Herpes DNAemia and TTV Viraemia in Intensive Care Unit Critically Ill Patients: A Single-Centre Prospective Longitudinal Study.Frontiers in Immunology 2021We analysed blood DNAemia of TTV and four herpesviruses (CMV, EBV, HHV6, and HSV-1) in the REAnimation Low Immune Status Marker (REALISM) cohort of critically ill...
We analysed blood DNAemia of TTV and four herpesviruses (CMV, EBV, HHV6, and HSV-1) in the REAnimation Low Immune Status Marker (REALISM) cohort of critically ill patients who had presented with either sepsis, burns, severe trauma, or major surgery. The aim was to identify common features related to virus and injury-associated pathologies and specific features linking one or several viruses to a particular pathological context.
Overall and individual viral DNAemia were measured over a month using quantitative PCR assays from the 377 patients in the REALISM cohort. These patients were characterised by clinical outcomes [severity scores, mortality, Intensive Care Unit (ICU)-acquired infection (IAI)] and 48 parameters defining their host response after injury (cell populations, immune functional assays, and biomarkers). Association between viraemic event and clinical outcomes or immune markers was assessed using χ-test or exact Fisher's test for qualitative variables and Wilcoxon test for continuous variables.
The cumulative incidence of viral DNAemia increased from below 4% at ICU admission to 35% for each herpesvirus during the first month. EBV, HSV1, HHV6, and CMV were detected in 18%, 12%, 10%, and 9% of patients, respectively. The incidence of high TTV viraemia (>10,000 copies/ml) increased from 11% to 15% during the same period. Herpesvirus viraemia was associated with severity at admission; CMV and HHV6 viraemia correlated with mortality during the first week and over the month. The presence of individual herpesvirus during the first month was significantly associated (p < 0.001) with the occurrence of IAI, whilst herpesvirus DNAemia coupled with high TTV viraemia during the very first week was associated with IAI. Herpesvirus viraemia was associated with a lasting exacerbated host immune response, with concurrent profound immune suppression and hyper inflammation, and delayed return to immune homeostasis. The percentage of patients presenting with herpesvirus DNAemia was significantly higher in sepsis than in all other groups. Primary infection in the hospital and high IL10 levels might favour EBV and CMV reactivation.
In this cohort of ICU patients, phenotypic differences were observed between TTV and herpesviruses DNAemia. The higher prevalence of herpesvirus DNAemia in sepsis hints at further studies that may enable a better understanding of host determinants of herpesvirus viral reactivation. Furthermore, our data suggest that EBV and TTV may be useful as additional markers to predict clinical deterioration in ICU patients.
Topics: Adult; Aged; Critical Illness; DNA Virus Infections; Female; Herpesviridae; Herpesviridae Infections; Hospital Mortality; Humans; Intensive Care Units; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Shock, Septic; Torque teno virus; Viremia
Comparison of cumulative viraemia following treatment initiation with different antiretroviral regimens: a real-life study in Brazil.Journal of the International AIDS... Nov 2019The relative efficacy of different antiretroviral (ART) regimens has been extensively evaluated in the context of clinical trials, using HIV viral load (VL) measurements...
The relative efficacy of different antiretroviral (ART) regimens has been extensively evaluated in the context of clinical trials, using HIV viral load (VL) measurements at pre-specified timepoints after ART onset. However, data from real-life studies using combined longitudinal measurements of cumulative viraemia are scarce. This study aimed to address the independent effect of different ART regimens on HIV cumulative viraemia over the first 12 months after treatment initiation, using programmatic data from the Ministry of Health of Brazil.
Retrospective cohort study analysing cumulative viraemia under the most frequently used ART regimens in Brazil (tenofovir, lamivudine and dolutegravir (regimen 1); tenofovir, lamivudine and efavirenz (regimen 2); tenofovir, lamivudine and ritonavir-boosted atazanavir (regimen 3)).
