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At least 289 records · Page 16Linked to original sources

PubMed2001

Titration of an SIVmac251 stock by vaginal inoculation of Indian and Chinese origin rhesus macaques: transmission efficiency, viral loads, and antibody responses.

The purpose of this study was to determine whether rhesus monkeys of Chinese origin are suitable for studies of mucosal lentivirus transmission by comparing the relative ability of these animals and rhesus macaques of Indian origin to become infected by vaginal (IVAG) inoculation with SIVmac251. In addition, we sought to test the hypothesis that differences in viral load during the first few weeks after inoculation were due to the relative strength of the anti-SIV immune responses in the two populations of rhesus macaques. Significant difference was not observed between the number of Indian and Chinese origin monkeys that were infected after IVAG SIV inoculation in this study. For 8-9 weeks after infection there was considerable overlap in the range of viral loads among the Indian and Chinese animals and the variation among the Indian origin animals was greater than the variation among the Chinese origin monkeys. By 6 weeks postinfection, viral loads in SIV-infected Chinese origin monkeys tended to be at the lower end of the range of viral loads observed in SIV-infected Indian origin monkeys. The strength of the anti-SIV antibody response was also more variable in the Indian origin rhesus macaques, but at 6-8 weeks postinfection, Chinese and Indian origin rhesus macaques had similar titers of anti-SIV antibodies. Microsatellite allele frequencies differed between Chinese and Indian rhesus macaques; however, the majority of alleles present in Indian-origin animals were also found in Chinese macaques. Together these results show that host factors, other than geographic origin, determine the ability of a rhesus macaque to be infected after IVAG SIV exposure and that geographic origin does not predict the viral load of SIV-infected animals during the first 8-9 weeks after IVAG inoculation.

Animals↗

PubMed2004

Assessment of drug resistance mutations in plasma and peripheral blood mononuclear cells at different plasma viral loads in patients receiving HAART.

BACKGROUND: HIV drug resistance mutations both in peripheral blood mononuclear cells (PBMCs) and plasma have the ability to influence the outcome of highly active antiretroviral therapy for HIV patients. PBMCs harbor archival proviral DNA, are a major source of HIV and also underdo latent infection during suppressive HAART. OBJECTIVES: The main objectives of this study were to assess whether specific viral load groups are better predictors of drug resistance and to examine the utility of PBMCs for drug resistance testing during HAART. STUDY DESIGN: Patients were grouped into a plasma panel comprising of 100 patients and a PBMC/plasma panel of 45 patients. These two groups were further divided according to plasma viral load (low, medium and high). Therapy naive patients were also included. Resistance to protease and reverse transcriptase inhibitors was assessed in each group over different viral load categories. RESULTS: Our data indicated that in addition to plasma, PBMCs also are a reliable predictor of drug resistance. Drug resistance mutations analyzed from each panel demonstrated that intermediate and high viral loads were strong indicators of drug resistance in both the plasma and PBMC compartments. Despite this, a significant portion of patients with high viral loads showed reduced levels of drug resistance indicating that factors including poor compliance, drug pharmacokinetics and host genetic factors are also likely to contribute to therapy failure. A significant degree of resistance to NRTI and PI resistance was found in treatment-naive individuals, demonstrating the transmission of circulating drug resistant HIV-1 variants. CONCLUSIONS: Our data emphasize the need for stronger pharmacokinetic evaluation during HAART, especially for patients with intermediate or high plasma viremia. The utility of PBMCs as an alternative source of resistance profiling was also demonstrated, and this approach may benefit the assessment of future drug regimens for HIV-infected patients.

Antiretroviral Therapy, Highly Active↗

PubMed2004

Prospective study of relationship between cytomegalovirus pneumonia and viral load in renal transplant recipients.

