TreatmentUpdate 66, Volume 8, No 2; February 1996
Sean Hosein

This Australian study was similar to those we reported earlier. During the first four weeks, subjects received either ritonavir (300 mg, 400 mg, 500 mg, 600 mg) twice daily or fake drug (placebo). After this, subjects on placebo received ritonavir according to one of the four dose-schedules. Although researchers enrolled 84 subjects for this study, detailed immunologic test results on only 21 subjects were published. No subject had less than 50 CD4+ cells. At the start of the study, the average CD4+ cell count was 153 cells, while the average CD8+ cell count was 813 cells.

Results - CD4+ and CD8+ cells

CD4+ cells

All 21 subjects had increases in their CD4+ cell counts once they began receiving ritonavir. The increased CD4+ cell count reached its highest level sometime between 2 and 14 weeks, depending on the subject. On average, subjects had an increase of 245 CD4+ cells as a result of ritonavir. This result was not statistically significant. Subjects on placebo did not have increas ed CD4+ cell counts.

CD8+ cells

The average CD8+ cell count of subjects receiving ritonavir increased by 954 cells. This increase was statistically significant; that is, not likely due to chance alone.

Results - production of HIV

The amount of virus in the blood (viral load) fell to about 10% of its pre-study level in all subjects who received ritonavir. There appeared to be no connection between the dose of ritonavir used and the size of the increase in CD4+ cells. The researchers found no link between the length of time viral load was suppressed and the size of the increase in CD4+ and CD8+ cells.

Results - probing the immune system

Researchers used blood cells taken from 7 subjects who received ritonavir. The ability of their cells to respond to an infection (in simulated tests) improved in 5 of 7 subjects on ritonavir during the first four weeks. No similar changes were seen in subjects on placebo. The improved immune responses were not complete; that is, the cells of some subjects responded to some, but not all, of the testing. For instance, 5 of 7 subjects had cells that responded to attack from relatively common bacteria, but only 2 subjects had cells that responded to attack from a bacterial poison. While only 2 other subjects had cells that responded to the HIV proteins p17 and p24. Indeed, researchers admitted that there were subjects whose cells did not respond to any of the bacterial or viral proteins. This research team did not conduct detailed immunologic tests to find out exactly what kind of response the cells produced (cell-mediated immunity or humoral immunity).

Overall

Use of ritonavir suppressed production of HIV at all doses used. As well, there were increased numbers of CD4+ and CD8+ cells among subjects who received ritonavir. The researchers did not report any clinical benefits such as:

improved resistance to life-threatening infections/cancers greater chance of survival

compared to subjects who did not receive the drug. Indeed, this research team has admitted that some of the increased numbers of CD4+ cells detected in this study were not new cells but merely cells that had moved from lymph nodes/tissues to the blood.

REFERENCES:

1. Kelleher AD, Carr A, Zaunders J and Cooper DA. Alterations in the immune response of Human Immunodeficiency Virus (HIV)-infected subjects treated with an HIV-specific proteinase inhibitor, ritonavir. Journal of Infectious Diseases 1996;173:321-329.

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