A guide to experimental HIV drugs in clinical trials

A quick look at the experimental HIV drugs involved in clinical trials will reassure any clinician that there will be new and more potent agents fighting the virus for decades to come. AIDS Alert offers this guide to some of the new antiretroviral drugs that are involved in Phase I, II, or III clinical trials, including many that are still recruiting patients.

• Capravirine: A nonnucleoside reverse transcriptase inhibitor (NNRTI) first called AG1549 by Agouron Pharmaceuticals of La Jolla, CA, this drug is being studied in several trials, including a Phase II, single-blind, randomized, placebo-controlled study in combination with nelfinavir. That study involves patients who have begun to fail an antiretroviral combination of NNRTIs and nucleoside reverse transcriptase inhibitors (NRTIs).

Another study will judge the effectiveness of the drug in a combination that includes nelfinavir plus a combination table containing zidovudine and lamivudine.

• Dextrin 2-sulfate: Sponsored by Steinhart Medical Associates of Miami, this Phase I study will look at the effectiveness of dextrin 2-sulfate in advanced AIDS patients who have failed conventional antiretroviral treatment. Patients will have a catheter placed in their abdominal area through which the drug will be administered three times a week for eight weeks.

• BMS-232632: Bristol-Myers Squibb of Plainsboro, NJ, is sponsoring this study on the safety and effectiveness of a new protease inhibitor. Patients are assigned randomly to a group that receives BMS-232632 plus saquinavir and two other antiretrovirals, a second group that receives a higher dose of the experimental PI plus saquinavir and two other antiretrovirals, and a third group that receives ritonavir plus saquinavir plus two other antiretrovirals. Participants are those who have been on an anti-HIV combination that includes a PI or NNRTI and they have begun to experience an increase in viral load.

• Interleukin-2: Sponsored by Chiron Corp. of Emeryville, CA, the study is looking at the effectiveness of giving HIV patients L2-7001, a type of interleukin-2, plus antiretroviral therapy. Interleukin-2 is produced by the body’s white blood cells and helps the body fight infection. The Phase I trial will assess safety, as well as whether the drug will boost HIV patients’ immune systems.

• HE2000: This experimental drug is an anti-HIV hormone that should make it more difficult for HIV to live in cells. The Phase I and Phase II open label, dose-response study, sponsored by Hollis-Eden Pharmaceuticals of San Diego, will assess the safety and effectiveness of the drug when administered to HIV-infected patients on salvage therapy.

• Tenofovir disoproxil fumerate: Sponsored by Gilead Sciences Inc. of Foster City, CA, the Phase III, open-label trial will study the safety and effectiveness of the drug when given in combination of other antiretrovirals. Participants have a viral load of 10,000 copies/mL or greater and have had an opportunistic infection within 90 days of the study entry. A second Phase III trial will evaluate people who have between 400 and 10,000 copies/mL when they are given one active dose of tenofovir DF daily vs. a placebo, when added to stable antiretroviral therapy. That study is a double-blind, randomized study.

• WF10: Sponsored by OXO Chemie of South San Francisco, CA, the study will evaluate the safety and effectiveness of this new drug among patients who have a CD4 cell count of less than 50 cells/mm3 and who have received antiretroviral drugs in the past. The drug will be administered intravenously. A macrophage regulator, WF10 modifies the function of the monocyte/ macrophage system by stimulating phagocytosis in macrophages and oxidative burst in monocytes. It is thought to enhance the immune function in late-stage HIV infection.

• L-756423: Sponsored by Merck & Co. of Whitehouse Station, NJ, the Phase II trial is examining the effectiveness of a new protease inhibitor when combined with indinavir and two other anti-HIV drugs in patients who have failed an indinavir-containing regimen. It’s an open-label pilot study.

• MKC-442: Triangle Pharmaceuticals of Durham, NC, is sponsoring the Phase II and III study of the virologic efficacy, short-term safety, and tolerability of this new antiretroviral when it is offered in triple-drug combination to patients who previously were treated with NRTIs and PIs but are naive to NNRTIs.

• Zintevir: Sponsored by Aronex Pharmaceuticals of The Woodlands, TX, this study focuses on a drug from a new class of drugs — integrase inhibitors — that block the protein integrase, which HIV uses to infect a cell. Integrase inhibitors potentially could stop HIV replication. The Phase I and II trials gives zintevir to patients who have CD4 cell counts of greater than 200 cells/mm3 and have a viral load of greater than 4,000 copies/mL. They receive doses of the drug for 14 days.

• PMPA Prodrug: Gilead Sciences Inc. of Foster City, CA, has sponsored a Phase II study of the new anti-HIV drug to evaluate the drug’s effectiveness and side effects when it’s added to an antiretroviral combination. Patients have viral loads of 400-50,000 copies/mL and have been taking a triple-drug regimen for at least eight weeks prior to the study.

• Fozivudine Tidoxil: This new antiretroviral drug has been studied for adverse events, tolerability, and anti-viral activity over a four-week period. Boehringer Mannheim Corp. of Gaithersburg, MD, sponsored the study.