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Results for “Viral Load”

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PubMed1999

Chronic hepatitis C virus infections in leukemia survivors: prevalence, viral load, and severity of liver disease.

The natural history of chronic hepatitis C (HCV) infections in long-term leukemia survivors has not been well characterized. We studied the prevalence of HCV infections, measured HCV RNA levels, and evaluated the severity of liver disease in patients with leukemia who achieved long-term remissions after intensive chemotherapy or bone marrow transplantation (BMT). HCV antibody tests were performed by the enzyme-linked immunosorbent assay (ELISA) and positive tests confirmed by the recombinant immunoblot assay (RIBA). HCV RNA levels were measured by the branched DNA (bDNA) assay. Seventy-five leukemia survivors with 25 or more blood donor exposures were identified. Nine (12%) were anti-HCV positive. All were infected before 1992 when second generation HCV screening tests were implemented. Mean HCV RNA levels were 10.3 x10(6) eq/mL versus 3.2 x 10(6) eq/mL (P =.056) in a control group of 20 anti-HCV positive immunocompetent individuals of comparable age who were infected twice as long (17.8 +/- 6.5 years v 9.0 +/- 4.4 years in leukemia survivors, P =.001). Liver biopsies were performed on six of the nine anti-HCV positive leukemia survivors. All showed at least moderate portal inflammation and half had evidence of bridging fibrosis. We conclude that viral loads in anti-HCV positive leukemia survivors are markedly higher than in immunocompetent controls. Our results suggest that long-term leukemia survivors with chronic HCV may have more rapidly progressive liver disease than has been previously recognized.

Adult↗

PubMed2002

Frequencies of ex vivo-activated human immunodeficiency virus type 1-specific gamma-interferon-producing CD8+ T cells in infected children correlate positively with plasma viral load.

HIV-specific CD8+ T cells are critical in controlling human immunodeficiency virus (HIV) replication. We present the evaluation of a gamma-interferon (IFN-gamma)-based enzyme linked immunospot (ELISPOT) assay for the quantification of HIV-specific CD8+ T cells from HIV-infected children. We studied 20 HLA-A*0201-positive HIV-infected children. The IFN-gamma production in response to stimulation with two HLA-A*0201-restricted immunodominant CD8 epitopes (SLYNTVATL [SL9] in Gag and ILKEPVHGV [IV9] in Pol) was tested using the ELISPOT assay. The results were compared to labeling with the corresponding tetramers. Among the 20 children, 18 had detectable responses against the SL9 and/or the IV9 epitope using the ELISPOT assay (medians, 351 and 134 spot-forming cells/10(6) peripheral blood mononuclear cells, respectively). Comparison of results from the tetramer and ELISPOT assays suggests that only a fraction of HIV-specific CD8+ T cells were able to produce IFN-gamma. Most importantly, we found that the frequencies of IFN-gamma-producing CD8+ T cells were positively correlated with the viral load whereas the frequencies of tetramer-binding CD8+ T cells were not. The high sensitivity of the ELISPOT assay and the fact that this functional assay provided information different from that of tetramer labeling support its use for measurement of HIV-specific CD8+ T cells. In conclusion, our results show that the ex vivo-activated IFN-gamma-producing HIV-specific CD8+ T-cell subset is dependent upon continuous antigenic stimulation.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Quantification of cytomegalovirus (CMV) viral load by the hybrid capture assay allows for early detection of CMV disease in lung transplant recipients.

