Blood Viral Load Research Articles

A mathematical model for the study of HIV/AIDS transmission with PrEP coverage increase and parameter estimation using MCMC with a Bayesian approach

In this article, we present a mathematical model for the study of HIV/AIDS considering the implementation of Pre-Exposure Prophylaxis (PrEP). As a novel element in the construction of the model, we consider the diagnosis of cases for attempting to enter the PrEP program, which allows us to study different forms of PrEP. The diagnosis of new infections helps to reduce transmission in the population because these patients are incorporated into the therapy and can achieve an undetectable viral load in blood which prevents them from infecting others. The model contains a compartment of infected persons with undetectable viral load in blood that is reached by adherence to treatment which is separated from those simply infected with the virus as they do not transmit it. Considering the structure of the model, we propose a method to study the effect of increased PrEP use and HIV incidence in a population. In the case of incidence, we took into account the stochasticity of the behavior. Besides, we find the basic reproduction number and present results that allow us to obtain the impact of the parameters associated with transmission, treatment and diagnosis on the basic reproduction number. We perform computational simulations, using demographic and HIV/AIDS data from Brazil, and utilize the Markov Chain Monte Carlo (MCMC) method with a Bayesian approach to estimate model parameters. We study two coverage increases at 25% and 35% that were selected according to the size of the Brazilian population and the daily use of PrEP. We compare the increases in coverage focused on HIV incidence, which is the number of new HIV cases infected and the number of HIV cases avoided, we conclude that by increasing PrEP coverage the incidence of HIV is reduced and the number of cases avoided increases.

Adenovirus infections: new insights for the clinical laboratory.

Since their discovery in 1953, research on human adenoviruses (HAdVs) has had diverse foci, resulted in groundbreaking discoveries, such as gene splicing, and generated powerful oncolytic constructs and expression vectors for vaccine development and gene therapy. In contrast, virologists working in this field have made relatively little progress toward the prevention and treatment of the wide spectrum of HAdV-associated diseases. The understanding of species-specific features of viral pathogenesis, or of the mechanisms underlying the establishment of latency and reactivation, is still limited. This group of viruses currently comprises 7 species, 51 serotypes, and 116 unique genotypes. This complexity manifests with a challenging pathophenotypic diversity. Some types are highly virulent, and others do not seem to cause disease in immunocompetent hosts. The assessment of viral load in blood and respiratory specimens has well-acknowledged clinical utility, but the lack of virus typing capabilities easily implementable in clinical laboratories represents a lingering major limitation to the interpretation of positive tests. Some HAdV infections do have severe consequences for both immunocompetent and immunocompromised patients, and the understanding of why this is the case will require more research. Clinical isolates and collections of positive specimens can provide unique resources to investigate the molecular bases of viral virulence and fitness and also help gather information of spatial-temporal patterns of viral circulation in susceptible communities, but they are extremely scarce. Clinical laboratories are underutilized interfaces between patients and academic scientists and have, therefore, a high potential to become valuable collaborators in research moving forward.

Quantitatively assessed blood leukocyte Epstein–Barr virus in adult HIV-infected patients

Coinfection with the human immunodeficiency virus (HIV) and Epstein–Barr virus (EBV) represents a current biomedical problem. The purpose of the study was to evaluate blood leukocyte EBV detection rate and viral load in adult HIV-infected patients. Materials and methods. There were examined blood leukocytes collected from 138 HIV(+) and 68 HIV(–) individuals aged 20–69 years. Statistical analysis was carried out differentiated according to the stages of HIV infection, the CD4+ T-lymphocyte count, and adherence to antiretroviral therapy. Results. It was shown that EBV DNA was detected significantly more often in HIV(+) vs HIV(–) individuals (70.3±3.9% and 48.5±6.1%, p = 0.008), with EBV viral load comprising 18 [5; 139] versus 2 [1; 3] copies/105 cells (р 0.001), respectively. It has been shown that the group of HIV(+) patients is heterogeneous in the frequency of EBV detection and viral load, with the peak EBV frequency (86.7±6.2%) and DNA (121 [34; 252] copies/105 cells) level observed in “naive” patients with severe immunodeficiency. Among “experienced” patients receiving therapy, the relative risk of detecting EBV DNA with low treatment adherence was significantly higher compared to those who developed high adherence (р 0.05). When the HIV viral load reached undetectable level, EBV DNA concentration was significantly lower where HIV RNA was detectable (1 [0; 8] versus 15 [1; 162] copies/105 cells, р 0.001). Detection of EBV DNA is associated with higher HIV viral load level and lower CD4+ T-lymphocyte count compared to patients with undetected EBV DNA. A relationship has been established between the CD4+ T-lymphocyte count in HIV(+) patients and the likelihood of active EBV infection. A threshold cut-off of 200 cells/μl was determined. CD4+ T-lymphocyte count 200 cells/μl vs ≥ 200 cells/μl (р 0.001) is associated with a 3.3-fold higher risk of detecting active EBV infection. Conclusion. It is necessary to continue interdisciplinary research to improve early diagnostics of EBV-associated diseases in HIV-infected individuals.

