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NCT00000643

Inclusion Criteria Concurrent Medication: Allowed: Zidovudine (AZT), didanosine (ddI), dideoxycytidine (ddC), erythropoietin (Eprex), other agents granted Treatment IND or expanded access status. Investigational triazoles. Pentamidine for primary prophylaxis of Pneumocystis carinii pneumonia (PCP). Patients with the following are excluded: History of cerebral toxoplasmosis or toxoplasmosis infection in any other organ or tissue. Focal neural abnormalities (except peripheral neuropathy) or mass lesions on a previous computerized tomography (CT) scan or magnetic resonance image (MRI), unless subsequent workup rules out toxoplasmosis, in which case abnormalities must have been stable for at least 2 months. Known or suspected allergy or severe intolerance to study drugs. Patients must have: Positive toxoplasma serology. HIV infection. Willingness and ability to comply with the protocol and capability of giving written informed consent. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Current diagnosis of cerebral toxoplasmosis or toxoplasmosis infection in any other organ or tissue. Known or suspected allergy or severe intolerance to study drugs. Concurrent Medication: Excluded: Anticoagulants. Other antifolates, sulfonamides, fansidar, macrolides, 5-fluorouracil, dapsone, or any other agent with known activity against Toxoplasma gondii.

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NCT00000644

Inclusion Criteria Concurrent Medication: Allowed: Didanosine (ddI). Dideoxycytidine (ddC). Zidovudine (AZT). Acetaminophen. Acyclovir. Fluconazole. Erythropoietin (EPO). Systemic Pneumocystis carinii pneumonia (PCP) prophylaxis (aerosolized or oral pentamidine, trimethoprim / sulfamethoxazole, or dapsone). Maintenance ganciclovir therapy (permitted only if dose and clinical and laboratory parameters have been stable for at least 4 weeks prior to study entry). Maintenance treatment for other opportunistic infections if the dose and clinical and laboratory parameters have been stable for 4 weeks prior to study entry. Patients must have: Positive results for HIV by ELISA confirmed by another method. Positive blood culture for Mycobacterium avium complex within 2 months of study entry and clinical symptoms of MAC infection. Discontinued all mycobacterial drugs (approved and investigational) for at least 4 weeks prior to the start of drug therapy (with the exception of isoniazid prophylaxis which should be discontinued at Study Day minus 14 to Study Day minus 7 Given written informed consent to participate in the trial. Met the listed laboratory parameters in the pre-treatment visit. Prior Medication: Allowed: Didanosine (ddI). Deoxycytidine (ddC). Zidovudine (AZT). Acetaminophen. Acyclovir. Fluconazole. Erythropoietin (EPO). Systemic Pneumocystis carinii pneumonia (PCP) prophylaxis (aerosolized or oral pentamidine, dapsone, trimethoprim / sulfamethoxazole). Maintenance ganciclovir therapy (permitted only if dose and clinical and laboratory parameters have been stable for at least 4 weeks prior to study entry). Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Active opportunistic infections. Maintenance treatment for other opportunistic infections will be permitted if the dose and clinical and laboratory parameters have been stable for 4 weeks prior to study entry. Concurrent Medication: Excluded: Aminoglycosides. Ansamycin (rifabutin). Quinolones. Other macrolides. Clofazimine. Cytotoxic chemotherapy. Rifampin. Ethambutol. Immunomodulators (except alpha interferon). Investigational drugs (except ddI, ddC, and erythropoietin). Patients with the following are excluded: History of allergy to macrolide antimicrobials. Currently on active therapy with any anti-mycobacterial drugs listed in Exclusion Prior Medications. Currently on active therapy with carbamazepine or theophylline, unless the investigator agrees to carefully monitor blood levels. Inability to comply with the protocol or judged to be near imminent death by the investigator. Active opportunistic infections. Requiring any of the excluded concomitant medications. Prior Medication: Excluded for at least 4 weeks prior to study entry: All anti-mycobacterial drugs (approved and investigational) with the exception of isoniazid prophylaxis, which should be discontinued at Study Day minus 14 to minus 7.

