Viral Load Research Articles

SARS-CoV-2 resistance analyses from the Phase 3 PINETREE study of remdesivir treatment in nonhospitalized participants.

Remdesivir inhibits the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp; Nsp12). Here, we conducted viral resistance analyses from the Phase 3 PINETREE trial of remdesivir in nonhospitalized participants at risk of severe COVID-19. Nasopharyngeal swabs (collected at baseline [Day 1], Days 2, 3, 7, and 14) were eligible for analysis if their viral load was above the lower limit of quantification for the RT-qPCR assay (2228 copies/mL). The SARS-CoV-2 genome was sequenced for all remdesivir participants and 50% of placebo participants (baseline, Days 3, 7, and 14) and for participants who progressed to COVID-19-related hospitalization or all-cause death (all time points). Emergent substitutions in Nsp12 and other replication complex proteins were phenotyped using site-directed mutagenesis in a SARS-CoV-2 subgenomic replicon system. Overall, emergent Nsp12 substitutions were detected in 8/115 (7.0%) remdesivir participants and 7/129 (5.4%) placebo participants (1 substitution overlap between groups). Based on a structural analysis, none of the emergent Nsp12 substitutions were in direct contact with the incoming nucleoside triphosphate substrate, the RNA, or the RNA template 5' overhang. One substitution (A376V) showed reduced susceptibility to remdesivir (12.6-fold change in remdesivir half-maximal concentration [EC50]); it also showed reduced fitness when introduced in the SARS-CoV-2 replicon and virus in vitro. Other substitutions had <1.1-fold change in remdesivir EC50. None of the emergent substitutions in Nsp8, Nsp10, Nsp13, or Nsp14 (remdesivir, 10/115 [8.7%]; placebo, 10/129 [7.8%]) showed reduced remdesivir susceptibility. In conclusion, emergent substitutions in the SARS-CoV-2 RdRp complex with reduced remdesivir susceptibility were uncommon, indicating a high barrier to remdesivir resistance.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04501952.

Does Epstein-Barr virus and intracellular Toll-like receptors affect the course of Hashimoto disease? Findings from studies on newly-diagnosed patients.

Epstein‑Barr virus (EBV) reactivation is increasingly recognized as a potential exacerbator of autoimmune diseases, including Hashimoto thyroiditis (HT). This study examined the association between EBV reactivation and intracellular Toll‑like receptor (TLR) expression in newly‑diagnosed, untreated HT patients. Its aim was to determine whether EBV reactivation and expression of specific TLRs (TLR3, TLR7, TLR8, and TLR9) contribute to the pathogenesis and progression of HT. The study involved a cohort was 54 newly‑diagnosed, untreated patients with HT and 20 healthy volunteers (HVs) matched for age and sex. Blood samples were collected to assess EBV viral load and intracellular expression levels of TLR3, TLR7, TLR8, and TLR9 using flow cytometry. The levels of specific anti‑EBV antibodies (eg, viral capsid A [VCA] immunoglobulin [Ig] M, VCA IgG, Epstein‑Barr nuclear antigen 1 [EBNA‑1] IgM, EBNA‑1 IgG) were measured to identify signs of EBV reactivation, while soluble TLRs (sTLR3, sTLR7, sTLR8, and sTLR9) were quantified in serum using enzyme‑linked immunosorbent assay. Notably, our HT patients were not euthyroid, as they exhibited significantly lower thyroid‑stimulating hormone levels and elevated free triiodothyronine and free thyroxine levels in comparison with the HVs. The study showed a significant increase in EBV reactivation among the HT patients, with 26 of 54 (48.1%) testing positive for EBV DNA, as compared with none of the HVs. The HT patients with reactivated EBV showed significantly higher intracellular expression of TLR3, TLR7, and TLR9, with TLR3+ cells constituting an average of 4.72% of CD4+ lymphocytes (vs 0.69% in the HVs), suggesting a potential synergistic effect. In addition, sTLR levels increased in the HT patients with reactivated EBV, suggesting a possible role of these receptors in potentiating autoimmune responses. These findings highlight the importance of considering both viral reactivation and TLR activity in the treatment of HT. Understanding the interplay between EBV and intracellular TLRs may lead to development of new therapeutic approaches to mitigate the impact of these factors on the disease progression. Further research is warranted to investigate the mechanisms underlying this interaction and its implications for treatment strategies.

