THE UNENLARGED LYMPH-NODES OF HIV-1-INFECTED, ASYMPTOMATIC PATIENTS WITH HIGH CD4 T-CELL COUNTS ARE SITES FOR VIRUS-REPLICATION AND CD4 T-CELL PROLIFERATION, THE IMPACT OF HIGHLY-ACTIVE ANTIRETROVIRAL THERAPY

The efficacy of triple drug therapy for HIV-1 infection encourages its early use to prevent damage to the immune system. We monitored the ef fects of such therapy on 13 patients with 14-75-mo histories of minima l disease, i.e., CD4(+) counts constantly >500/mu l and little or no l ymph node enlargement. In this way, we could first determine the exten t of viral replication and immunoarchitectural changes in unenlarged n odes early in disease, and second follow the response to triple therap y in plasma and lymphoid tissue in tandem. As is known for lymph nodes with more advanced disease, the germinal centers showed productively infected T cells, i.e., CD4(+)CD1a(-)CD68(-) cells labeling intensely for HIV-1 RNA after in situ hybridization. The unenlarged nodes also s howed extensive HIV-1 RNA retention on a well-preserved, follicular de ndritic cell (FDC) network, and the follicles were abnormal. There wer e numerous CD8(+) cells, many expressing TIA-1 granule antigen. Also, in contrast to normal follicles, CD4(+) T cell proliferation was activ e, with marked increases in the number of cycling, Ki-67(+)CD4(+)CD45R 0(+) cells. After 28 d and 3 mo of therapy, productively infected T ce lls decreased dramatically and often were not apparent. The labeling o f the FDC network for viral RNA also decreased, but not for gag protei n. We conclude that HIV-1 replicates and accumulates in lymphoid organ s before damage of the immune system, that at this stage of disease de novo production of T cells occurs in the lymphoid tissue, and that th e infection is sensitive to triple drug therapy in both plasma and lym ph nodes.