scholarly journals Efficacy of Low‐Dose Subcutaneous Interleukin‐2 to Treat Advanced Human Immunodeficiency Virus Type 1 in Persons with ⩽250/μL CD4 T Cells and Undetectable Plasma Virus Load

1999 ◽  
Vol 180 (1) ◽  
pp. 56-60 ◽  
Author(s):  
Albert Arnó ◽  
Lidia Ruiz ◽  
Manel Juan ◽  
Antoni Jou ◽  
Montserrat Balagué ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Human Immunodeficiency Virus Type ◽  
Low Dose ◽  
Interleukin 2 ◽  
Plasma Virus ◽  
Undetectable Plasma ◽  
Immunodeficiency Virus ◽  
Plasma Virus Load

scholarly journals A Novel Assay Allows Genotyping of the Latent Reservoir for Human Immunodeficiency Virus Type 1 in the Resting CD4+ T Cells of Viremic Patients

2005 ◽  
Vol 79 (8) ◽  
pp. 5185-5202 ◽  
Author(s):  
Daphne Monie ◽  
Rachel P. Simmons ◽  
Richard E. Nettles ◽  
Tara L. Kieffer ◽  
Yan Zhou ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Latent Reservoir ◽  
Drug Resistant ◽  
Plasma Virus ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT A latent reservoir for human immunodeficiency virus type 1 (HIV-1) consisting of integrated provirus in resting memory CD4+ T cells prevents viral eradication in patients on highly active antiretroviral therapy (HAART). It is difficult to analyze the nature and dynamics of this reservoir in untreated patients and in patients failing therapy, because it is obscured by an excess of unintegrated viral DNA that constitutes the majority of viral species in resting CD4+ T cells from viremic patients. Therefore, we developed a novel culture assay that stimulates virus production from latent, integrated HIV-1 in resting CD4+ T cells in the presence of antiretroviral drugs that prevent the replication of unintegrated virus. Following activation, resting CD4+ T cells with integrated HIV-1 DNA produced virus particles for several days, with peak production at day 5. Using this assay, HIV-1 pol sequences from the resting CD4+ T cells of viremic patients were found to be genetically distinct from contemporaneous plasma virus. Despite the predominance of a relatively homogeneous population of drug-resistant viruses in the plasma of patients failing HAART, resting CD4+ T cells harbored a diverse array of wild-type and archival drug-resistant viruses that were less fit than plasma virus in the context of current therapy. These results provide the first direct evidence that resting CD4+ T cells serve as a stable reservoir for HIV-1 even in the setting of high levels of viremia. The ability to analyze archival species in viremic patients may have clinical utility in detecting drug-resistant variants not present in the plasma.

scholarly journals Human Immunodeficiency Virus Type 1-Specific Immune Responses in Primates upon Sequential Immunization with Adenoviral Vaccine Carriers of Human and Simian Serotypes

2004 ◽  
Vol 78 (14) ◽  
pp. 7392-7399 ◽  
Author(s):  
A. Reyes-Sandoval ◽  
J. C. Fitzgerald ◽  
R. Grant ◽  
S. Roy ◽  
Z. Q. Xiang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Immune Responses ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Interleukin 2 ◽  
Cell Subset ◽  
Immunodeficiency Virus ◽  
Adenoviral Vaccine

ABSTRACT Two triple immunization vaccine regimens with adenoviral vectors with E1 deleted expressing Gag of human immunodeficiency virus type 1 were tested for induction of T- and B-cell-mediated-immune responses in mice and in nonhuman primates. The vaccine carriers were derived from distinct serotypes of human and simian adenoviruses that fail to elicit cross-neutralizing antibodies expected to dampen the effect of booster immunizations. Both triple immunization regimens induced unprecedented frequencies of gamma interferon-producing CD8+ T cells to Gag in mice and monkeys that remained remarkably stable over time. In addition, monkeys developed Gag-specific interleukin-2-secreting T cells, presumably belonging to the CD4+ T-cell subset, and antibodies to both Gag and the adenoviral vaccine carriers.

scholarly journals Prolonged immunostimulatory effect of low-dose polyethylene glycol interleukin 2 in patients with human immunodeficiency virus type 1 infection.

