scholarly journals Suppression of Plasma Virus Load below the Detection Limit of a Human Immunodeficiency Virus Kit Is Associated with Longer Virologic Response than Suppression below the Limit of Quantitation

1999 ◽  
Vol 180 (4) ◽  
pp. 1347-1350 ◽  
Author(s):  
J. M. Raboud ◽  
S. Rae ◽  
R. S. Hogg ◽  
B. Yip ◽  
C. H. Sherlock ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Detection Limit ◽  
Virologic Response ◽  
Plasma Virus ◽  
Virus Load ◽  
Limit Of Quantitation ◽  
Immunodeficiency Virus ◽  
Plasma Virus Load

scholarly journals Relationship between In Vitro Human Immunodeficiency Virus Type 1 Replication Rate and Virus Load in Plasma

2003 ◽  
Vol 77 (22) ◽  
pp. 12105-12112 ◽  
Author(s):  
Thomas B. Campbell ◽  
Kristina Schneider ◽  
Terri Wrin ◽  
Christos J. Petropoulos ◽  
Elizabeth Connick
Keyword(s):  
Replication Capacity ◽  
Replication Rate ◽  
Plasma Virus ◽  
Virus Load ◽  
Immunodeficiency Virus ◽  
Plasma Virus Load ◽  
Hiv 1 ◽  
Rna Concentration

ABSTRACT Although plasma human immunodeficiency virus type 1 (HIV-1) RNA concentration is a major determinant of the rate of HIV-1 disease progression, the reasons for variability in plasma virus loads among infected individuals are not fully understood. We conducted investigations with 15 HIV-1-infected individuals who were not receiving antiretroviral therapy to evaluate the hypothesis that HIV-1 replication rate in vitro is a significant determinant of plasma virus load. Virus could not be isolated from one subject. Two subjects were excluded because they had features previously associated with distinct plasma virus loads and altered rates of disease progression; one harbored a syncytium-inducing virus and the second was heterozygous for a 32-bp deletion from the CCR5 gene. HIV-1 replication rates were determined by culturing autologous virus isolates in phytohemagglutinin-treated peripheral blood mononuclear cells (PBMC) and determining the rate of p24 antigen production during the logarithmic phase of viral replication. The contribution of HIV-1 reverse transcriptase (RT) and protease (PR) alleles to replication capacity was assessed using recombinant viruses in a single-cycle infection assay. HIV-1 replication rates ranged from 0.15 to 0.76 log10 pg/ml/day and were reproducible within the same donor PBMC (coefficient of variation ± 4%). RT-PR replication capacity ranged from 14 to 95% of that of control virus and was linearly related to replication rate (r 2 = 0.53; P = 0.007). Plasma HIV-1 RNA concentration was linearly related to replication rate (r 2 = 0.71; P < 0.001) and RT-PR replication capacity (r 2 = 0.44; P = 0.019). These data suggest that different RT-PR alleles are important determinants of HIV-1 replication rates and that HIV-1 replication rate explains much of the variability in plasma virus load in chronic HIV-1 infection.

scholarly journals A Pathogenic Threshold of Virus Load Defined in Simian Immunodeficiency Virus- or Simian-Human Immunodeficiency Virus-Infected Macaques

1998 ◽  
Vol 72 (12) ◽  
pp. 10281-10285 ◽  
Author(s):  
Peter Ten Haaft ◽  
Babs Verstrepen ◽  
Klaus Überla ◽  
Brigitte Rosenwirth ◽  
Jonathan Heeney
Keyword(s):  
Human Immunodeficiency Virus ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Viral Rna ◽  
Pathogenic Potential ◽  
Virus Load ◽  
Immunodeficiency Virus ◽  
Plasma Virus Load ◽  
Plasma Rna ◽  
Rna Levels

