Mail & Guardian (Johannesburg) - January 31, 1997
Lesley Cowling

AS reports of a possible cure for Aids broke in South Africa last week, at the other end of the world about 2 300 HIV research-ers were hearing news about another potent new drug that could eradicate HIV, the virus that causes Aids.

Pharmaceutical company Abbot Laboratories announced at the 4th Conference on Retroviruses and Opportunistic Infections in Washington, DC, it had developed a new, improved version of protease inhibitors, the drugs hailed at last year's Aids conference in Vancouver as the possible death knell of the virus.

Protease inhibitors attack the enzyme protease, used by HIV to reproduce itself, and so damage the virus's ability to grow. Results in the many trials of protease inhibitors conducted in the past two years have been spectacular, and three types were licensed in countries across the world last year - including South Africa.

But the drugs had a drawback - the virus, which has an amazing ability to change itself when confronted with obstacles, learnt, in many cases, to adapt sufficiently to overcome protease inhibitors. This led to what doctors call "resistance", and many patients found HIV would regain its hold on them after some months or years.

But this week Abbot reported that experiments with its new protease inhibitor, ABT-378, on HIV grown in laboratory cultures and trials on rats showed the virus was not adapting and overcoming ABT, and resistance to this drug looked unlikely.

That problem being resolved makes protease inhibitors, particularly when used with other Aids drugs, the likeliest candidate for an Aids cure. And it gives it the edge over the yet untested and secret formula Virodene in every respect except cost.

The claims made for Virodene by the researchers are exciting, with certain of its properties touted as being better than any other drug available. But in fact, the results they pointed to as unique and superior have been equalled or bettered by protease inhibitors in many trials. The following claims have been made debatable by developments in HIV treatment:

* Newspaper reports said when Virodene was given to about 12 Aids patients in a drug trial, it reduced their viral load (amount of the virus detected in the blood) "dramatically" in two to three weeks. Other drugs could not do this as quickly, the reports said.

Not so. A number of combination drug studies, which included a protease inhibitor, were presented to the Washington conference last week showing that patients had dramatic drops in viral loads within four weeks.

For example, a study from Colorado, in which nine patients were treated for four weeks with the combination of a protease inhibitor and a drug of the same type as AZT showed a drop in viral load to undetectable levels in five patients.

Scientists at the conference theorised that there may be three phases of immune responses associated with combination drug (or antiviral) therapy.

The first phase of 15 days marks a rapid decrease in the virus's reproduction and a surge in the body's immune responses, like large-scale mobilisation of the body's fighter CD4 cells. This accounts for the dramatic results in the first days of a new drug regime.

* Researcher Olga Visser cited a rapid rise in CD4 cells (the immune cells that HIV attacks and kills) in her patients as a sign of Virodene's effectiveness, but acknowledged that other drugs push CD4 levels up higher than Virodene does. A number of studies at the conference confirmed this.

* Visser was quoted as saying Virodene fights HIV "in areas where other drugs can't reach it, such as in the lymph glands". The report went on to say the drug cocktail treatment can only fight the virus in the blood.

This is not strictly accurate. Studies presented to the conference showed the virus is generally higher in the lymph nodes than it is in the blood, and even when it is undetectable in the blood, it can be found in lymph nodes.

But international Aids expert Dr David Ho presented a study at the conference that showed if you clear the virus from the blood using a drug combination that includes protease inhibitors, this eventually reduces or clears the virus from the lymph organs. Other studies showed HIV can be cleared from the semen, too.

Ho said new research suggests it may take at least two to three years to clear the virus from a newly infected person, not one year as previously suggested. He refused to speculate on how long complete viral clearance might take in chronically infected patients, or even whether it was possible.

The fact that there are drug regimens as good as, or better than, Virodene currently available does not mean Virodene may not prove to be a cure, too, or that research into its effects should not be done. Research is especially necessary because the researchers say the cost of the drug will be low - R80 to R160 a month, against the R2 000 it currently costs Aids patients for protease inhibitors, and more for combination drugs.

But it will take years before Virodene has been sufficiently developed to be used as a treatment, and its fate is still uncertain. HIV patients need treatment now, and public health policy should focus not only on how to bring Virodene on to the market in the future, but on how to assist patients in their present predicament. This means looking at creative ways to fund combination treatment using protease inhibitors.

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