Path: utzoo!utgpu!watmath!att!tut.cis.ohio-state.edu!gem.mps.ohio-state.edu!usc!ucla-cs!phil@wubios.WUstl.EDU From: phil@wubios.WUstl.EDU (J. Philip Miller) Newsgroups: sci.med.aids Subject: Washington HIV News: V1N3, 1/3 Message-ID: <29328@shemp.CS.UCLA.EDU> Date: 20 Nov 89 00:08:00 GMT Sender: news@CS.UCLA.EDU Lines: 1538 Approved: aids@cs.ucla.edu Archive-number: 1493 Forwarded message: >From pyrdc!lighthouse!rock@uunet.UU.NET Tue Oct 24 19:15:38 1989 Date: Tue, 24 Oct 89 18:56:22 GMT-0500 From: pyrdc!lighthouse!rock@uunet.UU.NET (Roger Rock Rosner) Message-Id: <8910242356.AA01258@ lighthouse > To: phil@wubios, ddodell@stjhmc.fidonet.org Subject: Washington HIV News: V1N3, 1/3 *************************************************************************** TREATMENT - Table of Contents August 1989 - Vol 1, No 3 Anti-retroviral protocols Alpha Interferon and Interleukin-2 Alternating/Intermittent AZT and ddC (ACTG 047) AS-101 and AZT AzdU AZT and Acyclovir (ACTG 063) AZT and Alpha Interferon AZT and GM-CSF AZT and Interleukin-2 AZT for Veterans AZT in Hemophiliacs (ACTG 036) AZT, Alpha Interferon, and GM-CSF Betaseron and Reduced Dose AZT ddI (2',3'-dideoxyinosine) Recombinant Soluble CD4 Pneumocystis carinii Pneumonia (PCP) protocols Dapsone or Dapsone/Pyrimethamine Piritrexim and leucovorin CMV Retinitis protocols Foscarnet Gancicyclovir (ACTG 071) Toxoplasmosis protocols Pyrimethamine and Dapsone Miscellaneous protocols Blood Drawing Study Bronchoalveolar Lavage Study Bronchoscopy Study gp-160 (Vaccine) HIV & Heart Disease Study Megace Other protocols *************************************************************************** ANTI-RETROVIRAL PROTOCOLS ---------------------------------- ALPHA INTERFERON AND INTERLEUKIN-2 DESCRIPTION: An evaluation of the toxicity and effectiveness of the combination of alpha interferon and interleukin-2 in the treatment of patients with HIV infection. REQUIREMENTS: Participants must: have evidence of HIV demonstrated by ELISA and Western Blot or a positive culture for HIV; have a T4 cell count of greater than or equal to 200/mm^3; be between the ages of 18 and 60; and not have been exposed to chemotherapy, corticosteroid therapy or experimental therapy for six weeks prior to entry. A negative pregnancy test is required for women of child-bearing potential. All participants must have a primary physician involved and available to communicate with NIH staff during the study. TERM: As an outpatient during the time it takes to gradually increase alpha interferon doses to a maximum level, and hold the dose at maximum for two weeks. As an inpatient, an additional 21 days of IL-2 infusion, with outpatient follow-up visits for the next two months. ADMINISTRATION: Alpha interferon is self-administered by the patient by daily injection under the skin (much the same as the method used by diabetics). Interleukin-2 is administered by injection into the vein continuously for 21 days. There are weekly and bimonthly blood drawings and clinic visits during the term of the study. METHODOLOGY: Both alpha interferon and interleukin-2 are well-tolerated as individual drugs in HIV-infected persons. Researchers are trying to determine whether the use of both drugs simultaneously will result in beneficial effects not seen in either when taken as single agents, and what the side effects are of the combination. NOTES: Potential side effects of alpha interferon include flu-like symptoms, a decrease in white cells, mental changes, gastrointestinal disturbances, temporary hair loss, minor liver problems, and congestive cardiomyopathy. Interleukin-2 has also been associated with some side effects such as proteinuria, mild prolongation of PTT, fever, hepatitis, rigors, increased incidence of bacterial infection, and eosinophilia. All these effects improved or disappeared after discontinuation of the drugs. CONTROLS: None ORGANIZATION: National Institutes of Health/National Institute of Allergy and Infectious Diseases CONTACT: Dianne Lee, Building 10, 11th floor clinic, National Institutes of Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196 ---------------------------------------- ALTERNATING AND INTERMITTENT DOSES OF 2',3'-DIDEOXYCYTIDINE (DDC) AND AZT IN PATIENTS WITH AIDS AND ARC WHO ARE NOT ON AZT (ACTG 047) DESCRIPTION: To determine if alternating AZT and ddC (first one, then the other) or intermittent therapy (one week on, one week off) with either drug will decrease the side effects of either drug alone, while still suppressing HIV. REQUIREMENTS: Two groups of patients will be admitted to the study, one with ARC, the other with AIDS. Patients with ARC must have the documented presence of at least one of the following: weight loss in excess of 15 pounds or 10 percent of body weight within 120 days of the study; temperature greater than 38.5 degrees C (about 100 degrees F) with or without night sweats, persisting for more than 14 consecutive days or more than 15 days in a 30-day interval prior to entry into the study; diarrhea which is defined as three or more liquid stools per day, persisting for more than 30 days prior to entry into the study without definable cause; recurrent oral candidiasis (thrush in the mouth); hairy leukoplakia (white bumps which appear on the tongue and in the mouth); or a history of Herpes Zoster (Shingles). Patients with AIDS qualify for the study if they have CDC-defined AIDS (fulfill the Surveillance Definition of the Centers for Disease Control), and do not require systemic maintenance chemotherapy. All patients (ARC and AIDS), in order to qualify for the study, must also have a consistently positive p24 antigen test (at least 70 picograms/ml, defined by the Abbott HIV antigen test). This means the participant must have a positive p24 antigen test seen on two occasions, each within one month prior to entry in the study, separated by at least 72 hours, and the last of these observations must occur within two weeks of starting the therapy (any negative antigen test during this period will exclude the patient from the study). All participants must also have: a positive ELISA HIV test; the ability to care for most personal needs requiring at most occasional assistance; attained the age of 13 years (those between 13 and 18 must have written consent by parent or legal guardian); if a woman of child- bearing potential, must have a negative pregnancy test within 30 days of entry in the study and use an effective method of birth control during the study. All participants must also have laboratory values within certain limits: hemoglobin of at least 9.6 g/dl (patients requiring transfusions of two units of blood more than once a month are excluded and the last transfusion must occur before two weeks prior to entry); granulocyte count of at least 1200 cells/mm^3; platelet count of at least 100,000/mm^3; calculated creatinine clearance greater than 50 ml/min/1.73m^2; and transaminase less than five times the upper limit of normal. Patients with ARC will be excluded from the ARC study group if they have an opportunistic infection or malignancy (tumor) fulfilling the definition of AIDS, or have neoplasms (cancerous growths) other than basal cell carcinoma of the skin or in-situ carcinoma of the cervix. Patients with AIDS will be excluded from the study: if they have an active opportunistic infection and require ongoing systemic therapy and/or prophylaxis for an AIDS-defining opportunistic infection (an exception is the use of inhaled aerosolized pentamidine as a preventive for Pneumocystis Carinii pneumonia); if they have symptomatic visceral Kaposi's sarcoma (KS), progression of KS within one month prior to entry in the study or with neoplasms other than KS, basal cell carcinoma of the skin or in-situ carcinoma of the cervix; or if they require antineoplastic therapy. Patients with either AIDS or ARC will be excluded if they: demonstrate significant malabsorption (a condition in which the body does not properly absorb nutrients or drugs); are active substance abusers; have received any antiretrovirals within 60 days prior to entry or have received biological modifiers or corticosteroids within 30 days prior to entry; have significant cardiac, liver, or neurologic disease; suffer from diabetes, kidney failure, or alcoholism or take neurotoxic drugs such as dapsone or nitrofurantoin; have previously taken ddC; have experienced dose-limiting or transfusion- requiring toxicity during a previous course of AZT therapy; have a history of Idiopathic Thrombocytopenic Purpura; require prolonged acyclovir therapy; are women who are pregnant or are breast feeding; or are unwilling to be followed by the medical center during the study and follow-up. ADMINISTRATION: A total of 112 patients will be divided, randomly, into seven different treatment regimens. All medication will be given orally, and all patients completing the study will be followed for four weeks after completion. The seven groups of the study are described below: 1. Weekly Alternating. AZT is administered at 200 mg every four hours for one week, after which AZT is stopped and ddC administration begins at 0.01 mg/kg every four hours for one week, for 24 full cycles, or 48 weeks, of therapy administered. 2. Weekly Alternating (different dose of ddC). AZT is administered at 200 mg every four hours for one week, after which AZT is stopped and ddC administration begins at 0.03 mg/kg every four hours for one week, for 24 full cycles, or 48 weeks, of therapy administered. 