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PubMed1996

Male-to-female transmission of human T-cell lymphotropic virus types I and II: association with viral load. The Retrovirus Epidemiology Donor Study Group.

SUMMARY: Risk factors for male-to-female sexual transmission of human T-lymphotropic virus types I and II (HTLV-I/II) were investigated among HTLV-seropositive volunteer blood donors and their long-term (> or = 6 month) sex partners. Direction of transmission in concordantly seropositive pairs was assessed by analyzing risk factors for HTLV infection. Donors and their partners were also questioned regarding sexual behaviors during their relationships; HTLV antibody titers and viral load were determined for specimens from male partners. Among 31 couples in whom HTLV-infected men likely transmitted infection to their partners (11 HTLV-I and 20 HTLV-II) and 25 male-positive, female-negative couples (8 HTLV-I and 17 HTLV-II), HTLV transmitter men had been in their relationships longer (mean 225 months vs. 122 months) and had higher viral loads (geometric mean 257,549 vs. 2,945 copies/300,000 cells for HTLV-I; 5,541 vs. 118 copies/300,000 cells for HTLV-II) than non-transmitters (P = 0.018 and P = 0.001 for duration of relationship and viral load, respectively, logistic regression analysis). Transmitter men also tended to have higher antibody titers against various env and whole virus proteins than non-transmitters. The identification of high viral load and duration of relationship as risk factors provides a biologically plausible framework in which to assess risk of sexual transmission of the HTLVs.

Adult↗

PubMed2005

A stress and coping model of medication adherence and viral load in HIV-positive men and women on highly active antiretroviral therapy (HAART).

The authors tested a structural model that incorporated age, time since diagnosis, social support, coping, and negative mood as predictors of medication adherence and HIV viral load on 188 men and 134 women on highly active antiretroviral therapy (HAART). The authors used psychosocial latent factors formed from baseline measures to predict latent factors of adherence, as assessed by electronic monitoring and self-report, and viral load defined by indicators assessed over a 15-month period. Results from the model indicate that greater negative mood and lower social support are related to greater use of avoidance-oriented coping strategies. Use of these coping strategies by patients on HAART is related to poorer medication adherence and, subsequently, higher viral load. This model advances researchers' understanding of the contribution of psychosocial variables in predicting treatment adherence and disease progression in HIV-positive men and women.

Adaptation, Psychological↗

PubMed2002

Human papillomavirus prevalence, viral load and cervical intraepithelial neoplasia in HIV-infected women.

HIV-infected women from S o Paulo city were enrolled in a cross-sectional study on Human Papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN) prevalence and their association with laboratory markers of AIDS, namely HIV viral load and CD(4)(+) cell counts. A cervical specimen was collected and submitted to Hybrid Capture, a test for HPV viral load determination. HPV-DNA was detected in 173 of 265 women (64.5%). Twenty (7.5%) women were infected by one or more low-risk viruses, 89 (33%) by one or more high-risk viruses, and 64 (24%) harbored at least one HPV type from each risk group. Abnormal smears were observed in 19% of the patients, though there were no invasive carcinomas. Severely immunosuppressed patients (CD(4)/microL <100) were at the greatest risk of having a cytological abnormality and a high high-risk HPV viral load.

Adolescent↗

PubMed2003

Congenital cytomegalovirus infection in twin pregnancies: viral load in the amniotic fluid and pregnancy outcome.