Cytomegalovirus viremia and hepatitis B reactivation in patient with RET fusion-positive non-small cell lung cancer treated with pralsetinib.

Mutated rearranged during transfection (RET) kinase is found in approximately 1-2% non-small-cell lung cancer (NSCLC) patients. These patients are typically younger, non-smokers, and have non-squamous histology. Pralsetinib is a novel RET inhibitor that showed promising efficacy and tolerability in the ARROW trial. Due to the small percentage of patients that have RET mutated NSCLC, real world data on safety is still needed. This case report outlines a patient who was initiated on pralsetinib for RET mutated NSCLC and subsequently developed reactivation of cytomegalovirus (CMV) viremia and hepatitis B. The patient was initiated on valganciclovir and entecavir with subsequent improvement in viral loads. They were able to reinitiate pralsetinib at a lower dose following improvement of CMV and hepatitis B viral load with continuation of entecavir. RET is responsible for activation of several signaling paths including PI3K/AKT and JAK/STAT. Those pathways are involved in the immune system. When reviewing current JAK inhibitors and PI3K inhibitors on the market, there is mixed data on HBV reactivation and CMV viremia, though theoretically possible. Therefore, this should be evaluated and addressed in further studies. The educational value of this case could provide valuable insights for baseline monitoring and management for similarly effected patients.

Cumulative HIV viral load and lower CD4 cell count are associated with incident venous thromboembolism in people with HIV.

People with HIV (PWH) have benefited greatly from antiretroviral therapy, but face additional challenges from age-related comorbid conditions, particularly cardiovascular disease including venous thromboembolism (VTE). Little is known about the effect of HIV viremia and immunodeficiency on VTE risk in this population. We assessed incident, centrally adjudicated VTE among 21,507 PWH in care between 1/2009-12/2019 within the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort. We examined the association of three measures of HIV viral load (VL: baseline, current, cumulative) and current CD4 count with VTE. Cumulative VL (copy-days of viremia) was estimated with a time-weighted sum using the trapezoidal rule. We modeled the association between VL and VTE using Cox proportional hazards models (marginal structural Cox models for cumulative), adjusted for demographic and clinical characteristics. We compared the 75th percentile of the VL distribution with the 25th percentile using the hazard function from the model for all PWH with a VTE and those with a pulmonary embolism (PE). During a median of 4.8 years of follow-up, 424 PWH developed VTE. In adjusted analyses, higher cumulative VL (75th percentile vs. 25th percentile), the strongest VL predictor, was associated with a 1.45-fold higher risk of VTE (95%CI:1.22-1.72). Low CD4 cell count <100 cells/mm3 was associated with higher VTE risk (HR: 4.03, 95%CI: 2.76-5.89) as compared to ≥500 cells/mm3. Findings were similar for PWH who had a pulmonary embolism (n = 189). Reducing HIV VL and maintaining CD4 cell count may help mitigate VTE risk in PWH.

Protektem pikinini blong yu trial: protocol for a single arm field trial to assess the effectiveness of treating-all pregnant women with hepatitis B infection with tenofovir prophylaxis to prevent mother-to-child transmission in Vanuatu, 2024–2025

BackgroundHepatitis B infection is a major public health concern in Vanuatu, with approximately 9% of the general population estimated to be living with chronic hepatitis B. Most new infections are due to mother-to-child transmission (MTCT). Hepatitis B vaccination is available in Vanuatu, but coverage rates for first dose within 24 h of birth and third dose are suboptimal. While treatment of chronic hepatitis B infection with tenofovir disoproxil fumarate (TDF) is available in country, there is no capacity to test hepatitis B e antigen and limited capacity to test hepatitis B virus (HBV) DNA viral load, which is a current eligibility requirement for women in pregnancy to access hepatitis B prophylaxis for MTCT per National guidelines. Recently, the World Health Organization guidelines have been updated to recommend universal peripartum antiviral prophylaxis (PAP) of pregnant women living with hepatitis B to prevent MTCT of HBV, without assessment of viral load in places without access to testing. However, these recommendations are conditional based on low-certainty evidence. The aim of this trial is to evaluate the effectiveness and safety of universal PAP and provide evidence for the global guidelines.MethodsA single arm field trial compared to real world control sites will be conducted in Vanuatu involving pregnant women attending antenatal care services with positive HBsAg rapid tests. Participants at the control sites will undergo routine care. Participants at the intervention sites will all receive oral TDF prophylaxis from second trimester to completion of infant primary hepatitis B vaccination schedule. Primary data analysis will be by intention-to-treat. Initial analyses will be unadjusted comparisons of the intervention sites and control sites. Adjusted analyses will be performed, as needed, and presented in addition to unadjusted comparisons.DiscussionThis study will provide evidence of acceptability, effectiveness and cost-effectiveness of prophylaxis for all women with hepatitis B during pregnancy, as per the updated WHO guidelines, compared with current practice. The outcome of this trial will provide critical information to inform national and global guidelines around universal peripartum antiviral prophylaxis for hepatitis B during pregnancy.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR), ACTRN: ACTRN12623001202651p. Registered 21 November 2023.