RESULTS AND DISCUSSION
We included 112,243 patients >12 years old who received their first ART prescription between January 2014 and August 2017. Univariate analysis indicated that cumulative viraemia was significantly lower in patients receiving regimen 1 as compared with those receiving regimens 2 or 3 (p<0.0001 for both pairwise comparisons). In a multivariable analysis adjusted for age, sex, baseline T CD4+ counts and baseline HIV VL, ART regimen persisted with statistically significant effect on 12-month cumulative viraemia. The model predicted a 45-unit increase in log copy-days/mL cumulative viraemia for regimen 2 as compared with regimen 1, and a 70-unit increase in log copy-days/mL cumulative viraemia for regimen 3 as compared with regimen 1 (95%CI 41 to 49 and 61 to 79 respectively; p<0.001 for both comparisons). In models restricted to youths (13 to 24 years old) and female patients, ART regimen had similar effects. ART regimen with dolutegravir in association with a tenofovir-lamivudine backbone was superior to regimens containing efavirenz or boosted atazanavir in reducing HIV VL, as shown by cumulative viraemia over the first 12 months after treatment initiation. The superiority persisted even after adjusting the analysis for potential confounders.
Our findings could bring direct benefits to patients as suggested by lower viral replication during treatment, lower risk of HIV transmission, and a potential reduction in resistance mutations in the initial 12 months under ART.
Topics: Adolescent; Adult; Anti-HIV Agents; Anti-Retroviral Agents; Brazil; CD4 Lymphocyte Count; Child; Cohort Studies; Female; HIV Infections; HIV-1; Humans; Male; Middle Aged; Retrospective Studies; Viremia; Young Adult
Persistent Hepatitis B Viraemia with Polymerase Mutations among HIV/HBV Co-Infected Patients on HBV-Active ART in KwaZulu-Natal, South Africa.Viruses Apr 2022To understand the problem of persistent Hepatitis B virus (HBV) viraemia in HIV/HBV co-infected patients on HBV-active antiretroviral therapy (ART), we assessed the rate...
To understand the problem of persistent Hepatitis B virus (HBV) viraemia in HIV/HBV co-infected patients on HBV-active antiretroviral therapy (ART), we assessed the rate of HBV virological response in patients on HBV-active ART in KwaZulu-Natal, South Africa, and analysed factors associated with persistent HBV viraemia. One hundred and fifty eligible participants with a chronic HBV diagnosis, with or without HIV coinfection, were enrolled and followed up after 6 months. The HBV pol gene was sequenced by next-generation sequencing and mutations were determined using the Stanford HBVseq database. Logistic regression analysis was used to assess factors associated with HBV viraemia at 6-month follow-up. The mean duration of HBV-active ART was 24 months. Thirty-seven of one hundred and six (35%) participants receiving HBV-active ART for longer than 6 months had virological failure. Advanced immunosuppression with CD4+ cell counts <200 cells/μL was independently associated with persistent HBV viraemia, aOR 5.276 (95% CI 1.575-17.670) = 0.007. A high proportion of patients on HBV-active ART are unsuppressed, which will ultimately have an impact on global elimination goals. Better monitoring should be implemented, especially in HIV-coinfected patients with low CD4+ cell counts and followed by early HBV drug-resistance testing.
Topics: Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Coinfection; DNA, Viral; HIV Infections; Hepatitis B; Hepatitis B virus; Humans; Mutation; South Africa; Viral Load; Viral Replicase Complex Proteins; Viremia
Assessment of prevalence and load of torquetenovirus viraemia in a large cohort of healthy blood donors.Clinical Microbiology and Infection :... Oct 2020Torquetenovirus (TTV) is an emerging marker of functional immune competence with the potential to predict transplant-related adverse events. A large-scale...
Torquetenovirus (TTV) is an emerging marker of functional immune competence with the potential to predict transplant-related adverse events. A large-scale epidemiological study was performed to understand how basal values vary in healthy individuals according to age and gender.
We tested plasma from 1017 healthy blood donors aged 18-69 years. The presence and load of TTV were determined by a real-time PCR assay. A sub-cohort of 384 donors was tested for anti-cytomegalovirus IgG antibodies, and 100 participants were also tested for TTV viraemia on a paired whole blood sample.