Human cytomegalovirus (CMV) is the most common cause of viral intrauterine infection and fetal damage largely attributable to maternal primary infection. Most cases of congenital CMV infection in twins reported in the literature involved only 1 twin. We assessed the validity of polymerase chain reaction (PCR) and quantitative PCR on amniotic fluid (AF), at 21 to 22 weeks' gestation and at least 6 to 8 weeks after seroconversion, to predict the outcome of newborns in twin pregnancies. Two pregnant women with twin pregnancies and 1 woman with a triple pregnancy with primary CMV infection defined by the presence of immunoglobulin (Ig) M and low IgG avidity and/or by the presence of clinical symptoms and abnormal liver enzyme values were evaluated. CMV infection was found in 6 fetuses/newborns, 3 of whom were symptomatic. In the first twin pregnancy with diamniotic-dichorionic separate placentas, CMV symptomatic infection of the female twin was demonstrated by positive virus isolation and high viral load in AF. The male fetus was not infected as demonstrated by negative CMV culture and DNA detection in AF. In the triple pregnancy, the woman had a placenta with 2 monozygotic twins (females) and a separate placenta with a heterozygotic twin (male). The quantitative PCR results were 10(3) genome equivalents (GE)/mL of females AF and 1.9 x 10(5) GE/mL of male AF. Both female twins were asymptomatic at birth, whereas the male presented petechiae, thrombocytopenia, and cerebral ventriculomegaly. In the last twin pregnancy with fused dichorionic placentas, congenital CMV infection of both twins was diagnosed at birth in contrast with prenatal diagnosis. At time of amniocentesis, the left side twin was not infected as shown by negative results of CMV culture and DNA detection in the AF. CMV infection of the right side twin was demonstrated by positive CMV DNA detection with a CMV DNA load of 4.9 x 10(4) GE/mL and positive virus isolation in the AF. The morphologic and histologic examinations of the placentas strongly supported a prenatal horizontal acquisition of CMV infection. These twin pregnancies showed a marked difference in the quantity of virus load documented by the prenatal diagnosis suggesting that twin fetuses may react differently to primary maternal infection despite being exposed to the same maternal influences. A high viral load is correlated with congenital CMV infections symptomatic at birth. In such cases, with fetal infection of only 1 twin (at amniocentesis) and fusion of placentas, fetal outcome of both twins needs to be evaluated for the possibility of viral transfer from one fetus to the other.

Amniotic Fluid↗

PubMedDate not supplied

Effective interferon therapy for chronic hepatitis C patients with low viral loads.

BACKGROUND/AIMS: Possible short-term interferon therapy was investigated in chronic hepatitis C patients with genotype 2a or 2b and low viral-loads. Furthermore, initial changes of hepatic C virus RNA levels in early phase interferon therapy, and the number of pretreatment mutated clones at hypervariable region-1 were determined in order to upgrade interferon therapy efficacy prediction rates. METHODOLOGY: Study subjects were 31 patients with histologically proven chronic hepatitis C, having less than 1 Meq/mL of hepatic C virus RNA levels. Daily dose was defined as 9 MU of interferon; patients with genotype lb were treated for 26 weeks, while those with genotype 2a or 2b were treated for 16 weeks. RESULTS: Sustained response rates showed no difference in efficacy between the 2 groups (66.7% vs. 62.5%). Response rates based on the number of hypervariable region-1 clones indicated that the fewer the number of mutated clones, more significant was the increase in efficacy. Efficacy as hepatic C virus RNA in early phase treatment showed no difference in response rates between negative and positive groups at any time point from day 1. CONCLUSIONS: In a low viral-load group, the number of hypervariable region-1 clones was a critical factor influencing interferon therapy efficacy. Thus, 16-week interferon therapy was effective and economical.

Adult↗

PubMed2006

Expression of E6/E7 mRNA from 'high risk' human papillomavirus in relation to CIN grade, viral load and p16INK4a.

Detection of E6/E7 mRNA expression with real-time nucleic acid sequence-based amplification assay (NASBA) method (PreTect HPV-Proofer) from high-risk types of human papillomaviruses (HR-HPV) were compared with the presence of viral load, determined with quantitative real-time PCR in 80 cervical samples. Results regarding positivity and typing were in agreement using the two methods. However, there was no correlation between viral loads for HPV 16 or 18/45 and oncogene expression. Among 15 women with low grade atypia detected at a population-based cytology screening, and scored as 'within normal limits' according to histopathology, 14% were positive for oncogene expression, whereas 71% were HR-HPV positive. A correlation was observed between HR-HPV oncogene expression and high scores of p16(INK4a) positivity. Since HPV-Proofer detects full-length E6/E7 mRNA, a positive result should correlate with presence of integrated HPV, loss of HPV replication and stabilized E6/E7 full-length mRNA expression. Such expression from integrated HR-HPV generates a high and stable expression of full-length E6 proteins, which explains why a positive HPV-Proofer result was independent of viral load and correlate with high expression of p16(INK4a). Thus, E6/E7 oncogene expression analysis yielded information, which is consistent with and will complement the results from a real-time PCR method in a clinical prognostic procedure.