Characteristics of patients with non-severe infections of different SARS-CoV-2 omicron subvariants in China

ObjectiveThe aim of this study was to explore the clinical characteristics of patients infected with different Omicron subvariants presenting non-severe disease, evaluate the safety and efficacy of Azvudine for treatment of COVID-19, in order to broaden understanding of Omicron subvariant infections.MethodA total of 244 individuals with Omicron subvariant (BA.2.76, n = 158; BA.5.1, n = 86) were included in the study. Demographic, clinical, and laboratory data of the study participants were collected and analyzed.ResultPatients infected with BA.5.1 exhibited a higher incidence of clinical symptoms like fatigue (25.58% vs. 2.53%, p &amp;lt; 0.001), headache/dizziness (12.79% vs. 4.43%, p = 0.017), nausea/vomiting (10.47% vs. 1.27%, p = 0.002), viral loads and inflammatory factors, and shorter virus shedding time than those with BA.2.76. There are 28.1% patients reporting mild adverse events following Azvudine administration. After treatment, the levels of anti-SARS-CoV-2 IgG/IgM, white blood cell, and lymphocyte obviously increased, while C-reactive protein, procalcitonin, and D-dimer reduced. Azvudine speeded up the time for virus clearance compared to control treatment (10 vs. 11 days, p = 0.032). Low lymphocyte counts (odd ratio (OR) = 0.607, p = 0.001) and anti-SARS-CoV-2 IgG titer (OR = 0.990, p = 0.028) were the independent risk factors for long nucleic acid negativization duration after infection. Patients with pneumonia were often accompanied by dyspnea, fatigue and high level of D-dimer. Dyspnea (OR = 10.176, p = 0.019) could be used to identify the occurrence of pneumonia in patients infected with Omicron.ConclusionThe study demonstrated the difference in clinical and laboratory parameters between patients infected with Omicron BA.2.76 and BA.5.1, as well as the safety and efficacy of Azvudine therapy. Our study linked patient manifestations to Omicron subvariant, treatment, and clinical outcomes, which is conducive to healthcare providers/policymakers to revise and implement appropriate countermeasures, facilitating appropriately advise for individuals with Omicron subvariant infections.

Depressive Symptoms and HIV Viral Suppression: A Systematic Review and Meta-analysis.

Previous research suggests that depression impacts HIV outcomes, including viral suppression. This meta-analysis quantifies the association between depression and HIV viral suppression. A systematic literature search was conducted in PubMed, Web of Science, EBSCO, and OVID to identify studies published through 2012 to 2022. The software Rayyan was used to evaluate eligibility of studies, and the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were used for abstracting data. A random effects meta-analysis was performed using Review Manager 5.4.1. Of the 1911 articles screened, 16 studies were included covering 80,103 participants. The results showed individuals without depression were more likely to achieve HIV viral suppression or undetectable viral load compared to individuals with depression (OR 1.30; 95%CI 1.15, 1.48; I2 = 76%). Subgroup analysis indicated this effect was significant among the general population of people living with HIV (n = 75,353; OR 1.32; 95%CI 1.12, 1.55; I2 = 85%) and cisgender women living with HIV (n = 4553; OR 1.28; 95%CI 1.09, 1.50; I2 = 16%), but not among cisgender men living with HIV (most identified as men who have sex with men) (n = 197; OR 2.13; 95%CI 0.43, 10.61; I2 = 83%). This meta-analysis shows a significant positive association between the absence of depression and achieving HIV viral suppression overall and among the subgroup of cisgender women. Public health interventions for people living with HIV should include strategies to identify and address the depressive symptoms that impact adherence to treatment, increase the risk of psycho-behavioral co-morbidities, and exacerbate social or structural factors impeding viral suppression.