The present study prospectively examined the relationship between cytomegalovirus interstitial pneumonia (CMV-IP) and viral load among 56 renal transplant recipients. We sought to identify the cutoff of viral load to predict CMV-IP. Blood samples were obtained weekly within the first 2 months and every second week during 2 to 6 months after kidney transplantations. A commercial real-time polymerase chain reaction (PCR)-method was applied to quantify CMV-DNA in plasma or in leukocytes. Among 54 renal transplant recipients who were analyzed for CMV-DNA in the blood (96.4%), 8 experienced CMV-IP (14.3%) and 2 died (3.6%). After kidney transplantation, CMV-DNA loads were near 0 in plasma before the week 4 and before the week 3 in leukocytes among both groups. From week 5 (week 4, in leukocytes), plasma CMV-DNA loads in the CMV-IP group increased, the peak value reached at week 8 in plasma and the week 9 in leukocytes. Whereas, the CMV-DNA loads both in plasma and in leukocytes in the non-CMV-IP group fluctuated at lower levels, those in plasma were significantly different between the 2 groups at the weeks 5, 7, and 9. For CMV-DNA in leukocytes, there were significant differences between 2 groups from week 6 to week 11. The present study demonstrated that dynamic determination of CMV-DNA may predict the occurrence of CMV-IP. Viral loads over 10(4) copies/mL plasma continuing for 3 weeks may serve as a cutoff to predict CMV-IP.

Cytomegalovirus↗

PubMed2004

Patient predictions correlate with actual CD4+ lymphocyte and HIV-1 viral load changes in an urban, HIV-infected clinic population.

Patients who were undergoing CD4+ lymphocyte and HIV-1 viral load measurement as part of their routine clinical care were asked to predict the results of these tests compared to their last recorded CD4+ lymphocyte and HIV-1 viral load measurements. One hundred eight patients predicted the results of 240 CD4+ lymphocyte and 244 viral load measurements. Both Spearman bivariate correlation and a generalized estimating equation repeated measures analysis demonstrated a significant correlation between patient-predicted and actual laboratory values for both tests. Patients with a history of depression were less likely to predict their test results correctly than patients without such a history.

Adult↗

PubMed2005

Viral load distribution in SARS outbreak.

An unprecedented community outbreak of severe acute respiratory syndrome (SARS) occurred in the Amoy Gardens, a high-rise residential complex in Hong Kong. Droplet, air, contaminated fomites, and rodent pests have been proposed to be mechanisms for transmitting SARS in a short period. We studied nasopharyngeal viral load of SARS patients on admission and their geographic distribution. Higher nasopharyngeal viral load was found in patients living in adjacent units of the same block inhabited by the index patient, while a lower but detectable nasopharyngeal viral load was found in patients living further away from the index patient. This pattern of nasopharyngeal viral load suggested that airborne transmission played an important part in this outbreak in Hong Kong. Contaminated fomites and rodent pests may have also played a role.

Adult↗

PubMed2005

The risk of needle stick accidents during surgical procedures: HIV-1 viral load in blood and bone marrow.

Health-care workers are at risk to acquire HIV through occupational exposure to blood of HIV-infected patients. The mean risk after a percutaneous exposure is approximately 0.3%. A large inoculum and a source patient with a high plasma viral load increases the transmission risk. To ensure the safety of the operating team, we try to reduce HIV viral load in plasma prior to high-risk interventions (cardiothoracic and orthopaedic surgery). However, in 15.7% of the exposures occurring in the operating room, the possible source material is bone marrow. To make more accurate exposure risk assessments, we measured HIV-1 RNA in both plasma and bone marrow of five HIV-infected patients undergoing surgery. We found that the plasma viral load was not different from the viral load in bone marrow.

Bone Marrow↗

PubMed2006

Fecal viral load and norovirus-associated gastroenteritis.

We report the median cDNA viral load of norovirus genogroup II is >100-fold higher than that of genogroup I in the fecal specimens of patients with norovirus-associated gastroenteritis. We speculate that increased cDNA viral load accounts for the higher transmissibility of genogroup II strains through the fecal-oral route.

Adolescent↗

PubMed2000

Evaluation of performance of the Gen-Probe human immunodeficiency virus type 1 viral load assay using primary subtype A, C, and D isolates from Kenya.

