STUDIES ON LYMPHOID-TISSUE FROM HIV-INFECTED INDIVIDUALS - IMPLICATIONS FOR THE DESIGN OF THERAPEUTIC STRATEGIES

Lymphoid tissue is a major reservoir of human immunodeficiency virus ( HIV) infection in vivo. In addition, the lymphoid microenvironment pro vides a replicative advantage to the virus in that it provides a milie u of activated target cells that allows for efficient virus spread. Th e process of mobilization and activation of immune competent cells dir ected against the virus paradoxically contributes to the propagation o f virus replication. Disruption of the lymphoid microenvironment durin g the progression of HIV disease is a poorly understood process, which may be of considerable importance pathogenically. Studies of lymph no de biopsy samples taken 8 weeks apart from individuals who did not und ergo any change in their therapeutic regimen (i.e., patients who eithe r remained untreated or remained on their ongoing nucleoside analogue reverse transcriptase inhibitor monotherapy regimen) revealed little c hange in histopathology or viral load over the 8-week period. These re sults with successive lymph node biopsy samples taken from different s ites indicate that an isolated lymph node biopsy accurately reflects t he pathologic process associated with HIV infection and that this proc ess diffusely involves the lymphoid system. Treatment with reverse tra nscriptase inhibitor monotherapy of patients in relatively early stage HIV disease had no detectable impact on the viral load in lymphoid ti ssue, suggesting the need to investigate more potent antiretroviral re gimens during this stage of disease. Among patients with moderately ad vanced HIV disease, switching to combination therapy from a monotherap y regimen resulted in decreased viral replication in lymph nodes; this effect was associated with decreases in plasma viremia. Despite the f act that measures of viral replication decreased significantly, the ne t frequency of HIV-infected cells in peripheral blood and lymph nodes remained unchanged. Potent antiretroviral drug combinations may be cap able of profound and long-term downregulation of plasma viremia. It wi ll be essential to monitor the status of viral trapping, viral burden, and viral replication within lymphoid tissue during treatment with su ch drugs to determine accurately their true potential for impact on th ese key features of HIV pathogenesis.