HIV prevention and treatment cascades among female sex workers in Ghana: gaps and priorities that should be addressed by the national programme

BackgroundThere is currently limited knowledge about HIV prevention and treatment cascades among female sex workers (FSW) in Ghana. This study sought to use the 2020 bio-behavioural survey (BBS) among FSWs to identify gaps and priorities in HIV treatment and prevention cascades to help achieve the 95–95-95 fast track targets.MethodThe study used a cross-sectional design with Time Location Sampling (TLS) technique in all regions of Ghana. All eligible FSW at the selected venues and stipulated time frame were interviewed and tested for HIV onsite using the national testing algorithm. For condom use and HIV testing cascades, each step of the cascade was calculated as a percentage of all FSW. Analysis of treatment cascade was restricted to HIV positive participants and was presented using both conditional (% eligible PLHIV) and unconditional (% all PLHIV) approaches. Viral suppression level was defined as < 1000 copies/ml.ResultsA total of 6,773 participants took part in the behavioral interviews while 6,217 took part in the biological component which involves HIV testing. In all, 33% and 80% of all FSW do not consistently use condoms with their paying clients and non-paying partners respectively. The findings further show that 26.6% of FSW have never tested for HIV, and contrary to the HIV testing policy of every six months for FSW, 70.0% did not test for HIV 6 months preceding the survey and 40.7% of all FSW did not test for HIV 12 months preceding the survey.The conditional treatment cascade was 32%-71%-57% while the unconditional cascade was 32%-23%-49%. The study further shows 68% of the HIV positive FSW were not aware of their HIV positive status, 77% were not on treatment, while nearly 51% were not virally suppressed regardless of treatment status.ConclusionThe results show that both the prevention and treatment cascades are suboptimal. Key gaps identified include low: HIV testing, viral load suppression, condom use with both paying clients and non-paying partners. There is therefore the need to scale prevention and treatment interventions particularly HIV testing, treatment initiation, consistent condoms use with both paying clients and non-paying partners to help achieve the 95–95-95 fast track targets.

A Randomized, Blinded, Vehicle-Controlled Dose-Ranging Study to Evaluate and Characterize Remdesivir Efficacy Against Ebola Virus in Rhesus Macaques

Ebola virus (EBOV) causes severe disease in humans, with mortality as high as 90%. The small-molecule antiviral drug remdesivir (RDV) has demonstrated a survival benefit in EBOV-exposed rhesus macaques. Here, we characterize the efficacy of multiple intravenous RDV dosing regimens on survival of rhesus macaques 42 days after intramuscular EBOV exposure. Thirty rhesus macaques underwent surgical implantation of telemetry devices for the fine-scale monitoring of body temperature and activity, as well as central venous catheters, to enable treatment administration and blood collection. Treatment, consisting of a loading dose of RDV followed by once-daily maintenance doses for 11 days, was initiated 4 days after virus exposure when all animals were exhibiting disease signs consistent with incipient EBOV disease as well as quantifiable levels of EBOV RNA in plasma. In the RDV treatment groups receiving loading/maintenance doses of 5/2.5 mg/kg, 10/5 mg/kg, and 20/10 mg/kg, a total of 6 of 8 (75%), 7 of 8 (87.5%), and 5 of 7 (71.4%) animals survived, respectively. In the vehicle control group, one of seven animals (14.3%) survived. The improved survival rate compared to the control group was statistically significant only for the 10/5 mg/kg RDV treatment group. This treatment regimen also resulted in a significantly lower systemic viral load compared to the vehicle control after a single RDV treatment. All three RDV regimens produced a significantly lower systemic viral load after two treatments. For most animals, RDV treatment, regardless of dose, resulted in the amelioration of many of the clinical–pathological changes associated with EBOV disease in this model.

Association Between Dynamic Viral Rebound and Longitudinal Measures of Viral Load/CD4 Counts Among People with HIV in South Carolina.