Molecular genetic characterization of hepatitis B virus in blood donors from South Vietnam

The problem of transfusion safety preventing parenteral viral hepatitis transmission remains relevant. Viral hepatitis B (HB) is the most common viral infection transmitted through transfusion procedures. One of the natural phases of a chronic viral hepatitis B (CHB) course is occult hepatitis B infection (OBI) characterized by undetectable HBsAg level (regardless of other serological marker levels) along with detected hepatic HBV DNA as well as blood viral load ranging from extremely low to undetectable. In Vietnam, prevention of transfusion-based HBV transmission is focused on donor screening; it is still based solely on HBsAg serology. As such, OBI remains a potential threat to blood transfusion safety. Assessing hepatitis B virus (HBV) DNA is a reliable preventive measure against HBV transmission from HBsAg– donors, especially in highly endemic regions. The aim of our work was HBV identification and molecular genetic characterization in blood donors from South Vietnam. The study material was presented by 500 donor serum samples. Subjects were examined for HBV markers with qualitative detection of HBsAg, HBs IgG, and HBcore IgG. Amplification and subsequent HBV sequencing were performed using nested PCR with overlapping primer pairs jointly flanking the complete HBV genome (S, P, C, X genes). Full-size HBV genome nucleotide sequences were obtained for 58 samples. Among blood donors, taking into account HBsAg+ and HBsAg– samples, HBV DNA was detected in 11.6%, including 8.6% OBI. HBV phylogenetic analysis showed genotypes B and C. Vaccine escape mutations and mutations that contribute to disease progression were identified. Current screening in Vietnam is insufficient for eliminating the risk of transfusion-transmitted HBV infection. The major risk factor is OBI. PCR testing for HBV should be considered for blood donor screening.

Assessment of blood viral load in asymptomatic and symptomatic cases of congenital cytomegalovirus infection.

This study aimed to retrospectively evaluate the baseline and follow-up viral loads and viral clearance times in cases followed for asymptomatic and symptomatic congenital cytomegalovirus (cCMV) infection between August 2010 and August 2022. Among 93 cases, they had asymptomatic (n: 55) and symptomatic (n: 38). The median baseline blood viral load detected in the symptomatic cCMV (ScCMV) infection (13 054 IU/mL) was significantly higher than that of asymptomatic cCMV (AcCMV) infection (4636 IU/mL) (p < 0.013). There was no difference in median viral clearance times (75 and 90 days, respectively) in baseline viremic cases in the ScCMV and AcCMV infection groups. There were no differences in median baseline blood viral load (6930 IU/mL and 14 268 IU/mL, respectively) and median viral clearance times (75 and 85 days, respectively) between the 6-week and 6-month antiviral treatment group. No correlation was found between baseline blood viral load, clinical severity, and the number of systems involved. However, in initial viremic cases, the viral load threshold for a symptomatic case was 8856 IU/mL, with 85.7% sensitivity and 54.5% specificity.

The relevance of ultradeep sequencing for low HIV-1 viral loads and proviruses in the clinical setting.

