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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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Absence of CD4 T cell decrease in PDN-treated and control patients over 10 years. Percentage of patients maintaining their CD4 T cells over entry level in PDN-treated patients (solid lines) versus control patients (dashed lines) of total groups (A) and subgroups with an initial LVL (B) and HVL (C).
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Figure 5: Absence of CD4 T cell decrease in PDN-treated and control patients over 10 years. Percentage of patients maintaining their CD4 T cells over entry level in PDN-treated patients (solid lines) versus control patients (dashed lines) of total groups (A) and subgroups with an initial LVL (B) and HVL (C).

Mentions: From the third year, PDN was maintained only in the patients whose CD4 T cells remained over entry levels and no patient, whether belonging to the PDN-treated or to the control group, developed clinical AIDS or started any antiretroviral therapy while having CD4 T cells over entry levels. The long-term impact of PDN on the evolution of HIV-infection was therefore evaluated by measuring the Kaplan-Meier percentage of patients maintaining their CD4 T cell count above entry for a long time (since all patients were receiving PDN at least until such CD4 T cell levels). The percentage of patients of the control group maintaining their CD4 T cell count over baseline was also calculated. By two years, 43.2 ± 7.5% of the PDN group maintained their CD4 T cell count over entry; by five years, 11.4 ± 4.8% had still increased CD4 T cell counts (Figure 4). Finally, by ten years (30 March 2003), two patients (4.6 ± 2%) were still under PDN with CD4 cell counts over entry. In contrast, in the control group, percentages of patients with CD4 T cells remaining over entry were 12.2 ± 3.1%, 1.3 ± 1.3% and 0% at two, five and ten years respectively (PLRt < 0.01) (Figure 5A).


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

Andrieu JM, Lu W - BMC Med (2004)

Absence of CD4 T cell decrease in PDN-treated and control patients over 10 years. Percentage of patients maintaining their CD4 T cells over entry level in PDN-treated patients (solid lines) versus control patients (dashed lines) of total groups (A) and subgroups with an initial LVL (B) and HVL (C).
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Related In: Results  -  Collection

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

Figure 5: Absence of CD4 T cell decrease in PDN-treated and control patients over 10 years. Percentage of patients maintaining their CD4 T cells over entry level in PDN-treated patients (solid lines) versus control patients (dashed lines) of total groups (A) and subgroups with an initial LVL (B) and HVL (C).
Mentions: From the third year, PDN was maintained only in the patients whose CD4 T cells remained over entry levels and no patient, whether belonging to the PDN-treated or to the control group, developed clinical AIDS or started any antiretroviral therapy while having CD4 T cells over entry levels. The long-term impact of PDN on the evolution of HIV-infection was therefore evaluated by measuring the Kaplan-Meier percentage of patients maintaining their CD4 T cell count above entry for a long time (since all patients were receiving PDN at least until such CD4 T cell levels). The percentage of patients of the control group maintaining their CD4 T cell count over baseline was also calculated. By two years, 43.2 ± 7.5% of the PDN group maintained their CD4 T cell count over entry; by five years, 11.4 ± 4.8% had still increased CD4 T cell counts (Figure 4). Finally, by ten years (30 March 2003), two patients (4.6 ± 2%) were still under PDN with CD4 cell counts over entry. In contrast, in the control group, percentages of patients with CD4 T cells remaining over entry were 12.2 ± 3.1%, 1.3 ± 1.3% and 0% at two, five and ten years respectively (PLRt < 0.01) (Figure 5A).

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