Adult↗

PubMed2003

Prevalence of genotypic and phenotypic HIV-1 drug-resistant strains among patients who have rebound in viral load while receiving antiretroviral therapy in the UNAIDS-Drug Access Initiative in Abidjan, Côte d'Ivoire.

OBJECTIVE: To determine the prevalence of genotypic and phenotypic antiretroviral (ARV) drug-resistant HIV-1 strains among patients with viral load rebound while receiving ARV therapy in Abidjan, Côte d'Ivoire. METHODS: Between August 1998 and April 2000, we selected all patients (n = 241) who had received ARV drug therapy for at least 6 months in the UNAIDS-Drug Access Initiative (DAI), in Abidjan. We analyzed for genotypic and phenotypic drug resistance among 97 (40%) of the 241 patients who had a rebound in plasma viral load, defined as an initial decrease of > 0.5 log10 copies/ml followed by a subsequent increase of > 0.25 log10 copies/ml. RESULTS: Of the viruses isolated from the 97 patients, 86 (88.7%) had usable sequences and 68 (79%) of the 86 patients had genotypic resistance to at least one reverse transcriptase inhibitor (RTI) or protease inhibitor (PI). Resistant mutations were found for zidovudine in 50 (78%) of 64 patients who had received the drug, 11 (68.7%) of 16 patients on lamivudine, for nevirapine in two (2%), for indinavir in one (1%), and for ritonavir in one (1%). Phenotypic resistance to at least one nucleoside RTI was seen in 45 (56%) of the 80 patients tested, to non-nucleoside RTIs in eight (10%), and to PIs in one (1.3%). Multivariate regression analysis showed factors associated with resistance to be initial treatment with dual therapy (P = 0.04) compared with highly active antiretroviral therapy, and maximal initial viral load response (P = 0.006). CONCLUSION: Our results demonstrate a high prevalence of ARV drug resistance associated with dual ARV therapy. These results indicate the limited role for dual ARV therapy.

Adult↗

PubMed2006

IL-2 increased RANTES production and CD25 expression in cultured PBMCs only from antiretroviral treated HIV-1+ patients with detectable viral loads.

In order to better understand the possible beneficial effects of intermittent IL-2 treatment as complement of antiretroviral therapy in HIV-1+ patients, we have measured the levels of RANTES in the supernatants and the CD25 expression in cultured PBMCs obtained from HIV-1+ individuals in presence of IL-2. The results showed a significant increases in RANTES production and in the expression of CD25+ in the cultures with IL-2 of PBMC obtained from HIV-1+ patients with a detectable viral load in comparison with both, HIV-1+ patients with no detectable viral loads and with healthy individuals. These results suggest that therapeutic IL-2 administered in addition to highly active anti-retroviral therapy (HAART) may contribute to increase the effect of this therapy by rising both RANTES production and CD25 expression only in HIV-1+ patients with detectable viral loads.

Antigens, CD↗

PubMed2005

Natural FCoV infection: cats with FIP exhibit significantly higher viral loads than healthy infected cats.

Natural feline coronavirus (FCoV) infection has been shown to not only induce intestinal infection with viral shedding, but also systemic infection which either remains without clinical signs or leads to feline infectious peritonitis (FIP). As systemic infection is not the key event in the development of FIP, the question arises as to whether a potential difference in viral load might be of importance. Therefore, the purpose of this study was to quantitatively assess feline coronavirus (FCoV) RNA loads in haemolymphatic tissues of healthy, long-term FCoV-infected cats and cats with FIP. In cats that died from FIP, viral loads were significantly higher, indicating a higher rate of viral replication or a reduced capacity for viral clearance in cats developing and/or suffering from FIP.