Accurate and sensitive quantification of human immunodeficiency virus type 1 (HIV-1) RNA has been invaluable as a marker for disease prognosis and for clinical monitoring of HIV-1 disease. The first generation of commercially available HIV-1 RNA tests were optimized to detect the predominant HIV-1 subtype found in North America and Europe, subtype B. However, these tests are frequently suboptimal in detecting HIV-1 genetic forms or subtypes found in other parts of the world. The goal of the present study was to evaluate the performance of a new viral load assay with non-subtype B viruses. A transcription-mediated amplification method for detection and quantitation of diverse HIV-1 subtypes, called the Gen-Probe HIV-1 viral load assay, is under development. In this study we examined the performance of the Gen-Probe HIV-1 viral load assay relative to that of the commonly used commercial HIV-1 RNA assays using a panel of primary isolates from Kenya. For comparison, we included several subtype B cloned viruses, and we quantified each virus using an in-house quantitative-competitive reverse transcriptase PCR (QC-RT-PCR) method and gag(p24) antigen capture. The Gen-Probe HIV-1 viral load assay and a version of the Roche AMPLICOR HIV-1 MONITOR test (version 1.5) that was designed to detect a broader range of subtypes were both sensitive for the quantification of Kenyan primary isolates, which represented subtype A, C, and D viruses. The Gen-Probe HIV-1 viral load assay was more sensitive for the majority of viruses than the Roche AMPLICOR HIV-1 MONITOR test version 1.0, the Bayer Quantiplex HIV RNA 3.0 assay, or a QC-RT-PCR method in use in our laboratory, suggesting that it provides a useful method for quantifying HIV-1 RNAs from diverse parts of the world, including Africa.

Adult↗

PubMed1998

[Effects of double and triple antiretroviral agents on the HCV viral load in patients coinfected with HIV and HCV].

HIV infection accelerates natural course of HCV infection, but impact of antiretroviral treatment on HCV infection is not well known. The aim of this study is to compare the change of HCV viral load in patients on combination of 2 nucleoside analogues and in patients on combination of 2 nucleoside analogues and protease inhibitor. HCV and HIV viral load, lymphocyte CD4 counts, alanine aminotransferase (ALT) and aspartate amino transferase (AST) were measured before and 3 months after starting treatment in 2 groups: Group 1 (n = 15) treated with 2 nucleoside analogues and Group 2 (n = 15) treated with 2 nucleoside analogues and a protease inhibitor. Results show a significant increase in lymphocyte and a significant decrease in HIV viral load in the both group but no significant change in HCV viral load and in ALT and AST. In conclusion efficiency of anti-HIV therapy (combination of 2 nucleoside analogues with or without a protease inhibitor) doesn't seem to have any impact on the course of HCV viremia in HIV-coinfected patients.

AIDS-Related Opportunistic Infections↗

PubMed2003

The presence of an intrahepatic cytotoxic T lymphocyte response is associated with low viral load in patients with chronic hepatitis C virus infection.

BACKGROUND/AIMS: The role of cytotoxic T lymphocytes (CTL) in limiting viral replication and producing hepatocellular injury in patients with chronic hepatitis C virus (HCV) infection is controversial. METHODS: Intrahepatic and peripheral blood HCV-specific CTL activity against the entire HCV polyprotein was assessed in 26 patients. CTL responses were assessed after effector lymphocytes were re-stimulated for 6 days in vitro using HCV-vaccinia virus-infected autologous cells expressing HCV antigens. Serum and hepatic viral loads were measured and immunohistochemistry for CD3 and CD8 was performed to localise and enumerate effector cells in liver. RESULTS: A positive CTL response was detected in 39/52 (75%) of assays conducted with intrahepatic mononuclear cells and 21/52 (40%) of peripheral blood assays (P<0.001). The presence of an intrahepatic CTL response was associated with low hepatic viral load (P=0.004). Hepatic lobular infiltration by CD8(+)T cells correlated weakly with serum alanine aminotransferase levels (r=0.42, P=0.04) and no relationship was demonstrated between CTL activity and histological evidence of liver damage. CONCLUSIONS: HCV-specific CTL activity is found more commonly in liver than in blood. An inverse relationship between CTL responses and viral load supports the hypothesis that HCV-specific CTL limit viral replication in patients with chronic HCV infection.