Monitoring HIV viral rebound (VR) is crucial, as it indicates an increased risk of infection, transmission, disease progression, and drug resistance. This study aims to identify the association between dynamic VR and historical viral load (VL)/CD4 count measures. A 15-year South Carolina population-based electronic health record data were used for the study. VR was defined as the return of detectable levels of VL (>200 copies/mL) after stable viral suppression (VS) (two consecutive VS, i.e., VL ≤200 copies/mL). A generalized linear mixed model was used to evaluate the association between dynamic VR and historical time-dependent predictors, such as nadir CD4 count and comorbidities, within a year prior to each VR. Subgroup analysis for men who have sex with men (MSM) was also conducted. Among 8,185 people with HIV (PWH), 1,173 (14.3%) had a history of VR. Lower nadir CD4 count (≥500 vs. <200 cells/μL; adjusted odds ratio [aOR]: 0.51, 95% confidence interval [CI]: [0.43, 0.60]), younger age (>60 years old vs. 18-30 years old; aOR: 0.43, 95% CI: [0.29, 0.63]), and being Black (Black vs. White; aOR: 1.58, 95% CI: [1.34, 1.85]) were associated with a higher risk of VR, while MSM (MSM vs. heterosexual; aOR: 0.81, 95% CI: [0.67, 0.96]) were associated with decreased VR risk. The rate of VR among PWH in South Carolina is significant. Within-1-year VL/CD4 test is critical for identifying PWH at risk for VR. Tailored interventions are needed for PWH at risk for VR to achieve sustained suppression and better health outcomes.

Effectiveness of riamilovir in preventing respiratory viral infection among young people from organized collectives

Aim. To evaluate the efficacy of the antiviral drug riamilovir (trade name – «Triazavirin®») for the prevention of SARS-CoV-2 infection (COVID-19) and other acute respiratory viral infections in young people from organized groups. Materials and methods. The study involved 386 individuals aged 18–22 years: 199 received riamilovir at a daily dose of 250 mg for 15 days, while 187 did not receive prophylactic drugs. For 30 days, disease occurrence was monitored among volunteers. In case of illness, the duration, severity of clinical manifestations, complications, and pathogen elimination dynamics were assessed via PCR from nasopharyngeal and oropharyngeal swabs. Results. During riamilovir administration, a statistically significant reduction in cases of acute respiratory viral infections of non-coronavirus etiology was observed, with no COVID-19 cases reported, confirmed by the absence of SARS-CoV-2 RNA in this group. The shortest duration of acute respiratory viral infections was noted in patients taking the prophylactic drug. Conclusion. Riamilovir (trade name – «Triazavirin®») showed statistically significant prophylactic efficacy during its administration in an organized group. Its use decreased the frequency of detection of viral pathogens and resulted in milder acute respiratory disease, likely due to reduced viral load in individuals.

Role of Filter-Feeding Bivalves in the Bioaccumulation and Transmission of White Spot Syndrome Virus (WSSV) in Shrimp Aquaculture Systems

White spot syndrome virus (WSSV) poses a major risk to shrimp aquaculture, and filter-feeding bivalves on shrimp farms may contribute to its persistence and transmission. This study investigated the bioaccumulation and vector potential of WSSV in Pacific oysters (Crassostrea gigas), blue mussels (Mytilus edulis), and manila clams (Venerupis philippinarum) cohabiting with WSSV-infected shrimp. Sixty individuals of each species (average shell lengths: 11.87 cm, 6.97 cm, and 5.7 cm, respectively) cohabitated with WSSV-infected shrimp (Penaeus vannamei, average body weight: 16.4 g) for 48 h. In the experiments, bivalves accumulated WSSV particles in both the gill and digestive gland tissues, with the digestive glands exhibiting higher viral load (average viral load, 3.91 × 104 copies/mg), showing that the viral concentrations in bivalve tissues are directly influenced by seawater WSSV concentrations, reaching levels sufficient to induce infection and 100% mortality in healthy shrimp using tissue homogenates. After a 168 h release period in clean water, the WSSV levels in bivalve tissues decreased below the detection thresholds, indicating reduced transmission risk. These results highlight the role of bivalves as temporary reservoirs of WSSV in aquaculture settings, with the transmission risk dependent on the viral concentration and retention period. Our findings suggest that the management of bivalve exposure in WSSV-endemic environments could improve the biosecurity of shrimp farms.

