Immune Reconstitution and the Consequences for Opportunistic Infection Treatment and Prevention

Effective antiretroviral therapy that suppresses HIV replication is associated with dramatic increases in CD4 counts. Recent evidence suggests that this CD4 cell increase is biphasic in nature, with an initial phase (in the first 2 to 3 months) that represents redistribution of lymphocytes into the periphery and a second phase that is associated with true immunologic recovery and reconstitution. Immunologically there is evidence of increase in naive T cells, recovery of in vitro responses to microbial antigens, and repair of the damaged diversity of T cells. Clinically, this immune recovery has been characterized by decreasing morbidity and mortality from opportunistic infections, an ability to treat previously intractable infections, immune-mediated syndromes, and increasing reports of the ability to discontinue primary and secondary prophylaxis. Although there are still unresolved questions about the completeness of the immune recovery, most available evidence suggests in most patients the degree of immune reconstitution with effective antiretroviral therapy is sufficient to be protective against most opportunistic infections, and ultimately additional antimicrobial prophylaxis will be unnecessary.