyme-linked immunoassay (ELISA) to detect the levels of IL-33 cytokine. plasma level of IL-33 were higher in HIV/TB coinfected (33.1±30.9 pg/ml) and TB monoinfected individuals (15.1±2.9 pg/ml) compared to healthy controls (14.0±3.4 pg/ml) and could not be detected in most of the HIV-1 monoinfected individuals (12.6±8.7 pg/ml). Interestingly, the increased plasma level of IL-33 in HIV/TB coinfected patients showed a statistically significant difference between healthy controls (33.1±30.9 pg/ml vs 14.0±3.4 pg/ml, P<0.0001) and HIV-1 monoinfected patients (33.1±30.9 pg/ml vs 12.6±8.7 pg/ml, P=0.0002). We further found that IL-33 was higher in patients with high viral load group (40.6±59.7 pg/ml vs 12.6±1.8 pg/ml), P= 0.47) whereas patients under highly active antiretroviral therapy (HAART) showed decreased level of IL-33 concentration as the number of years under ART increased. Our data showed a positive association between plasma IL-33 and viral load in the context of HIV/TB coinfection in our study population with a positive Pearson coefficient of r=0.21. this study indicates that plasma level of IL-33 differs among HIV/TB coinfected patients and respective monoinfections patients. The increased level of plasma IL-33 reveals that IL-33 measurement in HIV-1 monoinfected patients may represent an early predictor of development of tuberculosis.

Nasopharyngeal viral load at admission is not an independent predictor of thromboembolic complications in unvaccinated COVID-19 hospitalized patients.

COVID-19 patients may develop thrombotic complications, and data regarding an association between nasopharyngeal viral load and thrombosis is scarce. The aim of our study was to evaluate whether SARS-CoV-2 nasopharyngeal viral load upon admission is a useful prognostic marker for the development of thromboembolic events in patients hospitalized for SARS-CoV-2 infection. We performed a retrospective study of all hospitalized patients with a positive PCR test for SARS-CoV2 who had deep vein thrombosis (DVT), pulmonary embolization (PE), or arterial thrombosis diagnosed during their clinical course in a single academic center. The study population was divided according to the cycle threshold (Ct) value upon admission in patients with high viral load (Ct < 25), intermediate/medium viral load (Ct 25-30), and low viral load (Ct > 30). A regression model for propensity was performed matching in a 1:3 ratio those patients who had a thrombotic complication to those who did not. Among 2,000 hospitalized COVID-19 patients, 41 (2.0%) developed thrombotic complications. Of these, 21 (51.2%) were diagnosed with PE, eight (19.5%) were diagnosed with DVT, and 12 (29.2%) were diagnosed with arterial thrombosis. Thrombotic complications occurred as frequently among the nasopharyngeal viral load or severity stratification groups with no statistically significant differences. Univariate logistic regression revealed increased odds for thrombosis only in mechanically ventilated patients OR 3.10 [1.37, 7.03] (p = 0.007). Admission SARS-CoV-2 nasopharyngeal viral loads, as determined by Ct values, were not independently associated with thromboembolic complications among hospitalized patients with COVID-19.

HIV-1C in-House RNA-Based Genotyping Assay for Detection of Drug Resistance Mutations in Samples with Low-Level Viral Loads.

Monitoring HIV-1 drug resistance mutations (DRM) in treated patients on combination antiretroviral therapy (cART) with a detectable HIV-1 viral load (VL) is important for the selection of appropriate cART. Currently, there is limited data on HIV DRM at low-level viremia (LLV) (VL 401-999 copies/mL) due to the use of a threshold of VL ≥1000 copies/mL for HIV DRM testing. We here assess the performance of an in-house HIV drug resistance genotyping assay using plasma for the detection of DRM at LLV. We used a total of 96 HIV plasma samples from the population-based Botswana Combination Prevention Project (BCPP). The samples were stratified by VL groups: 50 samples had LLV, defined as 401-999 copies/mL, and 46 had ≥1000 copies/mL. HIV pol (PR and RT) region was amplified and sequenced using an in-house genotyping assay with BigDye sequencing chemistry. Known HIV DRMs were identified using the Stanford HIV Drug Resistance Database. Genotyping success rate between the two groups was estimated and compared using the comparison of proportions test. The overall genotyping success rate was 79% (76/96). For VL groups, the genotyping success was 72% (36/50) at LLV and 87% (40/46) at VL ≥1000 copies/mL. Among generated sequences, the overall prevalence of individuals with at least 1 major or intermediate-associated DRM was 24% (18/76). The proportions of NNRTI-, NRTI- and PI-associated resistance mutations were 28%, 24%, and 0%, respectively. The most predominant mutations detected were K103N (18%) and M184V (12%) in NNRTI- and NRTI-associated mutations, respectively. The prevalence of DRM was 17% (6/36) at LLV and 30% (12/40) at VL ≥1000 copies/mL. The in-house HIV genotyping assay successfully genotyped 72% of LLV samples and was able to detect 17% of DRM amongst them. Our results highlight the possibility and clinical significance of genotyping HIV among individuals with LLV.

