Immune reconstitution after antiretroviral treatment

Data favoring immune reconstitution: Multiple drug therapies for HIV infect ion have enabled a major reduction in the viral load, higher CD4 counts, an d a lower incidence of opportunistic infections and tumor formations, and s ubsequently lower hospitalization rates and mortality. Two stages of CD4 reconstitution: In HIV-positive patients with advanced st age disease treated with a protease inhibitor associated with 2 nucleoside analog reverse transcriptase inhibitors and followed prospectively, it has been observed that CD4 counts rise considerably. with a rapid increase duri ng the first 2 months followed by a slower but still positive slope over a period of 18 months. Discordant results have however also been observed sug gesting an ineffective anti-viral effect or a retarded immune reconstitutio n. Several mechanisms: The lymphocyte amplification observed during the early phase corresponds to re-circulation of CD4 and CD8 lymphocytes which had be en sequestered in lymphoid organs; most of these CD4 lymphocytes are memory cells. A second phase corresponds to a more moderate and progressive rise in naive CD4 cells which originate from an unknown source, This biphasic re constitution of CD4 lymphocytes is associated-with a correction of the chro nic lymphocyte overactivation. Partial immune reconstitution: With treatment, the capacity to respond to k nown antigens reappears. This restored capacity is secondary to the amplifi cation of CD4 memory cells and appears prior to the expansion phase of naiv e cells. The response remains moderate and is only observed against antigen s from microorganisms highly prevalent during advanced stage infection.