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PubMed2001

Variation in breastmilk HIV-1 viral load in left and right breasts during the first 3 months of lactation.

The mechanism and risk factors associated with mother-to-child transmission of HIV-1 through breastfeeding remain unclear; breastmilk viral load may be an important determinant of transmission. Analysis of breastmilk cell-free viral load in samples taken from each breast at 1, 6 and 14 weeks postpartum showed that HIV-1 is shed intermittently and load may differ considerably between breasts of an individual woman at any given time. Breastmilk HIV-1 load was undetectable in approximately one-third of samples.

Breast↗

PubMed2006

Becoming a "treatment success": what helps and what hinders patients from achieving and sustaining undetectable viral loads.

Highly active antiretroviral therapy (HAART) adherence research has focused predominantly on individuals with less than optimal clinical outcomes; therefore, little is known about the experiences of individuals who sustain undetectable viral loads. The present study used a qualitative method to explore how individuals who have sustained undetectable viral loads account for their success, and to identify challenges, as well as possible needs, for continued success. Participants were 20 patients at an outpatient infectious disease clinic in an urban center. Participants completed two 60-minute interviews. The Critical Incident Technique was used to identify and classify critical incidents linked with sustaining treatment success. Of the 438 critical incidents collected, 316 were identified as helpful and 122 were identified as unhelpful. Helpful categories included resolving ambivalence, using personal strengths, and fostering helpful relationships. Unhelpful categories were mood, lack of social support, financial difficulties, and medication factors. Doing well on antiretroviral therapy is a dynamic process that requires ongoing attention from both the patient and care provider. The results of this study highlight the efforts of patients to maintain their health and remind care providers not to assume that patients are not facing continuous challenges. Findings from the present study suggest that psychosocial factors do contribute to improved clinical outcomes in patients taking HAART.

Adult↗

PubMed2006

HIV-1 viral load blips are of limited clinical significance.

Many patients on highly active antiretroviral therapy (HAART) who achieve undetectable HIV-1 RNA levels experience transient episodes of detectable viraemia or blips, suggesting there is incomplete suppression of viral replication. This raises concern that drug resistance mutations could develop and cause eventual treatment failure. However, data from recent studies indicate that most blips are actually random biological and statistical variations around a mean viral load below detectable levels (<50 copies/mL) or due to false elevations of viral load from laboratory processing artefacts. Blips are not typically associated with the development of resistance mutations and most importantly are not associated with virological or clinical failure of previously adequate HAART.

Antiretroviral Therapy, Highly Active↗

PubMed2002

The effect of N-acetylcysteine supplementation upon viral load, CD4, CD8, total lymphocyte count and hematocrit in individuals undergoing antiretroviral treatment.

Individuals infected with the human immunodeficiency virus (HIV-1) present with decreased CD4, a progressive increase in viral load, compromised cell immune defense, and hematologic alterations. The aim of this study was to assess the serum viral load, CD4, CD8, lymphocyte count and hematocrit at the beginning of antiretroviral therapy in individuals who were supplemented with N-acetylcysteine (NAC). Twenty volunteers participated in this double-blind, placebo-controlled 180-day study. Ten participants received 600 mg of NAC per day (NAC group) and the other ten serving as a control group received placebo. The above mentioned parameters were determined before treatment, and after 60, 120 and 180 days. In NAC-treated patients hematocrit remained stable and an increase in CD4 cell count took place earlier than that in the control group.

Acetylcysteine↗

PubMed2006

Expression of p16(INK4a) in relation to histopathology and viral load of 'high-risk' HPV types in cervical neoplastic lesions.

A total of 91 cervical archival biopsy series were analysed for the presence and viral load of 'high-risk' types of human papillomavirus (HR-HPV), and p16(INK4a) expression. The women had various degrees of CIN (cervical intraepithelial neoplasia). HPV 16 was the most prevalent type found, at 47% frequency. The frequency of HPV 16 increased with increasing immunoreactivity to p16(INK4a), from 39% to 44% at cases scored low to medium, to 65% at high reactivity. Thirty (33%) of the samples had negative p16(INK4a) analysis results, but were positive for HR-HPV. There was no significant correlation between viral load and the level of p16(INK4a) expression, while the grade of CIN correlated to such expressions. Thus, p16(INK4a) expression analysis yielded information which is consistent with results from the histopathology and might complement the HPV analysis in a clinical prognostic procedure in order to find women at risk for cervical cancer.

