Published in the Bulletin of Experimental Treatments for AIDS Summer 2000 issue, by the San Francisco AIDS Foundation.

Summer 2000 Table of Contents

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Open Clinical Trials for HIV/AIDS Treatments

David Townley

All listings are taken from Trials Search, an online database of open clinical trials for HIV-infected individuals. Trials Search, a comprehensive source for clinical trial information, is available at http://hivinsite.ucsf.edu/tsearch. The Community Consortium of the University of California at San Francisco (UCSF) Positive Health Program at San Francisco General Hospital Medical Center provides this free service.For further information about individual listings, call the number provided or consult Trials Search.

The American Foundation for AIDS Research (amfAR) also maintains a searchable database of clinical trials, available through their Treatment Directory at www.amfar.org. In addition, ClinicalTrials.gov -- a free service of the U.S. National Institutes of Health (NIH) -- can be accessed at http://clinicaltrials.gov. Individuals who do not have access to the Internet can obtain information on all government-funded trials by calling the AIDS Clinical Trials Information Service (ACTIS) toll-free at 1-800-TRIALS-A (1-800-874-2572). Protocol (study) numbers, if available, are provided in parentheses at the end of each listing.

Antiretroviral Therapy

AG-1549 (Capravirine), Nelfinavir (Viracept)

This study will determine if AG-1549 (a new non-nucleoside reverse transcriptase inhibitor, or NNRTI) when combined with nelfinavir and two new nucleoside analogs (NRTIs) can reduce HIV RNA viral load in persons who failed an initial treatment regimen containing an NNRTI. All subjects will take nelfinavir plus two NRTIs. In addition, subjects will be assigned by chance to receive one of two doses of AG-1549 or placebo. Neither participants nor their doctors will know to which group they have been assigned until the study is completed. Study visits will take place twice a week for the first week; once at weeks 2, 3, 4, and 6; and once a month thereafter. The study will last 24 weeks, with a possible 24-week extension. Participants must have a CD4 cell count above 50 cells/mm3 and a viral load above 2,000 copies/mL. They must also be currently taking an NNRTI plus at least one NRTI for at least 28 days. Prior use of AG-1549 or any protease inhibitors (PIs) is not allowed. The study is being offered in Atlanta (404-876-2317 ext. 331), Austin (512-480-9660), Boston (617-726-3819 or 617-927-6035), Denver (303-372-5535), Ft. Lauderdale (954-564-4222 or 954-467-4532), Los Angeles (310-222-3848 or 310-360-8800), Miami (305-695-1300), New York (212-241-0433 or 212-243-1980), San Diego (619-702-4448), San Francisco (415-353-6215), and Washington, DC (202-745-0201). (AG1549-509)

Tenofovir DF (TDF), Efavirenz (Sustiva), 3TC (Epivir), d4T (Zerit)

This study will compare TDF with d4T when combined with efavirenz and 3TC for safety, tolerability, and effectiveness in lowering viral load levels in persons who are antiretroviral naive. All participants will take efavirenz and 3TC, and will be assigned by chance to take TDF or d4T; subjects will not know which they are taking until the 48-week study ends. Study visits will take place once a month. There is no CD4 cell count requirement, but participants must have more than 5,000 copies/mL of HIV RNA. Prior use of any antiretroviral medications, current opportunistic infections (OIs), or any cancers other than Kaposi's sarcoma (KS) of the skin or basal cell carcinoma of the skin are not allowed. Study locations include Charlotte (704-355-7266), Dallas (214-520-1810 ext. 17), Houston (713-500-6751), Los Angeles (310-360-8800), Miami (305-695-1300), Oklahoma City (405-271-8001 ext. 38205), San Diego (619-543-8080), and San Francisco (415-221-4810 ext. 3763). (GS 99-903)

Peptide T

This study will determine if Peptide T (a fusion inhibitor) is safe and has any effect in reducing the HIV RNA viral load. After screening, eligible subjects will come to the clinic for a brief physical, have blood tests taken, and receive Peptide T. Peptide T is an intranasal solution sprayed into the nose three times a day. Study visits will take place twice a week for the first two months, then once a month. The study lasts 24 weeks. Participants must have more than 300 CD4 cells/mm3 and between 500 and 10,000 copies/mL of HIV RNA. Subjects taking antiretroviral medications must have been on stable (unchanged) therapy for at least 12 weeks prior to study entry. For information on this study being conducted in San Francisco, please call 415-353-6215.