The overall prevalence of TTV was 65% (657/1017) with a mean (±SD) growth of 5 ± 4% every 10 years of age increase, but stably higher in males (465/690, 67%) than in females (192/327, 59%). Mean (±SD) TTV load was 2.3 ± 0.7 Log copies/mL with no sex difference. TTV viraemia showed modest increases along 10-year age intervals (mean ± SD: 0.3 ± 0.1). TTV viraemia in donors sampled 2 years later remained stable (mean ± SD: 2.3 ± 0.8 versus 2.2 ± 0.7 Log copies between samples). Twenty-six per cent (9/34) of blood donors with TTV-negative plasma scored positive when whole blood was tested, and the donors with positive plasma showed a mean (±SD) 1.4 ± 0.5 Log increase in copy numbers when whole blood was tested.
This study establishes the mean value of TTV viraemia in plasma in healthy blood donors and suggests that ageing causes only minimal increases in TTV viraemia.
Topics: Adolescent; Adult; Aged; Aging; Blood Donors; Blood Transfusion; DNA Virus Infections; DNA, Viral; Female; Healthy Volunteers; Humans; Male; Middle Aged; Plasma; Real-Time Polymerase Chain Reaction; Torque teno virus; Viral Load; Viremia; Young Adult
Cytomegalovirus viraemia and mortality in renal transplant recipients in the era of antiviral prophylaxis. Lessons from the western Australian experience.BMC Infectious Diseases Jul 2017Cytomegalovirus (CMV) establishes a lifelong infection that is efficiently controlled by the immune system; this infection can be reactivated in case of...
Cytomegalovirus (CMV) establishes a lifelong infection that is efficiently controlled by the immune system; this infection can be reactivated in case of immunosuppression such as following solid organ transplantation. CMV viraemia has been associated with CMV disease, as well as increased mortality and allograft failure. Prophylactic antiviral medication is routinely given to renal transplant recipients, but reactivation during and following cessation of antiviral prophylaxis is known to occur. The aims of this study were to assess the incidence, timing and impact of CMV viraemia in renal transplant recipients and to determine the level of viraemia associated with adverse clinical outcomes.
Data from all adult (18 years and over) Western Australian renal transplant recipients transplanted between 1 January 2007 and 31 December 2012 were obtained from the Australia and New Zealand Dialysis and Transplant registry and were supplemented with data obtained from clinical records. Potential risk factors for detectable CMV viraemia (≥600 copies/ml) and all-cause mortality were assessed using univariable analysis and Cox Proportional Hazards Regression.
There were 438 transplants performed on 435 recipients. The following factors increased the risk of CMV viraemia with viral loads ≥600 copies/ml: Donor positive/Recipient negative status; receiving a graft from a deceased donor; and receiving a graft from a donor aged 60 years and over. CMV viraemia with viral loads ≥656 copies/ml was a risk factor for death following renal transplantation, as was being aged 65 years and above at transplant, being Aboriginal and having vascular disease. Importantly 37% of the episodes of CMV viraemia with viral loads ≥656 copies/ml occurred while the patients were expected to be on CMV prophylaxis.
CMV viraemia (≥656 copies/ml) was associated with all-cause mortality in multivariable analysis, and CMV viraemia at ≥656 copies/ml commonly occurred during the period when renal transplant recipients were expected to be on antiviral prophylaxis. A greater vigilance in monitoring CMV levels if antiviral prophylaxis is stopped prematurely or poor patient compliance is suspected could protect some renal transplant recipients from adverse outcomes such as premature mortality.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Australia; Cytomegalovirus Infections; Female; Humans; Incidence; Kidney Transplantation; Male; Middle Aged; New Zealand; Risk Factors; Tissue Donors; Transplant Recipients; Transplantation, Homologous; Viral Load; Viremia; Young Adult
Examination of viraemia and clinical signs after challenge with a heterologous PRRSV strain in PRRS Type 2 MLV vaccinated pigs: A challenge-dose study.PloS One 2018Vaccination with porcine reproductive and respiratory syndrome (PRRS) Type 2 modified-live vaccines (MLVs) has been shown to improve clinical signs and survival rates in...
