Science throws light on HIV suppression

BMJ 1995; 311 doi: (Published 16 December 1995) Cite this as: BMJ 1995;311:1591

The mystery of why some patients who are HIV positive do not develop AIDS may be closer to resolution, after the isolation of three potential HIV suppressor factors secreted by white blood cells. In this week's Science, researchers from the former National Cancer Institute including Professor Robert Gallo, the codiscoverer of the human immunodeficiency virus, claim that the three closely related polypeptides involved in inflammatory responses inhibited a broad range of strains of HIV-1 and HIV-2 and the simian form of HIV.

“This is the first time since the discovery of antibodies that we have identified a class of naturally occurring biological substances produced by individuals to fight infection. As such, it opens up new avenues of thinking,” said Professor Gallo.

As early as 1986 Jay Levy, a virologist, and colleagues at the University of California, San Francisco, reported that CD8 cells could suppress HIV replication. Three years later Levy's team showed that CD8 cells achieved this by secreting an unknown factor that seemed to interfere with HIV replication. Gallo now believes that this so called Levy factor has been finally identified.

Three chemokines--RANTES, MIP1-(alpha), and MIP1-£--have been identified that seem to work together to reduce HIV replication across a wide range of HIV strains. All these chemokines had been investigated individually by Levy and discounted. Gallo, however, used them for the first time in combination to achieve HIV suppression.

In the same week that Gallo published his findings Reinhard Kurth, director of the Paul Ehrlich Institute in Langen, Germany, wrote to Nature, claiming that another naturally occurring chemical messenger--this time the cytokine interleukin-16--also suppressed HIV. But Gallo's trio of chemokines works at concentrations up to 1000 times weaker than interleukin-16, which has important clinical implications.

Gallo hopes to begin toxicology and pharmacology trials shortly. Many variants will be produced to avoid toxicity. If the trials are successful, two possible therapeutic strategies could be envisaged: boosting the HIV suppressors endogenously (like increasing a diabetic patient's natural production of insulin) or boosting them exogenously (like current insulin supplementation).

Dr Janet Darbyshire, head of the Medical Research Council's HIV clinical trials unit at University College Hospital Medical School, London, said: “Promising results like these from in vitro studies are exciting but are still a long way from having a drug which is effective and safe.”--ALISON BOULTON, freelance journalist, London

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