Adult↗

PubMed2006

Slower rates of clearance of viral load and virus-containing immune complexes in patients with dengue hemorrhagic fever.

BACKGROUND: Although previous studies have revealed the contribution of an initial high level of dengue virus replication to the severe and potentially life-threatening diseases dengue hemorrhagic fever (DHF) and dengue shock syndrome, the involvement of dengue virus in the immunopathological processes during the transition from fever to defervescence, which is a critical stage in determining the progression to DHF, has not been appreciated. Previously, we reported that dengue virus can be detected in the immune complexes of patients with DHF during this period. METHODS: We investigated plasma dengue viral load, virus in immune complexes, antibody response, complements, and cytokines for 54 patients with dengue fever (a relatively mild form of disease) and 49 patients with DHF. The patients had confirmed secondary infection with dengue virus type 2 from a large outbreak in southern Taiwan in 2002. RESULTS: Patients with DHF had a significantly higher viral load and a slower rate of clearance than patients with dengue fever. For viral loads >5.7 log RNA copies/mL on the day of defervescence, the positive and negative predictive values for DHF are 0.88 and 0.95, respectively. A higher level and slower decline of dengue virus-containing immune complexes (and a subsequently higher elevation of C5a and soluble interleukin 2 receptor) were found in patients with DHF, compared with patients with dengue fever. CONCLUSIONS: These findings indicate that slower rates of clearance of viral load and virus-containing immune complexes are associated with subsequent immune activation and contribute to the progression of DHF at this critical stage. Moreover, viral load on the day of defervescence can predict cases of DHF.

Adolescent↗

PubMedDate not supplied

Quantitation of HIV-1 RNA viral load using nucleic acid sequence based amplification methodology and comparison with other surrogate markers for disease progression.

In this study, HIV-1 viral blood quantitation determined by Nucleic Acid Sequence Based Amplification (NASBA) was compared with other surrogate disease progression markers (antigen p24, CD4/CD8 cell counts and beta-2 microglobulin) in 540 patients followed up at São Paulo, SP, Brazil. HIV-1 RNA detection was statistically associated with the presence of antigen p24, but the viral RNA was also detected in 68% of the antigen p24 negative samples, confirming that NASBA is much more sensitive than the determination of antigen p24. Regarding other surrogate markers, no statistically significant association with the detection of viral RNA was found. The reproducibility of this viral load assay was assessed by 14 runs of the same sample, using different reagents batches. Viral load values in this sample ranged from 5.83 to 6.27 log (CV = 36%), less than the range (0.5 log) established to the determination of significant viral load changes.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Viral load at the time of liver transplantation and risk of hepatitis B virus recurrence.

Hepatitis B virus (HBV) recurrence after liver transplantation is significantly reduced by prophylaxis with hepatitis B immune globulins (HBIG) or antiviral drugs in nonreplicating patients and by the combination of both drugs in replicating patients. However, the load of HBV DNA, which defines replicating status in patients undergoing liver transplantation, remains unclear. This study analyzes the correlation between the viral load, tested with a single amplified assay, at the time of liver transplantation, and the risk of hepatitis B recurrence in 177 HBV carriers who underwent transplantation in a single center from 1990 to 2002. Overall, HBV relapsed after surgery in 15 patients (8.5%) with a 5- and 8-year actuarial rate of recurrence of 8% and 21%, respectively. After liver transplantation hepatitis B recurred in 9% of 98 selected subjects treated only with immune globulins and in 8% of 79 viremic patients who received immune globulins and lamivudine (P = NS). A linear correlation was observed between recurrence and viral load at the time of surgery. In transplant patients with HBV DNA higher than 100,000 copies/mL, 200-99,999 copies/mL, and DNA undetectable by amplified assay, hepatitis B recurred in 50%, 7.5%, and 0% of patients, respectively. Overall, a viral load higher than 100,000 copies/mL at the time of liver transplantation was significantly associated with hepatitis B recurrence (P = .0003). In conclusion, spontaneous or antiviral-induced HBV DNA viral load at the time of surgery classifies the risk of HBV recurrence after liver transplantation and indicates the best prophylaxis strategy.

