Baseline HIV levels, age determine degree of immune restoration with treatment

In HIV-positive individuals, the magnitude of the initial rise in CD4 T cell counts after antiretroviral therapy is determined by baseline HIV-1 levels, while long-term restoration of CD4+ cells is related to age, researchers report in the December 1st issue of AIDS.

Dr. Michael M. Lederman from the University Hospitals of Cleveland and a multi-centre team examined the phenotypes of CD4+ and CD8+ T cells in 71 HIV-1-positive adults during 48 weeks of treatment with abacavir and a protease inhibitor. Patients had not previously received antiretroviral treatment. The researchers observed that naive and memory CD4+ cells and B cells increased during the first 4 weeks of therapy. While CD8+ cells overall remained stable, naive CD8+ cells increased and memory CD8+ cells decreased.

After the first 4 weeks, total, naive, and memory CD4+ cells increased. In addition, naive CD8+ cells increased while total and memory CD8+ cells decreased. The expression of CD28 on CD4+ cells also increased significantly at the end of the study compared with baseline.

Overall, the researchers found that higher baseline plasma HIV-1 RNA levels were significant in predicting the magnitude of restoration of CD4+, memory CD4+, and CD28 CD4+ cells, but only during the early phase of treatment. In the later phase, increases in naive CD4+ cells were predicted by younger age.

“Higher baseline levels of HIV-1 replication determine the magnitude of first phase CD4+ cell increases after suppression of HIV-1 replication,” Dr. Lederman and colleagues conclude. “Second phase (primarily naive) CD4+ cell increases are not related to HIV-1 replication but are inversely related to age suggesting that thymic potential is a major determinant of long term cellular restoration in HIV-1 positive persons receiving antiretroviral therapy.”

They note that the cellular restoration observed in these patients is similar to the pattern seen in patients treated with three antiretroviral drugs.