BACKGROUND: We prospectively compared the hybrid capture system (HCS) assay with conventional cell culture and shell vial assay for the detection of cytomegalovirus (CMV) infection and disease in the lung transplant population. METHODS: Between January 1999 and February 2000, 34 lung transplant patients at Loyola University Medical Center, who were considered to be at risk for CMV disease, underwent surveillance testing for CMV cell culture, shell vial assay and HCS assay according to a pre-determined schedule. In addition, bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy were performed at regular intervals and for clinical indications. All BAL samples were sent for CMV cultures and biopsy specimens were analyzed for histopathologic evidence of CMV by immunoperoxidase staining using antibody to early immediate nuclear antigen. RESULTS: Ten patients developed CMV disease/syndrome during the course of the study. The sensitivity, specificity, positive predictive value and negative predictive value were >90% for the HCS assay. The sensitivity of the HCS assay (90%) was statistically significantly higher than the sensitivity of either the SV assay (40%) or the cell culture (50%). In addition, the HCS assay was able to detect CMV 50 +/- 67 days prior to clinical evidence of CMV disease and an average of 36 days prior to the other detection techniques. CONCLUSION: The HCS assay is a sensitive diagnostic technique able to reliably detect CMV disease earlier than other diagnostic methods in the lung transplant population. Future studies may be able to evaluate whether pre-emptive anti-viral therapy targeted to specific viral loads using the HCS assay will be beneficial in preventing morbidity associated with CMV disease.

Adult↗

PubMed2002

Viral load is a significant prognostic factor for hepatitis B virus-associated hepatocellular carcinoma.

BACKGROUND: Hepatitis B virus (HBV) is closely linked to hepatocellular carcinoma (HCC). The objective of the current study was to identify the factors involved in the prognosis of patients with HBV-associated HCC using multivariate analysis. METHODS: The current study included 74 patients with HBV-associated HCC who were admitted to Nagasaki University Hospital, Nagasaki, Japan, between 1983-1998. Of these, 13 patients underwent surgical tumor resection; 43 patients received nonsurgical treatment with transcatheter arterial embolization, percutaneous ethanol injection, or both; and 18 patients were followed without any active treatment. The significance of the patient's age; gender; history of blood transfusion; alcohol use; serum levels of alanine aminotransferase, alpha-fetoprotein, and HBV-DNA; number and size of liver tumors; clinical stage; and histologic diagnosis of HCC as prognostic factors was evaluated using univariate and multivariate analyses. RESULTS: The 3-year, 5-year, and 10-year postdiagnosis cumulative survival rates were 36%, 21%, and 17%, respectively. Multivariate analysis identified the level of serum HBV-DNA and tumor size at diagnosis as independent and significant prognostic factors (P = 0.0022 and P = 0.0106, respectively). In addition, a low level of viremia was found to be associated with longer survival (P = 0.0057) even in patients who were negative for the hepatitis B e antigen. CONCLUSIONS: The results of the current study suggest that viral load is a useful prognostic marker for HBV-related HCC and that HCC patients with a less favorable course appear either to clear the virus poorly or to have a greater level of virus production.

Adult↗

PubMed2005

Performance of hepatitis C virus core antigen immunoassay in monitoring viral load after liver transplantation.

BACKGROUND: In the liver transplantation (LTx) setting, there are several situations where measurement of hepatitis C virus (HCV)-RNA concentration may provide relevant information. However, HCV-RNA quantification is expensive and not routinely available in all laboratories. An assay to quantify total HCV core antigen in serum has been recently developed. The aim of this study was to compare the performance of HCV-RNA and HCV core antigen determination in a cohort of 116 HCV-infected patients who underwent LTx. METHODS: HCV-RNA and HCV core antigen concentrations were determined in serum samples (n=435) obtained before LTx and at weeks 4, 12, and 48 after LTx. RESULTS: There was an excellent correlation between HCV-RNA and HCV core antigen levels (r=0.802 P<0.001), with an equivalence of 9,900 IU/mL of HCV-RNA per pg/mL of HCV core antigen. The determination of core antigen was linear in samples containing between 20,000 and 2,500,000 IU/mL of HCV-RNA and highly reproducible (mean coefficient of variation, 15%). Overall, HCV core antigen tested positive in 378 (92%) of 410 samples with detectable HCV-RNA (>600 IU/mL); the percentage increased to 98% in samples taken later than 4 weeks after LTx. In fact, almost all samples (369 of 375 [98.4%]) with HCV-RNA levels higher than 20,000 IU/mL were positive for HCV core antigen, whereas 56 of 57 samples with undetectable core antigen had HCV-RNA levels below 50,000 IU/mL. CONCLUSIONS: The performance of total HCV core antigen immunoassay is appropriate for monitoring viral load in HCV-infected patients undergoing LTx and might be considered a useful alternative to HCV-RNA testing.