Improving the therapeutic management of HIV-positive persons is a major public health issue and includes better detection of drug resistance mutations (DRMs). The aim of this study was (i) to explore DRMs in HIV-1-positive persons presenting a blood viral load (VL) < 1000 genomes copies (gc)/mL, including the analyze of cerebrospinal fluid (CSF) and HIV-DNA from peripheral blood mononuclear cells using ultradeep sequencing (UDS) and (ii), to evaluate how these DRMs could influence the clinical practices. For each patient (n = 12), including five low-VL patients (i.e., <1000 gc/mL), HIV-1 UDS targeting the protease, reverse transcriptase and integrase genes was performed on plasma, proviral DNA, and CSF when available. Sequencing discordances or failures were mostly found in samples from low-VL patients. A 5% UDS cut-off allowed to increase the sensitivity to detect DRMs in different compartments, excepted in CSF. Patients with the highest viral quasispecies heterogeneity were naïve of treatment or presented a medical history suggesting low selection pressure or virological failures. When analyzing compartmentalization and following-up patients: low-frequency variants (LFVs) were responsible for 47% (n = 8) and 76% (n = 13) of changes in drug resistance interpretation, respectively. In such cases, we conclude that UDS is a robust technique, which still could be improved by increase the RNA and/or DNA extraction in low-VL samples to detect LFVs. Further studies are needed to define the impact of LFVs on antiretroviral treatments. At last, when considering a DRM, the use of mutational load would probably be more suitable than frequencies.

Antiviral activity of vitamin D derivatives against severe fever with thrombocytopenia syndrome virus in vitro and in vivo

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne virus that causes the severe fever thrombocytopenia syndrome, which manifests as fever and haemorrhage, accompanied by severe neurological complications. To date, no specific antiviral drugs have been approved for this indication. Herein, we investigated whether vitamin D derivatives inhibit SFTSV both in vitro and in vivo. An in vitro study demonstrated that vitamin D derivatives significantly suppressed viral RNA replication, plaque formation, and protein expression in a dose-dependent manner. Subsequently, in vivo studies revealed that doxercalciferol and alfacalcidol were associated with increased survival and reduced viral RNA load in the blood. Time-of-addition assay suggested that vitamin D derivatives primarily acted during the post-entry phase of SFTSV infection. However, cytopathic effect protective activity was not observed in RIG-I immunodeficient cell line Huh7.5, and the administration of vitamin D derivatives did not improve the survival rates or reduce the blood viral loads in adult A129 mice. Further transcriptome exploration into the antiviral mechanism revealed that alfacalcidol stimulates host innate immunity to exert antiviral effects. To expand the application of vitamin D derivatives, in vitro and in vivo drug combination assays were performed, which highlighted the synergistic effects of vitamin D derivatives and T-705 on SFTSV. The combination of alfacalcidol and T-705 significantly enhanced the therapeutic effects in mice. This study highlights the potential of vitamin D derivatives against SFTSV and suggests that they may have synergistic effects with other compounds used in the treatment of SFTSV infection.

Assessing the antiviral activity of antimicrobial peptides Caerin1.1 against PRRSV in Vitro and in Vivo

The Porcine reproductive and respiratory syndrome (PRRS) causes severe financial losses to the global swine industry. Due to continuous virus evolution, the protection against the PRRS provided by current vaccines is limited. In order to find new antiviral strategies, this study investigated the antiviral potential of antimicrobial peptides (AMPs) against PRRSV. Given the diversity of PRRSV strains and the limited effectiveness of existing vaccines in controlling PRRSV, this study evaluated the inhibitory effects of KLAK, Cecropin B, Piscidin1, and Caerin1.1 on 3 strains of PRRSV (lineage 5 classical strain, lineage 8 highly pathogenic strain, and lineage 1 NADC30-like strain). Caerin1.1 exhibited significant dose-dependent antiviral activity, with an effective concentration (EC50) of 7.5 μM. Caerin1.1 effectively inhibited PRRSV replication when added before or in early infection but showed reduced effectiveness when added in late infection, indicating its potential involvement in targeting early transcription mechanisms of viral RNA polymerase and significantly upregulating cytokine gene expression. In the NADC30 strain-based animal infection model, Caerin1.1 treatment significantly reduced lung viral loads and inflammation in the lungs of PRRSV-infected pigs, with a mortality rate of 0 % (0/5) in the treated group compared to 66.67 % (4/6) in the untreated group, indicating a reduction in the mortality rate. Additionally, compared with the untreated group, the Caerin1.1-treated group showed significant improvements, such as lighter fever, more daily weight gain, less clinical symptoms, less viral load in blood, and less virus oral shedding (P < 0.05). These findings reveal the potential of antimicrobial peptides as PRRSV therapeutic agents and suggest that Caerin1.1 is a promising candidate for a novel anti-PRRSV drug.