Mycobacterium tuberculosis and human immunodeficiency virus coinfection in Alagoas, Brazil: a picture from 2009 to 2019

Objective: The present study surveyed the sociodemographic characteristics of individuals affected by co-infection with Human immunodeficiency virus (HIV) and tuberculosis (TB) in Alagoas-Brazil. Methods: The study was conducted with two different databases of Sistema de Informação de Agravos e Notificação (SINAN) with cases notified between 2009 and 2019. An additional cohort of HIV infected patients from PAM Salgadinho Specialized Health Unit, Municipal Health Department of Maceió-Alagoas, Brazil was also evaluated. The data was analyzed descriptively and by statistical tests to evaluate the population profile and potential associations. Results: During the period evaluated, 14,318 cases of tuberculosis and 1,438 human immunodeficiency virus and tuberculosis co-infections were notified. Most co-infected cases were identified in men (63.13%), between 30 and 59 years old (72.53%), with incomplete primary education (27.88%), alcoholics (61.02%), and homeless (48.09%). Significant correlations suggest that death by co-infection was more common among men, population between 30 and 59 years old and with complete superior education. Also, the HIV viral load was significantly higher in the co-infected group. Conclusion: The results show the recent scenario of HIV/TB co-infection in Alagoas-Brazil, revealing a profile of social vulnerability situation and increased risk of death. These observations suggest that public health policies should be developed looking carefully at this portion of the population, to provide quality of life, less death and more adherence to TB treatment.

Cell-Cultured Influenza Vaccine Enhances IFN-γ+ T Cell and Memory T Cell Responses Following A/Victoria/2570/2019 IVR-215 (A/H1N1) Infection

Background: Influenza remains a significant public health challenge, with vaccination being a substantial way to prevent it. Cell-cultured influenza vaccines have emerged to improve on the drawbacks of egg-based vaccines, but there are few studies focusing on T cell immunity with both types of vaccines. Therefore, we studied the following 2022–2023 seasonal influenza vaccines manufactured and marketed in South Korea with a standard and high dose: cell-based (C_sd and C_hd) and egg-based (E_sd and E_hd) vaccines. Methods: Along with a saline control group, C_sd, C_hd, E_sd, and E_hd vaccines were administered to BALB/c mice, followed by a challenge with the A/Victoria/2570/2019 (H1N1) strain. Results: After the challenge, four out of five mice in the saline group died by day 7 post-infection (P.I.). None of the vaccinated groups experienced over 20% weight loss or any deaths. On day 7 P.I., the lung viral load in the saline group (mean log value of 4.17) was higher than that in the vaccinated groups, with the C_sd group showing the lowest viral load (mean log value of 3.47). The C_sd group showed a significantly high response in macrophage 1 (M1), IFN-γ+ T cells, and tissue-resident memory (TRM) T cells compared with the E_sd group on day 2 P.I. These M1, IFN-γ+ T cells, and TRM cells showed similar trends (p &lt; 0.01). In terms of humoral immunity, only the E_hd group showed HAI titers above 40 for all four strains before and after the challenge. Conclusions: The high levels of T cells in the cell-cultured vaccines suggest, pending further real-world research, that these vaccines may offer advantages.

Combined mutations in nonstructural protein 14, envelope, and membrane proteins mitigate the neuropathogenicity of SARS-CoV-2 Omicron BA.1 in K18-hACE2 mice.

Inoculation of transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) with SARS-CoV-2 often leads to a fatal brain infection. Omicron BA.1 variant, however, was found to be non-lethal in this model. Here, we systematically assessed the effect of individual mutations of Omicron BA.1 on the pathogenicity of the virus in hACE2 transgenic mice and found that combination of 5 mutations of Nsp14, E, and M of BA.1 variant significantly lowered brain viral load and reduced lethality. These results provide new insights into how SARS-CoV-2 Omicron BA.1 is attenuated.

Retention in care among people living with human immunodeficiency virus (HIV) in a low-resource setting.