3. Monthly Alternating. AZT is administered at 200 mg every four hours for one month, after which AZT is stopped and ddC administration begins at 0.01 mg/kg every four hours for one month, for six complete cycles, or 48 weeks, of therapy administered. 4. Monthly Alternating (different dose of ddC). AZT is administered at 200 mg every four hours for one month, after which AZT is stopped and ddC administration begins at 0.03 mg/kg every four hours for one month, for six complete cycles, or 48 weeks. 5. Intermittent AZT. AZT is administered at 200 mg every four hours for one week, then AZT is stopped and no drug is given for one week. After a week with no drug, AZT is again administered for a week, for 24 cycles, or 48 weeks. No ddC is given to this group. 6. Intermittent ddC. ddC is administered at 0.03 mg/kg every four hours for one week, alternating with one week of no drug. A total of 24 cycles, or 48 weeks, of one week on ddC and one week with no drug will take place. No AZT will be given to this group. 7. Continuous AZT. AZT will be administered at 200 mg every four hours for 52 consecutive weeks. No ddC will be given to this group. TERM: 52 weeks METHODOLOGY: Both AZT and ddC are potent inhibitors of HIV. They are Chain Terminators, which means they interfere with the ability of HIV to replicate. Both these drugs place the patient at risk for serious, but different, side effects. Researchers hope to demonstrate through this study that alternating the use of the two drugs will reduce the side effects while maintaining the positive aspects of HIV inhibition. CONTROLS: None ORGANIZATION: George Washington University, one of the AIDS Treatment Evaluation Units run by NIH CONTACT: Mary Beth Goldin, George Washington University AIDS Clinical Trials Unit, 2300 I Street, N.W., Room 202, Washington, DC 20037, (202) 994-2417 ---------------------------------------- AS-101 AND AZT DESCRIPTION: Phase I open label, dose-escalation study designed to obtain toxicity data and preliminary data on the immunologic, anti-viral and clinical effects of AS-101 in combination with zidovudine (AZT) in patients with HIV infection and CD4 counts less than 200/mm^3 (or 20% of lymphocytes). REQUIREMENTS: Participants must be: HIV infected; 18-60 years of age; able to provide informed consent; free from active infection or illness requiring specific therapy that could interfere with protocol; able to tolerate AZT 100 or 200 mg every four hours or have no prior history of AZT intolerance, and have a CD4 count less than 200/mm^3 or less than 20% of circulating lymphocytes. Those with a history of intolerance to aerosolized pentamidine are excluded. TERM: 12 weeks of outpatient drug therapy if currently on AZT; otherwise six weeks of AZT followed by 12 weeks of combination therapy. ADMINISTRATION: This is a dose escalation study with participants receiving escalating doses of AS-101 in combination with AZT. Participants will be enrolled sequentially in groups of five, receiving AS-101 intravenously at doses of 3, 5, or 8 mg/M^2 three times a week and AZT 100 or 200 mg orally every four hours depending on tolerance for 12 weeks. The drug infusions will take 15-60 minutes depending upon dosage. Three participants from each dose group will be treated for a minimum of four weeks before patients are entered at the next higher dose level. Participants not previously treated with AZT will be started at 200 mg orally every four hours, decreased to a minimum of 100 mg every four hours if necessary. All participants will be required to receive at least six weeks of AZT at a minimum of 100 mg every four hours prior to starting AS- 101. Participants will also receive aerosolized pentamidine 300 mg every four weeks during the study period for prophylaxis against pneumocystis. METHODOLOGY: AZT is a potent inhibitor of HIV, however it does not reverse the immunodeficiency associated with HIV infection, and progressive disease frequently occurs. AS-101, a synthetic compound, has been found in vitro to increase the response to and production of interleukin-2, a lymphokine with immune-modulating properties. Thus, a combined regimen of AZT with AS-101 may provide some anti-retroviral and immunomodulatory activity. NOTES: Possible side effects of AZT include nausea, headache, anemia, decrease in white cells, and myopathy. AS-101 can cause lightening and thinning of hair, garlic body odor, rash, nausea, headache, and abnormalities of the urine. CONTROLS: None ORGANIZATION: National Institutes of Health/National Institute of Allergy and Infectious Diseases CONTACT: Debbie Ogata-Arakaki, Building 10, Room 10D48, National Institutes of Health, Bethesda, MD 20892, (301) 496-9565 ---------------------------------------- AZDU DESCRIPTION: Phase I/II study of 3'-Azido-2',3'-dideoxyuridine (AzdU) in people with HIV infection. REQUIREMENTS: Participants in this study must be positive on the ELISA and the Western Blot, and have a CD4 (T4) count between 200 and 400/mm^3. Participants must be over age 18, have no previous use of AZT, have good veins, and be willing to come to NIH for weekly blood drawing and clinic visits. Participants must also have a private physician involved in their care and available for communication with the NIH doctors and nurses during the time they are on this study. TERM: 14 1/2 weeks, with participants who show a beneficial response having the option to continue treatment after the study period ends. ADMINISTRATION: Participants will be divided into one of five groups who will receive different dosages of AzdU. The first dose will be given intravenously over one hour at the Clinical Center at NIH, with frequent blood drawing to measure drug levels. Two days later, a single oral dose will be given to measure oral absorption. Two weeks later, a twelve week period of oral dosing of the drug will begin. There will be frequent sampling of blood and urine during the course of the study for monitoring and evaluation to minimize potential toxicities. Participants will be assessed monthly for three months, and then every three months after being on the drug for nine months. METHODOLOGY: AzdU is a Chain Terminator, a "nucleoside analog" similar to AZT. It works by interfering with the ability of HIV to replicate. NOTES: AzdU has not been given to humans before, so potential side effects are unknown. Animal studies have shown toxicities only at extraordinarily large doses. Other nucleoside analogues have caused elevations of liver function tests, nausea, headache, and bone marrow suppression. A total of 15 people will be enrolled in this study. CONTROLS: None ORGANIZATION: National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIAID), Laboratory of Immunoregulation CONTACT: Dianne Lee, Building 10, Room 11B09, National Institutes of Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196 ---------------------------------------- AZT AND ACYCLOVIR (ACTG 063) DESCRIPTION: A double-blind phase II/III study of different dosages of AZT and acyclovir in patients with AIDS. REQUIREMENTS: Participants must have been diagnosed with AIDS within the past four months, as defined by CDC category IV-C-1, i.e. with PCP, cryptosporidiosis, toxoplasmosis, extraintestinal strongyloidiasis, isosporiasis, candidiasis (esophageal, bronchial, or pulmonary), cryptococcosis, histoplasmosis, mycobacterial infection, cytomegalovirus, mucocutaneous or disseminated herpes simplex virus, or progressive multifocal leukoencephalopathy. Participants must also: be positive on the ELISA and the Western Blot; be greater than 13 years of age; and be able to take care of themse lves requiring only occasional assistance. Women of childbearing potential must have a negative pregnancy test within 30 days of the start of the study and be willing to practice a barrier method of contraception while on the study. Laboratory tests must also be within certain limits (total neutrophil count greater than 1000/mm^3; platelet count greater than 50,000 cells/mm^3; hemoglobin greater than 9.0 mg/dl, and the patient cannot be transfusion dependent--the last transfusion must be at least two weeks prior to the study; serum creatinine less than 1.5 times the upper limit of no rmal or clearance greater than 50 ml/min; SGOT less than five times the upper range of normal). People will be excluded who: have symptomatic visceral or progressive Kaposi's sarcoma (defined by more than 10 new lesions in the 30 days prior to the study); have neoplasms other than basal cell carcinoma of the skin; are pregnant women, nursing mothers, or women not employing birth control or abstinence; have malabsorption as defined by persistent diarrhea greater than six stools/day for more than four weeks; require acyclovir prophylaxis or frequent (more than once a month) courses of acyclovir therapy for herpes simplex virus infection, however episodic treatment with acyclovir is permitted; have received systemic acyclovir therapy within 14 days of the start of the study; have been previously treated with AZT for more than 120 days; have received other anti-retrovirals within 30 days of study entry; have received ribavirin within 60 days of study entry; have received cytotoxic chemotherapy or radiation therapy for KS within 30 days of study entry; are