High Cytomegalovirus Viral Load Is Associated With 182-Day All-Cause Mortality in Hospitalized People With Human Immunodeficiency Virus.

Cytomegalovirus (CMV) infection is associated with increased mortality in persons with HIV (PWH). It is less clear whether CMV infection is still associated with mortality when routinely screened and adequately treated. This retrospective cohort study recruited 1003 hospitalized adults with HIV with CD4 cell counts <200 cells/μL from May 2017 to June 2021. Blood CMV DNA was routinely measured and CMV DNAemia was treated if end-organ disease occurred. CMV viral load was categorized into below the limit of quantification (BLQ; <500 IU/mL), low viral load (LVL; 500-10 000 IU/mL), and high viral load (HVL; ≥10 000 IU/mL) groups. We compared the 182-day all-cause mortality among different groups. The median (IQR) CD4 cell count of patients was 33 (13-84) cells/μL. The prevalence of CMV DNAemia was 39.8% (95% CI: 36.7-42.9%) and was significantly associated with CD4 cell count. The 182-day all-cause mortality was 9.9% (95% CI: 8.0-11.7%). Univariable analysis showed that, compared with BLQ, LVL and HVL were associated with 1.73-fold and 3.81-fold increased risks of mortality, respectively (P = .032 and P < .001). After adjustment for predefined confounding factors, HVL but not LVL was still associated with increased risk of mortality (adjusted hazard ratio: 2.63; 95% CI: 1.61-4.29; P < .001). However, for patients on effective antiretroviral therapy, the impact of HVL on 182-day mortality was not significant (P = .713). High CMV viral load in hospitalized PWH was associated with higher mortality, even when identified early by screening. Optimalization of the management for those patients needs to be explored in future studies.

Presence of entry receptors and viral markers suggest a low level of placental replication of hepatitis B virus in a proportion of pregnant women infected with chronic hepatitis B

The transplacental route of vertical transmission of Hepatitis B Virus (HBV) has been known for over a decade. Here we present evidence which suggest HBV can replicate in placenta. Forty-one HBsAg positive and 10 control pregnant women were enrolled in the study after obtaining informed consent. HBV positives were further divided in the High Viral Load (HVL) Group and Low Viral Load (LVL) Group according to INASL guidelines 2018. The Presence of the HBV DNA and expression of NTCP in the placenta was analyzed by qPCR/RT-qPCR and/or immunohistochemistry (IHC). The presence of cccDNA was assessed using Digital Droplet PCR while the presence of pre-genomic (pg) RNA was assessed through qRT-PCR and sequencing. The presence of HBeAg and HBcAg in the placenta was assessed by IHC. Immunostaining of NTCP, HBeAg and HBcAg on trophoblasts along with the presence of total HBV DNA, cccDNA and pgRNA indicated, that these cells are not only susceptible to HBV infection but may also support viral replication. This is further supported by the finding that trophoblasts of the several HBeAg seronegative samples harbored the HBeAg. Although, we did not find any correlation in NTCP expression and viral markers with viral load indicates placental replication may not aping hepatocytes. The presence of the HBV receptor, NTCP along with the presence of cccDNA, pgRNA, and HBeAg in placenta of HBV infected females without circulating HBeAg suggest that placenta act as a replication host.

Dolutegravir Plus Lamivudine Dual-Drug Regimen in Treatment-Naive HIV-1-Infected Patients With High-Level Viral Load: Preliminary Data From the Real World.

Some inpatients with HIV-RNA ≥500,000 copies/mL in China need to use 2-drug regimen for some reasons, although limited data are available for dolutegravir plus lamivudine (3TC) in those patients with ultra-high viral loads. We conducted a single-center retrospective-prospective study in China and enrolled 42 ART-naive HIV-infected inpatients who use a once-daily 2-drug regimen because of various reasons (drug interaction, renal impairment, age, and other related comorbidities).They were divided into 2 groups, low viral load group (baseline viral load <500,000 copies/mL, n = 20) and high viral load group (baseline viral load ≥500,000 copies/mL, n = 22). All patients were followed up for 48 weeks. The median of baseline viral load was 5.74 log10 copies/mL and CD4+ T-cell count was 59 cells/μL. At week 48, there was no significant difference (P = 0.598) in proportions of participants with HIV-1 RNA <50 copies/mL [90%, 95% confidence interval (CI) (75.6% to 104.4%) in low viral load groups vs 95.5%, 95% CI (86.0% to 104.9%) in high viral load groups]. No differences were found in mean increase of CD4+ T-cell count from baseline between 2 groups (218 ± 122 vs 265 ± 127 cells/μL, P = 0.245). There is no grade 3 or higher treatment-related adverse events and none discontinued treatment because of adverse events. The results of our study in real world support dolutegravir + 3TC dual regimen as a promising therapy option for treatment-naive HIV-infected patient with baseline viral load ≥500,000 copies/mL.

