Clinical Trials for Individuals Failing Current Therapy

A decade ago, there were only two therapeutic options for people who tested positive for the human immunodeficiency virus: You could take AZT . . . or you could elect not to take AZT. If you chose therapy, you got some benefit -- partial suppression of viral replication, and a modest rebound in your CD4 count -- and these benefits often lasted for several years before they began to wane. If you chose to eschew AZT monotherapy, you were spared the side effects of therapy . . . but you were denied its benefits.

Today, individuals who are beginning antiretroviral therapy have dozens of therapeutic options -- and they have virtual assurance that whatever regimen they choose will suppress viral replication to levels so low they cannot be measured by the most sensitive of the commercially available HIV RNA assays. Moreover, they now have the option of choosing their initial anti-HIV regimen with its successor in mind. Newly diagnosed patients can begin their treatment with a combination of three nucleoside analogs -- AZT, 3TC, and abacavir, for example. Or they can start therapy with two nucleosides and a non-nucleoside reverse-transcriptase inhibitor -- say, d4T, 3TC, and either nevirapine or efavirenz.

In most treatment-naïve individuals, any one of these combinations will suppress viral replication to undetectable levels for a period of time ranging from months to years. And all of these therapeutic choices defer the use of the most powerful class of antiretroviral agents, the protease inhibitors, until a later date -- thereby reserving these potent drugs for use down the road.

But what about the thousands of HIV-positive people who are veterans of two, three, or even four antiretroviral regimens? For these treatment-experienced individuals, who have, over the years, moved from two-nucleoside therapy to an NNRTI-containing regimen, and from there to the first of several multidrug therapies that contained at least one protease inhibitor, the therapeutic options are much more limited. Some of these treatment veterans have developed high-level resistance to several once-effective anti-HIV drugs; others have "burned" whole classes of antiretroviral agents.

The following list -- of clinical trials that are open to individuals who have broken through on their current antiretroviral regimen -- offers a range of options to people who have been on therapy for many years, and who have, as an inevitable consequence, been on many therapies. This is a selective listing; for a complete list of clinical trials that are now enrolling treatment-experienced individuals, call 1-800-TRIALS-A.

In conformance with standard practice, we have listed the drugs that are being tested in these trials by their chemical name. For the brand names of these agents, see the box at the bottom of the page. Agents that are still undergoing clinical testing and have yet to win F.D.A. approval, such as MKC-442 and T-20, do not yet have brand names.