AEGiS-CATIE: HIV Bounces back

HIV Bounces back

TreatmentUpdate78 - Vol. 7, No. 8; June 1997
Sean Hosein

In general, treatment with protease inhibitors has driven the amount of HIV in the blood so low that it can barely be detected. This has given the immune system some relief and space for a limited recovery, allowing PHAs to withstand some infections and perhaps live longer than they otherwise might. There are drawbacks with these new drugs, however, one of which is the mystery surrounding how long it will be necessary for PHAs to keep using these drugs.

Stopping Therapy

Results from experiments in Germany and others in New York by Dr. David Ho show that if anti-HIV therapy is halted after 3 or 12 months, the amount of HIV in the blood returns to pre-therapy levels within 2 weeks. This happened even though the viral load in the blood was undetectable while people remained on therapy.

Focus on macs

Why was there such a quick upsurge in HIV levels even after lengthy therapy? It appears that even during aggressive anti-HIV treatment small quantities of the virus are still being produced. It now appears that there are two groups of "cells that are mostly responsible for virus production." One group is the CD4+ T cells (also called T4+ cells) which account for 99% of viral load. The other group, which accounts for the remaining 1% of viral load consists of cells called macs (macrophages). For reasons which are not clear, HIV-infected macs, unlike CD4+ cells, do not shut down production of HIV when treated with anti-HIV drugs. Also, despite one year of aggressive anti-HIV treatment, the immune system cannot destroy the few cells responsible for low-level HIV production. Indeed, once therapy is stopped, viral load quickly climbs out of control. So now some doctors hope that a combination of anti-HIV and immune boosting drugs will result in long-term suppression of the virus.

Which immune boosters?

Researchers think that IL-2 (interleukin-2) and IL-12 (interleukin-12), both of which are being studied in the US, may be a good foundation for helping to rebuild the immune system. Using IL-12 and interferon-gamma, researchers hope to make HIV-infected macs sensitive to anti-HIV drugs in order to shut down these virus factories. Another product which will enter clinical trials in North America shortly is IL-10 (interleukin-10). This drug could also prove to shut down production of HIV in macs, but unfortunately, it also has the potential to hinder the immune system's ability to fight off infections.

Fewer drugs?

Anti-HIV drugs can cause toxicity, need to be taken several times daily and can have an adverse impact on patients' quality of life. Some doctors plan therefore to test "aggressive anti-HIV therapy" combinations of 4 drugs for between 6 and 12 months, after which they will reduce the number of drugs and monitor their patients to see what effect this has on their health.

REFERENCES:

1. Pantaleo G. How immune-based interventions can change HIV therapy. Nature Medicine 1997;5(3):483-486.

2. Mackall CL, Hakim FT and Gress RE. T-cell regeneration: all repertoires are not created equal. Immunology Today 1997;18(5):245-251.

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ÆGIS is made possible through unrestricted grants from Boehringer Ingelheim, Elton John AIDS Foundation, iMetrikus, Inc., the National Library of Medicine, and donations from users l This article first appeard in 1997. This material is designed to support, not replace, the relationship that exists between you and your doctor.

Copyright © 1997 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284 http://www.catie.ca

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