participating in a protocol which compares AZT to a placebo (e.g. ACTG 016 and ACTG 019); or are active substance abusers (methadone maintenance therapy is permitted). TERM: Two years ADMINISTRATION: Participants will be divided into four groups: the first group will get 1000 mg/day of AZT and no acyclovir; the second will get 500 mg/day of AZT and no acyclovir; the third will get 1000 mg/day of AZT and 4000 mg/day of acyclovir; and the fourth will get 500 mg/day of AZT and 4000 mg/day of acyclovir. All medication will be taken orally, every four hours while awake (five times a day). Participants will have to come in once every two weeks for a clinic visit. If participants demonstrate significant toxicity, the dosage may be modified, or the therapy stopped. METHODOLOGY: There has been some conjecture that Human Herpes Virus Six (HHV-6) may activate HIV. Since acyclovir is an effective drug against the whole Herpes family of viruses, it is hoped that the combination of AZT, which has been shown to inhibit HIV replication, with acyclovir may have a greater effectiveness with fewer side effects than either drug taken alone. It may also allow for a lower dose of AZT while still being effective against HIV. The negative side effects of AZT have been shown to be dose- related, so the combination therapy of AZT and acyclovir may allow eff ective treatment with fewer side effects (primarily bone marrow suppression) from AZT. NOTES: Possible side effects include lowered white blood cell count, anemia, headache, mild confusion, fatigue, anxiety, nausea, skin rashes, dizziness, and muscle pain. Acyclovir has some of the same side effects as AZT, and also anorexia (loss of appetite). CONTROLS: None. All participants are guaranteed to receive some dosage level of AZT, and half the participants will receive some dosage level of acyclovir. ORGANIZATION: George Washington University, one of the AIDS Treatment Evaluation Units run by NIH CONTACT: Kathryn Grabowy, George Washington University AIDS Clinical Trials Unit, 2300 I Street, N.W., Room 202, Washington, DC 20037, (202) 994-2417 ---------------------------------------- AZT AND ALPHA INTERFERON DESCRIPTION: Study of AZT alone vs. AZT and Alpha Interferon vs. Alpha Interferon alone, for people in the early stages of HIV infection. REQUIREMENTS: Positive lymphocyte culture for HIV, or positive p24 antigen test, or positive PCR test, and T4 cell counts of more than 500 per cubic millimeter. Participants must be over age 18, have not participated previously in any other HIV protocols, have good veins, and be willing to come to NIH for weekly to biweekly blood drawing and clinic visits. Participants may have been on AZT before. Participants must also have a private physician involved in their care and available for communication with the NIH doctors and nurses during the time they are on this study. TERM: Indefinite. The study continues until the participant develops an opportunistic infection, their T4 cell counts drop below 200, or the participant develops severe side-effects or reactions (toxicity) to either of the medications. ADMINISTRATION: Participants will be divided into three groups: one will receive AZT alone, one will receive AZT and alpha interferon, and the last will receive alpha interferon alone. AZT is given orally; alpha interferon is given by injection. Persons enrolled in the study will be taught to give the alpha interferon to themselves. The AZT-only group will take 200 mg every four hours. The AZT/alpha interferon group will take 100 mg of AZT every 4 hours and 1 million units of alpha interferon every day. The alpha interferon-only group will initially receive 5 million units e very day. The doses of alpha interferon will be increased, as tolerated, to a maximum of 35 million units per day. METHODOLOGY: AZT is a "nucleoside analog" (a fake version of the base thymidine) which interferes with the ability of HIV to make copies of itself. Alpha Interferon interferes with the final assembly process of HIV which happens as HIV tries to bud off new copies of itself into the bloodstream. NOTES: Potential side effects of AZT include nausea, headaches, fatigue, and anemia that may require blood transfusion. Alpha interferon can cause flu-like symptoms (fevers, fatigue, muscle aches, decrease in appetite), a decrease in white blood cell count, and mental changes, including depression, memory loss, and difficulty concentrating. CONTROLS: None ORGANIZATION: National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIAID), Laboratory of Immunoregulation CONTACT: Victoria Davey, Building 10, Room 11B09, National Institutes of Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196 ---------------------------------------- AZT AND GM-CSF DESCRIPTION: Phase I study of AZT (Azidothymidine) combined with GM-CSF (Granulocyte/Macrophage-Colony Stimulating Factor) in patients with AIDS or symptomatic HIV infection. REQUIREMENTS: All participants must be at least 18 years old and have T4 cell counts of less than 200. Participants must have either never taken AZT, or have taken at least 600 mg a day, and discontinued because of toxicity to the patient's white blood cells. Participants who were on AZT must be off it for at least four weeks prior to the study. All participants must have a white blood cell count of less than 3,000 per cubic millimeter and hemoglobin of greater than nine grams per deciliter. All participants must have greater than 75,000 platelets per cubic millimeter and no t ransfusions within the past month. People with active opportunistic infections are excluded from the study. No other cytotoxic or antiretrovirals may be taken while participants are in the protocol, although prophalaxis for PCP with either Fanzidar, Bactrim, or aerosolized Pentamidine is permitted. Women of child-bearing potential must have a negative pregnancy test prior to the start of the study, and be willing to use birth control measures during and for two months after the study. TERM: 12 months, with the possibility of an extension if the patient responds favorably to the treatment. All treatment is on an outpatient basis from the NIH Clinical Center. ADMINISTRATION: The AZT is given orally every four hours; the GM-CSF is given two times a day by a self-administered injection just under the skin (similar to the way insulin is self-injected by diabetics). METHODOLOGY: AZT, while effective at suppressing the reproduction of HIV, has an unfortunate side effect of suppressing the production of granulocytes and macrophages, which are types of white blood cells, within the bone marrow. GM-CSF stimulates the production of granulocytes and macrophages, so it is hoped that by taking GM-CSF in combination with AZT, AZT's toxic side effects can be reduced or eliminated, or that a larger dose of AZT with tolerable side effects will be possible. NOTES: If the patient's white cell counts fall while he/she is in the study, the dosage of GM-CSF will be increased (two increases only) to try to counter the toxicity problems. CONTROLS: None. (In a Phase I study, all patients receive the actual drugs.) ORGANIZATION: National Institutes of Health/National Cancer Institute CONTACT: Dr. James Pluda, Building 10, Room 13N248, National institutes of Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-8398 ---------------------------------------- AZT AND INTERLEUKIN-2 DESCRIPTION: The study will evaluate the effectiveness and toxicity of the combination of AZT (also known as zidovudine and Retrovir) and Interleukin-2 (IL-2) in the treatment of persons with HIV infection. REQUIREMENTS: To be eligible to participate in the study, a person must have HIV diagnosed by ELISA and Western Blot or a positive culture. The person must not have had any of the opportunistic infections associated with AIDS and must have over 200 T4 cells per cubic millimeter. If the person is receiving AZT, he/she must be able to tolerate 200 mg every four hours. TERM: Seventeen weeks (with possible extension of therapy if significant improvement occurs). ADMINISTRATION: AZT alone will be given for six weeks (orally). Following that, AZT and IL-2 will be administered for three weeks. The IL-2 will be administered IV continuously for three weeks and this part of the study will be done on an inpatient basis. In addition there will be weekly or biweekly blood drawing for the duration of the study. METHODOLOGY: Studies have demonstrated that AZT can decrease the frequency of opportunistic infections, but it sometimes results in bone marrow suppression. IL-2 is a drug which stimulates the immune system. Researchers are trying to determine whether the IL-2 might reduce the side effects of AZT, thus allowing more patients to take full doses of AZT. CONTROLS: None ORGANIZATION: National Institutes of Health/National Institute of Allergy and Infectious Diseases CONTACT: Dianne Lee, Building 10, 11th floor clinic, National Institutes of Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196 ---------------------------------------- AZT FOR VETERANS DESCRIPTION: Study of the effectiveness of AZT in a double-blind, controlled study of patients with ARC (AIDS Related Complex). REQUIREMENTS: Participants in the study must be VA eligible. They must be HIV antibody positive, with T-cell counts between 200 and 500, and they must have some minor symptoms. TERM: The protocol lasts for three