HIV-Specific T Cells Persist in Those Infected With HIV, But High HIV Levels Diminish Ability of Immune System to Respond to InfectionT cells programmed specifically to target HIV persist in HIV-positive individuals, but high viral levels detract from the cells' ability to reproduce and respond to infection, according to a study published in the Nov. 20 issue of the Proceedings of the National Academies of Sciences. Researchers from the National Institute of Allergy and Infectious Diseases studied T cells from three groups of patients: those with progressive HIV, long-term nonprogressors who had not received treatment and patients on antiretroviral therapy who had ceased taking their medications long enough to allow viral levels to rebound. All three groups had equal numbers of HIV-specific T cells, indicating that the cells were not destroyed by HIV. Researchers had been uncertain whether HIV destroyed HIV-specific T cells or whether the virus inactivated the cells. The researchers did find, however, that the HIV-specific T cells of those with progressive HIV did not proliferate, indicating that they had "somehow been turned off."
Testing Drug Therapy Cessation
The researchers then examined anti-HIV T cell response in patients who demonstrated a proliferation of anti-HIV T cells while on antiretroviral drugs. They theorized that the T cells should hold HIV levels low even if drug therapy ceased, because the cells continued to proliferate in the presence of the virus. However, viral levels rebounded after therapy stopped. The anti-HIV T cells remained present, but lost their ability to proliferate and remained inactive until resumption of antiretroviral therapy lowered viral levels again. The results suggest that high viral levels may cause HIV-specific T cells to stop proliferating. Therefore, treatment interruption may not be the "best way" to elicit an anti-HIV immune response. "This presents a good news/bad news scenario. The good news is that HIV-specific CD4+ T cells are not completely deleted; the bad news is that measuring the activity or even frequency of those cells is not necessarily a good predictor of long-term virus control," co-author Dr. Mark Connors said. The study demonstrates how HIV can "manipulate the immune system for its own survival" and may provide some "important clues to how the virus accomplishes that goal," NIAID Director Dr. Anthony Fauci said (NIH release, 11/19).