Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
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Gay Men's Health Crisis Treatment Issues, Vol. 5, No. 8 - November 1991
Kevin Armington
AZT WITH CD4-IGG
This alphabet soup combination employs standard antiviral therapy with a new version of the antiviral "decoy" drug, CD4. CD4, in theory, should block the CD4 receptor, which acts as an entry way for HIV into a cell. Early trials of CD4 were very disappointing, but the new modified version, CD4-IgG, was designed to eliminate one of the problems associated with using CD4 as a single-drug therapy: its half-life was much too short to allow the drug to work.
Unfortunately, CD4-IgG did not perform any more impressively in this study, although it did stay in the bloodstream longer. In the study, 25 patients received varying doses of CD4-IgG three times a week through subcutaneous injections for at least 12 weeks.[1] p24 antigen levels declined only in the blood of patients who were administered concurrent AZT. Watch for results of a trial using even more drugs: AZT, CD4-IgG, and alpha interferon!
AZT WITH ACYCLOVIR
Studies to date have failed to demonstrate convincingly any anti-HIV benefit in combining AZT and acyclovir (ACV), the drug approved to treat herpes. No studies in Florence, however, directly compared AZT/ACV to other antivirals, and there are other reasons to continue taking the combination. One study took the novel approach of alternating three different antivirals in alternating weeks.[2] Participants took 600 mg AZT with 2400 mg ACV daily for the first week of the regimen. During the second week, participants took approximately 500 mg ddI/day, and during the third week, 3 mg of ddC/day. This three-week cycle was repeated throughout the trial.
Twenty-one patients with an average T4 count of 181 were enrolled in the trial. Increases in counts were observed and sustained for 34 weeks. Researchers document that this alternating drug approach showed anti-HIV activity for at least nine months. This complicated therapy, however, may not be realistic in clinical practice, since the alternating schedule may be difficult to juggle.
COMPOUND Q AND AZT OR DDI
A joint effort between Cancer Research Campaign Labs in England and Immunology, Inc. in San Francisco studied the effects of combining Compound Q (Tricosanthin) and ddI or AZT in people with declining T4 counts. Participants had been on ddI or AZT for at least one year and had T4 counts under 500. They received 1.2 mg Compound Q weekly for two weeks, then monthly. The authors claim that this is considered a low dose. An unusual statistical analysis was performed, showing that patients gained an average of 1.61 T4 cells per week after therapy with Compound Q began. Before Q, the same people had been losing 1.47 T4 cells per week. Absolute T4 values are not reported. The combination produced no effect on p24 antigen levels.[3]
AZT AND INTERLEUKIN-2
Interleukin-2 (IL-2) is a substance secreted by immune system cells and plays a role in the immune response. Because it may stimulate natural killer cells, complementing antiviral therapy with a synthetic version of the substance may be an attractive potential treatment. A small study of 15 patients at Duke University in Durham, NC administered escalating doses of IL-2 over one month. One of the concerns with IL-2 is the high degree of toxicity it has produced in trials so far; in this study, three patients became neutropenic, one developed thrombocytopenia, one experienced severe muscle aches and another developed labyrinthitis, an ear disorder which can lead to vertigo.
On the positive side, the authors saw a transient rise in T4 counts while participants were receiving the drug, but levels tapered off after treatment was interrupted. The authors also claim that several other parameters that measure cellular immunity improved. IL-2, when administered with AZT, did not enhance HIV reproduction (it does in the test tube). No advantage to higher doses was noted.[4]
THYMOSTIMULIN PLUS AZT
A small Italian study divided two groups of 30 asymptomatic people (T4 counts under 400) into two arms. The first group received 500 mg AZT per day alone; the second, AZT plus 70 mg thymostimulin intravenously three times a week. Thymostimulin is a thymic hormone that stimulates production of thymocytes, cells that develop into T cells. In the first group, six patients had rises in T4 counts, while, in 14 of 30 patients receiving the combination, small T4 cell increases remained elevated for at least 8 months. Three patients on AZT alone progressed to AIDS compared to no patients receiving combination. This is a small sample, and it is not possible to state with certainty whether AZT or thymostimulin was responsible for the additional benefit seen in those on combination.[5]
CONCLUSION
Combinations have the obvious attraction of a multi-pronged attack on HIV. Use of them should also delay development of resistance to any single drug. The challenge is now up to the pharmaceutical companies and the federal agencies conducting AIDS clinical research to move these combinations rapidly through the remainder of the licensing process.
REFERENCES
1. VIIth Internat Conf on AIDS, Abstract #W.B. 2123, Florence, June, 1991.
2. VIIth Internat Conf on AIDS, Abstract #TH.B. 84, Florence, June, 1991.
3. VIIth Internat Conf on AIDS, Abstract #W.B. 2171, Florence, June, 1991.
4. VIIth Internat Conf on AIDS, Abstract #W.B. 2154, Florence, June, 1991.
5. VIIth Internat Conf on AIDS, Abstract #W.B. 2130, Florence, June, 1991.
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