Cohort Studies↗

PubMed1998

RANTES production in HIV-1 antigen-stimulated whole blood culture: relationship with type 1 immune response and plasma viral load in individuals infected with HIV-1.

Host factors which control replication and clearance of human immunodeficiency virus (HIV) are poorly understood. RANTES (regulated on activation, normal T cell expressed and secreted) and other beta-chemokines may be HIV-1-suppressive factors but their role in the progression of HIV-1 infection is a subject of controversy. We investigated the relationship between production of RANTES and correlates of disease progression in 15 patients infected with HIV-1. We used whole blood culture to study the production of RANTES, interferon (IFN)-gamma, interleukin (IL)-4 and IL-13 in response to supernatant of T cells infected with HIV-1. A defect of RANTES production was associated with a predominant type 2 and decreased type 1 cytokine profile (IL-4 and/or IL- 13 > IFN-gamma). We obtained a positive correlation between RANTES and IFN-gamma (P = 0.004) and the ratio of type 1 and type 2 cytokines IFN-gamma/IL-4 (P = 0.04) and IFN-gamma/IL-13 (P = 0.003), and a negative correlation between RANTES production and HIV-1 RNA copy number in plasma (P = 0.01). The same pattern of correlation was observed between HIV-1 p24-stimulated production of RANTES and the plasma viral load (P = 0.02, n = 15). The measurement of RANTES produced by heparinized whole blood in response to HIV-1 antigens appears as a potentially valuable tool to assess the defect of type 1 immune response in individuals infected with HIV-1 and to define whether the absence of a RANTES response may play a role in the increased rate of HIV-1 replication.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Plasma SIV RNA viral load determination by real-time quantification of product generation in reverse transcriptase-polymerase chain reaction.

Internally controlled RT-PCR methods (QC-RT-PCR) for quantification of SIV RNA are effective, but are relatively cumbersome, expensive, and time and labor intensive. For greater throughput and efficiency, we have developed a method for quantification of plasma SIV RNA levels by real-time RT-PCR using the Applied Biosystems Prism 7700 sequence detection system. This assay format allows real-time kinetic analysis of PCR product generation, providing a broad linear dynamic range and ensuring that quantification is based on analysis during the exponential phase of amplification, regardless of the input template copy number. Simultaneous amplification and analysis eliminates any requirement for handling amplified products, increasing throughput and eliminating a potential source of assay contamination. The assay we have developed for quantification of SIV RNA has a nominal threshold sensitivity of 300 copy Eq/ml of plasma, although as little as 10 copy Eq/reaction of SIV RNA template can be detected. The linear dynamic range is in excess of 5 logs. Interassay reproducibility averages 25% (coefficient of variation), based on studies of extraction and analysis of replicate aliquots of the same plasma specimens. The combination of sensitivity, precision, and broad dynamic range allows reliable quantification of viral load even during dynamic phases of SIV infection, such as through the onset and resolution of primary infection, or during treatment with antiretroviral agents. The primer-probe combinations we have developed allow quantification of SIV isolates most commonly used for experimental studies. Availability of this assay should greatly facilitate studies of basic pathogenesis and evaluation of therapeutic and prophylactic approaches in the SIV-infected macaque.

Animals↗

PubMed2001

Low levels of HIV-1 plasma viral load in patients infected with HIV-1 subtype b and advanced immunosuppression.