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NCT00000645

Inclusion Criteria Concurrent Medication: Allowed: Prophylaxis for Pneumocystis carinii pneumonia (required for patients with CD4+ < 200). Symptomatic treatment with analgesics, antihistamines, antiemetics, antidiarrheal agents, or other supportive therapy. Short courses (< 10 days) with ketoconazole or fluconazole for oral candidiasis or acyclovir for herpes lesions. Topical medications such as clotrimazole troches or nystatin suspensions. Concurrent Treatment: Allowed: Blood transfusions. Patients must have HIV infection with CD+4 lymphocyte count of < 300 cells/mm3. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded. Kaposi's sarcoma requiring systemic therapy. Concurrent Medication: Excluded: Continued use of opiates or drugs known to induce photosensitivity. Patients with the following are excluded: Active or chronic opportunistic infection at time of study entry that required curative or suppressive therapy. Significant liver disease, orthostatic hypotension, cardiac disease, seizure disorder, lymphoma, hypotension. Prior Medication: Excluded: Zidovudine (AZT), dideoxyinosine (ddI), dideoxycytidine (ddC), interferon, other antiretroviral agents or immunomodulating drugs within 1 month prior to study entry. Ribavirin within 3 months of study entry. Ganciclovir (DHPG), antimycobacterial drugs, MAO inhibitors, hypertension-inducing, nephrotoxic, or hepatotoxic drugs within 14 days of entry. Cytotoxic chemotherapy within 1 month prior to study entry. Active substance abuse.

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NCT00000646

Inclusion Criteria Concurrent Medication: Required: Zidovudine (AZT), didanosine (ddI), dideoxycytidine (ddC), or a combination thereof, at current dosage for the 8 weeks of study treatment. Prophylaxis (e.g., aerosolized pentamidine, trimethoprim / sulfamethoxazole (TMP / SMX), dapsone for Pneumocystis carinii pneumonia (PCP) if CD4 cell count is < 200 cells/mm3 Allowed: Concurrent maintenance therapy for opportunistic infections. Prior Medication: Required: Zidovudine (AZT), didanosine (ddI), dideoxycytidine (ddC), or a combination thereof, for at least 2 months. Patients must have the following: Diagnosis of AIDS. Documented HIV seropositivity. Ability to give informed consent and willingness to comply with visit schedule and all procedures. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Lymphoma or visceral Kaposi's sarcoma. Active peptic ulcer or bleeding disorder. Hemophilia. Known intolerance to pentoxifylline, theophylline, or caffeine. Concurrent Medication: Excluded: Warfarin and heparin. Biological response modifiers (e.g., erythropoietin, interferon, G-CSF, GM-CSF). Cytotoxic chemotherapy. Megestrol acetate. Corticosteroids. Concurrent Treatment: Excluded: Radiation therapy. Blood products or transfusions. Patients with the following are excluded: Presence of an active opportunistic infection. Major surgery within 30 days of study treatment. Prior Medication: Excluded: Biological response modifiers (including interferon, interleukin), corticosteroids, or megestrol acetate within 14 days of first (screening) TNF level. Erythropoietin dependency or within 30 days of study treatment. Prior Treatment: Excluded: Transfusion or blood product dependency or use within 30 days of study treatment.

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NCT00000647

Inclusion Criteria Each patient must have an identical twin in a normal state of health with a normal screening lab panel and a normal immune profile who is documented to be antibody and culture and polymerase chain reaction (PCR) negative for HIV. Ability to provide informed consent. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Malignancy other than Kaposi's sarcoma. Patients with the following are excluded: Unwillingness to comply with current NIH Clinical Center guidelines concerning appropriate notification of all current sexual partners of an individual regarding his or her positive HIV serostatus and the risk of transmission of HIV infection. Presence of a serious opportunistic infection or other illness or condition that, in the opinion of the principal investigator, warrants exclusion from participation in the study. Current use of illicit drugs or significant amounts of alcohol that, in the opinion of the principal investigator, would interfere with compliance with the study.

