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Long-term clinical, immunologic and virologic impact of glucocorticoids on the chronic phase of HIV infection.

Andrieu JM, Lu W - BMC Med (2004)

Bottom Line: No clinical AIDS developed under prednisolone; side effects of the drug were mild.Initial viral load was highly predictive of the rate of CD4 decrease under prednisolone.Prednisolone postponed CD4 cell decrease in a viral load dependent manner for a median of two years and for up to 10 years in a fraction of the patients with a low viral load.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institut de Recherche sur les Vaccins et l'Immunothérapie des cancers et du SIDA, Laboratoire d'Oncologie et Virologie Moléculaire, Centre Biomédical des Saints-Pères, Université René Descartes, Paris, France. jean-marie.andrieu@biomedicale.univ-paris5.fr

ABSTRACT

Background: To test the hypothesis of down-regulating the increased immune system activation/destruction process associated with chronic HIV infection, we focused our interest on prednisolone (PDN), because we had showed that, in vitro, PDN had a strong anti-apoptotic activity on activated T cells of HIV-infected patients and no effect on viral replication. We thus designed in 1992 a pilot study to evaluate the clinical, immunologic and virologic effects of PDN. The drug was given to a group of 44 patients with CD4 T cells over 200/microl. After one year, no patient had developed clinical AIDS and the mean CD4 T cell count of the group had increased from 441 +/- 21 cells/microl to 553 +/- 43 cells/microl. Moreover, markers of immune activation had dropped back to normal levels while the mean viral load of the group had remained unchanged. Here we explore the long-term clinical, immunologic, and virologic impact of prednisolone on the chronic phase of HIV infection.

Methods: Retrospective study over 10 years starting between July 1992 and February 1993. A total of 44 patients with CD4 cells/microl ranging from 207 to 775 were treated with prednisolone, 0.5 mg/kg/d, over 6 months and 0.3 mg/kg/d thereafter.

Results: No clinical AIDS developed under prednisolone; side effects of the drug were mild. CD4 cells which increased from 421 cells/microl at entry to 625 cells/microl at day 15, slowly decreased to reach 426 cells/microl after two years; T cell apoptosis and activation markers dropped within 15 days to normal levels and reincreased slowly thereafter. Serum viral loads remained stable. The percentage of patients maintaining CD4 cells over entry was 43.2% at two years, 11.4% at five years and 4.6% at 10 years. Initial viral load was highly predictive of the rate of CD4 decrease under prednisolone.

Conclusions: Prednisolone postponed CD4 cell decrease in a viral load dependent manner for a median of two years and for up to 10 years in a fraction of the patients with a low viral load. These findings might stimulate clinical trials as well as biological research on the role of antiapoptotic drugs in HIV infection.

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Evolution of the percentage of apoptotic cells in PBMC, CD25+ and DR+ cells in CD4 T cells, and serum β2-microglobulin in PDN-treated patients. Mean ± SD of the percentage of apoptotic cells in PBMC (A), CD25+ cells in CD4 T cells (B), DR+ cells in CD4 T cells (C) and β2-microglobulin (D) in subgroups with an initial LVL (down-pointing triangles) and HVL (up-pointing triangles).
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Figure 3: Evolution of the percentage of apoptotic cells in PBMC, CD25+ and DR+ cells in CD4 T cells, and serum β2-microglobulin in PDN-treated patients. Mean ± SD of the percentage of apoptotic cells in PBMC (A), CD25+ cells in CD4 T cells (B), DR+ cells in CD4 T cells (C) and β2-microglobulin (D) in subgroups with an initial LVL (down-pointing triangles) and HVL (up-pointing triangles).

Mentions: The percentage of apoptotic cells in PBMC started from 21 ± 10%; it substantially decreased to 15 ± 9% at day 15 (PWt < 0.01) and remained decreased at one year (14 ± 5%, (PWt day 0 to one year) (Figure 3A). The percentage of CD25+ and DR+ phenotypes in CD4 cells followed almost the same profile; it started from 17 ± 3% at day 0, and then decreased to 14 ± 1% at day 15 (PWt = NS), 12 ± 1% at month 4 (PWt < 0.03) and 9 ± 1% at one year (PWt < 0.01) (Figure 3B). Finally, the percentage of DR+ cells started from 20 ± 2% at day 0, decreased to 17 ± 2% at day 15 (PWt = NS), 13 ± 1% at month 4 (PWt < 0.01) and remained significantly decreased at one year (18 ± 3, PWt < 0.05) (Figure 3C).


