Nurses in London, England, recruited nine adult male subjects for this study. At the start of the study, key lab values were as follows:
All subjects were free of symptoms of AIDS. Technicians took blood samples from subjects several times before and after the subjects began HAART. In addition to analysing blood samples for CD4+ and other cells, technicians looked for certain cytokines, particularly interferon-gamma (IFN-gamma) and interleukin-2 (IL-2).
According to the researchers, viral load in eight subjects fell below the 500-copy mark within four weeks of their starting HAART. The remaining subject's viral load took eight weeks to fall to below this level, probably because it exceeded the one-million copy mark at the start of the study. CD4+ cell counts remained stable or increased during the study.
Before subjects received HAART, production of IFN-gamma and IL-2 was weak and their levels were low or undetectable. In contrast, levels of the cytokines IL-4 and IL-10 were high.
Technicians found that CD4+ counts were generally lower, averaging 160 cells, in subjects who were producing only IL-4 and IL-10. Conversely, their viral load tended to be greater (averaging 100,000 copies) than in subjects who were producing other cytokines in addition to IL-4 and IL-10. Indeed, among those subjects with detectable IFN-gamma, CD4+ counts were higher and viral load were lower, averaging 450 cells and 44,000 copies, respectively. These differences in CD4+ cell counts were statistically significant: not likely due to chance alone. The differences in viral load did not become statistically significant.
Once subjects began HAART, their viral load fell and production of IFN-gamma and IL-2 rose significantly. Although some subjects continued to produce relatively high levels of IL-4 and IL-10, the overall balance shifted toward greater production of IFN-gamma and IL-2. Upon analysing the data, researchers found that viral load fell dramatically as IFN-gamma levels increased. Increased CD4+ cell counts appear to be linked to rising levels of IL-2.
The results of this study are important because they document the changes in cytokine levels that some researchers have predicted. The results linking production of IFN-gamma to increased CD4+ cell counts prior to use of HAART are very important. Doctors and their patients can now look more critically at other therapies, whether complementary or pharmaceutical, and ask about their impact on the immune system. Those therapies that do not boost a useful response (increased levels of IFN-gamma and IL-2) are not likely to help the immune system control HIV.
1. Imami N, Antonopoulos C, Hardy GAD, et al. Assessment of Type 1 and Type 2 cytokines in HIV Type-1-infected individuals: impact of Highly Active Antiretroviral Therapy. AIDS Research and Human Retroviruses 1999;15(17):1499-1508.
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