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NCT00000648

Inclusion Criteria Concurrent Medication: Allowed: Antiretroviral drugs. Concurrent treatment for opportunistic infections with non-antisyphilitic drugs. Metronidazole, aminoglycosides, trimethoprim / sulfamethoxazole (TMP / SMX), polymyxin, vancomycin, dapsone, pentamidine, acyclovir, antifungals, clindamycin, immunomodulators, and quinolones. Patients must: Have HIV infection. Have presumable or documented neurosyphilis. Be capable of giving informed consent. Have life expectancy of at least 52 weeks. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: History of penicillin or cephalosporin immediate hypersensitivity reaction characterized by angioneurotic edema, hyperemia, urticaria, bronchospasm, and/or anaphylaxis. History of mucosal or blistering rash in response to related treatment. Concurrent Medication: Excluded: Antitreponemal therapy (amoxicillin, doxycycline, tetracycline hydrochloride, erythromycin, procaine penicillin, any beta lactam, or chloramphenicol). Patients with the following are excluded: Other etiology of cerebrospinal (CSF) abnormalities other than HIV and syphilis infection in patients who present with clinical symptoms (this is not required in asymptomatic patients). Prior Medication: Excluded: Treatment for syphilis within 1 year prior to study entry. Antitreponemal therapy (amoxicillin, doxycycline, tetracycline hydrochloride, erythromycin, procaine penicillin, any beta lactam, or chloramphenicol) within 45 days prior to study entry. Unwilling or unable to comply with follow-up schedule, including repeat lumbar punctures.

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NCT00000649

Inclusion Criteria Concurrent Medication: Included: Pneumocystis carinii pneumonia prophylaxis (other than sulfamethoxazole alone or in combination with other medications). Antifungal prophylaxis with oral fluconazole or ketoconazole. Antiviral prophylaxis with a maximum of 1 g/day oral acyclovir. Patients must have the following: HIV infection. Ability to voluntarily provide written informed consent prior to treatment. Willing and able to follow protocol requirements. Patients with nonvisceral Kaposi's sarcoma or with visceral Kaposi's sarcoma not requiring chemotherapy and/or irradiation may be included. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Radiographic evidence of chronic pulmonary disease. Cytomegalovirus disease. Toxoplasmosis encephalitis requiring suppressive therapy. Mycobacteriosis requiring maintenance chemotherapy. Visceral Kaposi's sarcoma requiring chemotherapy and/or irradiation. Concurrent Medication: Excluded: Glucocorticoids and steroid hormones (including oral contraceptives). Dicumarol, warfarin, and other anticoagulant medications. Nitroglycerin. Digitoxin. Valproic acid. Tolbutamide. Doxycycline. Chloramphenicol. Isoniazid. Antiepileptics (Phenobarbital and other barbiturates). Sulfonamides. Excluded for up to 4 hours before and 4 hours after administration of drug 2: Antacids. Cimetidine. Carafate. Cholestyramine resin. Alcohol and alcohol-containing substances. Benzodiazepines (diazepam, triazolam). Patients with the following are excluded: History of clinically important disease (defined as a disease that, in the opinion of the investigator, may either put the patient at risk because of participation in the study or a disease that may influence the results of the study or the patient's ability to participate in the study) other than HIV infection. Malignancy other than Kaposi's sarcoma or limited cutaneous basal cell carcinoma. Prior Medication: Excluded within 4 weeks prior to administration of study drug 2: Antiretroviral (other than zidovudine (AZT)), immunosuppressive, or cytotoxic drugs. Glucocorticoids and steroid hormones (including oral contraceptives). Dicumarol, warfarin, and other anticoagulant medications. Nitroglycerin. Digitoxin. Valproic acid. Tolbutamide. Doxycycline. Chloramphenicol Isoniazid. Antiepileptics (Phenobarbital and other barbiturates). Sulfonamides.