Adult↗

PubMed2001

Transforming growth factor beta-1 and interferon-alpha in the AIDS dementia complex (ADC): possible relationship with cerebral viral load?

Mechanisms involved in the pathogenesis of the AIDS-dementia complex are still unclear. The dichotomy between a small number of HIV-infected cells in the brain and their marked dysfunction could be related to a cellular amplification and/or activation of cerebral viral load by several cytokines. This link between cytokines and viral load could play a role in the generation of the clinical dementia syndrome. We have studied cerebral levels of transforming growth factor-beta1 and interferon-alpha, both in the mild and severe AIDS-dementia complex and also compared these cytokines with HIV RNA load in patients with different degrees of dementia. Our data indicate that production of different cytokines characterized the expression of clinical dementia. In the mild AIDS-dementia complex, there was a significant inverse correlation between interferon-alpha and transforming growth factor-beta1 (r = - 0.743; p < 0.001), and HIV-RNA was present in inverse proportion to transforming growth factor beta1 (r = - 0.751; p < 0.001). In patients with severe AIDS-dementia, transforming growth factor-beta1 was undetectable, while interferon-alpha level were higher than in mild AIDS dementia and correlated positively to cerebral HIV-RNA. No significant difference was evident between these cytokines in the serum of ADC patients and in the control samples. Our study suggests that a relationship is possible between productive HIV infection in the cerebral nervous system and a heterogenous and different expression of the immune response via a complex interaction of cytokines with a differential modulation of the dementia phenotype.

AIDS Dementia Complex↗

PubMed2005

Relationship between HIV viral load and Langerhans cells of the cervical epithelium.

AIM: To determine the relationship between the density of cervical mucosa Langerhans cells, cervical histology, and HIV viral load. METHODS: Eighty-four HIV-infected and 17 women at high risk for HIV had cervical biopsies assessed for squamous intraepithelial lesions and Langerhans cell density. Langerhans cells were identified using the S-100 immunohistochemical stain and were counted manually. Polymerase chain reaction assays were used to detect cervical human papillomavirus (HPV)-DNA. T-cell subsets were determined using immunofluorescent flow cytometry. Plasma HIV RNA levels were measured using a nucleic acid sequence-based amplification technique. The associations between cervical Langerhans cell density, cervical histology, CD4 counts, HIV viral loads, HPV-DNA detection, and smoking status were assessed using multivariate statistical models. RESULTS: In multivariate analysis among women infected with HIV, the mean Langerhans cell density per high-powered field was 4.00 among women with no detectable plasma HIV-RNA, and 1.92 among those with detectable HIV-RNA (P = 0.01). The mean cervical Langerhans cell density was increased in women with high-grade squamous intraepithelial lesions compared with those with low-grade squamous intraepithelial lesions and normal/metaplastic histology (3.87 vs 2.11; P = 0.05). Neither HPV-DNA detection, smoking status, nor CD4 count was significantly associated with Langerhans cell density. CONCLUSIONS: The decrease in cervical Langerhans cell density in women with detectable HIV-RNA suggests an impaired mucosal immune response to local infections, such as HPV. Conversely, HPV infection resulting in high-grade dysplasia might be associated with an enhanced local immune response.

Analysis of Variance↗

PubMed1999

Specific immune response to human immunodeficiency virus (HIV)-1 in patients assessed through the production of interferon-gamma and interleukin-4 in HIV-1 p24-activated whole blood cultures: relationship with the viral load in plasma.