years. ADMINISTRATION: The study drug is taken orally in 250 mg doses every four hours, around the clock. METHODOLOGY: AZT is a Chain Terminator, which means it interferes with the ability of HIV to replicate. This study attempts to determine to what extent AZT helps people with ARC. CONTROLS: This is a double-blind, randomized, controlled study. This means that 50% of the participants will get AZT, and THERE IS A 50% CHANCE THAT THEY WILL NOT. No one (neither the researchers nor the patient) will know who is or who is not on AZT. ORGANIZATION: Veterans Affairs Medical Center CONTACT: Pat Kramer or John Scott, Veterans Affairs Medical Center, 50 Irving Street, N.W., Washington, DC 20422, (202) 745-8694 ---------------------------------------- AZT IN HEMOPHILIACS (ACTG 036) DESCRIPTION: This is a double-blind placebo-controlled study to determine whether AZT (also known as zidovudine or Retrovir) will delay or alter the progression of disease in HIV infected hemophiliacs. REQUIREMENTS: Participants must: have HIV infection confirmed by Western Blot; be at least 12 years old; and have been diagnosed with hemophilia, Von Willebrand's Disease, or other coagulation-deficient disorders. Participants must have laboratory results within certain limits: granulocyte count of at least 1000 cells/mm^3; platelet count of a least 75,000/mm^3; hematocrit greater than 30 percent; creatinine less than or equal to 1.5 times normal or clearance of at least 50 ml/min; and transaminases less than or equal to five times the upper limit of normal. Participants must al so have a Karnofsky performance status of 90 (able to carry on normal activity; minor signs or symptoms or disease), although if this measure is impaired by hemophilia complications, a status as low as 60 will be accepted (requires occasional assistance but is able to care for most of his/her needs). Patients will be excluded from the study if there is a history of AIDS defining infection or malignancy or an unexplained temperature higher than 38oC (about 100.5oF) for more than five consecutive days or on more than 10 days in any 30-day period in the two years before entering the study. Additional exclusions are: unexplained severe diarrhea; unintentional weight loss of more than 10 percent of body weight in the past two years; oral hairy leukoplakia (white spots or patches on the tongue or cheek); a history of oral candidiasis not related to antibiotics; or herpes zoster infec tion within the past two years. People will also be excluded if: they have taken antiretroviral agents (like AZT) within the last eight weeks or immunomodulating drugs (like steroids); they have taken other experimental therapy within three months; or if they require therapy with isoniazid or rifampin. All participants will be required to practice effective contraception, and pregnancy is a basis for exclusion from the study. TERM: Up to three years ADMINISTRATION: Participants will take orally three 100 mg capsules every four hours for five doses per day. Half of these persons will be receiving AZT, the other half will be receiving a harmless placebo. METHODOLOGY: AZT acts on HIV to inhibit its replication (reproduction or copy of itself). It is a Chain Terminator. CONTROLS: This is a double-blind, placebo-controlled study, which means 50% of the patients will get AZT, and 50% WILL GET NONE. Neither the patient nor the researchers will know which is which during the course of the study. ORGANIZATION: George Washington University, one of the AIDS Treatment Evaluation Units run by NIH CONTACT: Stacy Russell, George Washington University Hematology/Oncology Clinic, 2150 Pennsylvania Avenue, N.W., Washington, DC 20037, (202) 994- 4200 ---------------------------------------- AZT, ALPHA INTERFERON, AND GM-CSF DESCRIPTION: This study is designed to evaluate the safety and effectiveness of giving recombinant granulocyte-macrophage colony stimulating factor (GM-CSF) in combination with AZT and alpha interferon in patients with HIV infection. REQUIREMENTS: Participants must: be over age 18; have a CD4 count of 200 to 500 per cubic millimeter; be positive for HIV on both the ELISA and the Western Blot; have good veins; and be under the care of a physician with whom the researchers can communicate while they are on the study. People with active opportunistic infections are excluded. TERM: Sixteen weeks after the dosages have stabilized, all of which is outpatient. ADMINISTRATION: Newly enrolled patients will be divided into two groups. One group will receive 100 mg of AZT orally every four hours for four weeks, and then will begin on interferon with 10 million units/day by injection under the skin with the dose escalating by five million units/day every two weeks. When the granulocyte count falls below 1000/mm^3, GM-CSF will be started at a dose of one microgram (ug) per kilogram of body weight per day (ug/kg/day), by injection under the skin. The GM-CSF dose will be escalated to maintain the granulocyte count over 1500/mm^3. Once the patient's granulocyte count is stable on AZT, interferon, and GM-CSF, the patient will be treated for 16 weeks. The second group is identical to the first, except their starting AZT dose will be 200 mg every four hours. Enrollment will be done sequentially--the first 10 patients will be in the first group, and the second 10 will be in the second group. NIH patients who have previously been on combination AZT/interferon therapy will comprise a third group. Patients in this group will begin on AZT and interferon at the doses at which they became granulocytopenic (low counts of granulocytes) in the past, with GM-CSF at one mg/kg/day starting at the same time. Doses of AZT, interferon, and GM-CSF will be escalated, as tolerated, in an attempt to bring the patients up to an optimal dosing level of AZT 200 mg every four hours and interferon 10 million units per day. The treatment period for the third group, once the patient's granulocyte count is stabilized above 1500/mm^3, will also be 16 weeks. METHODOLOGY: While studies in the laboratory and in humans have shown that AZT and alpha interferon given together can inhibit HIV, up to 50% of patients taking this combination of drugs develop granulocytopenia, a potentially serious decrease in a particular infection-fighting white blood cell known as the granulocyte. Granulocyte-macrophage colony stimulating factor is a bone marrow growth factor that stimulates production of several types of cells found in blood, including the granulocyte. NOTES: Potential side effects of AZT include nausea, headaches, and anemia that may require blood transfusion. Interferon can cause flu-like symptoms (fevers, fatigue, muscle aches, decrease in appetite), a decrease in white blood cell count, and mental changes, including depression, memory loss, and difficulty concentrating. The combination of AZT and interferon has been known to cause a decrease in granulocytes and depression of liver function. GM-CSF can cause fever, bone pain, and flu-like symptoms in some patients. CONTROLS: None ORGANIZATION: National Institutes of Health/National Institute of Allergy and Infectious Diseases, Laboratory of Immunoregulation CONTACT: Victoria Davey, Building 10, Room 11B09, National Institutes of Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196 ---------------------------------------- BETASERON (BERA INTERFERON) AND REDUCED DOSE AZT IN AIDS AND ADVANCED ARC PATIENTS DESCRIPTION: Comparative study of high dose Betaseron, low dose Betaseron, or placebo in combination with reduced dose AZT. REQUIREMENTS: Patients must have: laboratory evidence of HIV infection; either AIDS by CDC criteria or documentation of an absolute T4 count less than 200; a reaction to AZT that requires dose reduction of AZT to 500-600 mg of AZT daily and the ability to tolerate this reduced dose; Karnofsky status of 60 or greater (be able to take care of daily needs requiring only occasional assistance); acceptable renal (kidney) function; acceptable hepatic (liver) function; attained at least age 18; be available for follow- up; and be willing to continue on reduced dose AZT at own expense. Participants must have laboratory results within certain limits: granulocyte count currently greater than 1000/mm^3; hemoglobin greater than 8.5 mg/dl; and platelet count greater than 50,000/mm^3. People will be excluded if they have: ineffectively controlled opportunistic infections; Kaposi's sarcoma requiring systemic chemotherapy; cytotoxic chemotherapy within 30 days of the first Betaseron dose; proteinuria of 2+ or greater; concurrent therapy with anti-virals other than AZT or Betaseron; chronic concurrent therapy with acyclovir; prior therapy with interferon; HIV encephalopathy (dementia); HIV wasting syndrome; pregnancy or lactation (women with childbearing potential must take adequate precautions to prevent pregnancy during treatment); active drug or alcohol abuse; New York heart classification III or IV; uncontrolled angina pectoris (severe pain about the heart, usually travelling down the left arm); or evidence of clinically significant multifocal uncontrolled cardiac dysrhythmias. TERM: Indefinite. The study will continue until the superiority of the treatment is clearly demonstrated or disproved. ADMINISTRATION: All patients continue on reduced dose AZT. Each patient is assigned to one of three treatment groups--high