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NCT00000650

Inclusion Criteria Patients must: Have HIV infection. Be asymptomatic (group 1) or have AIDS (group 2). Be able to understand and follow instructions. Concurrent Medication: Allowed: GROUP 2: Anti-HIV therapy. Systemic prophylaxis or maintenance therapy for any AIDS-defining opportunistic infection excluding agents considered immunomodulators or immunosuppressants. Topical nystatin. Clotrimazole troches. Acyclovir. Dapsone. Trimethoprim / sulfamethoxazole (T/S). Fluconazole. Ketoconazole. Aerosolized pentamidine. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: ALL PATIENTS: Known hypersensitivity to disulfiram or diethyldithiocarbamate (DTC). Transfusion dependence. GROUP 1 PATIENTS ONLY: Oral candidiasis documented by morphology or by a response to antifungal therapy. Oral hairy leukoplakia. Occurrence of herpes zoster in a single dermatomal distribution. Recurrent seborrheic dermatitis. Unintentional weight loss in excess of 10 pounds or 10 percent of usual body weight within 2 years prior to study. Unexplained temperature above 38 degrees C on more than 5 consecutive days or on more than 10 days in any 30 days within 2 years of expected study entry. Unexplained diarrhea defined by two or more stools/day for at least 14 days during a 120-day interval. Evidence of clinically significant cardiac, respiratory, hepatic, gastrointestinal, endocrine, hematologic, psychiatric, neurologic, renal, or dermatologic disease as demonstrated by history, physical, and laboratory evaluation. GROUP 2 PATIENTS ONLY: Concurrent neoplasms other than Kaposi's sarcoma or basal cell carcinoma of the skin. Diagnosis of an acute opportunistic infection within 3 weeks of study entry or had treatment initiated for an opportunistic infection within 3 weeks of study entry. Concurrent Medication: Excluded: ALL PATIENTS: Recombinant erythropoietin. GROUP 1: Antiretroviral medications. GROUP 2: Immunomodulators or immunosuppressants. Concurrent Treatment: Excluded: Requirement for blood transfusions more than once a month. Patients with the following prior conditions are excluded: GROUP 1 PATIENTS ONLY: Oral candidiasis documented by morphology or by a response to antifungal therapy. Oral hairy leukoplakia. Occurrence of herpes zoster in a single dermatomal distribution. Recurrent seborrheic dermatitis. Unintentional weight loss in excess of 10 pounds or 10 percent of usual body weight within 2 years prior to study. Unexplained temperature above 38 degrees C on more than 5 consecutive days or on more than 10 days in any 30-day period within 2 years of expected study entry. Unexplained diarrhea defined by two or more stools/day for at least 14 days during a 120-day interval. Evidence of clinically significant cardiac, respiratory, hepatic, gastrointestinal, endocrine, hematologic, psychiatric, neurologic, renal, or dermatologic disease as demonstrated by history, physical, and laboratory evaluation. GROUP 2 PATIENTS ONLY: Diagnosis of an acute opportunistic infection within 3 weeks of study entry or had treatment initiated for an opportunistic infection within 3 weeks of study entry. Prior Medication: Excluded: ALL PATIENTS: Corticosteroids, cytotoxic agents, or immunomodulating agents within 30 days prior to study entry. Chronic Antabuse (disulfiram) therapy. GROUP 1 ONLY: Antiretrovial medications within 1 week prior to study entry. Prior Treatment: Excluded: Transfusion within 7 days of study entry. Radiation therapy within 30 days prior to study entry. Unable to refrain from the use of alcohol for the duration of the study.

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NCT00000651

Inclusion Criteria Concurrent Medication: Required: Zidovudine (AZT) = or > 300 mg/day for 6 weeks prior to study entry. Allowed: Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP), candidiasis, and herpes. 21 day course of adjuvant systemic corticosteroids for moderate to severe PCP. Maintenance treatment with pyrimethamine, sulfadiazine, amphotericin, fluconazole, ketoconazole, acyclovir, ganciclovir, or medications for tuberculosis or Mycobacterium avium for patients who have recovered from toxoplasmosis, cryptococcosis, candidiasis, herpes virus infections, cytomegalovirus infections, tuberculosis or Mycobacterium avium intracellulare. 14 day course of metronidazole. Erythropoietin and megace if clinically indicated. Isoniazid if patient has no peripheral neuropathy at entry and is taking pyridoxine = or > 50 mg/day concomitantly. Phenytoin if patient has < grade 2 peripheral neuropathy at entry and has been stable on phenytoin = or > 3 months. Patients must have: Ability and willingness to give informed consent. Written informed consent from a parent or guardian if < 18 years old. Been tolerating zidovudine (AZT) therapy. Diagnosis of HIV infection. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Kaposi's sarcoma or other malignancy requiring therapy. Active opportunistic infections. Peripheral neuropathy as manifested by complaints of moderate pain, burning, numbness, or tingling in hands/arms or feet/legs; moderate sensory deficit in the upper or lower extremities; or motor weakness in the upper or lower extremities. Concurrent Medication: Excluded: Other experimental medications. Other anti-HIV drugs. Biologic response modifiers. Cytotoxic chemotherapy. Drugs that could cause peripheral neuropathy including phenytoin not specifically allowed, hydralazine, nitrofurantoin, vincristine, cisplatinum, dapsone, disulfiram, and diethyldithiocarbamate. Concurrent Treatment: Excluded: Radiation therapy. Patients with the following are excluded: Active opportunistic infection. Must have ended acute therapy at least 14 days prior to study entry. Peripheral neuropathy = or > grade 2. History of intolerance to 500 to 600 mg/day of zidovudine (AZT) as manifested by the same recurrent grade 3 toxicity requiring dose interruptions and dose reductions to < 500 mg/day or any prior grade 4 toxicity. Prior development of peripheral neuropathy on ddI = or > grade 2. Prior Medication: Excluded: Dideoxycytidine (ddC). Required: Zidovudine (AZT) for total of at least 24 weeks; and included within that time period, AZT = or > 300 mg/day for 6 weeks prior to the study entry.