Histopathologic evaluation system of African swine fever in wild boar infected with high (Arm07) and low virulence (Lv17/WB/Riel) isolates.

To understand the clinicopathological forms of African swine fever (ASF) in wild boar, it is crucial to possess a basic knowledge of the biological characteristics of the currently circulating ASF virus isolates. The aim of this work is to establish an accurate and comprehensive histopathologic grading system to standardize the assessment of the ASF lesions in wild boar. The study evaluated the differences between animals infected with a high virulence genotype II isolate (Arm07) (HVI) through intramuscular (IM) (n = 6) and contact-infected (n = 12) routes, alongside those orally infected with a low virulence isolate (Lv17/WB/Riel) (LVI) (n = 6). The assessment included clinical (CS), macroscopic (MS), and histopathologic (HS) scores, as well as viral loads in blood and tissues by real-time quantitative polymerase chain reaction (qPCR). Tissues examined included skin, lymph nodes, bone marrow, palatine tonsil, lungs, spleen, liver, kidneys, thymus, heart, adrenal glands, pancreas, urinary bladder, brain, and gastrointestinal and reproductive tracts. The HVI group exhibited a 100% mortality rate with elevated CS, MS, and HS values. Animals infected by contact (CS = 12; MS = 58.5; HS = 112) and those intramuscularly infected (CS = 14.8; MS = 47; HS = 104) demonstrated similar values, indicating that the route of infection does not decisively influence the severity of clinical and pathological signs. The LVI group showed a 0% mortality rate, an inconspicuous clinical form, minimal lesions (CS = 0; MS = 12; HS = 29), and a lower viral load. Histopathologic evaluation has proven valuable in advancing our comprehension of ASF pathogenesis in wild boar and paves the groundwork for further research investigating protective mechanisms in vaccinated animals.

Short Treatment of 42 Days with Oral GS-441524 Results in Equal Efficacy as the Recommended 84-Day Treatment in Cats Suffering from Feline Infectious Peritonitis with Effusion-A Prospective Randomized Controlled Study.

In the past, feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) was considered fatal. Today, highly efficient drugs, such as GS-441524, can lead to complete remission. The currently recommended treatment duration in the veterinary literature is 84 days. This prospective randomized controlled treatment study aimed to evaluate whether a shorter treatment duration of 42 days with oral GS-441524 obtained from a licensed pharmacy is equally effective compared to the 84-day regimen. Forty cats with FIP with effusion were prospectively included and randomized to receive 15 mg/kg of GS-441524 orally every 24h (q24h), for either 42 or 84 days. Cats were followed for 168 days after treatment initiation. With the exception of two cats that died during the treatment, 38 cats (19 in short, 19 in long treatment group) recovered with rapid improvement of clinical and laboratory parameters as well as a remarkable reduction in viral loads in blood and effusion. Orally administered GS-441524 given as a short treatment was highly effective in curing FIP without causing serious adverse effects. All cats that completed the short treatment course successfully were still in complete remission on day 168. Therefore, a shorter treatment duration of 42 days GS-441524 15 mg/kg can be considered equally effective.