OBJECTIVES: Some HIV-1 infected patients show low levels of viraemia despite having advanced immunosuppression. Cases with falsely undetectable viraemia by conventional PCR have been reported when patients were infected with non-B subtypes. The aim of this study was to investigate whether this immunovirological discordance can be due to the presence of HIV-1 non-B subtypes, and whether a modified PCR procedure can yield different HIV viraemia values in these cases. METHODS: Fifteen HIV-infected patients either naive for antiretroviral drugs or under treatment, with HIV plasma viraemia below 1000 copies/mm(3)and CD4+ cell counts lesser than 500 or 300 cells/mm(3), respectively, were included. Serotyping, genotyping and HIV plasmatic viraemia determinations were performed in all individuals. RESULTS: In five out of six treatment-naive patients the virus was categorized as non-B subtype by serotyping, although only one case was confirmed by genotyping as HIV-2. Eight out of nine patients under antiretroviral therapy were subtype B carriers by serotyping and confirmed by genotyping. The remaining patient was determined as a subtype A carrier by both procedures. A modified PCR procedure (Amplicor HIV Monitor Test version 1.5) did not yield higher viral load levels than the former version. CONCLUSIONS: The presence of HIV-1 subtypes non-B can explain a minority of cases of this immunovirological discordance, but in most of them the reason is still unknown. Likewise, a PCR procedure adapted for detecting HIV-1 non-B subtypes fails to find higher plasma viraemia in patients with such a discordance.

Adult↗

PubMed2002

Late cytomegalovirus disease and mortality in recipients of allogeneic hematopoietic stem cell transplants: importance of viral load and T-cell immunity.

Ganciclovir effectively prevents cytomegalovirus (CMV) disease in the first 100 days after allogeneic hematopoietic stem cell transplantation (HSCT), but late-onset CMV disease is increasingly observed. We designed a prospective cohort study to define the incidence and risk factors for late CMV infection in patients who undergo HSCT. CMV-seropositive patients were studied prospectively for CMV infection (quantitative pp65 antigenemia, quantitative CMV-DNA, blood culture), T-cell immunity (CMV-specific CD4(+) T-helper and CD8(+) cytotoxic T-lymphocyte responses, CD4 and CD8 T-cell count, absolute lymphocyte count), and other transplantation-related factors. Univariate and multivariable analyses were used to assess the risk for late CMV infection and disease and to assess overall survival. Late CMV disease developed in 26 of 146 (17.8%) patients a median of 169 days after transplantation (range, 96-784 days); the mortality rate was 46%. Thirty-eight percent of patients surviving late disease had a second episode a median of 79 days after the first episode. At 3 months after transplantation, preceding detection of CMV pp65 antigenemia, CD4 T-cell counts lower than 50 cells/mm(3), postengraftment absolute lymphopenia levels lower than 100 lymphocytes/mm(3), undetectable CMV-specific T-cell responses, and graft-versus-host disease (GVHD) were associated with late CMV disease or death. After 3 months, continued detection of pp65 antigenemia or CMV DNA in plasma or peripheral blood leukocytes and lymphopenia (fewer than 300 lymphocytes/mm(3)) were strong predictors of late CMV disease and death. In conclusion, CMV viral load, lymphopenia, and CMV-specific T-cell immunodeficiency are predictors of late CMV disease and death after allogeneic stem cell transplantation. Prevention strategies should be targeted at patients in whom CMV reactivated during the first 3 months and those with poor CMV-specific immunity or low CD4 counts.

Cytomegalovirus↗

PubMed2002

Granulocyte-macrophage colony-stimulating factor enhances viral load in human brain tissue: amelioration with stavudine.

BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is elevated in cerebrospinal fluid in HIV- associated dementia; in addition, therapeutic GM-CSF elevates plasma viral load. OBJECTIVE: To assess the effect of GM-CSF on viral replication and the potential ameliorative effect of antiretroviral therapy. DESIGN: A primary human brain aggregate system is used as a model of the in vivo situation. METHOD: Cultured aggregates were infected with the macrophage tropic strain HIV-1SF162 and then exposed to varying GM-CSF concentrations and 0.3 micromol/l stavudine. Viral replication was assessed by p24 expression in the supernatant and aggregates. Immunohistochemistry identified neurons, astrocytes, microglia and oligodendrocytes. RESULTS: A GM-CSF concentration of 1 ng/ml resulted in a fivefold increase in microglial cells, the main HIV cellular reservoir (P = 0.0001). Prior GM-CSF exposure before infection of the aggregates resulted in sixfold increase in p24 levels compared with non-GM-CSF-exposed infected aggregates. Infected aggregates with or without GM-CSF had significant neuronal loss of 50% and 45%, respectively, and astrocytosis. Addition of stavudine to the infected aggregates, even in the presence of GM-CSF, reduced p24 levels to zero and prevented neuronal loss and astrocytosis. CONCLUSIONS: This study demonstrates that GM-CSF enhances viral replication while addition of stavudine prevents this potentially detrimental process.

AIDS Dementia Complex↗

PubMed1997

Viral load and disease progression in infants infected with human immunodeficiency virus type 1. Women and Infants Transmission Study Group.

BACKGROUND: There are only limited data on human immunodeficiency virus type 1 (HIV-1) RNA in perinatally infected infants. Understanding the dynamics of HIV-1 infection and its relation to disease progression may help identify opportunities for effective antiviral treatment in infected infants. METHODS: We obtained plasma samples from 106 HIV-infected infants at birth; at 1, 2, 4, 6, 9, 12, 15, and 18 months of age; and subsequently every 6 months. HIV-1 RNA was assayed by means of a reverse-transcription polymerase chain reaction. The infants were born between 1990 and 1993, and only 21 percent of the infants' mothers received any treatment with zidovudine during pregnancy. RESULTS: Plasma HIV-1 RNA levels increased rapidly after birth, peaked at 1 to 2 months of age (median values at 1 and 2 months, 318,000 and 256,000 copies per milliliter, respectively), and then slowly declined to a median of 34,000 copies per milliliter at 24 months. Newborns with a first positive HIV-1 culture within 48 hours after birth had significantly higher HIV-1 RNA levels, although only during the first two months of life, than those with a first positive culture seven or more days after birth. Infants with a rapid progression of disease had higher peak HIV-1 RNA levels in the first two months of life than those without rapid progression (median value, 724,000 vs. 219,000 copies per milliliter; P=0.006), as well as a higher geometric mean value during the first year of life (median value, 330,000 vs. 158,000 copies per milliliter, P=0.001). CONCLUSIONS: In perinatally infected infants, HIV-1 RNA levels are high and decline only slowly during the first two years of life. Infants with very high viral loads in the first months of life are at increased risk for a rapid progression of disease, which suggests that early treatment with antiretroviral agents may be indicated for these infants.

Child, Preschool↗

PubMed1996

The prognostic significance of serum viral load, codon 215 reverse transcriptase mutation and CD4+ T cells on progression of HIV disease in a double-blind study of thymopentin.