Indinavir (Crixivan), Ritonavir (Norvir)

This study will determine if indinavir taken with ritonavir and two NRTIs can return the viral load to below 400 copies/mL after virologic failure (return to detectable viral load) has occurred while taking a combination that included indinavir or nelfinavir. All subjects will take indinavir and ritonavir twice a day plus either two new NRTIs or one new NRTI together with one NRTI that has not shown evidence of viral resistance. Study visits will take place once a month; the study will last six months. The NRTIs used in the trial will not be supplied by the study; participants must obtain them by prescription or by other means. Participants must have at least 50 CD4 cells/mm3 and between 400 and 20,000 copies/mL of HIV RNA. Subjects must have been taking antiretroviral therapy that contains indinavir or ritonavir for at least 16 weeks and at study entry. Participants must have had an initial response to this therapy with two viral load test results of less than 400 copies/mL followed by at least two measurements of between 400 and 20,000 copies/mL. More than seven days' prior use of two PIs at the same time and active hepatitis are not allowed. Participants must be able to take at least one new NRTI. This study is being offered in Boston (617-636-8642), Chicago (312-572-4545), Los Angeles (310-360-8800), New Orleans (504-584-3608), Oklahoma City (405-271-8001 ext. 38205), San Francisco (415-221-4810 ext. 3763 or 415-600-6660), Tampa Bay (813-272-6640 ext. 4619), and Wichita (316-293-2617). (Merck 107)

Abacavir (Ziagen)

This study will determine if adding abacavir to a combination of three or more anti-HIV drugs is effective in lowering the amount of HIV in the blood of persons who have recently started potent antiretroviral therapy. Subjects are randomized to add abacavir or placebo to their current antiretroviral combination. Abacavir and its placebo are taken twice a day; neither participants nor their doctors will know which they are taking until the 36-month study ends. Only abacavir and the placebo are supplied by the study; participants must obtain the other drugs by prescription or by other means. Study visits are once a month for the first three months, then every two months. Participants must have a viral load between 501 and 10,000 copies/mL and a 1 or more log10 decrease in viral load between 49 and 70 days of beginning antiretroviral therapy. Participants must be on stable antiretroviral therapy that was started at least 28 days prior to study entry. Prior use of abacavir, cancers requiring chemotherapy, or more than 90 days' use of antiretroviral therapy prior to study entry are not allowed. The study is enrolling subjects in Atlanta (404-616-6333), Baltimore (410-955-4370), Chicago (312-908-9636), Cincinnati (513-584-6385), Denver (303-372-5535), Los Angeles (310-222-5291), Miami (305-243-3838), New York (212-305-7897 or 212-263-8707), Philadelphia (215-349-8092), Seattle (206-731-3184), and St. Louis (314-454-0538). (ACTG A5064)

AIDS Vaccines

HIV-1 gag DNA Vaccine

This study will determine if the HIV-1 gag DNA vaccine is safe and well tolerated, and see what effect it has on CD4 cells, CD8 cells, and HIV RNA viral load. This is a dose-escalating study. The first subjects to enroll will be randomized to receive the lowest dose of HIV-1 gag DNA vaccine or placebo; neither participants nor their doctors will know which they are taking until the two-year study is completed. Vaccine is given by intramuscular injection at day 0 and at weeks 4, 8, and 26 for a total of four injections. If the vaccine is found to be safe, the next group of subjects to enroll will be randomized to receive the higher dose of vaccine or placebo. Vaccine safety visits will take place two days after the first injection and two weeks after each subsequent injection. Study visits for blood tests will take place at weeks 1, 2, 4, 6, 8, 10, 12, 16, 26, 28, 30, 34, 42, 52, 78, and 104. Participants must have at least 500 CD4 cells/mm3 and may never have had fewer than 200 cells/mm3. Participants must be on highly active antiretroviral therapy (HAART) for at least 24 months and stable therapy for at least 12 weeks prior to study entry. Positive antigen tests for hepatitis B and/or C or prior participation in an HIV vaccine study are not allowed. The study is being conducted in Pittsburgh (412-647-8125) and San Diego (619-543-8080). (Merck 004-00)