dose Betaseron, low dose Betaseron, or placebo. The patient administers daily injections of the study drug into the skin (in the same way that diabetics inject themselves). The patient must visit the test site for lab and physical evaluations once a week for a month, biweekly for two months, and monthly thereafter. METHODOLOGY: Many patients on AZT develop side effects which involve the blood and must, therefore, be put on a reduced dose of AZT. In the laboratory, Betaseron (a recombinant form of interferon Beta) has been shown to enhance the action of AZT in blocking the ability of the HIV to make copies of itself, to kill lymphocytes, and to spread between lymphocytes. In clinical studies, patients who have taken Betaseron have shown evidence of suppression of the HIV copying mechanism and a low incidence of opportunistic infections. Although there may be side effects from Betaseron, they are seldom related to the blood. As a result, researchers believe that a level of AZT which is not toxic to the patient might be combined with Betaseron to get positive results similar to a higher AZT dose without the negative side effects of AZT on the blood. NOTES: Possible side effects of Betaseron include mild flu-like symptoms and redness at the injection site. These effects generally decrease and disappear with continuing treatment. Sometimes a mild depression in blood cell counts occurs. CONTROLS: Two out of three patients will be given Betaseron, with the third patient on a placebo. Although the study is placebo controlled, it should be noted that all patients will be maintained on low doses of AZT, thus ensuring that all patients will be receiving at least some anti-viral therapy. ORGANIZATION: George Washington University Hospital CONTACT: Grace Gianturco, George Washington University AIDS Clinical Trials Unit, 2300 I Street, N.W., Room 202, Washington, DC 20037, (202) 994-2417 ---------------------------------------- DDI (2',3'-DIDEOXYINOSINE) DESCRIPTION: Phase I Study of drug to fight HIV. REQUIREMENTS: This study is for people with AIDS or severe ARC, PARTICULARLY PEOPLE WHO HAVE NOT BEEN ON AZT OR HAVE BEEN ON AZT FOR SIX WEEKS OR LESS. Participants must be off AZT and other anti-viral therapy for at least four weeks before the study. All participants must have a count of less than 350 T4 cells per ml, and must not be anemic or have a low white blood count. ARC patients must have either oral thrush or weight loss. People with severe Kaposi's sarcoma or active opportunistic infections are excluded. TERM: The initial phase lasts for a total of 13 months; two weeks as an inpatient and 12 1/2 months as an outpatient. If the initial results prove favorable, it is possible that permission will be obtained from the FDA to continue the study for a longer period of time. ADMINISTRATION: On the first day, the drug will be given once intravenously; on the second day, the drug will be given once orally; and for the remainder of the (two week) inpatient period, the drug will be given intravenously two or three times a day. The volunteer will then take the drug by mouth two or three times a day as an outpatient. The volunteer will be required to return to NIH once a week for monitoring for the first six weeks as an outpatient. After that, the patient will come to clinic every two weeks for six weeks, then every three weeks while on the study. With a Phase I Study, everything is very much up in the air and subject to negotiation and changes as the study progresses. At completion of the study, patients can either be transferred to other treatment protocols if they are eligible, or drop out, at their option. METHODOLOGY: ddI is a Chain Terminator. ddI changes in your body to an activated form of ddA, a "fake" version of adenosine which doesn't let anything else chain onto it. This means that when HIV tries to replicate itself by copying its RNA to DNA, the "fake" ddA gets added to the DNA strand instead of real adenosine. ddA doesn't have the necessary "hooks" for the next compound in the chain to link into. The DNA strand just stops, halted in its tracks, incomplete and ineffective. ddI is handled by the body differently than AZT, and it appears to be less toxic for bone-marrow cells than AZT (in the test tube). NOTES: Preliminary results with another form of this drug, ddA, indicated that, at the doses tested, it could be tolerated for up to eight weeks without major side effects (toxicity problems). Some patients on ddA had increases in their T4 cell counts. ddA is converted in the body to ddI, and as mentioned above, ddI is converted back again to an activated form of ddA, so it is likely that similar therapeutic results will be obtained with ddI. The doses that will be tested in this study are similar to the doses that have already been tested with ddA. CONTROLS: None. (In a Phase I study, all patients receive the actual drug.) ORGANIZATION: National Institutes of Health/National Cancer Institute CONTACT: Dr. Robert Yarchoan, Building 10, Room 12N214, National Institutes of Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-0328 ---------------------------------------- RECOMBINANT SOLUBLE CD4 DESCRIPTION: Phase I study of the effectiveness of Recombinant Soluble CD4 in patients with AIDS/ARC. REQUIREMENTS: This study is for people with AIDS who have had one opportunistic infection, or symptomatic ARC patients. The study is particularly for people WHO HAVE NOT BEEN ON AZT OR HAVE BEEN ON AZT FOR SIX WEEKS OR LESS. Participants must be off AZT and other anti-viral therapy for at least four weeks before the study. All participants must have a count of less than 400 T4 cells per ml, and a positive HIV p24 antigen. TERM: The study lasts for two and a half weeks, all of which is in-patient at the NIH Clinical Center. The possibility exists for an extension to six months, if the participant shows a positive response. ADMINISTRATION: The drug will be administered by a continuous infusion through an IV. METHODOLOGY: The CD4 receptors on the surface of your T4 cells are the places that HIV attaches to when it binds to and attacks your T4 cells. Recombinant Soluble CD4 is like the attachment points without the T4 cells underneath it. It is hoped that HIV will attach to the CD4 on the R.S. CD4 instead of on your actual T4 cells, and since R.S. CD4 is not attached to a real T4 cell, and is thus useless to HIV (because it is not a real T4 cell, and thus cannot be taken over and used by HIV to hide and to replicate itself), that HIV will thus be rendered ineffective and unable to rep licate. NOTES: Preliminary studies revealed no apparent side effects (no toxicity problems). There is currently a long waiting list to get onto the CD4 protocol. CONTROLS: None. (In a Phase I study, all patients receive the actual drug.) ORGANIZATION: National Institutes of Health/National Cancer Institute CONTACT: Dr. Robert Yarchoan, Building 10, Room 12N214, National Institutes of Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-0328 *************************************************************************** PNEUMOCYSTIS CARINII PNEUMONIA (PCP) PROTOCOLS ---------------------------------------------------- DAPSONE OR DAPSONE/PYRIMETHAMINE FOR PCP PROPHYLAXIS DESCRIPTION: Phase I/II study designed to evaluate the toxicity and efficacy of weekly dapsone or dapsone/pyrimethamine in HIV-infected persons with prior history of PCP or who have less than 250/mm^3 CD4 cells. REQUIREMENTS: Participants must be: 18 years of age or older; HIV positive; and able to provide informed consent. Participants must have either a history of documented PCP that has been successfully treated or a CD4 count of less than 250/mm^3. Participants must be at least two weeks from other anti-PCP prophylaxis. This study is only practical for people living within a 100 mile radius of NIH. TERM: One year if beneficial, or stopped if the participant develops PCP or significant toxicity while on therapy. ADMINISTRATION: This is an outpatient study comprised of two phases. The initial phase will consist of open dose escalation with the first five participants receiving dapsone 100 mg orally once a week. Dose escalation will continue in increments of 100 mg every five participants until dose- limiting toxicity is reached in 20% of patients at a given dose. After establishment of a tolerated dose of dapsone, pyrimethamine 25 mg will be added. After the dose escalating phase is completed, all subsequently entered participants will be randomized to receive either dapsone or dapsone/ pyrimethamine. Participants will be seen in the outpatient clinic weekly for four weeks, then every two weeks for lab work and every six weeks for nursing visits for a period of one year. METHODOLOGY: A study of PCP in a rat model suggests that intermittent administration of dapsone, which is a sulfone, could prevent development of PCP. Efficacy of dapsone appears to be enhanced by a dihydrofolate reductase inhibitor, trimethoprim, therefore it is possible that such agents used in combination could result in improved prevention against PCP. Pyrimethamine is a more potent agent against PCP than trimethoprim and is effective for a longer period in the body. Combination dapsone and pyrimethamine therapy has the advantage of being potentially well-tolerated, easily administered, and inexpensive. NOTES: Possible side effects include