Community Update: New Drugs to Watch

On November 6 a community forum, "HIV Therapy Update from the Recent ICAAC and Glasgow Meetings," was sponsored by three San Francisco AIDS organizations (the Conant Foundation, the San Francisco AIDS Foundation, and the AIDS Research Institute of the University of California San Francisco); unlike most medical meetings, this one was funded by the organizations themselves without seeking pharmaceutical-company support. Here are a few bottom-line treatment messages that we found most important:

  • The medical community is favorably impressed with Kaletra (lopinavir, formerly ABT-378), the newly-approved "second generation" protease inhibitor. A major Abbott trial presented 24-week data at ICAAC (40th Interscience Conference on Antimicrobial Agents and Chemotherapy, Toronto, September 17-20, 2000) and some 48-week data at the Fifth International Congress on Drug Therapy in HIV Infection (Glasgow, UK, October 22-26, 2000); complete 48-week data will be available at the Retroviruses conference (8th Conference on Retroviruses and Opportunistic Infections, Chicago, February 4-8, 2001). Stephen Becker, M.D. noted the impressive results with patients who were highly treatment experienced (but naive to the NNRTI class of antiretrovirals, in this trial). Also, very few patients discontinued the trial because of toxicity or because of virologic failure. Even patients with substantial resistance to other protease inhibitors were likely to do well.

    Doctors do not agree on whether to reserve this drug for "salvage" therapy when other treatment options have failed, or to use it earlier in treatment, perhaps in initial therapy. At least at this time Dr. Becker chooses to wait and use it later.

    Also, the development of Kaletra has been important as a "proof of concept" for the strategy of using a low dose of ritonavir (Norvir®), another protease inhibitor from Abbott Laboratories) in order to keep another protease inhibitor in the body longer (by blocking a liver enzyme which destroys these drugs). Kaletra has the ritonavir included in the formulation, as it must be used with ritonavir or it would be eliminated from the body too quickly.

  • Steven Deeks, M.D. discussed some of the most promising new HIV drugs in the pipeline. He named four: T-20, tipranovir (a new kind of protease inhibitor), DAPD, and tenofovir. All of these are active against many viruses which are highly resistant to other drugs.

    He also noted that there is now much excitement about HIV integrase inhibitors, a major target for new drugs. But these are farther away, probably about five years from widespread use.

  • Paul Volberding, M.D. discussed some of the major challenges of HIV research today, including acute infection (finding the cases is a challenge), finding people who are not currently in care so that they can be offered treatment, when to start antiretroviral therapy (the medical community has backed off from the "hit early" part of "hit hard, hit early" -- but still treats hard, once one does start antiretrovirals). A survey of very experienced HIV physicians in San Francisco found that most started treatment at a CD4 count averaging around 350 (and some as late as a count of 200) -- depending on other information about the patient, of course. The survey also found that combinations including the NNRTI drug class were the most popular to start with [as opposed to either protease inhibitors, or the triple nucleoside analog treatment with abacavir].

    [Note that this community forum took place in November 2000, and treatment strategies later will be different. Sometimes our articles circulate on the Internet forever and are read as fresh information after they are no longer applicable.]

    Other talks at the forum reviewed progress in preventive vaccines, and in microbicides to prevent HIV transmission.

ISSN # 1052-4207

Copyright 2000 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used.

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