Animals↗

PubMed2002

High CD4+ T-cells percentage and/or low viral load are predictors of 1-5 years survival in HIV-1 vertically infected Thai children.

OBJECTIVE: Enrolling pediatric HIV children into the clinical trial of when to initiate antiretroviral therapy is a crucial ethical issue. CD4+ T-cells percentage and/or viral load were able to identify potential cases of survival through 5 years of age. METHOD: HIV infected cohort from 1992 to 1994 from Children's and Siriraj Hospitals were followed from 1 through 5 years of age. The outcome was survival or death. The predictors were CD4 percentage and viral load (without age and clinical status adjustment). RESULT: 16 of 35 (45.71%) of the cohort survived through 5 years of age. The probability of survival increased to almost 100 per cent either with CD4+ T-cells percentage of over 22 or viral load of less than 500,000.

Adult↗

PubMed2005

New combination test for hepatitis C virus genotype and viral load determination using Amplicor GT HCV MONITOR test v2.0.

AIM: To develop a new sensitive and inexpensive hepatitis C virus (HCV) combination test (HCV Guideline test) that enables the determination of HCV genotypes 1, 2 and 3, and simultaneous determination of HCV viral load using commercial Amplicor GT HCV MONITOR test v2.0 (microwell version). METHODS: The HCV Guideline test used the PCR product generated in commercial Amplicor GT HCV Monitor test v2.0 for viral load measurement using microwell plate version of Amplicor HCV Monitor and also captured on separate plates containing capture probes and competitive oligonucleotide probes specific for HCV genotypes 1, 2 and 3, The HCV genotype was subsequently determined using the biotin-labeled PCR product and five biotin-labeled HCV-specific probes. RESULTS: The sensitivity of the HCV Guideline test was 0.5 KIU/mL. Specificity of the HCV Guideline test was confirmed by direct sequencing of HCV core region and molecular evolutionary analyses based on a panel of 31 samples. The comparison of the HCV Guideline test and an in-house HCV core genotyping assay using 252 samples from chronic hepatitis C patients indicated concordant results for 97.2% of samples (59.5% genotype 1, 33.7% genotype 2, 6.0% genotype 3, and 0.8% mixed genotypes). Similarly, the HCV Guideline test showed concordance with a serological test, and the serological test failed to assign any serotype in 12.7% of the samples, indicating a better sensitivity of the HCV Guideline test. CONCLUSION: Clinically, both viral load and genotypes (1, 2 and 3) have been found to be major predictors of antiviral therapy outcome regarding chronic hepatitis C based on guidelines and they are, in normal circumstances, performed as separate stand-alone assays. The HCV Guideline test is a useful method for screening large cohorts in a routine clinical setting for determining the treatment regimen and for predicting the outcome of antiviral therapy of chronic hepatitis C.

Evolution, Molecular↗

PubMed2002

Epstein-Barr viral load assessment in immunocompetent patients with fulminant infectious mononucleosis.

We describe 2 immunocompetent adolescents with fulminant infectious mononucleosis and virus-associated hemophagocytosis. A new quantitative polymerase chain reaction revealed high serum Epstein-Barr virus DNA levels in these patients. One patient died with an increasing viral load not responding to corticosteroids followed by antiviral and intensified immunomodulatory treatment. The other patient received corticosteroids and acyclovir at diagnosis; her rapid recovery was heralded by a steep decline of viral load. We propose monitoring the clinical course of fulminant infectious mononucleosis in immunocompetent patients by Epstein-Barr virus DNA quantification and prompt corticosteroid and antiviral therapy when viral load is high.

Acyclovir↗

PubMed2001

The effects of an HIV-1 immunogen (Remune) on viral load, CD4 cell counts and HIV-specific immunity in a double-blind, randomized, adjuvant-controlled subset study in HIV infected subjects regardless of concomitant antiviral drugs.

