Evolving understanding of the immunopathogenesis of HIV

Understanding of the immunopathogenesis of HIV infection is becoming more advanced as the activity of HIV infection in lymph nodes is appreciated and as improved virological measures permit more accurate quantitation of viral burden in patients at all stages of HIV disease. Although CD4+ cell counts remain important prognostic indicators, their role as a surrogate for direct antiviral activity has been questioned and increasing focus has been placed on more direct quantitative viral measures that are now available. After an initial explosive burst of viral replication during acute seroconversion that is downregulated by the immune system, these newer markers have revealed that viral replication is ongoing during the so-called "clinically latent" period of HIV infection. One of the most active sites of viral replication during this asymptomatic period is in lymphoid tissues. Over time, however, immunological control of HIV wanes, the site of replication shifts from the lymph nodes to other lymphoid organs, and disease progression ensues. The role of viral diversity in late-stage HIV disease is now well established, yet its role in pathogenesis and establishment of viruses resistant to antiviral agents is not fully established. Increased understanding of how HIV causes immune dysfunction may help us control direct and indirect (opportunistic) complications of HIV infection.