anemia, methemoglobinemia (a condition in which the hemoglobin has been changed by a toxic substance), decreased white blood cells, hepatitis, rash, nausea, and fatigue. CONTROLS: None ORGANIZATIONS: Georgetown University Hospital: Center for HIV Disease; National Institutes of Health: National Institute of Allergy and Infectious Diseases (NIAID)/National Cancer Institute (NCI)/Clinical Center CONTACTS: Georgetown University Hospital (Center for HIV Disease): Dr. James Lavelle, Georgetown University Hospital, 3800 Reservoir Road, N.W., Washington, DC 20007, (202) 687-8826 National Institutes of Health: Debbie Ogata-Arakaki, Building 10, Room 10D48, National Institutes of Health, Bethesda, MD 20892, (301) 496-9565 ---------------------------------------- PIRITREXIM AND LEUCOVORIN THERAPY FOR PCP DESCRIPTION: Phase I/II study designed to evaluate the toxicity, tolerance, and efficacy of oral piritrexim and leucovorin for the initial treament of Pneumocystis carinii pneumonia (PCP) in people with AIDS. REQUIREMENTS: Participants must have AIDS as defined by the Centers for Disease Control, be at least 18 years of age, and able to sign an informed consent form. Participants must have untreated PCP (first or second episode) documented within 36 hours of initiation of study therapy. Laboratory values must also be within certain limits (PaO2 greater than 60 or A-A gradient less than 30, and fever, respiratory symptoms or abnormal CXR). TERM: 21 days of therapy with two month follow-up ADMINISTRATION: Participants will receive oral daily doses of piritrexim for 21 days and leucovorin for 23 days. METHODOLOGY: Piritrexim is`a dihydrofolate reductase inhibitor that has demonstrated the ability to block folate metabolism, essential in the growth of Pneumocystis organisms. The use of piritrexim is complicated by its potential for bone marrow suppression, demonstrated in initial trials of the drug as an anti-cancer agent. Therefore, leucovorin, a pre-made folate with the ability to rescue human cells without reversal of the anti-Pneumocystis effects of piritrexim, will be used concurrently. NOTES: Possible side effects include a decrease in white blood cell count or platelet count, anemia, mouth sores, rash, and increase in liver enzymes. CONTROLS: None ORGANIZATION: National Institutes of Health: National Institute of Allergy and Infectious Disases (NIAID)/National Cancer Institute (NCI)/Clinical Center CONTACT: Donna O'Neill, Building 10, Room 10D48, National Institutes of Health, Bethesda, MD 20892, (301) 496-9565 *************************************************************************** CMV RETINITIS PROTOCOLS ---------------------------------------- FOSCARNET FOR CMV RETINITIS DESCRIPTION: Study of the safety and effectiveness of foscarnet in AIDS patients who have CMV retinitis. REQUIREMENTS: This study is for people ages 18 to 60 with AIDS and a positive HIV test who have CMV retinitis which is not immediately sight- threatening. One or both eyes may be affected by the retinitis. Participants must designate someone with a Durable Power of Attorney, and must also satisfy certain laboratory conditions (serum creatinine less than or equal to 2.0 mg/dl; neutrophil counts of greater than 1000/mm^3; hemoglobin of greater than or equal to 8 g/dl; and platelets of greater than 25,000/mm^3). The following people are excluded: those who have been treated with gan ciclovir or foscarnet for CMV retinitis in the past; those who are currently taking acyclovir orally or intravenously; those who have a history of intolerance to AZT; those with corneal, lens, or vitreous opacification which precludes fundus examination, or other retinal diseases; and people taking other investigational drugs. Women must have a negative pregnancy test within 14 days of the start of the study, and agree to practice contraception for the duration of the study plus three months afterwards. TERM: Three weeks of inpatient treatment at the NIH Clinical Center for those receiving foscarnet, then outpatient treatment until significant progression of the CMV retinitis is observed. Patients who complete the study can continue receiving foscarnet from the manufacturer at no charge until it becomes a marketed drug. ADMINISTRATION: Patients must undergo a physical examination including blood tests, a chest x-ray, electrocardiogram, and tests to determine the severity of the CMV retinitis. Patients will be randomly divided into three groups. The first group will receive foscarnet intravenously three times a day as inpatients at NIH for three weeks, and then once a day as outpatients. The second group will receive the same treatment as the first group, plus oral AZT. A third group will receive only AZT. Patients in all groups will also receive aerosolized pentamidine to lower the risk of P neumocystis carinii pneumonia. Patients receiving foscarnet will have a Hickman catheter inserted. This device is a plastic tube inserted in a large central vein through which the drug is administered. This eliminates the need to administer the drug into a peripheral vein each time. The tube is placed during a simple surgical procedure performed under general anesthesia. Patients will be examined weekly to check for progression of the CMV retinitis. If significant disease progression occurs in the patients receiving only AZT, foscarnet will be made available to them. Frequent blood testing is also required, up to 450 ml in a six-week period. Urine tests will be taken once a week during the first three weeks, then once every two weeks for the rest of the study. METHODOLOGY: Foscarnet has been proven to inhibit viral activity in human herpes viruses by interfering with the ability of the viruses to reproduce themselves without significantly interfering with the ability of the rest of the body's cells to reproduce. Foscarnet has been used as a treatment for CMV in Europe, Canada, and the United States. Foscarnet also does not appear to have the toxic effects on bone marrow that AZT does, thus giving hope that people with CMV retinitis may have an effective treatment for this disease without having to stop taking AZT. Ganciclovir (also k nown as DHPG), the other treatment being explored for CMV retinitis, cannot be taken at the same time as AZT. Foscarnet also has some action against HIV. NOTES: Possible side effects of foscarnet include decreased kidney function, confusion, inflammation of the veins, anemia, headache, fatigue, and seizures. The Hickman catheter used for injection of the Foscarnet can also become infected. AZT may cause decreased white blood cell counts, making the patient more susceptible to infection, or anemia. Aerosolized pentamidine may cause constriction of the bronchial airways. CONTROLS: None ORGANIZATION: National Institutes of Health/National Eye Institute/National Institute for Allergy and Infectious Diseases CONTACT: Barbara Baird, Building 10, Room 10D48, National Institutes of Health, Bethesda, MD 20892, (301) 496-9565 ---------------------------------------- GANCICYCLOVIR (DHPG) FOR CMV RETINITIS (ACTG 071) DESCRIPTION: Study of the effectiveness of gancicyclovir (DHPG) in patients with AIDS who have peripheral CMV retinitis which is not immediately sight- threatening. REQUIREMENTS: Participants must: be at least 13 years old; have AIDS by the CDC definition or have confirmation of HIV infection by a positive ELISA, p24 antigen, or HIV culture; have a life expectancy of at least four months; be able to sign an informed consent form; and have CMV retinitis diagnosed by an ophthalmologist using indirect ophthalmoscopy, and documented by retinal photographs. The retinitis must not be immediately sight-threatening, i.e. retinal lesions must be greater than 1500 microns from the edge of the optic disc, outside of the major temporal vascular arcades, and greater than 3000 microns from the fovea. People will be excluded who: have immediately sight-threatening retinitis; only have retinal lesions which cannot be photographed; require continued treatment with other medications such as antimetabolites, alkylating agents, nucleoside analogs (except AZT as noted below under Administration); have ocular media opacities (corneal, lenticular, or vitreal) which prevent ophthalmologic and photographic retinal assessment; have ocular conditions requiring immediate surgical correction, e.g. retinal tear, detachment; have had previous treatment with anti-cytomegalovirus therapy, e.g. gan cicyclovir, foscarnet, or CMV hyperimmune globulin; are receiving another investigational drug other than aerosolized pentamidine; or who have demonstrated hypersensitivity to acyclovir. Women who are pregnant, nursing mothers, or who test positive on a pregnancy test, and men or women who are not using adequate birth control measures are also excluded. Laboratory tests must also be within certain limits (absolute neutrophil count greater than or equal to 1000/mm^3; platelets count of greater than or equal to 50,000/mm^3; serum creatinine less than 1.5 mg/dl). TERM: 16 weeks, with the option of continuing on "open-label" gancicyclovir after the study period ends. Participants must use an effective method of birth control during and after the conclusion of the study: 30 days for women, 90 days for men. ADMINISTRATION: Participants will be divided into two groups. The first group will receive immediate gancicyclovir treatment. The