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NCT00000652

Inclusion Criteria Concurrent Medication: Allowed: Corticosteroids for treatment of lymphocytic interstitial pneumonitis. Concurrent Treatment: Allowed: Intravenous hyperalimentation. Patients must have the following: P-2 class symptomatic HIV infection as defined by CDC OR who are asymptomatic but whose total CD4 cell count is < 500 cells/mm3. Freedom from significant active opportunistic or other infection requiring specific therapy. Part B patients: Prior treatment with zidovudine (AZT) that was discontinued because of hematologic toxicity. Availability of a parent or legal guardian who is sufficiently reliable to give informed consent and follow necessary study procedures including administration of medications and return for follow-up visits. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Critically ill, clinically unstable, or receiving drug therapy for an opportunistic or other infection. History of acute or chronic pancreatitis. Patients with the following are excluded: Critically ill, clinically unstable, or receiving drug therapy for an opportunistic or other infection. History of acute or chronic pancreatitis. Prior Medication: Excluded: Antiretroviral or other antiviral agent within 14 days of entry into study. Immunomodulating agents, cytolytic chemotherapeutic agents, corticosteroids within 30 days (except for lymphocytic interstitial pneumonitis). Part A patients: Zidovudine (AZT) or didanosine (ddI). Part B patients: Didanosine (ddI). Prior Treatment: Excluded: Radiation therapy within 30 days. Intravenous immunoglobulin preparations within 14 days of entry into study.