Importance of sequential infection order of porcine circovirus type 2 and porcine reproductive and respiratory syndrome virus to divergent clinical outcomes

This study was designed to investigate the different sequential order of infection for porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV). Thirty-six pigs were randomly assigned to six different treatment groups. The first (hereafter referred to as PRRSV-PCV2) group was inoculated with PRRSV first followed by PCV2d. The second (hereafter referred to as PCV2+PRRSV) group was co-infected with both viruses at the same timepoint (42 days of age). The third (hereafter referred to as PCV2-PRRSV) group was inoculated with PCV2d first followed by PRRSV. A fourth group was only inoculated with PCV2d at 42 days of age, while a fifth group was only inoculated with PRRSV at the same timepoint. The sixth group served as a negative control group. The most important observation discovered that PRRSV only had a potentiation effect on PCV2 in both PRRS-PCV2 and PCV2+PRRSV groups. Both PRRSV-PCV2 and PCV2+PRRSV groups experienced a significant reduction in growth performance compared with control pigs. In addition, PRRSV-PCV2 and PCV2+PRRSV groups exhibited a greater severity in their clinical signs, and/or had higher PCV2 blood and lymphoid viral loads that resulted in a stronger severity of lymphoid lesions compared with PCV2-PRRSV group. Serum TNF-α levels were significantly higher in both PRRS-PCV2 and PCV2+PRRSV groups compared with those in PCV2-PRRS, PCV2, and PRRSV groups. The results of this study demonstrated that divergent clinical outcomes are dependent on the sequential infection order of PCV2 and PRRSV.

Lower Neutrophil Count Without Clinical Consequence Among Children of African Ancestry Living With HIV in Canada.

To investigate the association between African ancestry and neutrophil counts among children living with HIV (CLWH). We also examined whether medications, clinical conditions, hospitalization, or HIV virologic control were associated with low neutrophil counts or African ancestry. We conducted a secondary analysis of the Early Pediatric Initiation Canada Child Cure Cohort (EPIC4) Study, a multicenter prospective cohort study of CLWH across 8 Canadian pediatric HIV care centers. We classified CLWH according to African ancestry, defined as "African," "Caribbean," or "Black" maternal race. Longitudinal laboratory data (white blood cells, neutrophils, lymphocytes, viral load, and CD4 count) and clinical data (hospitalizations, AIDS-defining conditions, and treatments) were abstracted from medical records. Among 217 CLWH (median age 14, 55% female), 145 were of African ancestry and 72 were of non-African ancestry. African ancestry was associated with lower neutrophil counts, white blood cell counts, and neutrophil-lymphocyte ratios. Neutrophil count <1.5 × 109/L was detected in 60% of CLWH of African ancestry, compared with 31% of CLWH of non-African ancestry (P < 0.0001), representing a 2.0-fold higher relative frequency (95% CI: 1.4-2.9). Neutrophil count was on average 0.74 × 109/L (95% CI: 0.45 to 1.0) lower in CLWH of African ancestry (P < 0.0001). Neither neutrophil count<1.5 × 109/L nor African ancestry was associated with medications, hospitalizations, AIDS-defining conditions, or markers of virologic control (viral load, sustained viral suppression, and lifetime nadir CD4). In CLWH, African ancestry is associated with lower neutrophil counts, without clinical consequences. A flexible evaluation of neutrophil counts in CLWH of African ancestry may avoid unnecessary interventions.

Enterovirus A71 crosses a human blood-brain barrier model through infected immune cells.

Enterovirus A71 (EV-A71) is associated with neurological conditions such as acute meningitis and encephalitis. The virus is detected in the bloodstream, and high blood viral loads are associated with central nervous system (CNS) manifestations. We used an in vitro blood-brain barrier (BBB) model made up of human brain-like endothelial cells (hBLECs) and brain pericytes grown in transwell systems to investigate whether three genetically distinct EV-A71 strains (subgenogroups C1, C1-like, and C4) can cross the human BBB. EV-A71 poorly replicated in hBLECs, which released moderate amounts of infectious viruses from their luminal side and trace amounts of infectious viruses from their basolateral side. The barrier properties of hBLECs were not impaired by EV-A71 infection. We investigated the passage through hBLECs of EV-A71-infected white blood cells. EV-A71 strains efficiently replicated in immune cells, including monocytes, neutrophils, and NK/T cells. Attachment to hBLECs of immune cells infected with the C1-like virus was higher than attachment of cells infected with C1-06. EV-A71 infection did not impair the transmigration of immune cells through hBLECs. Overall, EV-A71 targets different white blood cell populations that have the potential to be used as a Trojan horse to cross hBLECs more efficiently than cell-free EV-A71 particles.IMPORTANCEEnterovirus A71 (EV-A71) was first reported in the USA, and numerous outbreaks have since occurred in Asia and Europe. EV-A71 re-emerged as a new multirecombinant strain in 2015 in Europe and is now widespread. The virus causes hand-foot-and-mouth disease in young children and is involved in nervous system infections. How the virus spreads to the nervous system is unclear. We investigated whether white blood cells could be infected by EV-A71 and transmit it across human endothelial cells mimicking the blood-brain barrier protecting the brain from adverse effects. We found that endothelial cells provide a strong roadblock to prevent the passage of free virus particles but allow the migration of infected immune cells, including monocytes, neutrophils, and NK/T cells. Our data are consistent with the potential role of immune cells in the pathogenesis of EV-A71 infections by spreading the virus in the blood and across the human blood-brain barrier.