second group will receive delayed gancicyclovir treatment. While AZT is not permitted while on the study (because both gancicyclovir and AZT cause bone marrow suppression, and the combination can be too toxic), people in the delayed treatment group can continue on AZT until their gancicyclovir treatment starts. People in the delayed treatment group who show progression of their retinitis will be eligible to start immediate gancicyclovir therapy. Gancicyclovir is administered intravenously, usually through a Hickman or similar catheter (which is a plastic tube in your chest which goes directly into a vein), over the course of one hour. Gancicyclovir is given at 5 mg/kg once every twelve hours for the first two weeks, and then once a week at 5 mg/kg for the next 14 weeks. If the participant develops severe side effects, gancicyclovir therapy will be either at a reduced dosage, suspended, or discontinued. METHODOLOGY: Gancicyclovir (also known as dihydroxy-propoxymethyl guanine or DHPG) interferes with the DNA synthesis necessary for cytomegalovirus to reproduce. NOTES: Participants must be referred by their physician. Side effects from gancicyclovir range from lowered white blood cell counts, decreased platelet counts, skin rashes, hives, nausea, vomiting, dizziness, bleeding and bruising, irritation of the veins, and possible impairment of reproductive or sexual function (possibly permanently). Other side effects which have been observed include abnormalities in liver or kidney function, low blood pressure, fainting, headache, anemia, swelling, fever, damage to nerves, loss of hair, intestinal bleeding, seizures, loss of hearing, and p sychological changes including confusion, irritability, nightmares, hallucinations, or psychosis. Damage to eggs or sperm may result, which is one of the reasons why contraception while on gancicyclovir is essential (in addition to not passing HIV on to future offspring). CONTROLS: None. All participants will receive gancicyclovir eventually, but 50% of participants will receive it immediately, and 50% will receive it on a delayed basis. ORGANIZATION: George Washington University, one of the AIDS Treatment Evaluation Units run by NIH CONTACT: Interested people should have their doctor call Dr. David Parenti, George Washington University, (202) 994-4716, or call Mary Beth Goldin at (202) 994-2417 for more information. *************************************************************************** TOXOPLASMOSIS PROTOCOLS ------------------------------------------- PYRIMETHAMINE AND DAPSONE FOR TOXOPLASMOSIS DESCRIPTION: Phase I/II study designed to evaluate the toxicity, tolerance and effectiveness of combination therapy with dapsone and pyrimethamine for the treatment of central nervous system toxoplasmosis in persons with AIDS who are resistant to or intolerant of conventional therapy. REQUIREMENTS: Participants must: have AIDS as defined by the Centers for Disease Control; be at least 18 years of age; be able to sign an informed consent; and be willing to sign a durable power of attorney. Participants must have cerebral toxoplasmosis and either have been intolerant of or failed conventional therapy (pyrimethamine and sulfadiazine). TERM: Life-long if therapy is beneficial. Study will be stopped if the participant deteriorates at 14 days of therapy or fails to improve at 21 days of therapy. ADMINISTRATION: Participants will receive oral daily doses of pyrimethamine 25 mg, dapsone 100 mg, and leucovorin 10 mg. Adjustments of pyrimethamine and dapsone will be made if the participant fails to respond. All participants will be admitted to the NIH Clinical Center for induction of therapy. After seven inpatient days, participants medically stable and reliable will be discharged to continue therapy as outpatients. Participants will be seen in the NIH outpatient clinic weekly for the first three weeks, and every two weeks thereafter. METHODOLOGY: Toxoplasmosis is a life-threatening parasitic infection caused by a protozoa, toxoplasma gondii. Pyrimethamine, a dihydrofolate reductase inhibitor and dapsone, a sulfone agent, are known to block folic acid metabolism, an important pathway in both humans and toxoplasma organisms. Leucovorin, mentioned above, allows the body's cells to bypass the blockade without affecting the anti-protozoan activity. In combination, these drugs have the potential to be at least as effective as the conventional regimen, pyrimethamine and sulfadiazine, but less toxic, for treatment of toxoplasmosis. NOTES: Possible side effects include a decrease in white blood cell count or platelet count, anemia, methemoglobinemia, hepatitis, kidney problems, rash, nausea, and vomiting. CONTROLS: None ORGANIZATION: National Institutes of Health: National Institute of Allergy and Infectious Diseases (NIAID)/National Cancer Institute (NCI)/Clinical Center CONTACT: Debbie Ogata-Arakaki, Building 10, Room 10D48, National Institutes of Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-9565 *************************************************************************** MISCELLANEOUS PROTOCOLS ---------------------------------------- BLOOD DRAWING STUDY DESCRIPTION: Blood is drawn for research on the immune response to the AIDS virus. REQUIREMENTS: Patients must be positive for antibodies to HIV-1, without severe anemia. Medication usage is acceptable. TERM: Several hours as an out-patient at the NIH Clinical Center. ADMINISTRATION: One unit of blood is drawn, the same amount that would be given when donating blood for transfusion. COMPENSATION: Participants in the study will receive compensation of $30.00. METHODOLOGY: The blood drawn will be used in research to fight HIV. CONTROLS: Not applicable ORGANIZATION: National Institutes of Health/National Heart, Lung, and Blood Institute/Pulmonary Branch, Bethesda, MD 20892 CONTACT: Pulmonary Branch, (301) 496-2449 ---------------------------------------- BRONCHOALVEOLAR LAVAGE STUDY DESCRIPTION: Study to assess the impact of HIV-1 infection on lung defense mechanisms. REQUIREMENTS: Patients must be between the ages of 18 and 60, be positive for antibodies to HIV, and not had active pulmonary opportunistic infections (e.g. Pneumocystis Carinii Pneumonia or other lung disorders) in the last three months. Infection prior to three months, current medication use or Kaposi's sarcoma are not exclusions. TERM: The study involves one full day as an in-patient at the NIH Clinical Center. ADMINISTRATION: Participants will receive a complete medical evaluation including a medical history, physical examination, chest X-rays, electrocardiogram, urinalysis, blood tests, lung function studies, and bronchoscopy with washes for analysis of cells and potential pneumonias. COMPENSATION: Participants in the study will receive compensation of $122.00. METHODOLOGY: Analysis will be made of the washes of the lungs so researchers can gather more information on what organisms attack the lungs, and how the lungs' defense mechanisms operate. NOTES: No prescriptions are dispensed. Results of testing are made available to the participant and a referring physician. CONTROLS: Not applicable ORGANIZATION: National Institutes of Health/National Heart, Lung, and Blood Institute/Pulmonary Branch, Bethesda, MD 20892 CONTACT: Pulmonary Branch, (301) 496-2449 ---------------------------------------- BRONCHOSCOPY STUDY DESCRIPTION: A study to determine the existance of pneumocystis in individuals with prior history of PCP and the presence of pneumocystis, cytomegalovirus, or other pulmonary pathogens in asymptomatic HIV-positive individuals without past history of PCP. A secondary goal is to determine whether conventional and experimental laboratory techniques such as bronchoscopy and sputum induction can detect the early presence of cytomegalovirus, and how these findings correlate with future clinical developments. REQUIREMENTS: Participants must: be at least 18 years of age; be able to sign an informed consent form; have a normal chest X-ray; and show no respiratory symptoms such as cough, fever, chest pain, or shortness of breath. TERM: Approximately one to two days ADMINISTRATION: Participants will not receive any therapeutic treatment. Participants will be screened, and if eligible undergo the following: 1. Blood tests 2. Pulmonary function test, a breathing test which is done as an outpatient and takes approximately 15-30 minutes 3. Two induced sputum collections, where the participant breathes in a mist for appoximately 15 minutes, and then coughs into a sterile cup 4. Bronchoscopy with biopsy, a procedure that involves placing a thin flexible tube into your airways, washing the cells of the lining of the lung with a salt water solution, and obtaining several small pieces of lung tissue under X-ray guidance. This tissue is then examined under a microscope. The procedure is done under local anesthesia and involves admission into the hospital for one to two days. METHODOLOGY: Pneumocystis and cytomegalovirus (CMV) are the most common life-threatening causes of morbidity and mortality in patients with HIV infection. Whether these organisms are present in an asymptomatic HIV- infected cohort with varied respiratory histories, and the role various tests play in diagnosis of these infectious pulmonary pathogens is unclear. Of special interest is determining the importance of various diagnostic specimens