Vaccination with porcine reproductive and respiratory syndrome (PRRS) Type 2 modified-live vaccines (MLVs) has been shown to improve clinical signs and survival rates in PRRS virus (PRRSV)-challenged pigs. This study evaluated the dose of PRRSV challenge needed to cause and maintain viraemia in PRRS Type 2 MLV-vaccinated pigs and assessed clinical responses to various doses of virulent challenge. This controlled, randomised, blinded vaccination-challenge study involved 95 pigs who were either vaccinated with 2 mL of a PRRS Type 2 MLV on Day 0 or left unvaccinated. On Day 28, pigs were challenged intranasally with virulent PRRSV isolate (dose range <1.5 to 4 log10 50% tissue culture infectious dose/mL). Five pigs were left unchallenged and served as environmental controls. Viraemia levels, pyrexia, average daily weight gain and clinical signs were assessed. At all challenge doses, vaccinated groups had reduced viraemia levels and clinical signs, and higher average daily weight gain compared with non-vaccinated groups. Vaccinated groups challenged with ≤2 log had similar viraemia levels and clinical performance (days pyrexic and average daily weight gain) as the non-challenged group. Vaccinated groups had significantly reduced pyrexic days compared with non-vaccinated groups across all challenge doses (P <.05). Vaccinated pigs challenged with <3 log had significantly improved average daily weight gain (P <.05). In vaccinated groups, challenge dose correlated positively with viraemia levels and number of days pyrexic, and negatively with average daily weight gain. This is the first study to use a challenge-dose model to evaluate the efficacy of vaccination against PRRSV. PRRS Type 2 MLV was shown to mitigate the consequences of PRRSV infection at all evaluated PRRSV challenge doses. Lower levels of challenge had minimal impact on health and performance of vaccinated pigs, supporting the benefit of vaccinating swine with PRRS Type 2 MLV.
Topics: Administration, Intranasal; Animals; Antibodies, Viral; Porcine Reproductive and Respiratory Syndrome; Porcine respiratory and reproductive syndrome virus; Random Allocation; Swine; Viral Vaccines; Viremia
Patterns of detectable viraemia among children and adults with HIV infection taking antiretroviral therapy in Zimbabwe.International Journal of Infectious... Jan 2019To investigate the incidence and predictors of viraemia among individuals on antiretroviral therapy (ART) in Harare, Zimbabwe.
To investigate the incidence and predictors of viraemia among individuals on antiretroviral therapy (ART) in Harare, Zimbabwe.
Children (0-19 years) and adults (>19 years) starting ART between 2013 and 2015 were followed for a median of 2.8 and 2.7 years, respectively. The incidence rates of virological failure (VF), low-level viraemia (LLV), and viral blips were assessed and the predictors of viraemia were determined using logistic and parametric survival regression analyses.
A total of 630 individuals initiated ART, and 19.7% of children and 5.6% of adults did not achieve viral suppression by 12 months. Younger age and CD4 count ≤200 cells/mm at baseline were associated with not being virally suppressed at 12 months in adults. Among those who achieved viral suppression during the follow-up period, the incidence of VF was higher in children (4.0/100 person-years vs. 0.4/100 person-years in adults; p<0.001), as was the incidence of LLV (1.9/100 person-years vs. 0.3/100 person-years in adults; p=0.03). The incidence rate of blips was 10.9 per 100 person-years in children and 4.0 per 100 person-years in adults.
Children are less likely to reach viral suppression and are at higher risk of viraemia while on ART than adults. The significance of LLV and blips needs further study.
Topics: Adolescent; Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Child; Child, Preschool; Female; HIV Infections; Humans; Incidence; Male; Retrospective Studies; Viral Load; Viremia; Zimbabwe
Viruses Jun 2018Dengue is a worldwide problem characterized by a multifactorial pathogenesis. Considering the viral components, it is known that high viremia or high levels of the...
Dengue is a worldwide problem characterized by a multifactorial pathogenesis. Considering the viral components, it is known that high viremia or high levels of the secreted nonstructural protein 1 (NS1) may be associated with a more severe disease. We aimed to characterize the NS1 antigenemia and viremia in dengue fatal and non-fatal cases, as potential markers of progression to a fatal outcome. NS1 antigenemia and viremia were determined in Brazilian dengue fatal cases ( = 40) and non-fatal cases ( = 40), representative of the four dengue virus (DENV) serotypes. Overall, the fatal cases presented higher NS1 levels and viremia. Moreover, the fatal cases from secondary infections showed significantly higher NS1 levels than the non-fatal ones. Here, irrespective of the disease outcome, DENV-1 cases presented higher NS1 levels than the other serotypes. However, DENV-2 and DENV-4 fatal cases had higher NS1 antigenemia than the non-fatal cases with the same serotype. The viremia in the fatal cases was higher than in the non-fatal ones, with DENV-3 and DENV-4 presenting higher viral loads. Viral components, such as NS1 and viral RNA, may be factors influencing the disease outcome. However, the host immune status, comorbidities, and access to adequate medical support cannot be ruled out as interfering in the disease outcome.
