Serial Determinations of HIV-1 Titers in HIV-Infected Homosexual Men: Association of Rising Titers with CD4 T Cell Depletion and Progression to AIDS

Nicholson, Janet K. A.; Spira, Thomas J.; Aloisio, Carol H.; Jones, Bonnie M.; Kennedy, Melanie S.; Holman, Robert C.; McDougal, J. Steven

doi:10.1089/aid.1989.5.205

Cited by 38 publications

(14 citation statements)

References 31 publications

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“…More studies are necessary to examine more carefully the effect of IL-15 on B cell function. The decreased anti-SIV Abs could indeed influence the outcome of SIV infection, as it was shown before that during progression to HIV and SIV, Abs specific for HIV and SIV decrease or are absent (65,66). We observed an inverse correlation between the amount of anti-SIV Abs and viral replication at week 16.…”

Section: Discussionsupporting

confidence: 77%

IL-15 Treatment during Acute Simian Immunodeficiency Virus (SIV) Infection Increases Viral Set Point and Accelerates Disease Progression despite the Induction of Stronger SIV-Specific CD8+ T Cell Responses

Mueller

Altork

et al. 2008

The Journal of Immunology

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In this study, we examined the effect of in vivo treatment of acutely SIV-infected Mamu-A*01+ rhesus macaques with IL-15. IL-15 treatment during acute infection increased viral set point by 3 logs and accelerated the development of simian AIDS in two of six animals with one developing early minimal lesion SIV meningoencephalitis. Although IL-15 induced a 2- to 3-fold increase in SIV-specific CD8+ T cell and NK cell numbers at peak viremia and reduced lymph node (LN) SIV-infected cells, this had no impact on peak viremia and did not lower viral set point. At viral set point, however, activated SIV-specific CD8+ T cells and NK cells were reduced in the blood of IL-15-treated animals and LN SIV-infected cells were increased. Week 30 LN from IL-15-treated animals had significantly increased Gag-specific CD8+ T cell numbers, whereas total cell, lymphocyte, and CD4+ T cell numbers were reduced. IL-15 treatment significantly reduced anti-SIV Ab concentrations at week 3 and viral set point. IL-15 increased Ki-67+CD4+ T cells at week 1 of treatment and reduced blood CCR5+ and CD45RA−CD62L− CD4+ T cells. The frequency of day 7 Ki-67+CD4+ T cells strongly correlated with viral set point. These findings suggest that CD4+ T cell activation during acute infection determines subsequent viral set point and IL-15 treatment by increasing such activation elevates viral set point. Finally, IL-15-treated acutely SIV-infected primates may serve as a useful model to investigate the poorly understood mechanisms that control viral set point and disease progression in HIV infection.

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Section: Discussionsupporting

confidence: 77%

IL-15 Treatment during Acute Simian Immunodeficiency Virus (SIV) Infection Increases Viral Set Point and Accelerates Disease Progression despite the Induction of Stronger SIV-Specific CD8+ T Cell Responses

Mueller

Altork

et al. 2008

The Journal of Immunology

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“…In this study we identified 3 additional HIV-1-positive chimpanzees in the Yerkes cohort that have experienced profound reductions in both absolute numbers and percentages of CD4 ϩ T lymphocytes, similar to what has been described for human progressors [67-70, 72, 73, 112]. Furthermore, as with human progressors [67,73,[76][77][78], progressor chimpanzees showed reductions in both memory (CD29 ϩ ) and naïve (CD45RA ϩ ) subsets of CD4 ϩ T cells. In addition, the observation of significant increases in memory (CD29 ϩ ), but not naïve (CD45RA ϩ ), subsets of CD8 ϩ T cells of progressor chimpanzees is in direct agreement with the CD8 ϩ T cell subset changes that have been observed to occur during progressive HIV infection in humans [74,83].…”

Section: Discussionsupporting

confidence: 63%

Progressive Infection in a Subset of HIV‐1–Positive Chimpanzees

O’Neil

Novembre

Hill³

et al. 2000

J INFECT DIS

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Chimpanzees are susceptible to infection with human immunodeficiency virus (HIV)-1; however, infected animals usually maintain normal numbers of CD4(+) T lymphocytes and do not develop immunodeficiency. We have examined 10 chronically infected HIV-1-positive chimpanzees for evidence of progressive infection. In addition to 1 animal that developed AIDS, 3 chimpanzees exhibit evidence of progressive HIV infection. All progressors have low CD4(+) T cell counts (<200 cells/microL), severe CD4:CD8 inversion, and marked reduction in interleukin-2 receptor expression by CD4(+) T cells. In comparison with HIV-positive nonprogressor chimpanzees, progressors have higher plasma and lymphoid virus loads, greater CD38 expression in CD8(+)/HLA-DR(+) T cells, and greater serum concentrations of soluble tumor necrosis factor type II receptors and beta2-microglobulin, all markers of HIV progression in humans. These observations show that progressive HIV-1 infection can occur in chimpanzees and suggest that the pathogenesis of progressive infection in this species resembles that in humans.

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“…3). As reported in other studies, there was a statistically significant difference between CD4 cell number for the asymptomatic patients and the AIDS patients (P < .OOOl) [3,12,24,25].…”

Section: Cross-sectional Studysupporting

confidence: 75%

Humoral immune responses to gag and env proteins from human immunodeficiency virus type 1 in hemophiliac patients

Kinney¹,

Conway

Hilgartner

et al. 1991

American J Hematol

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Solid-phase enzyme immunoassays using recombinant gag and env proteins were developed to study humoral immune responses to HIV infection in a cohort of 105 hemophiliac patients. Thirteen patients with ARC or AIDS and 92 asymptomatic patients were studied. A cross-sectional study showed a wide range of antibody responses to gag and env proteins; however, the differences between the ARC/AIDS and asymptomatic patients were statistically significant for both antigens (P less than .0004). In a longitudinal study, antibody levels in sera from 11 asymptomatic patients with gag antibody log units less than or equal to 1.5 were compared to levels in sera from 10 ARC/AIDS patients and 8 asymptomatic patients with gag antibody greater than 1.5. These patient groups were followed for comparable periods of time (67.1-71.7 mo). The asymptomatic patients with low gag antibody and the ARC/AIDS patients showed a similar pattern of antibody response to gag protein overtime. In hemophiliac patients with HIV-1 infection a low titer of antibody to gag protein is not invariably associated with clinical deterioration and is not a useful serologic marker of impending progression to AIDS.

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Serial Determinations of HIV-1 Titers in HIV-Infected Homosexual Men: Association of Rising Titers with CD4 T Cell Depletion and Progression to AIDS

Cited by 38 publications

References 31 publications

IL-15 Treatment during Acute Simian Immunodeficiency Virus (SIV) Infection Increases Viral Set Point and Accelerates Disease Progression despite the Induction of Stronger SIV-Specific CD8+ T Cell Responses

IL-15 Treatment during Acute Simian Immunodeficiency Virus (SIV) Infection Increases Viral Set Point and Accelerates Disease Progression despite the Induction of Stronger SIV-Specific CD8+ T Cell Responses

Progressive Infection in a Subset of HIV‐1–Positive Chimpanzees

Humoral immune responses to gag and env proteins from human immunodeficiency virus type 1 in hemophiliac patients

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