HIV infection causes fibrosis in lymphatic tissue, diminishing CD4+ pool

Chronic infection with HIV-1 causes severe fibrosis and scarring in the paracortical T cell zone of lymphatic tissues, which may explain why HAART fails to restore the peripheral CD4+ T cell count in some patients even when it results in good viral suppression, researchers suggest.

Their full report, “Collagen Deposition in HIV-1 Infected Lymphatic Tissues and T Cell Homeostasis,” was published in the 15 October issue of the Journal of Clinical Investigation.

Examining lymph node biopsies in HIV-infected patients “has the potential to provide yet another look at how the body’s immune defences are reacting to viral infection, and gives potentially prognostic information about what the impact of therapy will be,” said lead author Dr Timothy W Schacker.

Schacker, of the University of Minnesota-Minneapolis, and colleagues prospectively studied inguinal lymph node biopsies of 11 HIV-infected patients who were HAART-naïve at baseline. Seven patients initiated HAART after the first biopsy; four chose to defer treatment.

Researchers noted significant depletion in the CD4+ T cell population in all samples at baseline. They also found evidence of chronic inflammation and fibrosis that altered the structural organisation of the tissue.

At one month and six months, investigators found improvement in the size and number of B cell follicles in three treated patients, and a general trend toward expansion of the CD4+ T cell numbers in lymphoid tissue. Yet, researchers found no improvement in three other patients who had also initiated HAART.

In one HIV-negative patient, less than 1% of the T cell zone area consisted of collagen. In infected persons, collagen comprised 2.2% to 19.9% of the T cell zone area. The study found a significant inverse relationship between the percentage area collagen and the size of the CD4+ T cell population in the baseline biopsies. The area occupied by collagen was not associated with other clinical markers of disease severity, including duration or stage of infection, baseline plasma CD4+ T cell count, or plasma HIV-1 RNA level. However, there was a significant relationship between the change in the peripheral CD4+ count after six months of HAART and the baseline percent area occupied by collagen, after controlling for baseline peripheral CD4+ count and viral load.

“In the state of chronic immune activation and inflammation from ongoing HIV-1 replication, there is damage and disruption to the lymph tissue microenvironment that results in the impaired recruitment, retention, and proliferation of CD4+ T cells,” the investigators stated. They likened the fibrosis process to that found in the pathogenesis of cirrhosis in chronic active hepatitis B and C infection.

Schacker noted that such findings could be used to advise patients. “For example, if you were to perform a staging biopsy on a new patient, you could tell that patient, ‘based on the evidence, we think your lymph tissue will suffer a significant amount of damage even though you have no clinical symptoms yet.’ This individual you might want to put on HAART earlier rather than later to protect the lymph tissues.”

He also suggested “something as simple as a nontoxic anti-inflammatory agent started immediately after infection could perhaps limit damage to the lymphoid space in a significant way.”