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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 serum viral load and CD4 T cell count in 44 PDN-treated patients and 74 control patients. (A-C), Geometric mean ± SE of serum viral load in PDN-treated patients (filled squares) versus control patients (open squares) of total groups (A) and subgroups with an initial low viral load (LVL) (B) and high viral load (HVL) (C). (D-F), Mean ± SE of CD4 T cell count in PDN-treated patients (filled circles) versus control patients (open circles) of total groups (D) and subgroups with an initial LVL (E) and HVL (F).
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Figure 1: Evolution of serum viral load and CD4 T cell count in 44 PDN-treated patients and 74 control patients. (A-C), Geometric mean ± SE of serum viral load in PDN-treated patients (filled squares) versus control patients (open squares) of total groups (A) and subgroups with an initial low viral load (LVL) (B) and high viral load (HVL) (C). (D-F), Mean ± SE of CD4 T cell count in PDN-treated patients (filled circles) versus control patients (open circles) of total groups (D) and subgroups with an initial LVL (E) and HVL (F).

Mentions: Viral loads of PDN-treated and control patients were almost similar (PMWt = NS at each time points) and remarkably stable over time: PDN-treated group: entry, 4.1 ± 0.1 log copies/ml; two years, 4.2 ± 0.1 log copies/ml (PWt = NS); control group: entry 3.8 ± 0.1 log copies/ml; two years 3.9 ± 0.2 log10 copies/ml (PMWt = NS) (Figure 1A). At entry, viral load levels of LVL and HVL subgroups were different (PMWt < 0.01). However, the evolution of the viral load of PDN-treated and control patients with LVL was almost identical (PMWt = NS each time point) with a significant increase at two years compared to entry levels (PWt < 0.01 in both subgroups) (Figure 1B), while entry and two-year viral load levels of PDN-treated and control patients with HVL were similar (PMWt P = NS at each time points) and remained stable over two years (PWt = NS) (Figure 1C).


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 serum viral load and CD4 T cell count in 44 PDN-treated patients and 74 control patients. (A-C), Geometric mean ± SE of serum viral load in PDN-treated patients (filled squares) versus control patients (open squares) of total groups (A) and subgroups with an initial low viral load (LVL) (B) and high viral load (HVL) (C). (D-F), Mean ± SE of CD4 T cell count in PDN-treated patients (filled circles) versus control patients (open circles) of total groups (D) and subgroups with an initial LVL (E) and HVL (F).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Evolution of serum viral load and CD4 T cell count in 44 PDN-treated patients and 74 control patients. (A-C), Geometric mean ± SE of serum viral load in PDN-treated patients (filled squares) versus control patients (open squares) of total groups (A) and subgroups with an initial low viral load (LVL) (B) and high viral load (HVL) (C). (D-F), Mean ± SE of CD4 T cell count in PDN-treated patients (filled circles) versus control patients (open circles) of total groups (D) and subgroups with an initial LVL (E) and HVL (F).
Mentions: Viral loads of PDN-treated and control patients were almost similar (PMWt = NS at each time points) and remarkably stable over time: PDN-treated group: entry, 4.1 ± 0.1 log copies/ml; two years, 4.2 ± 0.1 log copies/ml (PWt = NS); control group: entry 3.8 ± 0.1 log copies/ml; two years 3.9 ± 0.2 log10 copies/ml (PMWt = NS) (Figure 1A). At entry, viral load levels of LVL and HVL subgroups were different (PMWt < 0.01). However, the evolution of the viral load of PDN-treated and control patients with LVL was almost identical (PMWt = NS each time point) with a significant increase at two years compared to entry levels (PWt < 0.01 in both subgroups) (Figure 1B), while entry and two-year viral load levels of PDN-treated and control patients with HVL were similar (PMWt P = NS at each time points) and remained stable over two years (PWt = NS) (Figure 1C).

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