Long-term clinical, immunologic and virologic impact of glucocorticoids on the chronic phase of HIV infection.

Andrieu JM, Lu W - BMC Med (2004)

Evolution of the percentage of apoptotic cells in PBMC, CD25+ and DR+ cells in CD4 T cells, and serum β2-microglobulin in PDN-treated patients. Mean ± SD of the percentage of apoptotic cells in PBMC (A), CD25+ cells in CD4 T cells (B), DR+ cells in CD4 T cells (C) and β2-microglobulin (D) in subgroups with an initial LVL (down-pointing triangles) and HVL (up-pointing triangles).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC411065&req=5

Figure 3: Evolution of the percentage of apoptotic cells in PBMC, CD25+ and DR+ cells in CD4 T cells, and serum β2-microglobulin in PDN-treated patients. Mean ± SD of the percentage of apoptotic cells in PBMC (A), CD25+ cells in CD4 T cells (B), DR+ cells in CD4 T cells (C) and β2-microglobulin (D) in subgroups with an initial LVL (down-pointing triangles) and HVL (up-pointing triangles).
Mentions: The percentage of apoptotic cells in PBMC started from 21 ± 10%; it substantially decreased to 15 ± 9% at day 15 (PWt < 0.01) and remained decreased at one year (14 ± 5%, (PWt day 0 to one year) (Figure 3A). The percentage of CD25+ and DR+ phenotypes in CD4 cells followed almost the same profile; it started from 17 ± 3% at day 0, and then decreased to 14 ± 1% at day 15 (PWt = NS), 12 ± 1% at month 4 (PWt < 0.03) and 9 ± 1% at one year (PWt < 0.01) (Figure 3B). Finally, the percentage of DR+ cells started from 20 ± 2% at day 0, decreased to 17 ± 2% at day 15 (PWt = NS), 13 ± 1% at month 4 (PWt < 0.01) and remained significantly decreased at one year (18 ± 3, PWt < 0.05) (Figure 3C).

Bottom Line: No clinical AIDS developed under prednisolone; side effects of the drug were mild.Initial viral load was highly predictive of the rate of CD4 decrease under prednisolone.Prednisolone postponed CD4 cell decrease in a viral load dependent manner for a median of two years and for up to 10 years in a fraction of the patients with a low viral load.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institut de Recherche sur les Vaccins et l'Immunothérapie des cancers et du SIDA, Laboratoire d'Oncologie et Virologie Moléculaire, Centre Biomédical des Saints-Pères, Université René Descartes, Paris, France. jean-marie.andrieu@biomedicale.univ-paris5.fr

ABSTRACT

Background: To test the hypothesis of down-regulating the increased immune system activation/destruction process associated with chronic HIV infection, we focused our interest on prednisolone (PDN), because we had showed that, in vitro, PDN had a strong anti-apoptotic activity on activated T cells of HIV-infected patients and no effect on viral replication. We thus designed in 1992 a pilot study to evaluate the clinical, immunologic and virologic effects of PDN. The drug was given to a group of 44 patients with CD4 T cells over 200/microl. After one year, no patient had developed clinical AIDS and the mean CD4 T cell count of the group had increased from 441 +/- 21 cells/microl to 553 +/- 43 cells/microl. Moreover, markers of immune activation had dropped back to normal levels while the mean viral load of the group had remained unchanged. Here we explore the long-term clinical, immunologic, and virologic impact of prednisolone on the chronic phase of HIV infection.

Methods: Retrospective study over 10 years starting between July 1992 and February 1993. A total of 44 patients with CD4 cells/microl ranging from 207 to 775 were treated with prednisolone, 0.5 mg/kg/d, over 6 months and 0.3 mg/kg/d thereafter.

Results: No clinical AIDS developed under prednisolone; side effects of the drug were mild. CD4 cells which increased from 421 cells/microl at entry to 625 cells/microl at day 15, slowly decreased to reach 426 cells/microl after two years; T cell apoptosis and activation markers dropped within 15 days to normal levels and reincreased slowly thereafter. Serum viral loads remained stable. The percentage of patients maintaining CD4 cells over entry was 43.2% at two years, 11.4% at five years and 4.6% at 10 years. Initial viral load was highly predictive of the rate of CD4 decrease under prednisolone.

Conclusions: Prednisolone postponed CD4 cell decrease in a viral load dependent manner for a median of two years and for up to 10 years in a fraction of the patients with a low viral load. These findings might stimulate clinical trials as well as biological research on the role of antiapoptotic drugs in HIV infection.

Show MeSH
Related in: MedlinePlus