OBJECTIVE: To determine in asymptomatic HIV-infected subjects the prognostic value of virion reverse transcriptase (RT) codon 215 mutation, serum HIV RNA level, CD4+ T-cell count and immune complex dissociated (ICD) p24 level. The retrospective evaluation of thymopentin treatment effect on subjects in high risk groups for progression was a secondary objective. PARTICIPANTS: Zidovudine (ZDV)-experienced asymptomatic HIV-infected subjects (n = 352) who had been enrolled in a 48-week placebo-controlled double-blind trial of thymopentin treatment were studied. METHODS: Post hoc analyses were conducted to determine which subjects at study entry were at greater risk for progression to AIDS-related complex (ARC), AIDS or death, and to determine the effect of treatment on these subjects. Four potential prognostic variables (virion RT codon 215 mutation, circulating HIV virion RNA copies, CD4+ T-cell count, and ICD p24) were evaluated by dichotomizing subjects for each variable based on the median of the observed values. CD4+ T-cell count was evaluated prospectively, whereas frozen samples were evaluated under blinded conditions for the other variables after the study was completed. RESULTS: The presence of the codon 215 mutation [P = 0.044; relative hazard (RH), 2.6], > or = 20,000 HIV RNA copies/ml (P = 0.002; RH, 5.5), and < 350 CD4+ cells 10(6)/l (P = 0.042; RH, 2.2) were prognostic factors, and > or = 30 pg/ml ICD p24 level (P = 0.52; RH, 1.4) was not a prognostic factor in predicting progression. Subjects were prestratified by previous ZDV use (< or = 6 or > 6 months). Across both strata thymopentin delayed treatment progression to ARC, AIDS, or death (P = 0.015; RH, 3.0). This effect was magnified in the ZDV-experienced subjects at greater risk, where thymopentin delayed progression compared to placebo in the presence of the codon 215 mutation (P = 0.007; RH, 10.1), > or = 20,000 RNA copies/ml (P = 0.012; RH, 8.9), and CD4+ T-cell count < 350 x 10(6)/l (P = 0.005; RH, 10.4). CONCLUSIONS: Codon 215 mutation, serum HIV RNA and CD4 T-cell count are independent predictors of progression in ZDV-experienced asymptomatic subjects. Furthermore, thymopentin delays HIV disease progression in the presence of a key ZDV resistance mutation as well as high viral load and low CD4+ T-cell counts.

Adjuvants, Immunologic↗

PubMed2005

Blood micronutrient, oxidative stress, and viral load in patients with chronic hepatitis C.

AIM: To assess the extent of micronutrient and oxidative stress in blood and to examine their linkages with viral loads in chronic hepatitis C patients. METHODS: Hepatitis C virus (HCV)-RNA levels were quantified in the serum from 37 previously untreated patients with chronic hepatitis C. The plasma and erythrocyte micronutrients (zinc, selenium, copper, and iron) were estimated, and malondialdehyde (MDA) contents were determined as a marker to detect oxidative stress. Antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione reductase (GR) activities in blood were also measured. The control group contained 31 healthy volunteers. RESULTS: The contents of zinc (Zn), and selenium (Se) in plasma and erythrocytes were significantly lower in hepatitis C patients than in the controls. On the contrary, copper (Cu) levels were significantly higher. Furthermore, plasma and erythrocyte MDA levels, and the SOD and GR activities in erythrocytes significantly increased in hepatitis C patients compared to the controls. However, the plasma GPX activity in patients was markedly lower. Plasma Se (r = -0.730, P<0.05), Cu (r = 0.635), and GPX (r = -0.675) demonstrated correlations with HCV-RNA loads. Significant correlation coefficients were also observed between HCV-RNA levels and erythrocyte Zn (r = -0.403), Se (r = -0.544), Cu (r = 0.701) and MDA (r = 0.629) and GR (r = 0.441). CONCLUSION: The levels of Zn, Se, Cu, and oxidative stress (MDA), as well as related anti-oxidative enzymes (GR and GPX) in blood have important impact on the viral factors in chronic hepatitis C. The distribution of these parameters might be significant biomarkers for HCV.

Adult↗

PubMed2005

Effect of cytokine gene polymorphism on histological activity index, viral load and response to treatment in patients with chronic hepatitis C genotype 3.