OBJECTIVE: We examined the activity of an HIV-1 immunogen (Remune) on viral load, CD4 cells and HIV-1 specific immunity. METHODS: Plasma and peripheral blood mononuclear cells were obtained in a predefined random subset of subjects (n = 252) from a multicentre, double-blind, adjuvant-controlled phase III clinical endpoint study. RESULTS: The subjects treated with the HIV-1 immunogen had a significantly greater decline in viral load at multiple time points (P < 0.05), a trend towards increased CD4+ T cell counts and significantly enhanced HIV-1 specific immune responses as measured by HIV-1 lymphocyte proliferation (P < 0.001) compared to the adjuvant control group. Furthermore, in the HIV-1 immunogen treated group, enhanced HIV-1 specific lymphocyte proliferative immune responses were associated with decreased HIV-1 plasma RNA. CONCLUSION: These results suggest that, in a predefined, random subset of subjects, a beneficial effect of the HIV-1 immunogen was observed on viral load, CD4+ T cells, and HIV-specific immunity. These differences were observed in a background of multiple drug therapies. Ongoing trials are evaluating the effect of the combination of this HIV-1 specific, immune-based therapy with potent antiviral drug therapy on virological outcomes.

AIDS Vaccines↗

PubMed2002

Longitudinal analysis of Epstein-Barr viral load in plasma and peripheral blood mononuclear cells of transplanted patients by real-time polymerase chain reaction.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a significant cause of morbidity and mortality in transplant recipients and is caused by iatrogenic suppression of T cell function. Elevations in the Epstein-Barr viral (EBV) load in plasma (>1000 EBV copies/100 microL plasma) or peripheral blood mononuclear cells (PBMC) (>5000 EBV copies/microg PBMC DNA) as determined by real-time quantitative polymerase chain reaction (RQ-PCR) have been shown to be sensitive indicators for the development of PTLD in patients. METHODS: The diagnostic value of frequent monitoring of EB viral load in peripheral blood from 46 patients after heart transplantation was investigated compared with 21 healthy controls in a prospective longitudinal study. EB viral load was detected in PBMC and plasma using real-time quantitative (RQ)- polymerase chain reaction (PCR)-based assays and compared with serological parameters of EBV infection or with the occurrence of CMV reactivations. RESULTS: EB viral load was significantly increased in PBMC and in plasma from transplanted patients compared with healthy controls. Regarding levels and fluctuations of EB viral load in PBMC, patients were grouped in three distinct categories with high, intermediate, or low EB viral load. Although in one patient without PTLD, the EB viral load exceeded the threshold value for PTLD of 5000 EBV copies/microg PBMC DNA, all patients had an EB viral load in plasma of less than 1000 EBV copies/100 microL plasma. No correlation was found between the level of EB viral load and serological parameters of EBV reactivations in patients or in healthy control individuals. EBV and cytomegalovirus reactivations occurred independently in the majority of patients. CONCLUSIONS: EB viral load measurements in plasma and PBMC of patients using RQ-PCR are superior to serology and are a powerful tool for monitoring transplanted patients.

Adolescent↗

PubMed2005

Memory responses in human immunodeficiency virus type 1-infected individuals with long-term viral load suppression are independent of CD4 cell nadir.

The persistence of memory responses in suppressive highly active antiretroviral therapy (HAART) has been an area of controversy. By using a previously described proliferation assay that augments specific responses, peripheral blood lymphocytes (PBL) from 61 human immunodeficiency virus type 1-seropositive individuals with CD4 counts of >300/mm3 and suppressed viral burdens were studied for response to p24 antigen as a function of time of viral load suppression on HAART. In the majority of cases, proliferative responses could be measured in PBL from patients with plasma viral load suppression. No differences could be found in proliferative responses from PBL between individuals with a low and those with a high CD4 cell nadir. PBL that did not respond to either Casta antigen or p24 were found to have a higher percentage of naive cells than did PBL that responded well to antigen. These data support the contention that, after long-term viral load suppression, PBL from infected individuals have memory cell populations that can respond to antigenic stimulation under inducible conditions.