Synergy of Subgroup J Avian Leukosis Virus and Chicken Infectious Anemia Virus Enhances the Pathogenicity in Chickens.

Subgroup J avian leukemia virus (ALV-J) and chicken infectious anemia virus (CIAV) are widely acknowledged as significant immunosuppressive pathogens that commonly co-infect chickens, causing substantial economic losses in the poultry industry. However, whether co-infection of ALV-J and CIAV have synergistic pathogenicity remains uncertain. To explore their synergistic pathogenesis, we established a co-infection model of ALV-J and CIAV in HD11 cells and specific-pathogen-free (SPF) chickens. We discovered that ALV-J and CIAV can synergistically promote the secretion of IL-6, IL-10, IFN-α, and IFN-γ and apoptosis in HD11 cells. In vivo, compared to the ALV-J and CIAV mono-infected group, the mortality increased significantly by 27% (20 to 47%) and 14% (33 to 47%) in the co-infected group, respectively. We also discovered that ALV-J and CIAV synergistically inhibited weight gain and exhibited more severe organ damage in co-infected chickens. Furthermore, we found that CIAV can promote the replication of ALV-J in HD11 cells and significantly enhance ALV-J viral load in blood and tissues of co-infected chickens, but ALV-J cannot promote the replication of CIAV. Moreover, by measuring the immune organ indexes and proportions of blood CD3+CD4+ and CD3+CD8+ lymphocytes, more serious instances of immunosuppression were observed in ALV-J and CIAV co-infected chickens than in mono-infected chickens. Taken together, our findings demonstrate that ALV-J and CIAV synergistically enhance pathogenicity and immunosuppression.

Cerebrospinal Fluid Viral Escape on Highly Active Antiretroviral Therapy: Analysis from Single Tertiary Care Centre.

HIV-infected individuals receiving regular antiretroviral therapy (ART) can present with a high viral load in cerebrospinal fluid (CSF) at times when it is suppressed in blood. This study presents data of HIV-infected patients who had undetectable or low plasma viral load in blood but presented with neurological signs and symptoms and were diagnosed to have CSF HIV viral escape. Records were reviewed for clinical manifestations, details of opportunistic or coinfection, and HIV viral copies in plasma and CSF at time of diagnosis of CSF escape. A total of 10,200 HIV-infected individuals were registered in HIV care till December 31, 2021. Nineteen individuals (14 virologically confirmed and 5 clinically) were diagnosed with high viral copies in CSF from June 2014 to December 2021. Mean age was 41.5 ± 9.2 (median, 39.5; range, 30-62) years. Average duration of antiretroviral treatment received at the time of diagnosis of CSF escape was 10.1 years. Median plasma HIV-viral copies were 2,469.8 (undetectable to 29,418) and in CSF were 12,773.7 (n = 14, range, 1,340-48,530) copies/mL. HIV viral copies in CSF were significantly higher than in plasma at the time of presentation (p = .003). ART regimen switch was done after identification of HIV CSF escape. Seventeen patients were alive with a regular follow-up of average 35 (range 7-66) months. All had documented clinical improvement with reversal of neurological impairment after ART switch. There was one death and one lost to follow-up. Early identification and timely intervention in CSF viral escape could revert severe neurological impairment and improves treatment outcome.