AIM: To investigate the association between cytokine gene polymorphism and disease status in chronic hepatitis C genotype 3 by liver biopsy, ALT, HCV RNA levels and response to treatment. METHODS: Patients with chronic hepatitis C genotype 3 were analyzed for single nucleotide polymorphisms of interleukin (IL)-10, IL-1 beta, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) by polymerase chain reaction using sequence-specific oligonucleotide primers. Liver biopsies were assessed by modified histological activity index (HAI) scoring system using a scale of 0-18 for grading the necro-inflammatory activity and 0-6 for staging the fibrosis. HCV RNA levels were determined by bDNA assay. The patients were treated with interferon alpha and ribavirin for 6 mo. Sustained virological response was assessed 6 mo after the completion of the treatment. RESULTS: Out of the 40 patients analyzed, 26 were males. Mean age was 40.5+/-12.5 years (range 18-65 years). The frequencies of different dimorphic polymorphisms based on single nucleotide substitution were as follows: IL-10-1082 G/A 85%, A/A 12.5%, G/G 2.5%; IL-10-819 A/C 87.5%, C/C 10%, A/A 2.5%; IL-10-592 C/A 72.5%, C/C 27.5%; IL-1 C 90%, U 10%; IFN-874 T/A 50%, T/T 27.5%, A/A 22.5%; TNF-308 A/G 95%, G/G 5%; TGF-10 T/C 52.5%, C/C 35%, T/T 12.5%. The mean grades of necro-inflammatory activity of different genotypes of IL-10 at promoter site -1082 were A/A = 3.6, A/G = 5.0, and G/G = 10.0 and the difference was significant (P = 0.029). The difference in the stage of disease at a scale of 0-6 was A/A 0.8, A/G 2.3, and G/G 4.0 (P = 0.079). The difference in the HAI seemed to be related to the presence of allele -1082G. For IL-10 -819 genotypes, mean scores of fibrosis were A/A = 6.0, A/C = 2.2, and C/C = 1.0 (P = 0.020) though the inflammatory activity was not much different. No significant differences in HAI were noted among polymorphisms of other cytokines. Moreover, ALT and HCV RNA levels were not significantly different among different cytokine polymorphisms. There was a significant correlation of HAI and HCV RNA levels with the duration of disease. TGFbeta -10 genotype CC patients had a better end of treatment response than those with other genotypes (P = 0.020). Sustained virological response to the treatment was not influenced by the cytokine polymorphism. No effect of other factors like viral load, degree of fibrosis, gender, steatosis, was observed on sustained virological response in this population infected with genotype 3. CONCLUSION: There is no significant correlation between cytokine polymorphisms and HAI except for the polymorphisms of anti-inflammatory cytokine IL-10, which may influence hepatic inflammatory activity and fibrosis in patients with chronic hepatitis C genotype 3. Sustained virological response in this genotype does not seem to be influenced by cytokine gene polymorphisms.

Adolescent↗

PubMed1994

Correlation between surrogate markers, viral load, and disease progression in HIV-1 infection.

Surrogate markers generally used for observation of patients infected with human immunodeficiency virus (HIV) and their plasma and cellular viral load were assayed in a series of 40 patients before initiation of zidovudine therapy. Plasma viremia was positive in 62.5% of patients and was statistically correlated with clinical stage, CD4+ T cell count, CD8+ T cell count, beta 2-microglobulin level, neopterin level, and immunoglobulin A level. Cellular viremia was positive in 95% of patients and was correlated with clinical stage, CD4+ T cell count, beta 2-microglobulin, neopterin levels, and disease progression during the following months. A discordance was found between p24 antigenemia, even after acid dissociation of immune complexes, and plasma viremia. In fact, p24 antigenemia was correlated with only biological markers of immune activation as beta 2-microglobulin and neopterin levels. The measurement of anti-p24 antibodies did not appear discriminative in our staging. Plasma viremia, like CD4+ T cell count, reflects the patient's status at the time of assessment. Cellular viremia could be more informative for the prediction of future clinical progression.

Adult↗

PubMed2005

TaqMan RT-PCR and VERSANT HIV-1 RNA 3.0 (bDNA) assay Quantification of HIV-1 RNA viral load in breast milk.