We studied the in vitro HIV-1 antigen-stimulated production of IFN-gamma and IL-4 in HIV-1-infected patients and its relationship with viral replication as assessed through the plasma level of HIV-1 RNA. The levels of IFN-gamma and IL-4 were higher in supernatants of stimulated whole blood cultures than in stimulated peripheral blood mononuclear cell cultures, therefore whole blood cultures were used in the rest of the study. Specific IFN-gamma and IL-4 responses to HIV-1 p24 antigen were observed in HIV-1-infected patients but not in healthy controls (n = 23). A lower proportion of individuals with a positive IFN-gamma response to HIV-1 p24 was observed in patients at a declining clinical stage: 62% in asymptomatic patients (CDC group A, n = 16) versus 19% in symptomatic patients (CDC groups B and C, n = 21; P = 0.007, chi2 testing), whereas the proportion of individuals with a positive IL-4 response to HIV-1 p24 was almost similar in both groups of patients (25% versus 23.8%). Increased IL-4 production by HIV-1 p24-activated immunocompetent cells of patients and a predominant IL-4 response to HIV-1 p24 (with IL-4/IFN-gamma > 1) were positively correlated with an increased viral load. In contrast, there was no correlation between the mitogen-stimulated production of IL-4 and IFN-gamma and the viral load in plasma. The CD8 T cells from whole blood of patients, but not from controls played a significant role in the HIV-1 p24-activated production of IFN-gamma and IL-4. In conclusion, HIV-1-antigen-stimulated whole blood appears to be a valuable tool to study the production of IL-4 in HIV-1-infected patients. The cytokine profile pattern in response to epitopes of HIV-1 gag p24 may play an important role in the host immune response to HIV-1.

Adult↗

PubMed2004

Human papillomavirus type 16 viral load is higher in human immunodeficiency virus-seropositive women with high-grade squamous intraepithelial lesions than in those with normal cytology smears.

Human papillomavirus type 16 (HPV-16) viral load in cervicovaginal lavage samples collected from 66 human immunodeficiency virus-seropositive women was inversely correlated with blood CD4 count (P = 0.002). HPV-16 viral load was 81-fold higher in women with cervical smears suggestive of high-grade lesions (median, 4,425,883 copies/ micro g of DNA) than in women with normal smears (median, 54,576), controlling for age (P = 0.006).

Base Sequence↗

PubMed2000

Plasma HIV-1 RNA viral load and serum vitamin A and E levels in HIV-1 infected pregnant women.

The aim of this study was to assess the correlation between plasma HIV-1 RNA viral load and serum vitamin A and E concentrations and vitamin E/cholesterol ratio in HIV-1 infected pregnant women not receiving antiretroviral therapy There were no significant correlations between plasma HIV-1 RNA viral load and serum vitamin A and E concentrations and vitamin E/cholesterol ratio. However, the presence of underlying vitamin A deficiency in these pregnant women was common.

Adult↗

PubMed1999

Simultaneous treatment of cytomegalovirus and varicella zoster infections in a renal transplant recipient with ganciclovir: use of viral load to monitor response to treatment.

Disseminated zoster occurring simultaneously with cytomegalovirus (CMV) disease in a renal transplant recipient is potentially life threatening. We describe the use of intravenous ganciclovir to treat both infections. The efficacy of treatment was assessed clinically and by the measurement of CMV viral load using the hybrid capture (Murex version 2) and varicella zoster (VZV) viral load using an in-house assay. Results from this case suggest that clinical resolution in severe viral infections such as described below may be related to early control of viraemia.

Adult↗

PubMed2003

The use of data mining to investigate a possible quality problem with ultrasensitive HIV viral load data at a large reference laboratory.

Suppression of HIV viral load to <50 copies/mL, the lower limit of detection for the ultrasensitive assays, has been shown to correlate with favorable clinical outcome. Patients periodically exhibited transient or sustained low-level viremia based on this test. In order to investigate a possible quality concern, we used our corporate data warehouse to examine the patterns in our data over time as well as across geographic regions.

Data Interpretation, Statistical↗

PubMed2006

A comparison between abacavir and efavirenz as the third drug used in combination with a background therapy regimen of 2 nucleoside reverse-transcriptase inhibitors in patients with initially suppressed viral loads.