Divergent clinical outcomes depending on the sequential infection order of porcine circovirus type 2 and Mycoplasma hyopneumoniae

This study compared the different sequential order of infection of porcine circovirus type 2d (PCV2d) and Mycoplasma hyopneumoniae. Thirty-six pigs were allocated randomly across six different groups. Pigs underwent various inoculation sequences: M. hyopneumoniae administered 14 days before PCV2d, simultaneous PCV2d-M. hyopneumoniae, PCV2d given 14 days before M. hyopneumoniae, PCV2d only, M. hyopneumoniae only, or a mock inoculum. Overall, the pigs inoculated with M. hyopneumoniae 14 days prior to PCV2d (Mhyo-PCV2 group) and those inoculated simultaneously with PCV2d and M. hyopneumoniae (PCV2+Mhyo group) displayed notably higher clinical disease severity and experienced a significant decrease of their average daily weight gain than pigs inoculated with PCV2d 14 days prior to M. hyopneumoniae (PCV2-Mhyo group). M. hyopneumoniae infection potentiated PCV2 blood and lymph node viral loads, as well as PCV2-associated lesions, while the infection of PCV2d did not impact the intensity of M. hyopneumoniae infection. Tumor necrosis factor-α (TNF-α) sera levels were significantly increased in the Mhyo-PCV2 and PCV2+Mhyo groups as compared to the PCV2-Mhyo, PCV2, and Mhyo groups. The most important information was that the potentiation effect of M. hyopneumoniae on PCV2d was found only in pigs inoculated with either M. hyopneumoniae followed by PCV2d (Mhyo-PCV2 group) or a simultaneous inoculation of PCV2d and M. hyopneumoniae (PCV2+Mhyo group). The sequential infection order of PCV2d and M. hyopneumoniae resulted in divergent clinical outcomes.

Evaluation of tear film in patients with AIDS without opportunistic ocular infections in the era of COVID-19: A case-control study.

The assessment of tear film and ocular surface conditions in patients with acquired immunodeficiency syndrome (AIDS) has been poorly studied thus far. We aim to assess tear film parameters, ocular surface characteristics, and dry eye disease (DED) symptoms of patients with AIDS who did not undergo highly active antiretroviral treatment (HAART). This case-control study included 154 age-, sex-, and ethnicity-matched healthy controls and patients with AIDS. All participants underwent comprehensive ocular surface assessment and subjective DED symptomology evaluation. Data were collected between March 2022 and July 2022. HAART-naïve patients with AIDS had a shorter noninvasive tear film breakup time (median 3.76 vs. 8.54 s), thinner tear film lipid layer thickness (median 73.00 vs. 91.00 nm), and lower Schirmer I test values (median 5.00 mm/5 min vs. 12.00 mm/5 min) (all P < 0.001). Moreover, higher corneal fluorescein staining scores (median 1.00 vs. 0.00) and higher upper, lower, and total meibomian gland grades were observed in AIDS patients (all P < 0.05). Negative correlations between the blood viral load and the Ocular Surface Disease Index score ( r = -3.50, P = 0.027) and the Schirmer I test score ( r = -0.374, P = 0.017) were detected in patients with AIDS. Altered tear film status was observed in individuals with HAART-naïve AIDS, even when there were no other ocular symptoms present. Therefore, patients with AIDS should be encouraged to undergo comprehensive ocular surface examinations to detect any subclinical tear film alterations occurring.

Oral Valganciclovir Initiated Beyond 1 Month of Age as Treatment of Sensorineural Hearing Loss Caused by Congenital Cytomegalovirus Infection: A Randomized Clinical Trial

ObjectiveTo determine if valganciclovir initiated after 1 month of age improves congenital cytomegalovirus (cCMV(-associated sensorineural hearing loss (SNHL). Study designWe conducted a randomized, double-blind, placebo-controlled phase 2 trial of 6 weeks of oral valganciclovir at United States (n=12) and United Kingdom (n=9) sites. Patients ages1 month through 3 years with baseline SNHL were enrolled. The primary outcome was change in total ear hearing between baseline and study month 6. Secondary outcome measures included change in best ear hearing and reduction in CMV viral load in blood, saliva, and urine. ResultsOf 54 participants enrolled, 35 were documented to have cCMV infection and were randomized (active group: 17; placebo group: 18). Mean age at enrollment was 17.8 ± 15.8 months (valganciclovir) versus 19.5 ± 13.1 months (placebo). Twenty (76.9%) of the 26 ears from subjects in the active treatment group did not have worsening of hearing, compared with 27 (96.4%) of 28 ears from subjects in the placebo group (p= 0.09). All other comparisons of total ear or best ear hearing outcomes were also not statistically significant. Saliva and urine viral loads decreased significantly in the valganciclovir group but did not correlate with change in hearing outcome. ConclusionsIn this randomized controlled trial, initiation of antiviral therapy beyond the first month of age did not improve hearing outcomes in children with cCMV-associated SNHL.