Adult↗

PubMedDate not supplied

Cost to achieve an undetectable viral load using recommended antiretroviral regimens.

PURPOSE: The April 2005 Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents recommended 9 regimens to be combined with 2 nucleoside reverse transcriptase inhibitors (NRTIs). These regimens are effective in lowering viral load but are expensive. This study aimed to determine the cost for each regimen to achieve an undetectable viral load. METHOD: 52 clinical trials were reviewed. The outcome measure was cost per undetectable patient, C/PU, where C = cost of a drug, and PU = percent of patients with undetectable viral loads. RESULTS: For 30 weeks, cost per undetectable (<400 copies/mL) ranged from 4,416 dollars (efavirenz) to 23,110 dollars (nelfinavir); for 42 weeks, the range was 5,729 dollars (efavirenz) to 24,071 dollars (indinavir/ritonavir); for 60 weeks, it ranged from 9,535 dollars (efavirenz) to 26,829 dollars (fosamprenavir); and for 84 weeks, it ranged from 12,203 dollars (efavirenz) to 22,960 dollars (nelfinavir). For <50 copies/mL, at 30 weeks the range was from 7,140 dollars (efavirenz) to 17,548 dollars (atazanavir); for 42 weeks, it ranged from 9,849 dollars (lopinavir/ritonavir) to 13,181 dollars (nelfinavir); for 60 weeks, it ranged from 8,702 dollars (nevirapine) to 36,034 dollars (atazanavir); and for 84 weeks, it ranged from 15,660 dollars (efavirenz) to 29,177 dollars (indinavir/ritonavir). CONCLUSION: Efavirenz's low price and high effectiveness make it the least expensive means of achieving an undetectable viral load.

Anti-HIV Agents↗

PubMed2000

CMV viral load measurements in whole blood and plasma--which is best following renal transplantation?

BACKGROUND: Quantitative commercial assays for cytomegalovirus (CMV) detection have recently been developed. Their role in the management of patients after transplantation needs to be evaluated. Widespread use of these assays will allow for comparison of results between centers and meaningful interpretation of the significance of viral load measurements. METHODS: Sequential samples from 52 patients after renal transplantation were tested in the murex hybrid capture assay (HCA) and the Roche Amplicor CMV DNA assay (QPCR) and correlated with the development of CMV disease. A comparison of viral loads in plasma and whole blood was also made. RESULTS: Both assays were sensitive and detected all cases of CMV disease. The specificity and positive predictive value increased from 0.34 and 0.36 to 0.85 and 0.96 for the HCA and 0.37, 0.37 to 0.72 and 0.63 for the QPCR following a receiver operator curve analysis. Higher viral loads were measured using the HCA compared to the QPCR. Response to ganciclovir was associated with a greater than 80% reduction in viral load by HCA or greater than 70% using the QPCR. CONCLUSIONS: Both assays were highly sensitive. By using a receiver operator curve analysis a cutoff viral load can be determined which maximizes the clinical utility of these assays.

Adult↗

PubMed2005

High level of correlation of human papillomavirus-16 DNA viral load estimates generated by three real-time PCR assays applied on genital specimens.

