Interleukin-2 improves CD4+ cell counts in patients with poor immune response to HAART

Successful highly active antiretroviral therapy (HAART) generally leads to both virologic control and immunologic improvement. In some patients, however, there may be poor virologic control accompanied by a significant CD4+ cell count rise, while in other patients there may be excellent virologic control with a minimal CD4+ cell count increase.

Patients with a good virologic, but poor immunologic, response to HAART may remain at high risk for opportunistic infections and other HIV-related complications, especially if their CD4+ cell counts remain below 200 cells/mm3.

It is well known that CD4+ cell counts can be significantly increased by the use of interleukin-2 (IL-2), a CD4 T lymphocyte-produced cytokine. A recent study from European investigators, published in The Journal of Infectious Diseases, indicates that IL-2 can improve CD4+ cell counts in patients with a poor immunologic response to HAART. The study enrolled 13 Patients on stable HAART for at least 9 months with a viral load less than 50 copies/mL and a CD4+ cell count less than 200 cells/mm3. Before starting IL-2, despite excellent virologic suppression, these patients’ CD4+ cell counts had only risen a median of 37 cells/mm3.

After enrolment in the study, 7 of the patients immediately started the first of three IL-2 cycles, consisting of 4.5 million international units subcutaneously twice daily for 5 consecutive days every 6 weeks, while 6 of the patients continued on HAART alone for 12 weeks before starting IL-2. Following 2 cycles of IL-2, the CD4+ cell counts had risen a median of 32 cells/mm3 in the IL-2 treated group, but only 6 cells/mm3 in the HAART-only group. After all of the patients had received just 3 cycles of IL-2 (a total of about 18 weeks), the median CD4+ cell count had risen from 123 cells/mm3 at baseline to 229 cells/mm3 and 11 of 13 patients had a CD4+ cell count greater than 200 cells/mm3, a crucial value for decreasing risk of opportunistic infections. 7 patients who completed 9 IL-2 cycles had a median CD4+ cell count of approximately 500 cells/mm3 and when IL-2 was discontinued the CD4+ cell count appeared to remain stable. The viral load of these patients was not affected by IL-2 therapy.

The researchers also evaluated the nature of the CD4+ cell count rise. The rise in CD4+ cell counts was found to be associated with a significant improvement in the percentage of CD4+ lymphocytes and in the CD4:CD8 ratio. Further, the CD4+ cells resulting from IL-2 treatment were largely na•ve cells, which may have important implications regarding the patients’ immune recovery. The authors also noted that baseline levels of Bcl-2, an intracellular protein that protects cells from apoptosis (cell death), may be predictive of IL-2 response.

The authors of the study did not specifically list side effects encountered during IL-2 treatment, which commonly involves a “flu-like” syndrome that has been significant and problematic in other studies, but they stated that the treatments were “well tolerated by all patients and did not hinder daily lifestyle in most patients.” The authors concluded that their study “provides a solid basis in favour of large clinical trials aimed at defining the effects of IL-2 in the treatment of HIV-infected patients with low CD4 cell counts.”

David D and others. Rapid Effect of Interleukin-2 Therapy in Human Immunodeficiency Virus-Infected Patients whose CD4 Cell Counts Increase Only Slightly in Response to Combined Antiretroviral Treatment. The Journal of Infectious Diseases. 2001; 183: 730-5.