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NCT00000653

Inclusion Criteria Concurrent Medication: Allowed: Procrit. Amphotericin B (1 mg/kg up to 5 days/week). Prophylaxis treatment as per ACTG recommendations for Pneumocystis carinii pneumonia. Acyclovir (up to 1000 mg/day PO; for > 1000 mg/day PO or for any IV dose, suggest interrupting ddC). Ketoconazole (up to 10 mg/kg/day). Nystatin. Aspirin, acetaminophen, sedatives, and barbiturates (for up to 72 hours). Isoniazid (INH), if there is no evidence of peripheral neuropathy at entry. Children should receive pyridoxine, 25 50 mg/day to avoid possible INH-associated neuropathy. Trimethoprim / sulfamethoxazole (T/S). Immunoglobulin therapy. Aerosolized pentamidine. Drugs with little nephro-, hepato-, cytotoxicity that the patient has been taking and tolerating well for an ongoing condition. Concurrent Treatment: Allowed: Immunoglobulin therapy. Nutritional support (for children with wasting syndrome and/or malnutritional) including hyperalimentation (TPN) of dietary supplements. AMENDED: Patients enrolled in ACTG 051 may participate in ACTG 138 if they show intolerance to AZT or show disease progression after 6 months of AZT therapy and meet entry criteria for the study. ORIGINAL design: Patients enrolled in ACTG protocols 051 or 128 must meet study end points or meet protocol definitions for being permanently off zidovudine (AZT) before enrolling in this protocol. Patients must have the following: Absence of acute opportunistic infection at time of entry. However, if patient is successfully treated for opportunistic infection and has remained stable for 2 weeks after treatment, the patient is then allowed to enter the study. Children receiving maintenance therapy for > 4 weeks are eligible. Parent or guardian available to give written informed consent. Allowed at time of study entry: Prophylaxis treatment as per ACTG recommendations, for Pneumocystis carinii pneumonia (PCP). Immunoglobulin therapy. Prior Medication: AMENDED: AZT or ddI up until study entry, other antiretrovirals up until 4 weeks of study entry Allowed: Zidovudine (AZT) within 4 weeks of entry. Dideoxyinosine (ddI) within 43 weeks of entry if no peripheral neuropathy has been observed while receiving ddI. Other toxicities observed while on ddI must resolve to level 2 or better before patient can begin treatment with ddC. Vitamin, folate, iron supplements. Exclusion Criteria Co-existing Condition: AMENDED: 04-25-91 Additional excluded symptoms and conditions: Symptomatic cardiomyopathy. Seizures which are not well controlled by ongoing anticonvulsant therapy. Active malignancy requiring concomitant chemotherapy. Symptomatic pancreatitis. Grade I or greater peripheral neuropathy. Receiving concomitant zidovudine (AZT). Patients with the following conditions or symptoms are excluded: Acute bacterial infections requiring IV or oral antibiotic treatment at time of entry. Known hypersensitivity to dideoxycytidine (ddC). Concurrent Medication: Excluded: Other antiviral agents, biological modifiers, and investigational medications. Drugs with potential to cause peripheral neuropathy, including chloramphenicol, iodoquinol, phenytoin, ethionamide, gold, ribavirin, vincristine, cisplatin, dapsone, disulfiram, glutethimide, hydralazine, metronidazole, nitrofurantoin. Patients with the following are excluded: Acute bacterial infections requiring IV or oral antibiotic treatment at time of entry. Known hypersensitivity to dideoxycytidine (ddC). Active opportunistic infection requiring treatment with an excluded concomitant medication. Prior Medication: Excluded: Antiretroviral agents (other than zidovudine (AZT) or didanosine (ddI)) within 4 weeks of entry. Immunomodulating agents such as interferons, isoprinosine, or interleukin-2 within 2 weeks of entry. Any other experimental therapy, drugs that cause prolonged neutropenia, significant nephrotoxicity, or peripheral neuropathy within 1 week of entry.

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NCT00000654

Inclusion Criteria Concurrent Medication: Allowed: Pentamidine aerosol for prophylaxis of recurrent Pneumocystis carinii pneumonia (PCP) in patients currently receiving such treatment. Zidovudine (AZT). Prior Medication: Allowed: Zidovudine (AZT) but only if patient has been taking the drug for > 6 weeks at a dose = or < 600 mg/day, and had < 10 percent decrease in hematocrit, neutrophils, and platelets in the last 30 days. Patients must: Have a diagnosis of HIV infection by ELISA or Western blot. Be able to participate as an outpatient. Be ambulatory. Have Grade 0 or 1 AIDS Clinical Trial Group toxicity grades for specified laboratory tests. Be competent to sign informed consent. Be able to cooperate with the treatment plan and evaluation schedule. NOTE: The screening tests must be initiated and completed within 4 weeks prior to the first dose of FIAU, except for diagnostic herpes simplex virus (HSV), varicella zoster (VZV), or cytomegalovirus (CMV) cultures which may have been done previously. Concomitant diseases allowed: Stable mucocutaneous disease. Superficial or uncomplicated infections such as thrush. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: HIV wasting syndrome (involuntary weight loss > 10 percent of baseline body weight and/or chronic diarrhea or weakness and documented fever for at least 30 days). Clinical or x-ray evidence of bronchitis, pneumonitis, pulmonary edema, effusion, or suspected active tuberculosis. Any unstable medical condition including serious infections or cardiovascular, oncologic, renal, or hepatic condition. Primary or initial infection with herpes simplex (HSV), varicella zoster (VZV), or hepatitis B (HBV). Cytomegalovirus (CMV) end organ disease. Kaposi's sarcoma requiring chemotherapy. Systemic fungal infection requiring amphotericin therapy. Diagnosis of idiopathic thrombocytopenic purpura (persistent platelet counts < 100000 platelets/mm3 for = or > 3 months). Patients with the following are excluded: HIV wasting syndrome. Clinical or x-ray evidence of bronchitis, pneumonitis, pulmonary edema, effusion, or suspected active tuberculosis. Any unstable medical condition including serious cardiovascular, infections, oncologic, renal, or hepatic condition. Primary or initial infection with herpes simplex (HSV), varicella zoster (VZV), or hepatitis B (HBV). Cytomegalovirus (CMV) end organ disease. Prior Medication: Excluded within 4 weeks of study entry: Ganciclovir (DHPG). Foscarnet. Interferon. Other drug with putative antiviral activity (except zidovudine (AZT)). Any immunostimulating drug not specifically allowed. Excluded within 1 week of study entry: Acyclovir.