Adult↗

PubMed2005

The impact of improved self-efficacy on HIV viral load and distress in culturally diverse women living with AIDS: the SMART/EST Women's Project.

The purpose of the present study was to determine whether changes in self-efficacy over time would be related to changes in disease progression markers (CD4, viral load) in a sample of women with AIDS. A self-efficacy measure was developed and two sub-scales emerged via factor analysis of 391 HIV-positive women: AIDS Self-efficacy and Cognitive Behavioral Skills Self-efficacy. Subsequently, the sub-scales and an additional adherence self-efficacy item were given to 56 HIV-positive women who were measured at two time points three months apart. Half of these women were randomly assigned to a CB intervention and half to a low intensity comparison condition. Increases in AIDS Self-efficacy over the three-month period were significantly related to increases in CD4 and decreases in viral load. Similarly, increases in Cognitive Behavioral Skills Self-efficacy were significantly related to decreases in distress over time. Findings were maintained within the intervention group alone. Interestingly, increases in cognitive behavioral skills self-efficacy and increases in the self-efficacy adherence item were also significantly related to decreases in viral load. Implications of the findings and suggestions for future research are discussed.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Nutritional status impairments in HIV-infected patients are associated with increased TNF-alpha and IL-6 serum levels but not with viral load.

BACKGROUND: Cytokines may alter metabolic pathways and contribute to malnutrition among human immunodefiency virus (HIV)-positive individuals. PATIENTS AND METHODS: Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), soluble IL-2 receptors (sIL-2R), beta2-microglobulin serum levels and plasma viral load of 45 HIV-positive patients were determined and correlated to nutritional status impairment. Patients were grouped by CD4 counts into categories I (< 200/microl), II (200-499/microl), III (> or = 500/microl). There were 15 healthy controls. A nutritional grading system, based on anthropometric and laboratory data, was devised. Scores ranged from 0 to 5 (eutrophic to malnutrition). RESULTS: AIDS patients' cytokines and immune marker levels were significantly higher than those of the controls, but not always higher than those of other categories. AIDS patients had higher nutritional deficit grades than category III (p < 0.05) or the controls (p < 0.02) which, except for viral load, correlated with the parameters studied. CONCLUSION: Nutritional status impairments in HIV-positive individuals were associated with immune activation but not with viral load.

Adult↗

PubMed2002

Ratio between Epstein-Barr viral load and anti-Epstein-Barr virus specific T-cell response as a predictive marker of posttransplant lymphoproliferative disease.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is closely linked to primary Epstein-Barr virus (EBV) infection and a defect of EBV specific cellular immunity is supposed to be the basis of PTLD. However, EBV load is so far the only marker proposed to evaluate PTLD risk, and no study has investigated the role of specific anti-EBV T lymphocytes (EBV-TL). METHODS: We therefore prospectively measured the EBV-TL by enzyme-linked immunospot (elispot) assay, in correlation to EBV load by real-time quantitative PCR and lymphoproliferation occurrence in 45 liver transplanted children. RESULTS: EBV load at the time of primary infection was high in all patients irrespective to subsequent emergence of PTLD. Seven patients developed PTLD, all of them following primary EBV infection. All seven had low EBV-TL (<2/mm3) associated with high viral load (>25,000 copies/microg DNA). Both parameters can be combined in a 100% positive predictive index. Healing from lymphoma was characterized by rapid EBV-TL increase concomitant to decreasing viral load. EBV-TL follow-up helped to adapt immunomodulation. No patient had PTLD whenever EBV-TL were above 2/mm3. CONCLUSIONS: We conclude that high viral load is systematic in patients who underwent primary EBV infection and is indicative of the PTLD risk only if there is low concomitant cellular immune response. Healing from PTLD requires modulation of immunosuppression, and appearance of EBV-TL.

Adolescent↗