ABSTRACT To determine if a specific pathogenic threshold of plasma viral RNA could be defined irrespective of virus strain, RNA levels in the plasma of more than 50 infected rhesus macaques (Macaca mulatta) were measured. Animals were inoculated intravenously with either simian immunodeficiency virus (SIV) or simian-human immunodeficiency virus (SHIV) strains of known pathogenic potential (SIV8980, SIVsmm-3, SIVmac32H/J5, SIVmac32H/1XC, reverse transcriptase-SHIV, SHIV89.6p) or with attenuated strains (SHIVW6.1D, SHIVsf13, SHIVhan-2, SIVmacΔnef, SHIVsf33). In animals inoculated with nonpathogenic strains, shortly after the primary peak of viremia viral RNA levels declined and remained below 104 RNA equivalents/ml of plasma between 6 and 12 weeks postinoculation. Animals infected with documented pathogenic strains maintained viral RNA levels higher than 105 RNA equivalents/ml of plasma. In animals infected with strains with low virulence, a decline in plasma RNA levels was observed, but with notable individual variation. Our results demonstrate that the disease-causing potential was predicted and determined by a threshold plasma virus load which remained greater than 105 RNA equivalents/ml of plasma 6 to 12 weeks after inoculation. A threshold virus load value which remained below 104 RNA equivalents/ml of plasma was indicative of a nonpathogenic course of infection.

scholarly journals Simian immunodeficiency virus resistance of macaques infused with interferon β-engineered lymphocytes

2000 ◽  
Vol 81 (11) ◽  
pp. 2741-2750 ◽  
Author(s):  
Franck Matheux ◽  
Evelyne Lauret ◽  
Véronique Rousseau ◽  
Jérôme Larghero ◽  
Bertrand Boson ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Unknown Origin ◽  
Good Health ◽  
Cell Number ◽  
Peripheral Blood Lymphocytes ◽  
Plasma Virus ◽  
Virus Load ◽  
Immunodeficiency Virus ◽  
Plasma Virus Load

To test the in vivo anti-simian immunodeficiency virus (SIV) efficacy of interferon (IFN)-β-engineered lymphocytes, peripheral blood lymphocytes harvested from two uninfected macaques were transduced with a retroviral vector carrying a constitutively expressed IFN-β gene and reinfused, resulting in approximately 1 IFN-β-transduced cell out of 1000 circulating cells. The gene-modified cells were well tolerated and could be detected for at least 74 days without causing any apparent side effects. These two animals together with three untreated control macaques were then infected with SIVmac251. The two IFN-β-infused macaques are in good health, 478 days after infection, with a reduced plasma virus load and sustained numbers of CD4+ and CD8+ cells. Throughout the study, the proportion of IFN-β-transduced cells has been maintained. Of the three control macaques, two were characterized by a high plasma virus load and a decrease in CD4+ cells. One was moribund and was sacrificed 350 days after infection and the other now has fewer than 100 circulating CD4+ cells/ml. Unexpectedly, the third control macaque, which, like the two IFN-β-infused animals, had a low plasma virus load and a maintenance of CD4+ and CD8+ cell number, was characterized by a permanent level of serum IFN-β, of unknown origin, already present before SIV infection. Although no definite conclusion can be made in view of the limited number of animals, these data indicate that further exploration is warranted of an IFN-β-based anti-human immunodeficiency virus gene therapy.

scholarly journals Quantitation of Intracellular Triphosphate of Emtricitabine in Peripheral Blood Mononuclear Cells from Human Immunodeficiency Virus-Infected Patients

1999 ◽  
Vol 43 (9) ◽  
pp. 2245-2250 ◽  
Author(s):  
Albert Darque ◽  
Gilles Valette ◽  
Frank Rousseau ◽  
Laurene H. Wang ◽  
Jean-Pierre Sommadossi ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Anion Exchange ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Solid Phase ◽  
Peripheral Blood Mononuclear ◽  
Limit Of Quantitation ◽  
Immunodeficiency Virus ◽  
Blood Mononuclear Cells