1993 ◽  
Vol 177 (2) ◽  
pp. 483-492 ◽  
Author(s):  
H Teppler ◽  
G Kaplan ◽  
K A Smith ◽  
A L Montana ◽  
P Meyn ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Polyethylene Glycol ◽  
Human Immunodeficiency Virus Type ◽  
Low Dose ◽  
Killer Cell ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Killer Cell Activity ◽  
Immunodeficiency Virus

13 patients with human immunodeficiency virus type 1 infection class II-IV, but without opportunistic infection or neoplasm, received 6 micrograms (3.6 x 10(4) IU) of polyethylene glycol recombinant human interleukin 2 (PEG IL-2) intradermally twice a week for 4 mo were then followed for an additional 6 mo. Clinical, immunological, and viral parameters were monitored in the patients, all of whom were taking zidovudine. The cutaneous administration of PEG IL-2 resulted in an indurated zone resembling a delayed-type hypersensitivity response of 26 +/- 1 mm diameter (676 mm2) at 72-96 h after injection throughout the 4 mo of administration. This dose, which was appreciably lower than in most previous trials, was not associated with local or systemic toxicity. No increase in the viral burden of circulating leukocytes or plasma occurred. A number of immunological functions were stimulated by this course of therapy. All patients demonstrated high levels of lymphokine-activated killer cell activity by cells freshly removed from the circulation and in the absence of in vitro exposure to IL-2. Natural killer cell activity was also enhanced. Limiting dilution analysis revealed an increase in the frequency of IL-2-responsive cells from abnormally low to levels above normal during the course of injections. In a subgroup of four patients with > or = 400 CD4+ T cells/microliter at entry, there was a trend to sustained increases in CD4+ T cell numbers. However, this increase did not reach statistical significance. This subset of patients also exhibited higher proliferative responses to phytohemagglutinin as mitogen. Several of these effects persisted for 3-6 mo after cessation of therapy. In conclusion, low-dose IL-2 regimens lead to sustained immune enhancement in the absence of toxicity. We suggest pursuit of this approach for further clinical trials both as prophylaxis and therapy.

scholarly journals Human Immunodeficiency Virus Type 1 Escapes from Interleukin-2-Producing CD4+ T-Cell Responses without High-Frequency Fixation of Mutations

2009 ◽  
Vol 83 (17) ◽  
pp. 8722-8732 ◽  
Author(s):  
R. Brad Jones ◽  
Feng-Yun Yue ◽  
Xiao Xiao Jenny Gu ◽  
Diana V. Hunter ◽  
Shariq Mujib ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Human Immunodeficiency Virus Type ◽  
Interleukin 2 ◽  
T Cell Responses ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The presence of interleukin-2 (IL-2)-producing human immunodeficiency virus type 1 (HIV-1)-specific CD4+ T-cell responses has been associated with the immunological control of HIV-1 replication; however, the causal relationship between these factors remains unclear. Here we show that IL-2-producing HIV-1-specific CD4+ T cells can be cloned from acutely HIV-1-infected individuals. Despite the early presence of these cells, each of the individuals in the present study exhibited progressive disease, with one individual showing rapid progression. In this rapid progressor, three IL-2-producing HIV-1 Gag-specific CD4+ T-cell responses were identified and mapped to the following optimal epitopes: HIVWASRELER, REPRGSDIAGT, and FRDYVDRFYKT. Responses to these epitopes in peripheral blood mononuclear cells were monitored longitudinally to >1 year postinfection, and contemporaneous circulating plasma viruses were sequenced. A variant of the FRDYVDRFYKT epitope sequence, FRDYVDQFYKT, was observed in 1/21 plasma viruses sequenced at 5 months postinfection and 1/10 viruses at 7 months postinfection. This variant failed to stimulate the corresponding CD4+ T-cell clone and thus constitutes an escape mutant. Responses to each of the three Gag epitopes were rapidly lost, and this loss was accompanied by a loss of antigen-specific cells in the periphery as measured by using an FRDYVDRFYKT-presenting major histocompatibility complex class II tetramer. Highly active antiretroviral therapy was associated with the reemergence of FRDYVDRFYKT-specific cells by tetramer. Thus, our data support that IL-2-producing HIV-1-specific CD4+ T-cell responses can exert immune pressure during early HIV-1 infection but that the inability of these responses to enforce enduring control of viral replication is related to the deletion and/or dysfunction of HIV-1-specific CD4+ T cells rather than to the fixation of escape mutations at high frequencies.

scholarly journals A Randomized Trial of High‐ versus Low‐Dose Subcutaneous Interleukin‐2 Outpatient Therapy for Early Human Immunodeficiency Virus Type 1 Infection

1999 ◽  
Vol 179 (4) ◽  
pp. 849-858 ◽  
Author(s):  
Richard T. Davey, Jr. ◽  
Doreen G. Chaitt ◽  
Jeffrey M. Albert ◽  
Stephen C. Piscitelli ◽  
Joseph A. Kovacs ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Randomized Trial ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Low Dose ◽  
Interleukin 2 ◽  
Outpatient Therapy ◽  
Immunodeficiency Virus ◽  
Early Human
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