BACKGROUND: Our objective was to compare the rate of viral rebound and therapy failure in patients receiving abacavir or efavirenz as the third drug (in addition to 2 non-abacavir nucleosides) in combination antiretroviral therapy (cART) and to compare the rate of metabolic alteration associated with these regimens. METHODS: We conducted a multicohort prospective observational study of human immunodeficiency virus-infected patients who had attained viral loads < or = 80 copies/mL while receiving cART, without having previously received antiretrovirals. The rates of virological rebound, therapy failure, and lipid-level alteration during follow-up were calculated as the number of events divided by person-years of follow-up (PYFU). A multivariable analysis was performed using a Poisson regression model. RESULTS: We studied a total of 744 patients; the median age was 37 years, 27% of the patients were female, and 41% were heterosexual. There was a total of 854 PYFU spent receiving efavirenz and 285 spent receiving abacavir. The nucleoside reverse-transcriptase inhibitor pairs most frequently used were zidovudine/lamivudine (66% of PYFU), stavudine/lamivudine (17.6%), and stavudine/didanosine (5.4%). The adjusted relative rates of virological failure and therapy failure for abacavir, compared with those for efavirenz, were 2.17 (95% confidence interval [CI], 1.12-4.18; P = .02) and 1.41 (95% CI, 1.01-2.01; P = .05), respectively. CONCLUSIONS: Patients with virological suppression while receiving regimens containing abacavir appear more likely to experience virological and therapy failure than those receiving efavirenz as their third drug. Although this is a selected group of adherent patients, bias cannot be ruled out, because this is a nonrandomized comparison.

Acquired Immunodeficiency Syndrome↗

PubMed2004

Evidence for a relation between the viral load and genotype and hepatitis C virus-specific T cell responses.

BACKGROUND/AIMS: The reason why patients with hepatitis C virus (HCV) genotype non-1 infection respond better to antiviral therapy than patients with genotype 1 infection is not known. The aim of this study is to explore the relation between the viral genotype, viral load, and the endogenous T cell response. METHODS: The viral genotype, the viral load, and the endogenous proliferative T cell response to the non-structural 3 protein (NS3) was analysed using serum and peripheral blood mononuclear cells from 103 patients with chronic HCV infection. RESULTS: Among 71 nontreated patients a T cell response was more common among those infected by genotype 3, as compared to those infected with genotype 1 (P<0.05). Among 32 patients undergoing antiviral therapy, presence of a T cell response was more common in genotype non-1 infected patients than in those infected by genotype 1 (P<0.01). Presence of a T cell response was related to a more rapid viral clearance (P<0,05), a negative HCV RNA test at week 12 (P<0.05), and a shorter viral half-life (P<0.05). CONCLUSIONS: The presence of an NS3-specific T cell response is related to the viral genotype and to a more rapid clearance of HCV RNA during antiviral therapy.

Antiviral Agents↗

PubMedDate not supplied

[Amantadine-HCL in the treatment of chronic hepatitis C in non-responders to alpha-interferon. Effect on ALT serum levels and viral load].

Due to the limited efficacy of alpha-interferon for chronic hepatitis C amantadine has been proposed as a possible alternative method of treatment. However, few studies about efficacy of amantadine in chronic hepatitis C are available with controversial results. Stimulated by recent data in the literature, we studied the effect of 100 mg of amantadine HCL (alone) PO bid, for a four month period on alanine aminotransferase serum levels and viral load in a cohort of 18 patients (14 males and 4 females) with chronic hepatitis C, non-responders to alpha-interferon. Inclusion criteria were: detectable serum HCV-RNA, alanine aminotransferase above the upper limit of normal, chronic inflammation on liver biopsy, no other associated chronic liver disease and written informed consent. Available biopsies showed initially four cases of cirrhosis, six of chronic persistent hepatitis and eight of chronic active hepatitis. The most prevalent HCV genotypes were 3a (n = 9, 52.94%) and 1b (n = 6, 32.29%). Viral load (Amplicor HCV Monitor, Roche, USA) and alanine aminotransferase levels were obtained at baseline and after four months of treatment. All patients enrolled into the study but one completed the treatment. One patient discontinued amantadine due to severe depression. No significant reduction was observed between baseline and final values of alanine aminotransferase (139.118 +/- 79.789 vs. 99.588 +/- 62.583 U/L, P = 0.059) and viral load (7.154 +/- 1.596 vs. 6.574 +/- 1.584 log copies/mL, P = 0.147). Amantadine alone was not effective neither eradicating viremia nor normalizing alanine aminotransferase levels in chronic hepatitis C non-responders to alpha-interferon patients. It is suggested that only a study with amantadine alone in-patients without previous treatments could determine its efficacy in comparison with alpha-interferon.