Human papillomavirus-16 (HPV-16) viral load could be a biomarker predictive of the presence of high-grade cervical lesions. Recently, several real-time PCR assays have been developed to accurately measure HPV-16 viral load. However, results from various reports using these assays cannot be compared because interassay test correlation has not been documented. The variability of HPV-16 DNA quantitation was assessed by comparing three real-time PCR assays (HPV-16 L1, HPV-16 E6, and HPV-16 E6 PG) applied on 144 genital samples (125 cervicovaginal lavages and 19 specimens collected using vaginal tampons) obtained from 84 women (66 HIV seropositive and 18 HIV seronegative). Correlation was greater between the HPV-16 E6 assays [correlation coefficient (rho) = 0.92] than between each E6 assay and HPV-16 L1 assay (rho = 0.83 and 0.84, respectively). The median HPV-16 copies measured by HPV-16 E6 PG (14,609 HPV-16 copies/2 muL sample) and HPV-16 E6 (18,846 HPV-16 copies/2 muL) were similar (P = 0.27) but were both greater than the median HPV-16 copies measured with the L1 assay (4,124 HPV-16 copies/2 muL; P < 0.001). Correlations between HPV-16 E6 assays were similar for samples containing non-European (rho = 0.93) or European (rho = 0.95) variants. However, the correlation between HPV-16 L1 and HPV-16 E6 PG or HPV-16 E6 was lower for specimens containing non-European variants (rho = 0.80 and 0.76, respectively) compared with specimens containing European variants (rho > 0.85). HPV-16 DNA quantity estimated with the three assays was comparable although lower with the HPV-16 L1 assay. The level of correlation depended on viral polymorphism, viral load, and cervical disease status.

Adolescent↗

PubMed2002

Viral dynamics and pharmacokinetics in combined interferon alfa-2b and ribavirin therapy for patients infected with hepatitis C virus of genotype 1b and high pretreatment viral load.

OBJECTIVE: The aim of this study was to clarify the viral dynamics and single- and multiple-dose pharmacokinetics of ribavirin and interferon (IFN) alfa-2b in the virologic response to combination therapy with both compounds in patients infected with hepatitis C virus (HCV) genotype 1b and high viral load. METHODS: Fourteen patients received high-dose daily induction therapy followed by intermittent maintenance therapy with IFN alfa-2b and daily oral ribavirin for 24 weeks, and followed up for 24 weeks after treatment. Single- and multiple-dose pharmacokinetic studies and viral dynamics were assessed by serial measurements of serum concentrations of both compounds and HCV RNA, respectively, at weeks 1 and 24. RESULTS: During treatment, all 14 patients showed biochemical response (i.e., normalization of serum alanine transaminase activity), while 11 showed virologic response (i.e., undetectable serum HCV RNA level by qualitative polymerase chain reaction assay). Sustained biochemical and virologic response after cessation of treatment was noted in 8 and 2 patients, respectively. Serum ribavirin concentrations asymptoted by 4 weeks of treatment. Serum ribavirin concentrations in steady state, and maximum concentration and accumulation rate of ribavirin after multiple dosing were significantly higher in the presence of sustained virologic response. HCV-related parameters were not significantly associated with sustained virologic response. CONCLUSIONS: Continuous exposure and tissue accumulation of ribavirin may be necessary for sustained virologic response to combination therapy in chronic hepatitis C with genotype 1b and high viral load. Pharmacokinetic analysis of ribavirin provides information on its mechanism of action and for developing more rational treatment for IFN-resistant HCV.

Adult↗

PubMed2004

Frequent human leukocyte antigen class I alleles are associated with higher viral load among HIV type 1 seroconverters in Thailand.

The loss of viral control by the host may be due to the evolution of viruses with mutations that limit presentation by human leukocyte antigen (HLA) to cytotoxic T cells. The authors hypothesized that the consequence of such evolution might be that persons with common HLA class I alleles would be less able to control viremia, on average, than would those with rare alleles. HLA class I typing was completed for 128 injection drug users who seroconverted in a prospective cohort study in Bangkok, Thailand. Logistic regression was used to model viral load (greater than or equal to the median) at 9 and 12 months after seroconversion with an HLA score that profiled the relative prevalence of each individual's alleles. At 12 months after seroconversion, injection drug users with the most common HLA alleles (highest quartile HLA score) had an almost 4-fold increased risk for higher viral load (> or = 32,055 copies/mL) than injection drug users with less common HLA alleles (adjusted odds ratio, 3.92; 95% confidence interval, 1.3-11.8). These findings support the importance of frequency-dependent effects of host genes on HIV type 1 evolution in different populations and suggest that HLA-driven viral evolution critically influences control of viremia in early HIV type 1 infection.

Alleles↗