Topics: Antigens, Viral; Biomarkers; Brazil; Dengue; Dengue Virus; Humans; Prognosis; Survival Analysis; Viral Load; Viremia
Cytomegalovirus viraemia is associated with poor growth and T-cell activation with an increased burden in HIV-exposed uninfected infants.AIDS (London, England) Aug 2017Factors associated with poor health in HIV-exposed-uninfected (HEU) infants are poorly defined. We describe the prevalence and correlates of cytomegalovirus (CMV)... (Observational Study)
Factors associated with poor health in HIV-exposed-uninfected (HEU) infants are poorly defined. We describe the prevalence and correlates of cytomegalovirus (CMV) viraemia in HEU and HIV-unexposed-uninfected (HUU) infants, and quantify associations with anthropometric, haematological, and immunological outcomes.
Cross-sectional, including HEU and HUU infants from rural coastal Kenya.
Infants aged 2-8 months were studied. The primary outcome was CMV viraemia and viral load, determined by quantitative PCR. Correlates were tested by logistic and linear regression; coefficients were used to describe associations between CMV viraemia and clinical/immunological parameters.
In total, 42 of 65 (64.6%) infants had CMV viraemia [median viral load, 3.0 (interquartile ranges: 2.7-3.5) log10 IU/ml]. Compared to community controls, HEU infants had six-fold increased odds of being viraemic (adjusted odds ratio 5.95 [95% confidence interval: 1.82-19.36], P = 0.003). Age, but not HEU/HUU status, was a strong correlate of CMV viral load (coefficient = -0.15, P = 0.009). CMV viral load associated negatively with weight-for-age (WAZ) Z-score (coefficient = -1.06, P = 0.008) and head circumference-for-age Z-score (coefficient = -1.47, P = 0.012) and positively with CD8 T-cell coexpression of CD38/human leucocyte antigen DR (coefficient = 15.05, P = 0.003).
The odds of having CMV viraemia was six-fold greater in HEU than HUU infants when adjusted for age. CMV viral load was associated with adverse growth and heightened CD8 T-cell immune activation. Longitudinal assessments of the clinical effects of primary CMV infection and associated immunomodulation in early life in HEU and HUU populations are warranted.
Topics: Adult; Child, Preschool; Cross-Sectional Studies; Cytomegalovirus Infections; Developmental Disabilities; Female; HIV Infections; Humans; Infant; Kenya; Lymphocyte Activation; Male; Maternal Exposure; Prevalence; Real-Time Polymerase Chain Reaction; Retrospective Studies; Rural Population; T-Lymphocytes; Viral Load; Viremia
BMJ Case Reports Feb 2021COVID-19 is a biphasic illness with an initial viraemia phase and later effective adaptive immune phase, except in a minority of people who develop severe disease....
COVID-19 is a biphasic illness with an initial viraemia phase and later effective adaptive immune phase, except in a minority of people who develop severe disease. Immune regulation is the key target to treat COVID illness. In anticipation, an elderly man self-medicated himself with dexamethasone on the day of symptom onset of a flu-like illness, took other symptomatic measures and was tested positive for SARS-CoV-2. His condition deteriorated with each passing day resulting in hospitalisation. He demanded oxygen and declared as severe COVID. With supportive treatment, he recovered after the 20th day of illness. Immunosuppression and anti-inflammation are likely to benefit when the immune response is dysregulated and turning into a cytokine storm. A medication that has saved many could be the one predisposing to severity if taken as a preventive measure, too early in the disease course, especially the viraemia phase.
Topics: Aged; Anti-Infective Agents; Anti-Inflammatory Agents; COVID-19; Dexamethasone; Hospitalization; Humans; Hydroxychloroquine; Male; Pneumonia, Viral; SARS-CoV-2; Self Medication; Steroids; Treatment Outcome; Viremia