A small German study has contributed to the debate about the role of corticosteroids in slowing the loss of CD4 T-cells in HIV infection. The investigators, writing in the 29th March edition of the European Journal of Medical Research, claim that low doses of prednisolone can stabilise CD4 cell counts, delaying the time to initiation of antiretroviral therapy.
Corticosteroids, such as prednisolone, act as inhibitors of the immune system. Although their use in HIV disease may seem counter-intuitive, they have been investigated as they are thought to reduce the over-activation of HIV-infected CD4 T-cells. This over-activation usually causes the cells to commit suicide, or ‘apoptosis’. By reducing this process, corticosteroids may delay the fall in CD4 cell counts caused by HIV.
Findings from previous studies of corticosteroids in HIV-positive patients have been mixed. While some have shown no benefit of the drugs, others have shown that they can help some patients maintain elevated CD4 cell counts either before starting antiretroviral therapy or during structured treatment interruptions.
The investigators of the latest study gave daily doses of 5 or 7.5mg prednisolone to 65 HIV-positive patients for between six months and twelve years. None of the patients had ever taken highly active antiretroviral therapy (HAART). The researchers compared these patients’ CD4 cell counts to those of a control group of 136 patients who did not receive the drug.
All of the patients started the trial with CD4 cell counts above 300 cells/mm3 and none were co-infected with hepatitis B.
“There is little doubt that our findings show a CD4-stabilising effect of low dose prednisolone,” claim the investigators. “The observed results clearly suggest the possibility to prolong HAART-free time in many patients.”
After three years, the CD4 cell counts of the patients taking prednisolone had increased by a mean of 50 cells/mm3. In contrast, the control patients had a mean CD4 cell count decrease of 186 cells/mm3 (p = 0.002). A similar trend was seen when they analysed CD4 percentages.
The investigators also saw that patients with lower viral loads at the start of the study tended to have a better response to prednisolone. In the first three and a half years, fewer of the patients with viral loads below 30,000 copies/ml needed to start HAART or stopped taking prednisolone than those with higher viral loads (11 vs. 52%; p
After a year’s treatment, the investigators found that fewer patients in the prednisolone group had started HAART or experienced a CD4 cell count fall of more than 100 cells/mm3 (35 vs. 64%). Although they do not provide the results of a statistical analysis, these data suggest that this low-cost drug could delay the costs and side-effects associated with starting anti-HIV therapy.
However, the researchers acknowledge that more research is needed to clarify the role of corticosteroids in HIV treatment. “Due to the distinctness and the possibly important implications of the encouraging results, further, randomised and prospective studies should be conducted,” they write.
“Treatment with low dose prednisolone could become both an important addition and partial alternative to HAART after further assessment in basic and clinical studies,” they claim. However, “the optimal dose of prednisolone has to be evaluated in further studies.”
The use of corticosteroids can also have undesired effects, such as causing a flare-up of diseases such as thrush or herpes. The drugs have also been associated with bone damage in patients with HIV, although the causes of this have not been established.
Ulmer A et al. Low dose prednisolone reduces CD4+ T cell loss in therapy-naive HIV-patients without antiretroviral therapy. Eur J Med Res 10: 105-109, 2005.