Retroviruses Conference Notes

The 5th Conference on Retroviruses and Opportunistic Infections, February 1-5 in Chicago, was one of the most important AIDS scientific conferences, yet it left unanswered most of the immediate questions of physicians and patients. Much of the progress has been in basic science, opening doors for future research and development but not affecting patient care immediately. On the whole, people came out of the conference at least as optimistic as when they went in; the HIV treatments which have greatly improved patient outcomes are still working as well as ever, and there are important new potential treatments and new research leads.

No one person could possibly cover all of the over 750 presentations--many given simultaneously with no tape or video recordings. Excellent in-depth reports are available, however (see "Retroviruses Conference: For More Information," in this issue). Here are some of the topics and presentations that caught our attention as particularly important. We plan more coverage in future issues.

* Clinical consequences of virological treatment failure. See interview with Steven Deeks, M.D., in this issue.

* New data on drug combinations now in use. There were no big surprises, but physicians and patients who are making medical decisions may want to review the latest information available. One of the best places to look is "Update from the 5th Conference on Retroviruses and Opportunistic Infections," a concise report by Steven Deeks, M.D., on the presentations of most interest to physicians. It is available on HIV InSite, the Web site of the University of California San Francisco AIDS Research Institute, http://hivinsite.ucsf.edu. Some of the major topics covered include d4T, double protease inhibitors, experimental twice-daily regimens of indinavir or nelfinavir, hydroxyurea, and two drugs now on expanded access and likely to be approved this year, efavirenz (DMP-266, Sustiva (tm)) and abacavir (1592). Also note the discussion of ACTG 320, and its possible implications for treatment of patients with advanced HIV disease. The review also includes brief presentations on two important potential drugs now in early human testing: bisPOC PMPA, and FTC.

* Hydroxyurea, especially when combined with ddI. It has become increasingly clear that this drug, which has long been used in cancer, will have a role in HIV treatment. However, there is little clinical-trial data on use by patients with CD4 count under 200. We are preparing a separate article on this drug.

* Zinc-finger inhibitors. The "zinc finger" is a structure found in HIV. Parts of it are identical across almost all retroviruses--meaning that it would be very difficult for HIV to develop resistance to a drug which destroyed this structure or prevented it from working. Many cells also have a zinc finger structure--but different from that of retroviruses--so any inhibitor would have to be selective. At least one zinc-finger inhibitor (CI 1012) is now in early human trials; no data on it was presented at the Retroviruses conference, however. About 150 articles mentioning zinc fingers have been published and are referenced in AIDSLINE; much of the early work on this class of drugs was done by the U.S. National Cancer Institute. This research has been low profile; it deserves more attention.

Fortunately one of the presentations at the Retroviruses conference1 reached an audience of several hundred physicians and researchers. The speaker noted that there is an almost endless supply of potential candidate drugs--at least one which is non-toxic, can be taken orally, and reduces retroviral replication in animals. Another group from the National Cancer Institute also examined zinc finger inhibitors as a potential treatment;2 two other posters looked at potential uses in vaccine development.3,4

* New technology for measuring how long immune cells live in the body. Until recently there has not been a practical way to directly measure how long CD4, CD8, and other immune-system cells live in people. A new method for tracking these cells in the body5 is likely to be important for research on AIDS and other diseases as well.

The approach uses glucose with a non-radioactive isotope of either hydrogen or carbon, to label new cells as they are formed in the body. An isotope is an atom with a slightly different weight than ordinary atoms of the same element; chemically and biologically it behaves identically to ordinary atoms. Many isotopes are radioactive; this makes them easy to measure, but unsafe for human research. The non-radioactive isotopes now being used are safe; they can be measured with a machine called a mass spectrometer which is now commercially available for this purpose. This technique provides the best data yet on the dynamics of immune cells in the body, and may prove useful for clinical diagnosis as well as for research.

There were dozens of other conference presentations worth mentioning; we cannot list them all.


References

1. Henderson E and others. In vitro and in vivo activity of antiretroviral compounds attaching NC zinc fingers. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, February 1-5, 1998 [abstract #007].

2. Huang M and others. Anti-HIV agents that selectively target the retroviral nucleocapsid protein zinc fingers without affecting cellular zinc finger proteins. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, February 1-5, 1998 [abstract #643].

3. Rossio JL and others. Inactivation of HIV-1 infectivity with preservation of conformational and functional integrity of virion surface proteins. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, February 1-5, 1998 [abstract #103].

4. Gorelick R and others. Full length SIV nucleocapsid mutant DNA vaccine: Immunization and challenge. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, February 1-5, 1998 [abstract #535].

5. Cesar D and others. Direct measurement of CD4+ and CD8+ T cell proliferation rates in vivo in AIDS patients using a stable isotope-mass spectrometric technique. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, February 1-5, 1998 [abstract #273].