AIDSWEEKLY Plus, Monday, 21 July 1997
Daniel J. DeNoon, Senior Editor
Highly active antiretroviral therapy (HAART) can greatly reduce lymph-node HIV levels, but even a short interruption means starting all over again.
This sobering new finding shows that there are strict limits to the even the most effective anti-HIV regimens.
HIV infection of the lymph nodes is often spoken of as the central lesion of HIV disease. With the advent of HAART, hopes that HIV can be eliminated or permanently suppressed hang on whether the drug combinations are able to reduce viral burdens in the lymph nodes as well as they do in the peripheral blood.
The good news, announced Joseph K. Wong of the University of California, San Diego, is that HIV in lymphoid tissues is reduced by 4 log[10] in patients whose plasma viral loads remain undetectable after a year of HAART.
The bad news is that lymph-node HIV levels remain high in patients with relatively low-level plasma viremia. Perhaps even more disappointing is the finding that lymph-node virus levels rebound back to pre-treatment levels during brief interruptions of therapy.
"Even modest plasma viremia during therapy can be associated with very significant virus loads in lymphoid tissues," Wong said. "Even temporary interruptions [of therapy] appear to allow for repopulation of lymphoid tissues and the resetting of the clock for the decay of lymph-node virus."
Wong announced the findings in a presentation to "New Opportunities for HIV Therapy - From Discovery to Clinical Proof-of-Concept," the 2nd Joint Conference of the National Institute of Allergy and Infectious Diseases (NIAID) Strategic Program for Innovative Research on AIDS Treatment (SPIRAT) and the National Cooperative Drug Discovery Groups for the Treatment of HIV Infection (NCDDG-HIV), held June 22-26, 1997, in Vienna, Virginia.
Wong and colleagues evaluated HIV RNA and DNA levels and determined resistance mutations in blood and inguinal lymph- node biopsies from patients enrolled in the Merck 035 study comparing indinavir plus zidovudine (AZT) plus lamivudine (3TC) to indinavir alone and to AZT plus 3TC.
Nine of the patients examined by Wong et al. received the triple-drug therapy; they had relatively advanced disease with baseline CD4 counts ranging from 69 to 274 cells/(micro)L and a median plasma virus load of 41,100 copies/ml. All had previously received nucleoside therapy, but all were naive for indinavir and 3TC.
"After one year of therapy, viral RNA levels in the lymphoid tissues of individuals receiving triple-drug therapy who had undetectable plasma RNA levels were reduced by 4 log[10] but were still detectable," Wong et al. wrote in their presentation abstract. "However, in subjects on the triple- drug regimen with interruption of therapy or in those treated with AZT/3TC alone, lymphoid viral loads were 10(7) to 10(9) copies of HIV RNA/g of tissue: levels indistinguishable from those expected for untreated patients."
In patients with "suboptimal" response to triple-drug therapy (i.e., measurable plasma virus load), replication- competent virus could be recovered from both blood and lymphoid tissue. And this virus apparently acquires resistance to the treatment medications.
"Virus in subjects with inadequate suppression accumulate drug-resistance mutations indicating high levels of virus replication," Wong said.
When patients interrupted therapy due to adverse reactions or failure to comply with strict dosage requirements, the virus quickly rebounded in lymphoid tissue.
"I guess this means that close is good enough only in horseshoes and not in retrovirology," commented Roger Pomerantz of Thomas Jefferson University, Philadelphia, Pennsylvania. - by Daniel J. DeNoon, Senior Editor
970721
AW970706
Copyright © 1997 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.
Published by Charles Henderson, Publisher. Editorial & Publishing Office: P.O. Box 5528, Atlanta, GA 30307-0528 / Telephone: (800) 633-4931; Subscription Office: P.O. Box 830409, Birmingham, AL 35283-0409 / FAX: (205) 995-1588 http://www.newsfile.com
AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, iMetrikus, Inc., the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 1997. This material is designed to support, not replace, the relationship that exists between you and your doctor.
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.
Copyright ©1990, 2000. AEGiS & the Sisters of Saint Elizabeth of Hungary. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of ÆGIS, or the party credited as the provider of the content.