The interview with Dr. Margaret Poscher, below, is the first in a series of articles and interviews on combination anti-HIV treatment. For over a year, it has been almost a cliche that combination treatment is the wave of the future; however, the actual data on how well drug combinations work in people has been, and still remains, minimal and disappointing. But new information has recently renewed our interest in this potential advance: * Laboratory studies are showing that some combinations work much better -- or much worse -- than might have been predicted, in suppressing HIV in laboratory cultures.

Some of these studies have been conducted over the last five years by Marty St. Clair, Ph.D., of Burroughs-Wellcome (now Glaxo Wellcome). Among the few drugs that she has tested so far, she has found that certain triple combinations work best. Some of the best results have been with AZT, plus either ddI or ddC, plus either 3TC or nevirapine.

These laboratory studies have also suggested that it is better to combine drugs than to alternate them. Also, it is usually best to begin the different drugs at or close to the same time, if possible; the combinations may be less effective if the patient has already been using one of them for months or years, allowing resistance to develop. And the laboratory tests suggest that these combinations may be most active when the viral concentration is low, suggesting that they may work better in early stage HIV infection, than in late stage.

Conditions in the human body, of course, are very different than in laboratory cultures. Therefore this laboratory work can only provide guidance or suggestions as to what combinations may be likely to work. Only human trials can tell whether or not a particular regimen is truly promising.

Dr. St. Clair presented a preliminary report on this laboratory work last January at the 2nd National Conference on Human Retroviruses and Related Infections, in Washington, D. C. A full report will be published soon.

* Recently we heard about a case of very successful use of one of the combinations suggested by the laboratory work (AZT plus 3TC plus ddC), by a person we know. His CD4 (T-helper) count was 300 a year ago, then declined rapidly to 110 last November 1, and to 70 last December 1, when he started the triple combination treatment. In February his count was 320, and in March it was 540. In April he had a bad case of flu, and his count dropped to 420. Then it went up to 450, and in June 1995 was 480.

In November he had hairy leukoplakia, bad thrush, and bad scalp lesions; he had lost weight and was sleeping up to 18 to 20 hours a day. Now all symptoms are gone, and he has gained 25 pounds and is sleeping normally. He appears to be in perfect health.

This person, importantly, was treatment naive when he started the triple combination. He used standard doses of the drugs, but sometimes reduced the AZT dose from 500 mg to 400 or 300, due to stomach upset. He was using no other treatment at the time except for acyclovir.

Certainly no single case can prove that a treatment works; and we suspect that few people will find equally good results from this combination. But still cases like this compel attention, since comparable results are never seen with conventional HIV treatment. We mentioned this experience because it suggests a possibility, a goal, worth aiming for. Also, it suggests designs for clinical trials; for example, if a patient has a CD4 count below 50 and has CMV retinitis, and combination HIV therapy raises the CD4 count to a level where CMV is not normally a risk, will the retinitis stop progressing, thus reducing or eliminating the need for specific CMV treatment? * On June 30, Glaxo Wellcome applied to the FDA for accelerated approval for 3TC, for use in combination with AZT as first-line treatment for adults with CD4 counts under 500, and for children who meet the CDC guidelines for treatment with antiretrovirals. If the drug is approved for this indication, it will probably make combination treatment the standard of care for many (though not all) persons under 500, making it much easier to get this treatment paid for. It will also encourage experimentation with three-drug combinations, as approved drugs like ddI or ddC are added to the regimen.

Today, combination antiretroviral treatment, especially triple combinations, are more talked about than used. As we asked around for referrals to physicians who might have experience with triple combinations, the same names kept coming up again and again. Most of them have only used triple combinations with a few patients. And they have different approaches to when and how they use these treatments; consensus has not yet developed. This slow start for combination treatment is not surprising, due to the lack of definitive data from clinical trials.

The interviews in this series will examine some of the different approaches which are in use, and why physicians make the choices they do. Note that these interviews will focus primarily but not only on combination treatment; they will also look at related medical topics when they arise.

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