Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.
Protease inhibitor-containing regimens compared with nucleoside analogues alone in the suppression of persistent HIV-1 replication in lymphoid tissue.
AIDS. 1999 Jan 14;13(1):F1-8. Unique Identifier : AIDSLINE MED/99223945 Ruiz L; van Lunzen J; Arno A; Stellbrink HJ; Schneider C; Rull M; Castella E; Ojanguren I; Richman DD; Clotet B; Tenner-Racz K; Racz P; Retrovirology Laboratory, Fundacio irsiCaixa, Badalona, Spain.
Abstract:
OBJECTIVE: Lymphoid tissue provides a reservoir where HIV can persist. However, therapies incorporating a protease inhibitor can target this reservoir. This study was designed to investigate the relative long-term effects on lymph-node viral load and cellular architecture of regimens containing multiple nucleosides alone or in combination with protease inhibitors. METHODS: Axillary lymph-node biopsies from 12 patients with undetectable viraemia (viral load < 20 copies/ml: mean CD4 cells 525 x 10(6)/l) for a mean period of 25 months (range, 10-52 months) were investigated for the presence of HIV by in situ hybridization and coculture. Four patients were receiving multiple nucleoside analogues alone or in one case with a suboptimally dosed protease inhibitor (group I). Protease inhibitor was added to the regimen of seven patients at least 6 months prior to lymph-node biopsy (group II). Standard flow cytometry and virological data were obtained from peripheral blood every 3 months. RESULTS: By in situ hybridization, more productively infected CD4+ T cells were found in the lymph nodes of group I patients treated with nucleoside analogues alone. Very low numbers of productively infected lymph node cells were detected in the protease inhibitor-treated group II. No trapping of virions on the follicular dendritic cell (FDC) network was detectable in protease inhibitor-treated patients. In contrast, large deposits of FDC-bound virions were observed in three out of five patients from group I. Virus cultures from lymph node cells were positive in these three group I patients compared with only one out of seven patients from group II. Sequencing reverse transcriptase and protease genes from these isolates revealed typical mutations conferring resistance to the previously administered nucleoside analogue. A more preserved lymph node architecture and less signs of immunopathological change were also observed in protease inhibitor-treated patients. CONCLUSIONS: Undetectable plasma viraemia using the ultrasensitive PCR assay for prolonged periods of time does not always reflect complete HIV-1 suppression within the lymphoid compartment. Our results suggest that protease inhibitor-containing regimens target HIV reservoirs in lymphoid tissue more effectively and preserve or restore lymph node architecture.
Keywords: JOURNAL ARTICLE Anti-HIV Agents/*THERAPEUTIC USE Coculture CD4 Lymphocyte Count CD4-CD8 Ratio Dendritic Cells Drug Resistance, Microbial Drug Therapy, Combination Human HIV Infections/IMMUNOLOGY/PATHOLOGY/*VIROLOGY HIV Protease Inhibitors/*THERAPEUTIC USE HIV-1/DRUG EFFECTS/GENETICS/*PHYSIOLOGY Lymphoid Tissue/VIROLOGY Nucleosides/*THERAPEUTIC USE RNA, Viral Support, Non-U.S. Gov't Viral Load *Virus Replication 990930
A9991367
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.