AIDS-Related Illnesses

AIDS Wasting Treatment: Human Growth Hormone (HGH, Serostim)

This study will determine if Serostim is safe and effective in treating HIV wasting in persons who are taking combination antiretroviral therapy with or without a PI. All subjects will receive Serostim; there are no placebos in this study. Serostim is given by injection under the skin each night; participants will be taught how to give themselves injections and dispose of needles safely. Study visits will take place at weeks 2, 6, 12, and every three months thereafter. Study visits include blood tests, physical exams, and body composition analysis using Bioelectrical Impedance Analysis (BIA), a technique for measuring body fat and body cell mass. The study lasts 48 weeks. Participants must have AIDS wasting with (1) unintentional weight loss of at least 5% (of total weight) over a period of two weeks to 12 months, (2) weight less than 95% of ideal body weight, or (3) a body cell mass loss of 3% to 5%. Chronic diarrhea, pancreatitis, carpal tunnel syndrome, glucose intolerance, angina pectoris, or coronary artery disease are not allowed. Study locations include Albuquerque (505-272-9390), Louisville (502-852-1149), New York (212-604-2684), Philadelphia (215-985-4448), and Tampa Bay (813-870-4760). (IMP 21020)

KS Treatment: SU5416

This study will determine if SU5416 is effective in treating KS lesions that have not responded to prior KS treatment. All subjects will receive SU5416 by infusion into a vein twice a week for four weeks (one cycle). Participants will be treated for two cycles. Those subjects who do not experience serious side effects from SU5416 may continue to receive treatment for up to one year. There is no CD4 cell count requirement. Participants must have biopsy-proven KS that has not responded to a previous, approved KS treatment. Insulin-dependent diabetes, surgery within four weeks prior to study entry, or any KS therapy within two weeks of study entry is not allowed. The study is being offered in Baltimore (410-614-5541), Boston (617-414-5404), Los Angeles (310-206-6414 or 323-993-7517), Philadelphia (215-829-6306), San Francisco (415-353-6215), and St. Louis (314-362-8836). (AMC 022)

Peripheral Neuropathy Treatment: Topical Aspirin

This study will determine if topical aspirin (i.e., in liquid form) is effective in treating painful neuropathy in people with HIV. During screening, subjects will have a physical exam, answer questions about their medical history, and fill out a form called the Brief Pain Inventory Scale. Over the course of the five-week study, participants will be given two bottles of solution: one will contain the topical aspirin solution and the other will be an inactive placebo. Neither participants nor their doctors will know in which order these bottles will be given. Participants will apply the solution on the skin over the painful area three times a day. Study visits will take place on days 7, 17, 24, and 31 of treatment. Participants must have painful sensory peripheral neuropathy that has been present for at least a month prior to study entry. Allergies to aspirin or bleeding disorders are not allowed. This study is being conducted in New York (212-924-3934 ext. 126).

Genital Herpes Suppression: Valacyclovir (Valtrex)

This study will determine if valacyclovir is safe and effective in preventing outbreaks of genital herpes in people infected with HIV. Participants are assigned by chance to receive valacyclovir or placebo; neither participants nor their doctors will know which they are taking until the six-month study is completed. Valacyclovir and its placebo are pills taken orally twice a day. Any participants who develop an outbreak of genital herpes will be treated with open label (real) valacyclovir for six months, then resume suppressive therapy with open label valacyclovir, not placebo. Study visits will take place once a month. Participants must have more than 100 CD4 cells/mm3 and be on stable antiretroviral therapy for at least six months prior to study entry. They must have a history of four or more outbreaks of genital herpes per year, and may not be lactose intolerant. The study is being offered in Berkeley (510-204-4109), Los Angeles (323-930-2324), Palm Beach (561-689-0606), Philadelphia (215-985-4448), San Francisco (415-759-4126), and Seattle (206-720-4340). (H5230018)

HIV and Hepatitis C (HCV) Treatment: Pegylated Interferon (PEG Intron), Interferon-Alpha, Ribavirin (Rebetol)

