Human Immunodeficiency Virus Pathogenesis: Insights from Studies of Lymphoid Cells and Tissues

Although plasma virus load is invaluable for monitoring human immunodeficiency virus (HIV) infection, key pathogenesis events and most viral replication take place in lymphoid tissues. Decreases in virus load associated with therapy occur in plasma and tissues, but persistent latent infection and ongoing viral replication are evident. Many unanswered questions remain regarding mechanisms of HIV-associated lymphocyte depletion, but partial CD4(+) cell reconstitution after therapy likely reflects retrafficking from inflamed tissues, increased thymic or peripheral production, and decreased destruction. Rapid establishment of latent infection and the follicular dendritic cell-associated viral pool within lymphoid tissues suggest that only early intervention could substantially alter the natural history of HIV. If therapy is started prior to seroconversion, some individuals retain potent HIV-specific cellular immune responsiveness that is suggestive of delayed progression. Although complete virus eradication appears out of reach at present, more attention is being directed toward the prospect of boosting HIV-specific immune responses to effect another type of "clinical cure": immune-mediated virus suppression in the absence of therapy.