Adult↗

PubMed2006

Prolonged negative HCV-RNA status led to a good outcome in chronic hepatitis C patients with genotype 1b and super-high viral load.

OBJECTIVE: We examined whether a sustained negative HCV-RNA status for 48 weeks affects the outcome in patients with genotype 1b and super-high viral load, and also investigated whether the outcome is affected by the induction therapy of twice-daily pre-administrated interferon (IFN)-beta. METHODS: 78 eligible patients were divided into four groups. 40 were patients assigned to the short treatment protocol. 13 patients received 3 MU IFN-beta twice daily for 2 weeks followed by IFN-alpha2b+ribavirin for 22 weeks (beta-induction group: group 1). 27 patients received IFN-alpha2b+ribavirin for 24 weeks (standard combination group: group 2). 38 patients were assigned to the maintenance treatment protocol. All of the 13 in the beta-induction group (group 3) and 21 of 25 patients in the standard combination group (group 4) who were negative HCV-RNA PCR at week 24 had IFN monotherapy to maintain a negative HCV-RNA result for 48 weeks. RESULTS: An HCV-RNA-negative status at week 24 was observed in 96% (25/26) of groups 1 and 3 versus in 79% (41/52) of groups 2 and 4 (p<0.01). The sustained virological response (SVR) was 38% (5/13) in group 1 and 11% (3/27) in group 2 (p<0.05). In the maintenance treatment, SVR was observed in 46% (6/13) of group 3 and 32% (8/25) of group 4 (NS). CONCLUSIONS: A sustained negative HCV-RNA status for 48 weeks might be associated with viral elimination in patients with genotype 1 and super-high viral load.

Adult↗

PubMed2004

The role of non-viral load surrogate markers in HIV-positive patient monitoring during antiviral treatment.

Monitoring the efficacy of highly active antiretroviral treatment (HAART) is crucial if disease progression and the emergence of viral mutants are to be avoided. Classical viral load monitoring is too expensive for large-scale use in resource-limited settings. Three alternative measures, CD4 count, total lymphocyte count (TLC) and haemoglobin, were evaluated as surrogate markers of treatment success (viral load below detection level) among 710 HIV-positive patients who started HAART in an HIV treatment centre in Belgium. TLC correlated well with changes in CD4 counts during HAART, but an increase in TLC alone was a poor predictor of treatment success. A combination of increases in both haemoglobin levels and TLC proved a reliable predictor of successful treatment outcome comparable to the increase in CD4 count, but its specificity and sensitivity were low.

Adult↗

PubMed2006

CD4 count and viral load time-courses in patients treated with highly active antiretroviral therapy and association with the CDC staging system.

OBJECTIVES: The aim of the study was to analyse CD4 cell count and viral load dynamics in patients undergoing antiretroviral therapy and their association with the Centers for Disease Control and Prevention (CDC) classification system. METHODS: CD4 cell count and viral load were determined in 2982 patients who were classified according to clinical and immunological CDC stages. Measurements were carried out at baseline and at the 3rd, 6th and 12th months. RESULTS: Clear differences in the immunological and virological responses to therapy were observed depending on the CDC stage, with better results associated with less advanced stages. There was a marked parallelism in the CD4 cell count curves of the different CDC stages over the year of follow up, in both naïve and experienced patients, indicating that the increase in CD4 cell count at each time-point was similar for all clinical and immunological CDC stages. However, as the baseline values were closely associated with CDC stage, the CD4 cell counts finally reached were clearly dependent on CDC stage. The highest virological responses were observed during the initial 3 months, particularly in naïve patients, but whereas naïve patients showed additional increases up to the 6th month experienced patients reached a plateau at the 3rd month. The CD4 increases were also higher during the initial 3 months but persisted during the year of follow-up. CONCLUSION: Both clinical and immunological CDC stages at baseline are highly predictive of the immunological and virological response to therapy, a finding that could have clinical implications.

Adult↗