This study aimed to evaluate the retention in care among a cohort of Egyptian people living with HIV (PLWHIV). The study was conducted on PLWHIV attending Kasr Alainy HIV and Viral Hepatitis Centre, Cairo, Egypt, from January 1, 2019, to March 31, 2023. PLWHIV were considered not retained in care if there was no documented clinical visit or HIV viral load (VL) or CD4 count test for more than 6 months from their last recorded visit or test. Multivariable logistic regression analysis was used to test factors associated with retention in care. After excluding those who died and were referred, 369 PLWHIV were included in the analysis, and retention in care was observed in 325 (88%). The majority were males (81.8%) with a median age of 34 [29-41] years. Undetectable VL (OR: 3.555; 95% CI: 1.49-8.47), hepatitis B vaccination (OR: 2.835; 95% CI: 1.07-7.48), CD4 test availability (OR: 2.604; 95% CI: 1.02-6.64), receiving dolutegravir based antiretroviral therapy (OR: 2.429; 95% CI: 1.06-5.537), and longer duration of know HIV infection (OR: 1.025; 95% CI: 1.01- 1.04) were correlated with retention in care. Surprisingly, higher education levels were negatively correlated with retention in care (OR: 0.195, 95%: CI: 0.071-0.533), suggesting the need for further research to explore this relationship. These results are invaluable for developing targeted interventions and informing health policies to improve retention in HIV care in Egypt. Enhancing access to VL and CD4 testing, promoting VL suppression, and focusing on specific groups at risk of dropping out of care are essential strategies.

In-Hospital Screening Campaign Against Hepatitis C Could Be Effective for Identifying More Patients Who Still Need Treatment.

Screening programmes for the detection of patients with hepatitis C virus (HCV) and positive viral load have been developed in many countries to achieve the World Health Organization's goal of HCV elimination by 2030. In Italy, a phased screening programme starting with individuals born between 1969 and 1989 has been implemented. To assess the prevalence of patients with positive viraemia identified through a universal screening campaign conducted among hospitalised patients at our centre during the calendar year 2022. All adult (aged ≥ 18 years) hospitalised patients, who participated in HCV screening from January to December 2022 were included, without any age restriction. Screening initially involved testing for anti-HCV antibodies and then patients who tested positive underwent further HCV-RNA testing. A total of 10,846 samples were collected. Five hundred and thirty cases (4.8%) tested positive for HCV antibodies, and 109 (1%) tested positive for both HCV antibodies and HCV-RNA. Among patients with a positive viral load, the median [IQR] age was 62 [53-77] years, with a significant age difference between males and females (59 [48-67] vs. 78 [62-88]; Mann-Whitney U-test, p = 0.001). Eighty-four (77%) patients with a positive viral load were outside the target age range specified in the current National Recommendations for free-of-charge screening. The non-negligible prevalence of patients with a positive viral load among an unselected group of hospitalised patients suggests that such settings could effectively enhance screening programmes aimed at HCV elimination. Additionally, this approach may help identify patients who are not currently included in the National Recommendations.

The trend of Epstein-Barr virus DNA loads and CD8+ T lymphocyte numbers can predict the prognosis of pediatric liver transplant recipients with PTLD

Abstract Objectives Epstein-Barr virus (EBV) can cause lymphoproliferative disorders (PTLD) in immunodeficiency individuals. The pathogenesis of EBV infection depends on its effective recognition and elimination. Our study investigated the effect of peripheral lymphocyte subsets (PLS) on the elimination of EBV. Methods A retrospective single-center study included 63 patients with 17 pediatric liver transplant recipients with EBV-induced PTLD (PTLD group) and 46 patients diagnosed with EBV-induced mononucleosis (IM group). Dynamic monitoring of PLS with EBV-DNA loads was performed. Results EBV-DNA replicated at a high level (5.2E3∼5.93E7 copies/mL in PBMC) before treatment in all patients in PTLD group. B lymphocytes were the main infected cells. After treatment with Rituximab, the EBV-DNA loads decreased below the lower limit of detection in 10 patients (PTLD-stable disease, PTLD-SD group), and the viral loads replicated at lower level in six patients (PTLD-partial response, PTLD-PR group). In the PTLD-SD group, the percentage of CD3+CD8+ T lymphocytes increased beyond the normal range with the ascending of EBV-DNA loads, then it decreased to the normal range accompanied by the clearance of EBV. In the PTLD-PR group, the CD3+CD8+ T lymphocytes kept in the normal range, while the EBV kept on replication. Conclusions The increased number of CD3+CD8+ T lymphocytes occurred in parallel with the decline in EBV-DNA loads, which is the most useful index in estimating the host capacity of immuno-surveillance against EBV.