Cytomegalovirus detection is associated with ICU admission in non-AIDS and AIDS patients with Pneumocystis jirovecii pneumonia.

Cytomegalovirus (CMV) is frequently detected in lung and/or blood samples of patients with Pneumocystis jirovecii pneumonia (PJP), although this co-detection is not precisely understood. We aimed to determine whether PJP was more severe in case of CMV detection. We retrospectively included all patients with a diagnosis of PJP between 2009 and 2020 in our centre and with a measure of CMV viral load in blood and/or bronchoalveolar lavage (BAL). PJP severity was assessed by the requirement for intensive care unit (ICU) admission. The median age of the 249 patients was 63 [IQR: 53-73] years. The main conditions were haematological malignancies (44.2%), solid organ transplantations (16.5%), and solid organ cancers (8.8%). Overall, 36.5% patients were admitted to ICU. CMV was detected in BAL in 57/227 patients; the 37 patients with viral load ≥3 log copies/mL were more frequently admitted to ICU (78.4% vs 28.4%, p<0.001). CMV was also detected in blood in 57/194 patients; the 48 patients with viral load ≥3 log copies/mL were more frequently admitted to ICU (68.7% vs 29.4%, p<0.001). ICU admission rate was found to increase with each log of BAL CMV viral load and each log of blood CMV viral load. PJP is more severe in the case of concomitant CMV detection. This may reflect either the deleterious role of CMV itself, which may require antiviral therapy, or the fact that patients with CMV reactivation are even more immunocompromised.

Risk Factors Associated with Opportunistic Infections among People Living with HIV/AIDS and Receiving an Antiretroviral Therapy in Gabon, Central Africa.

The Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) is still one of the main causes of death in sub-Saharan Africa. Antiretroviral therapies (ARTs) have significantly improved the health conditions of people living with HIV/AIDS (PLWHA). Consequently, a significant drop in morbidity and mortality, along with a reduced incidence of opportunistic infections (OIs), has been observed. However, certain atypical and biological profiles emerge in ART patients post-examination. The objective of this study was to identify the risk factors that contributed to the onset of OIs in HIV patients undergoing ART in Gabon. Epidemiological and biological data were obtained from medical records (2017 to 2019) found at the outpatient treatment centre (CTA) of Franceville in Gabon. Samples for blood count, CD4, and viral load analysis at CIRMF were collected from PLWHA suffering from other pathogen-induced conditions. A survey was carried out and data were analysed using Rstudio 4.0.2 and Excel 2007 software. Biological and socio-demographic characteristics were examined concerning OIs through both a univariate analysis via Fisher's exact tests or chi2 (χ2), and a multivariate analysis via logistic regression. Out of the 300 participants initially selected, 223 were included in the study, including 154 (69.05%) women and 69 (30.95%) men. The mean age was 40 (38.6; 41.85), with individuals ranging from 2 to 77 years old. The study cohort was classified into five age groups (2 to 12, 20 to 29, 30 to 39, 40 to 49, and 50 to 77 years old), among which the groups aged 30 to 39 and 40 to 49 emerged as the largest, comprising 68 (30.5%) and 75 (33.6%) participants, respectively. It was noted that 57.9% of PLWHA had developed OIs and three subgroups were distinguished, with parasitic, viral, and bacterial infections present in 18%, 39.7%, and 55.4% of cases, respectively. There was a correlation between being male and having a low CD4 T-cell count and the onset of OIs. The study revealed a high overall prevalence of OIs, and extending the study to other regions of Gabon would yield a better understanding of the risk factors associated with the onset of these infections.