Important note: Information in this article was accurate in June 1999. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, June 14 & 21, 1999
Daniel J. DeNoon, Senior Editor
CW HENDERSON PUBLISHER -- Immune reconstitution is possible even in AIDS patients with advanced disease, new data indicate.
Follicular dendritic cells (FDCs) in lymphoid tissues trap and retain antigens, allowing the development of humoral immunity and the interaction of B and T lymphocytes. FDCs thus are the keystone of the immune system. Untreated HIV infection steadily erodes the delicate network of FDCs, leading to a rapid deterioration in immune competence.
A major question about highly active antiretroviral therapy (HAART) is whether treatment comes too late for AIDS patients whose lymphoid follicles have been severely affected. The unexpectedly unequivocal answer is yes, it can.
"We show that treatment, initiated even at advanced stages of HIV- 1 disease, can slowly reverse pathological changes in the FDC network," wrote Zhi-Qiang Zhang and Ashley T. Haase of the University of Minnesota Medical School, Minneapolis, Minnesota, and colleagues.
Zhang et al. reported their findings in the Proceedings of the National Academy of Sciences ("Reversibility of the Pathological Changes in the Follicular Dendritic Cell Network with Treatment of HIV-1 Infection," Proc Natl Acad Sci U S A 1999 Apr 27;96(9):5169-72.
The multicenter research team obtained tonsil and lymph-node tissues from participants in two HAART (two reverse-transcriptase and one protease inhibitor) clinical trials. All of the patients responded successfully to HAART, with viral load becoming undetectable. Ten participants had early-stage HIV infection and 12 participants had late-stage disease. Tissues from six uninfected individuals served as controls.
Six months of treatment showed some nonsignificant indications of improvement. After 12 months' treatment, significant improvement clearly had occurred. And with 2.5 years of treatment, patient FDCs (as measured by FDC fraction in lymphoid tissue) was equivalent to that of healthy controls.
"The FDC network is nearly destroyed after prolonged HIV-1 infection, but this destruction is reversible," Zhang et al. wrote. "Although the kinetics of regeneration varied among individuals, the FDC network could be fully anatomically reconstituted in some HIV-1 infected individuals with sustained reduction in the FDC viral load."
The authors noted that functional restoration apparently follows the anatomic restoration they observed (Morris, L. et al., V Conf Retrovirus Opportun Infect, 1998).
"It is encouraging that the immune system may benefit from control of viral replication and the reduction of viral load in the FDC compartment without complete eradication of virus or infected cells," they wrote.
This work was supported by National Institutes of Health grants, by the Research Center for AIDS and HIV Infection of the San Diego Veterans Affairs Medical Center, by a Swiss National Science Foundation grant, and by Abbott, Glaxo-Wellcome, and Merck Research Laboratories.
The corresponding author for this study is Ashley T. Haase, Department of Microbiology, University of Minnesota, 420 Delaware St. SE, Minneapolis, Minnesota 55455. Email: <ashley@lenti.med.umn.edu>.
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