Antiretroviral therapy enhances production of new T-cells independently of HIV

Antiretroviral drugs can stimulate the production of new T-cells from the thymus gland independently of their effect on HIV, investigators from the United States report in the 23^rd September edition of AIDS.

While the reconstitution of T-cell counts in HIV-positive patients is known to be caused by reductions in the levels of HIV, some experts believe that antiretroviral drugs may have an additional, direct effect on T-cell production. This is thought to be due to protease inhibitors preventing the death of uninfected T-cells within the thymus, the small gland under the breastbone where T-cells are produced.

To assess the effect of antiretroviral therapy independently of HIV, the investigators examined the rate of production of new T-cells from the thymus gland in seven HIV-negative healthcare workers taking post-exposure prophylaxis (PEP). PEP is a month-long course of antiretroviral drugs used to prevent HIV infection after a possible exposure to the virus.

“Our findings suggest that the administration of HIV protease inhibitors may promote immune reconstitution in various clinical settings”, they conclude.

The seven participants took a combination of 1250mg nelfinavir (Viracept) with 300mg AZT (zidovudine) and 150mg 3TC (lamivudine) as Combivir twice daily for 28 days. After comparing white cells from the participants’ blood samples taken before and one to two weeks after PEP, the investigators found evidence of a dramatic increase in the production of new cells from the thymus in five of the patients. None of the participants became HIV-positive.

Overall, there were more ‘signal joint T-cell receptor recombination excision circles’ (sjTRECs), a marker of new T-cells, after PEP treatment (p

Despite the increase in the production of T-cells, there were no significant changes in the total CD4 or CD8 cell counts across the study. Although there was a small increase in the CD4 percentage, this did not account for the increased levels of sjTRECs.

“These observations suggest that peripheral T-cell homeostasis was not dramatically affected by antiretroviral therapy, and that the observed increases in sjTRECs … were most likely attributable to effects on antiretroviral therapy on thymopoiesis [formation of new cells in the thymus],” the investigators explain.

“Together, the data indicate that the net effect of antiretroviral therapy is an increase in thymic output and a rejuvenation of the T-cell compartment,” they conclude.

A small experiment carried out in mice revealed that nelfinavir did not affect ‘negative selection’, a normal cell-death process that occurs in the thymus. This process is necessary to prevent the thymus producing immune cells that might attack the body’s own cells.