ABSTRACT An analytical methodology combining solid-phase extraction (SPE) and high-performance liquid chromatography (HPLC) was developed to quantitate the intracellular active 5′-triphosphate (TP) of β-l-2′,3′-dideoxy-5-fluoro-3′-thiacytidine (emtricitabine) (FTC) in human peripheral blood mononuclear cells (PBMCs). The FTC nucleotides, including 5′-mono-, di-, and triphosphates, were successively resolved on an anion-exchange SPE cartridge by applying a gradient of potassium chloride. The FTC-TP was subsequently digested to release the parent nucleoside that was finally analyzed by HPLC with UV detection (HPLC-UV). Validation of the methodology was performed by using PBMCs from healthy donors exposed to an isotopic solution of [3H]FTC with known specific activity, leading to the formation of intracellular FTC-TP that was quantitated by an anion-exchange HPLC method with radioactive detection. These levels of FTC-TP served as reference values and were used to validate the data obtained by HPLC-UV. The assay had a limit of quantitation of 4.0 pmol of FTC-TP (amount on column from approximately 107 cells). Intra-assay precision (coefficient of variation percentage of repeated measurement) and accuracy (percentage deviation of the nominal reference value), estimated by using quality control samples at 16.2, 60.7, and 121.5 pmol, ranged from 1.3 to 3.3% and −1.0 to 4.8%, respectively. Interassay precision and accuracy varied from 3.0 to 10.2% and from 2.5 to 6.7%, respectively. This methodology was successfully applied to the determination of FTC-TP in PBMCs of patients infected with human immunodeficiency virus after oral administration of various dosing regimens of FTC monotherapy.

scholarly journals Discordant Outcomes following Failure of Antiretroviral Therapy Are Associated with Substantial Differences in Human Immunodeficiency Virus-Specific Cellular Immunity

2003 ◽  
Vol 77 (10) ◽  
pp. 6041-6049 ◽  
Author(s):  
David A. Price ◽  
George Scullard ◽  
Annette Oxenius ◽  
Ruth Braganza ◽  
Simon A. Beddows ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
T Lymphocyte ◽  
Virologic Failure ◽  
Multiple Drug Resistance ◽  
Testable Hypothesis ◽  
Plasma Virus ◽  
Immunodeficiency Virus ◽  
Lymphocyte Responses ◽  
Hiv 1

ABSTRACT Many individuals chronically infected with human immunodeficiency virus type 1 (HIV-1) experience a recrudescence of plasma virus during continuous combination antiretroviral therapy (ART) due either to the emergence of drug-resistant viruses or to poor compliance. In most cases, virologic failure on ART is associated with a coincident decline in CD4+ T lymphocyte levels. However, a proportion of discordant individuals retain a stable or even increasing CD4+ T lymphocyte count despite virological failure. In order to address the nature of these different outcomes, we evaluated virologic and immunologic variables in a prospective, single-blinded, nonrandomized cohort of 53 subjects with chronic HIV-1 infection who had been treated with continuous ART and monitored intensively over a period of 19 months. In all individuals with detectable viremia on ART, multiple drug resistance mutations with similar impacts on viral growth kinetics were detected in the pol gene of circulating plasma virus. Further, C2V3 env gene analysis demonstrated sequences indicative of CCR5 coreceptor usage in the majority of those with detectable plasma viremia. In contrast to this homogeneous virologic pattern, comprehensive screening with a range of antigens derived from HIV-1 revealed substantial immunologic differences. Discordant subjects with stable CD4+ T lymphocyte counts in the presence of recrudescent virus demonstrated potent virus-specific CD4+ and CD8+ T lymphocyte responses. In contrast, subjects with virologic failure associated with declining CD4+ T lymphocyte counts had substantially weaker HIV-specific CD4+ T lymphocyte responses and exhibited a trend towards weaker HIV-specific CD8+ T lymphocyte responses. Importantly the CD4+ response was sustained over periods as long as 11 months, confirming the stability of the phenomenon. These correlative data lead to the testable hypothesis that the consequences of viral recrudescence during continuous ART are modulated by the HIV-specific cellular immune response.

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