This study will compare the efficacy of pegylated interferon alone with pegylated interferon plus ribavirin and with (nonpegylated) interferon-alpha plus ribavirin against plasma HCV levels. There are three study groups. The first group will take pegylated interferon plus ribavirin placebo. The second group will take pegylated interferon and ribavirin. The third group will take interferon-alpha and ribavirin. Pegylated interferon will be given by injection under the skin once a week. Interferon-alpha will be given by injection under the skin three times a week. Ribavirin and its placebo are pills taken orally. Subjects assigned to take pegylated interferon will not know if they are taking ribavirin or placebo until the 48-week study is over. Study visits will take place every two weeks for the first two months, then at week 12, and every six weeks thereafter. Participants must have a CD4 cell count of at least 200 cells/mm3 with any viral load level or between 100 and 199 CD4 cells/mm3 with a viral load below 5,000 copies/mL. Subjects must also have detectable HCV (more than 1,000 copies/mL). Participants may not be pregnant or be male partners of women who are pregnant. Prior use of ribavirin or interferon, active OIs, seizure disorder, or chronic liver diseases other than hepatitis C are not allowed. Study sites include Atlanta (404-876-2317 ext. 328), Boston (617-636-8642), Cleveland (216-368-2437), Salt Lake City (801-585-7245), and San Francisco (415-353-0800). (NR15961)

Children

HIV-Associated Growth Failure: Serostim

This study will determine the effect of Serostim on children's growth (height and weight), and determine if growth hormone has any effect on the ability to gain and maintain lean body mass (muscle). Since growth hormone has not been tested in HIV-infected children before, this study will also determine the safety of using Serostim in this population. During the screening process, children will have an MRI (magnetic body scan) to determine fat and muscle content, a body water measurement (using a saliva test), and a BIA test. Participating children will be assigned by chance to one of four groups. Children in Group 1 will receive one dose of growth hormone once a day for 96 weeks. Children in Group 2 will receive half the dose given to Group 1 once a day for 96 weeks. Children in Groups 3a and 3b will receive no Serostim for the first 24 weeks of the study. After 24 weeks, they will receive either a full dose once a day (Group 3a) or half the full dose (Group 3b) once a day for the remaining 72 weeks of the 96-week study. Serostim will be given by the child's parent or guardian once a day at bedtime by injection under the skin. Parents/guardians will be taught how to give injections at home and dispose of needles safely. There is no CD4 cell count requirement but subjects must have fewer than 20,000 copies/mL of HIV RNA or a documented viral load decrease of at least 1 log10 from baseline viral load while on antiretroviral therapy. Girls must be between 4 and 12 years of age; boys, between 4 and 13 years of age. Participants must have documented height growth failure and a dietary intake of at least 100% of the recommended dietary allowances for calories and protein. Persistent fevers, serious infections, retractable diarrhea, cancers, and diabetes are not allowed. The study is being conducted in Long Island (718-470-3300), Los Angeles (310-206-6369), Newark (973-972-3118), San Diego (619-543-8080 ext. 204), and San Francisco (415-476-6480). (ACTG P1011)

Antiretroviral Therapy and Body Composition

This study will determine if any changes occur in children's body weight, growth, body fat, muscle mass or fat, and muscle distribution after starting or changing anti-HIV medications. This is an observational study. After screening, there will be four study visits at weeks 12, 24, 36, and 48. During these visits, participating children will undergo physical exams, blood tests, and body measurements such as weight, height, arm size, and leg size. The distribution of fat and muscle will be measured using calipers to determine the thickness of the child's or baby's skin. Subjects will also undergo a BIA, which measures body fat as well as lean body mass; the BIA tests are quick and painless. Children and their parents will also answer questions about the types of food eaten on certain days. The study will last 48 weeks. Children must be between one month and 13 years of age and beginning or changing antiretroviral therapy. Acute illnesses, cancers, metal prostheses or implanted electrical devices, previous limb amputation, and diabetes requiring insulin are not allowed. Study sites include Newark (973-972-3118), Oakland (510-428-3885 ext. 2827), and San Francisco (415-476-6480). (ACTG P1010)