in documenting the presence of CMV pneumonitis. To date, there is no consensus about how best to diagnose CMV pulmonary infection. Due to t he increase in PCP prophylactic therapy, it is likely that other pathogens such as CMV will be a greater cause of morbidity and mortality. CONTROLS: None ORGANIZATION: National Institutes of Health: Clinical Center/National Institute of Allergy and Infectious Diseases (NIAID) CONTACT: Debbie Ogata-Arakaki, Building 10, Room 10D48, National Institutes of Health, Bethesda, MD 20892, (301) 496-9565 ---------------------------------------- GP-160 (VACCINE) DESCRIPTION: Experimental vaccine against HIV REQUIREMENTS: You must be male, negative (non-reactive) on the ELISA test for antibodies to HIV, and have had no unsafe sex for at least three months prior to the screening. Participants cannot be promiscuous or in an unsafe sexual relationship with a HIV-positive partner. A commitment is required to not have sex which will place you at risk for HIV infection (either oral or anal, with or without condoms) for at least three months following vaccination (a year is desired). TERM: Approximately 13 months ADMINISTRATION: Initial screening, blood work, and a tetanus/diptheria booster shot for people who aren't current; followed by an intensive physical examination four weeks later; then administration of the vaccine by intramuscular injection. Required follow-up visits once a week for four weeks, then once a month for the next year. METHODOLOGY: gp-160 is the protein that forms the protein coat of HIV. This vaccination is NOT a "dead" virus, so there is zero chance of HIV infection from the vaccine. gp-160 is synthesized using recombinant DNA techniques (gene splicing). The hope is that your body will respond to the protein and form antibodies to it (just like any other vaccine). One result of this is that if the vaccine works, volunteers may then test positive for HIV antibodies on the ELISA test. The more sophisticated Western Blot test, done by a competent laboratory, should be able to tell the differ ence between HIV infection and antibodies formed in response to gp-160. Volunteers will get notarized copies of their Western Blot tests before and after participation in the study, as well as a detailed description. Be warned, however, that insurance companies (both health and life) may still discriminate against you because of testing positive for HIV antibodies, and other problems could arise with regard to employment in the military, or the State Department, etc. NOTES: Because the study relies on the Western Blot test to make sure that individuals do not have HIV before the study begins, 50% of the volunteers have been rejected after the initial screening (because of problems in getting a clear Western Blot test). The researchers think that this may be because the Western Blot test is too sensitive, and is reacting to non-HIV proteins. Until something can be proved, they are rejecting anyone who does not have a completely clear Western Blot. CONTROLS: Very few. One fifth of the volunteers at the highest dosage levels will get a harmless substance called KLH as a control group to see how their immune response differs from the immune response of the volunteers getting gp-160. But, basically, almost all of the volunteers get the actual vaccine. ORGANIZATION: National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIAID) CONTACT: Margaret Easter, Building 10, Room 11B-13, National Institutes of Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196 ---------------------------------------- HIV & HEART DISEASE STUDY DESCRIPTION: Long-term study of heart disease in people who are infected with HIV. REQUIREMENTS: Participants must be HIV positive. TERM: The study is expected to run until June, 1993. ADMINISTRATION: Participants will go to the study center every four months, and will undergo three non-invasive tests of their hearts: an EKG (electrocardiogram), an echocardiogram, and a Signal Averaged EKG (a more sensitive, computer-processed version of the EKG). Blood will also be drawn for analysis. Study hours are on Tuesdays, from 8:00 a.m. to 1:00 p.m. If abnormalities are detected, participants will be asked to return every two months. METHODOLOGY: The EKG and other tests help analyze the condition of your heart. The blood work checks for antibodies to heart antigens. The two primary heart diseases being watched for are cardiomyopathy (enlargement of the heart), and pericardial effusions (which are fluids in the sack around the heart). Seventy percent of AIDS patients showed cardiac problems at autopsy, many of these problems might have been amenable to treatment with appropriate drugs. Monitoring can help detect these types of problems early enough that they can be treated. Many people who aren't HIV-positive but have a history of heart disease in their family undergo this type of monitoring as a matter of routine. No actual treatment is performed during this study. If problems are detected, participants are referred to their physician for treatment. Full cooperation and access to medical records will be provided by the researchers. NOTES: Participants will have their results evaluated by and be seen by a cardiologist every time they come in for testing. Confidentiality of patient records is maintained. Copies of all testing records are sent on request to either the participant or the participant's physician. CONTROLS: Not applicable ORGANIZATION: George Washington University Hospital, Division of Cardiology CONTACT: Sara Adams, Room 2440 North, George Washington University Hospital, 901 23rd Street, N.W., Washington, DC 20037, (202) 994-3909 ---------------------------------------- MEGACE DESCRIPTION: This is a double-blind, controlled study of Megace (Megestrol Acetate) in people with AIDS who have severe weight loss because of HIV. REQUIREMENTS: Participants must have a diagnosis of AIDS according to the CDC definition, with weight loss of at least 10% of normal body weight. TERM: Three month study period, followed by a period in which the participants can continue on their assigned drug, or go to "open-label" megace where they are guaranteed to be receiving the actual drug. Participants can go on "open-label" Megace if their weight loss continues during study. ADMINISTRATION: Participants will be divided into four groups: one group will receive 800 mg/day of Megace, another group will receive 400 mg/day of Megace; another group will receive 100 mg/day of Megace; and the fourth group will receive a placebo. Megace is a suspension in a liquid which is taken once per day, either before or after breakfast. METHODOLOGY: Megace (Megestrol Acetate) is a derivative of progesterone (one of two the female sex hormones) that has been used in the past to treat breast cancer patients. The study is to determine the efficacy of Megace in AIDS patients. Megace has been reported to stimulate appetite and weight gain. CONTROLS: Four arm, controlled study. This means that there is an 86% chance that you will receive some level of Megace, and A 14% CHANCE THAT YOU WILL RECEIVE A PLACEBO. ORGANIZATION: Veterans Affairs Hospital Medical Center, in conjunction with the Washington Hospital Center (participants do not have to be VA eligible); also George Washington University AIDS Clinical Trials Unit. CONTACT: Pat Kramer or John Scott, Veterans Affairs Medical Center, 50 Irving Street, N.W., Washington, DC 20422, (202) 745-8694; Mary Beth Goldin, George Washington University AIDS Clinical Trials Unit, 2300 I Street, N.W., Room 202, Washington, DC 20037, (202) 994-2417 *************************************************************************** OTHER PROTOCOLS For the most up-to-date information, call the NIAID AIDS Trial Line at 1- (800) TRIALS-A [874-2572]. Aerosolized pentamidine, long term, open-label, Georgetown University, Dr. James Lavelle, (202) 687-8826 AZT & Acyclovir, double-blind, placebo-controlled, in mildly symptomatic HIV+, Georgetown University, Dr. James Lavelle, (202) 687-8826 AZT & Chemotherapy for untreated HIV-related CNS lymphoma, George Washington University, Dr. Rick Schulof, (202) 994-4200 B12/Folate for people on AZT, Georgetown University, Pamela Harding, (202) 687-7163 Neuro-psychiatric characterization of HIV+ people on AZT, Georgetown University, Pim Brouwers, 687-4954 HIV+ with symptoms for study of physical and psychological needs, Catholic University of America, Dr. Mary O'Brien, (301) 635-5400 Salivary Function in HIV+, National Institute of Allergy and Infectious Diseases, Dr. Yeh, (301) 496-1478 Eye movement in asymptomatic gay men, National Institute of Allergy and Infectious Diseases, Robert Lipman, (301) 496-6295 Eye examinations for people with AIDS and ARC, Whitman-Walker Clinic in conjunction with Howard University, Dr. Basil Vareldzis, (202) 797-3534 Vaccine against HIV, Johns Hopkins University, Carol Hilton, (301) 955-7283 (collect) *************************************************************************** Copyright (C) 1988,1989 by Washington HIV News, all rights reserved. Permission is granted for non-commercial use only. -- J. Philip Miller, Professor, Division of Biostatistics, Box 8067 Washington University Medical School, St. Louis MO 63110 phil@wubios.WUstl.edu - Internet (314) 362-3617 phil@wubios.wustl - bitnet uunet!wucs1!wubios!phil - UUCP C90562JM@WUVMD - alternate bitnet