Detection Value of EB Virus DNA, IL-2, and IL-6 Level in Peripheral Blood of Children with Infectious Mononucleosis

To investigative the detection value of EB virus DNA (EBV-DNA), interleukin-2 (IL-2), and interleukin-6 (IL-6) level in peripheral blood of children with infectious mononucleosis (IM). A total of 59 children clinically confirmed with IM in Anhui Provincial Children's Hospital from January 2018 to September 2020 were enrolled as IM group, while other 30 healthy children undergoing physical examination during the same period were enrolled as healthy group. The level of EBV-DNA load, IL-2, and IL-6 were compared between the two groups, and their diagnostic values for IM children were explored. According to the median level of EBV-DNA load, positive children were divided into high viral load group and low viral load group. The hepatomegaly and splenomegaly, and levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), IL-2, and IL-6 were compared between the two groups. The relationship between EBV-DNA load and IL-2, IL-6 levels were explored. The positive rate of EBV-DNA was 67.80% in IM group, which was significantly higher than 10.00% in healthy group (P<0.001), and the levels of serum IL-2 and IL-6 were also significantly higher than healthy group (P<0.001). The results of ROC curve analysis showed that AUC of IL-2 combined with IL-6 and EBV-DNA load was 0.948, which was significantly greater than that of IL-2, IL-6, and EBV-DNA load alone (0.847, 0.728, 0.789) (P<0.001). The cut-off value of IL-2 and IL-6 was 15.545 pg/ml and 56.560 pg/ml, respectively. Both the proportions of cases with moderate to severe hepatomegaly and splenomegaly in high viral load group were significantly higher than those in low viral load group (P<0.01, P<0.05). The levels of ALT, AST, and IL-2 in high viral load group were significantly higher than those in low viral load group (P<0.001), as well as IL-6 (P<0.01). In high and low viral load groups, EBV-DNA load was positively correlated with IL-2 and IL-6 (in high viral load group, rIL-2=0.598, rIL-6=0.416; in low viral load group, rIL-2=0.621, rIL-6=0.527, P<0.001). The detection of EBV-DNA load combined with IL-2 and IL-6 can improve the diagnostic accuracy of IM, and EBV-DNA load, IL-2 and IL-6 levels are related to the disease progression.

The Role of Autophagy in the Mother-to-Child Transmission of Pregnant Women With a High Level of HBV DNA.

BackgroundMother-to-child transmission (MTCT) is the most common propagation mode of hepatitis B virus (HBV) transmission. Exploring the mechanisms of HBV MTCT is the key to protect infant from infection. In this study, we aim to clarify the important role of autophagy complicated in HBV MTCT.MethodsA total of 169 placental samples were collected in this study, includes 144 HBV positive pregnant women and 25 normal pregnant women. In vitro, JEG-3 cells were treated with serum contained different HBV viral loads. Electron microscope was used to observed the number of autophagosome. RT-qPCR and western blotting were used to measure the expression level of autophagy relative genes and proteins respectively. Immunofluorescence was used to analyzed the expression of LC-3 of the frozen section of placental tissue.ResultsAccording to the number of autophagosomes and the expression level of autophagic genes mRNA and protein, autophagy was increased in HBV maternal placenta. Among the control, low viral load, medium viral load and high viral load groups, autophagy was significantly up-regulated with the increase of HBV viral loads. Also, autophagy was increased in the HBeAg positive pregnant women compared with their HBeAg negative counterparts. Also, autophagy in infant-infected group was up-regulated compared with infant-uninfected group. In vitro, choriocarcinoma JEG-3 cells were treated with the different HBV viral loads or different time incubation, the mRNA and protein of autophagy related genes was maximum expression in the medium viral load or treatment in a short period, but decreased in the high viral load treatment or with long-term HBV exposure.ConclusionOur study determines the high levels of viremia could be the cause of both increase autophagy activities and MTCT. Autophagy was significantly up-regulated in pregnant women with high viral load or HBeAg positive, which plays an important part in the HBV MTCT.