Retroviruses Conference Overview: Consolidating the Advances

While little was surprising or revolutionary at this year's4th Conference on Retroviruses and Opportunistic Infections(January 22-26 in Washington D.C.), the work presented washigh quality and contributed solid advances in many fields.This Conference is widely regarded as in many respects a very successful one -- to the credit, of course, of the thousands of researchers, who made more progress in 1996 than in any previous year of the epidemic.

The meeting had its problems as well. Most people with HIV who wanted to attend were barred from this meeting (seearticle below). And some areas, such as nutrition, were largely absent. The rejected abstracts may be as important astory as any other from this meeting, but it is hard to learn about them because no list is available. This Conference reflected one particular group's vision of scientific quality and prestige.

Here are some of the central messages which we took away:

* New HIV treatments have greatly reduced deaths, illnesses,and hospitalizations, when they are available. They can partly or completely pay for themselves by reducing other medical costs -- which is important to know for getting reimbursement and therefore treatment access. But cost savings do not automatically translate into institutional motivation to do the right thing, since different medical expenses often come from different budgets. Therefore, advocacy is necessary.

* The AIDS medical community is clearly moving toward the view that when antiretroviral treatment is used, the goal should be complete suppression of HIV (plasma viral loadbelow the limit of detection of the test used). Unless viral replication is essentially shut off, by continuous use of antiretroviral drug combinations, the patient's HIV will evolve to become resistant to the drugs. But if viral load is kept undetectable by continuous use of the drugs, then resistance develops very slowly or not at all.

* When to start antiretroviral therapy has been a more difficult question, but a practical consensus does seem to be building around starting "when the patient is ready." In other words, there are biological reasons to start anti-HIV treatment as early as possible; but if a person is not ready to follow the regimen, the drugs will do more harm than good because that patient will be likely to develop resistant virus, and lose most of the benefit of some important drugs forever. The resistant viruses can also be transmitted to others.

* There is no case yet where an established HIV infection has been eradicated by treatment. Mathematical calculations based on patient data suggest that if all viral replication could be stopped, in all body compartments known to harbor the HIV, the virus might be eliminated from the body eventually by normal cell turnover -- but this would be expected to take at least two and a half years of complete viral suppression,based on known compartments, and it could take much longer if HIV is also present in other cells where it is not now known to be. The mathematical models have been revised since the last major conference in Vancouver, and it is now realized that viral eradication, if possible at all with drugs now available, will take longer than had been thought. As aresult, researchers have decided to wait before encouraging any volunteer in their trials to stop drugs in order to test whether eradication has occurred.

Much new data was presented on combinations of existing drugs. One especially important finding was that acombination of indinavir (Crixivan(R)), AZT, and 3TC reduced viral load to below the limit of detection (500 copies) at week 24 in 65% of patients who had advanced AIDS and much prior experience with AZT. When they began the study, these volunteers had a median CD4 count of 15, a median viral load of 89,500 copies, and all had used AZT for at least six months previously. (By contrast, only 2% of those randomly assigned to indinavir alone, and no one assigned to AZT plus3TC, had viral load reduced to under 500 copies.) This study contributes to the critical task of finding effective treatment for the most difficult patients -- those with advanced disease and much prior antiretroviral therapy.

* Information was also released on new drugs, on which little or nothing has been published before. One important exampleis ABT-378, a "second generation" protease inhibitor from Abbott. Another potential treatment to watch is pentafuside(T-20), a synthetic peptide which prevents HIV from entering cells.

* Basic science involving HIV also had its most successful year in 1996. A particularly important area concerned understanding of "co-receptors" -- molecules in addition toCD4 which HIV uses when it enters cells. These discoveries have not produced new treatments yet, but they are likely to,because there are various processes which occur, and molecules which are formed, only when HIV interacts with cells. These can be targets for development of new classes of drugs.

* Progress continues in the prevention and treatment of opportunistic infections and other conditions. For example, a study by the U.S. AIDS Clinical Trials Group (ACTG) has found that pneumocystis prophylaxis with Bactrim (Septra) can be tolerated by more patients if the dose is increased gradually at first, instead of being started suddenly. (This result was released in December 1996 at a meeting of the ACTG, but was presented to a larger audience at the Retroviruses conference.) And for CMV, information was presented on new drugs, including 1263GW94, lobucavir, and valganciclovir.

AIDS TREATMENT NEWS will publish more detailed reports in separate articles on these and other results.