Immunologic and Virologic Effects of Subcutaneous Interleukin 2 in Combination With Antiretroviral Therapy

Davey, Richard T.; Murphy, Robert L.; Graziano, Frank M.; Boswell, Stephen L.; Pavia, Andrew T.; Cancio, Margarita; Nadler, Jeffrey P.; Chaitt, Doreen G.; Dewar, Robin; Sahner, David; Duliege, Anne Marie; Capra, William B.; Leong, Wai Ping; Giedlin, Martin; Lane, H. Clifford; Kahn, James O.

doi:10.1001/jama.284.2.183

Cited by 162 publications

(79 citation statements)

References 20 publications

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“…Multiple randomized trials have demonstrated that the administration of intermittent cycles of IL-2 to HIV-infected patients can lead to profound, sustained increases (often greater than 100%) in CD4 cell number and percentage (1)(2)(3). After 3 to 6 five-day cycles of IL-2 administered every 2 months, CD4 cell numbers may remain elevated for years without additional cycles.…”

Section: Introductionmentioning

confidence: 99%

Induction of prolonged survival of CD4+ T lymphocytes by intermittent IL-2 therapy in HIV-infected patients

Kovacs¹,

Lempicki²,

Sidorov³

et al. 2005

J. Clin. Invest.

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114

101

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HIV infection leads to decreases in the number of CD4 + T lymphocytes and an increased risk for opportunistic infections and neoplasms. The administration of intermittent cycles of IL-2 to HIV-infected patients can lead to profound increases (often greater than 100%) in CD4 cell number and percentage. Using in vivo labeling with 2 H-glucose and BrdU, we have been able to demonstrate that, although therapy with IL-2 leads to high levels of proliferation of CD4 as well as CD8 lymphocytes, it is a remarkable preferential increase in survival of CD4 cells (with half-lives that can exceed 3 years) that is critical to the sustained expansion of these cells. This increased survival was time-dependent: the median half-life, as determined by semiempirical modeling, of labeled CD4 cells in 6 patients increased from 1.7 weeks following an early IL-2 cycle to 28.7 weeks following a later cycle, while CD8 cells showed no change in the median half-life. Examination of lymphocyte subsets demonstrated that phenotypically naive (CD27 + CD45RO -) as well as central memory (CD27 + CD45RO + ) CD4 cells were preferentially expanded, suggesting that IL-2 can help maintain cells important for host defense against new antigens as well as for long-term memory to opportunistic pathogens.

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Section: Introductionmentioning

confidence: 99%

Induction of prolonged survival of CD4+ T lymphocytes by intermittent IL-2 therapy in HIV-infected patients

Kovacs¹,

Lempicki²,

Sidorov³

et al. 2005

J. Clin. Invest.

Self Cite

114

101

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“…1,2 The initial induction regimen consists of 5-day cycles that are administered every 8 weeks for 3 to 6 cycles. The majority of treated patients then require only infrequent cycling for maintenance of these CD4 expansions.…”

Section: Introductionmentioning

confidence: 99%

IL-2–induced CD4+ T-cell expansion in HIV-infected patients is associated with long-term decreases in T-cell proliferation

Sereti

Anthony

Martinez-Wilson

et al. 2004

Blood

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“…The CD45RO ϩ CD4 ϩ memory T cells appear to harbor the majority of the latent virus. To date, several approaches have been aimed at eliminating these cells (9,(25)(26)(27)(28)(29), but none have been highly successful (29)(30)(31). Another proposed strategy involves the use of HIVbased vaccines to stimulate anti-HIV cytotoxic T lymphocytes, which might recognize and eliminate the latent reservoir (32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

“…However, even after years with viremia below the limit of quantitation (BLQ), the frequency of these infected cells does not decrease further (1,4,6,7). The therapeutic approaches evaluated to date have failed to demonstrate a significant and persistent decline of this latent viral reservoir (8,9).…”

mentioning

confidence: 99%

An anti-CD45RO immunotoxin kills HIV-latently infected cells from individuals on HAART with little effect on CD8 memory

Saavedra-Lozano

Cao

Callison

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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CD4+ CD45RO+ T cells are the major latent viral reservoir in HIV-infected individuals and hence a major obstacle in curing the disease. An anti-CD45RO immunotoxin (IT) can decrease the number of both productively and latently infected CD4+ T cells obtained from HIV-infected individuals with detectable viremia. In this study, we determined whether this IT could also kill latently infected replication-competent CD4+ T cells obtained from infected individuals without detectable plasma viremia. Our results demonstrate that ex vivo treatment with the anti-CD45RO IT significantly reduced the frequency of these cells. In contrast, the IT had only a modest effect on the cytomegalalovirus-specific memory responses of CD8+ T cells. These results suggest that purging latent cells from infected individuals on highly active antiretroviral therapy with the anti-CD45RO IT might reduce the HIV latent reservoir without seriously compromising CD8+ T cell memory responses

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Immunologic and Virologic Effects of Subcutaneous Interleukin 2 in Combination With Antiretroviral Therapy

Cited by 162 publications

References 20 publications

Induction of prolonged survival of CD4+ T lymphocytes by intermittent IL-2 therapy in HIV-infected patients

Induction of prolonged survival of CD4+ T lymphocytes by intermittent IL-2 therapy in HIV-infected patients

IL-2–induced CD4+ T-cell expansion in HIV-infected patients is associated with long-term decreases in T-cell proliferation

An anti-CD45RO immunotoxin kills HIV-latently infected cells from individuals on HAART with little effect on CD8 memory

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