A Cetylpyridinium Chloride Oral Rinse Reduces Salivary Viral Load in Randomized Controlled Trials.

Evaluating the antiviral potential of commercially available mouthrinses on SARS-CoV-2 holds potential for reducing transmission, particularly as novel variants emerge. Because SARS-CoV-2 is transmitted primarily through salivary and respiratory secretions and aerosols, strategies to reduce salivary viral burden in an antigen-agnostic manner are attractive for mitigating spread in dental, otolaryngology, and orofacial surgery clinics where patients may need to unmask. Patients (n = 128) with confirmed COVID-19-positive status within 10 days of symptom onset or positive test result were enrolled in a double-blind randomized controlled trial of Food and Drug Administration-approved mouthrinses containing active ingredients ethanol, hydrogen peroxide, povidone iodine, chlorhexidine gluconate, cetylpyridinium chloride (CPC), or saline. The CPC, ethanol, and sterile water rinses were followed in a second double-blind randomized controlled trial (n = 230). Participants provided a saliva sample before rinsing (baseline) and again at 30 and 60 min after rinse. Quantitative polymerase chain reaction was used to determine salivary SARS-CoV-2 viral load at all time points. An adjusted linear mixed-effect model was employed to compare viral load after rinsing relative to baseline. The rinse containing CPC significantly reduced salivary SARS-CoV-2 viral load 30 min postrinse relative to baseline (P = .015), whereas no other rinse significantly affected viral load at 30 min after rinsing. At 60 min postrinsing, no group had a significant reduction in SARS-CoV-2 copy number relative to baseline, indicating a rebound in salivary viral load over a 1-hour window. Participants indicated a fair to good rinsing experience with the CPC product and high willingness to use oral rinses before and during dental and medical health care visits. Our findings suggest that preprocedural oral rinsing could be implemented as a feasible, inexpensive approach to mitigate spread of SARS-CoV-2 and potentially other enveloped viruses for short periods, which is relevant to clinical procedures involving the nasal and oropharyngeal region. Rinsing with a cetylpyridinium chloride-containing mouthrinse can significantly reduce salivary SARS-CoV-2 viral load for up to 30 min; patients are willing to use mouthrinses in medical and dental settings to limit transmission risk in clinics.

Risk Factors for Viral Non-suppression Among Youth Living with HIV in Nigeria: Findings from the iCARE Nigeria Study.

Viral suppression with antiretroviral therapy (ART) is a critical component of UNAIDS objectives to end the HIV epidemic. Youth living with HIV (YLH) have worse viral suppression rates than adults. The aim of this study was to identify risk factors for viral non-suppression among YLH in Nigeria. A secondary analysis of enrollment data from the iCARE Nigeria study, collected April-October 2021 for 541 YLH comprised demographic, psychosocial, behavioral, clinical variables, and viral load quantification. Viral non-suppression was defined as viral load ≥ 200 copies/mL. Generalized linear models using Akaike information criterion for selection of indicator variables in a stepwise approach were used to determine the risk factors for viral non-suppression. The final analytic sample was 491 and the proportion of non-suppressed participants at baseline was 40%. In the final model, substance use (other than alcohol, tobacco and/or cannabis) (aOR = 3.20 [95% CI: 1.05, 10.34]), missed medication doses (aOR = 1.09 [95% CI: 1.04, 1.15]), and a higher number of self-reported medication barriers (e.g., forgot, busy, change in routine) (aOR = 1.08 [95% CI: 1.00, 1.16]) were associated with a higher likelihood of viral non-suppression. Being prescribed a first-line regimen (aOR = 0.28 [95% CI: 0.17, 0.44]), disclosure to at least one brother (aOR = 0.64 [95% CI: 0.42, 0.97]), and higher treatment outcome expectancies (e.g., taking medication will improve health) (aOR = 0.81 [95% CI: 0.66, 0.98]), were all associated with a lower likelihood of viral non-suppression. Viral non-suppression among YLH in Nigeria is associated with psychosocial and behavioral factors, including missed doses, medication barriers, treatment outcome expectancies, and disclosure, that are potential targets for intervention to achieve ART goals.