BACKGROUND: Transmission of HIV via breast milk is a primary cause of pediatric HIV infection in developing countries. Reliable methods to detect breast milk viral load are important. OBJECTIVE: To correlate the ability of the VERSANT HIV 3.0 (bDNA) assay to real-time (RT) TaqMan PCR in quantifying breast milk HIV-1 RNA. STUDY DESIGN: Forty-six breast milk samples that had been spiked with cell-free HIV-1 and eight samples spiked with cell-associated HIV-1 were assayed for HIV-1 RNA by both VERSANT HIV 3.0 and TaqMan RNA assays. RESULTS: Only assays on the cell-free samples were statistically compared. Both a Deming regression slope and a Bland-Altman slope indicated a linear relationship between the two assays. TaqMan quantitations were on average 2.6 times higher than those of HIV 3.0. A linear relationship was observed between serial dilutions of spiked cell-free HIV-1 and both the VERSANT HIV 3.0 and the TaqMan RNA assays. CONCLUSION: The two methods correlated well although the VERSANT HIV 3.0 research protocol quantified HIV-1 RNA slightly lower than TaqMan.

Branched DNA Signal Amplification Assay↗

PubMed1997

Hepatic expression of inducible nitric oxide synthase transcripts in chronic hepatitis C virus infection: relation to hepatic viral load and liver injury.

Hepatitis C virus (HCV) causes acute and often also chronic liver disease. Hepatocellular injury might result from both a host response directed to inhibit viral spread and from processes initiated by the virus itself. To study mechanisms involved in hepatocellular injury, liver tissue from chronically HCV-infected patients was analyzed for the expression of the inducible isoform of nitric oxide synthase (iNOS) and for interferon gamma (IFN-gamma) by a quantitative, competitive reverse-transcription-polymerase chain reaction (RT-PCR) technique. Moreover, hepatic viral load was determined by two independent techniques, and liver tissue was evaluated histopathologically in detail. Liver tissue from HCV-infected patients was shown to express elevated levels of iNOS transcripts compared with non-HCV-infected patients. Increased iNOS transcript expression, however, was not accompanied by significantly elevated serum nitrite plus nitrate (NOx) concentration, although some of the chronic HCV-infected patients reached markedly higher serum NOx levels than the control group or healthy individuals, respectively. Hepatic iNOS expression was found to be positively correlated to hepatic HCV-RNA content on the one hand, and weakly to hepatic IFN-gamma expression, previously shown to be solely associated with hepatic necro-inflammatory activity among the histopathological parameters studied, on the other hand. In contrast to IFN-gamma transcript expression, neither hepatic iNOS expression nor hepatic HCV-RNA content were related to hepatic inflammatory activity. The presented data are compatible with the assumption that HCV might be able to stimulate iNOS expression both directly and indirectly via its capacity to induce IFN-gamma.

Adult↗

PubMedDate not supplied

Cytokine patterns and viral load in lymph nodes during the early stages of SIV infection.

To elucidate the initial pathogenic events in lymphoid organs, the major reservoir of virus in HIV infection, follow-up of viral load and cytokine mRNA production was performed in the rhesus macaque SIV mac251 model. In the first experiment, lymph nodes (LN) obtained from animals sacrificed at early time points following intravenous (i.v.) inoculation with a high viral dose, showed that the production of cytokine mRNA in LN (IFN gamma, IL1 beta, IL2, IL4, IL12p40, IL6, IL10, TNF alpha and TNF beta) was correlated with viral replication and persisted during the two months post-inoculation (p.i.). In the second experiment, LN were sequentially analysed in two groups of animals receiving i.v. a high or a low viral dose. The initial higher local production of IFN gamma mRNA in LN was associated with weak viraemia, the capacity of the host to decrease productive infection in LN measured at one and two months p.i., and slow disease progression.

Animals↗