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NCT00000655

Inclusion Criteria Patient must have the following: Presumptive diagnosis of AIDS as defined by the CDC. Untreated Pneumocystis carinii pneumonia (PCP). Willingness and ability to give informed consent. Prior Medication: Allowed: Prophylactic therapy for Pneumocystis carinii pneumonia (PCP) including aerosolized pentamidine or sulfamethoxazole/trimethoprim (SMX/TMP) (at a dose no greater than two DS tablets twice daily). Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Judged by the investigator to be in impending respiratory failure. Malabsorption or vomiting that would, in the judgment of investigator, potentially limit the retention and absorption of an oral therapy. Concurrent bacterial, fungal, or viral pneumonitis, pulmonary Kaposi's sarcoma or other concurrent illness, or chronic pulmonary disease that, in the investigator's opinion, would make interpretation of drug efficacy difficult. Concurrent Medication: Excluded: Corticosteroid treatment (except replacement therapy or patients in Group B). Ganciclovir. Zidovudine (AZT). Investigational agents including antiretroviral agents (didanosine (ddI), dideoxycytidine (ddC), etc.). Drugs likely to have anti-pneumocystis effect such as: Sulfonamides. Pentamidine. Dapsone. Trimethoprim. Other DHFR inhibitors. Primaquine. Clindamycin. Sulfonylureas. Patients with the following are excluded: Judged by the investigator to be in impending respiratory failure. Prior therapy for this episode of PCP or treatment within 4 weeks of entry for a prior episode of PCP. Unable to or refuse to discontinue zidovudine, ganciclovir, or other antiretroviral agents during the 21 day treatment period. Unable to take medication orally or unwilling or unable to take study medication with food. Significant psychosis or emotional disorder such that, in the investigator's opinion, the patient would not be compliant with the study protocol. Prior documented glucose-6-phosphate dehydrogenase (G6PD) deficiency. Prior history of life-threatening toxicity to SMX/TMP such as severe rash or Stevens-Johnson syndrome. Prior Medication: Excluded: Prior therapy for this episode of Pneumocystis carinii pneumonia (PCP) or treatment within 4 weeks for a prior episode of PCP. Blood transfusions.

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NCT00000656

Inclusion Criteria Concurrent Medication: Allowed: Aerosolized pentamidine. Acute and intermittent therapy with mycostatin and mycelex. Isoniazid, if no alternative therapy is available. Allowed for up to 2 weeks: Acyclovir for Herpes infection (withhold didanosine during therapy). Acute therapy with fluconazole or ketoconazole. Allowed but preferably not on a continuous basis for > 72 hours: Acetaminophen. Ibuprofen. Nonsteroidal antiinflammatory agents. Patients must be: HIV antibody positive. Asymptomatic or have persistent generalized lymphadenopathy. Diagnosed with one of the listed coagulopathies. OR Sexual partner of someone with the above criteria. Allowed: Basal cell carcinoma or in situ carcinoma of the cervix. NOTE: As of January, 1991 full accrual of patients with prior AZT use has been reached - NOW ACCRUING ONLY THOSE WITH NO PRIOR AZT USE. Hemophilia restriction has been lifted. Prior Medication: Allowed: Zidovudine (AZT) for a total of = or < 13 months. NOTE: As of January, 1991 accrual of these patients was reached, NOW ONLY PATIENTS WITH NO PRIOR AZT. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Unexplained temperature > 38 degrees C for more than 5 consecutive days or on more than 10 days in any 30-day period in the 2 years prior to study entry. Unexplained diarrhea defined as at least 3 liquid stools/day persisting more than 7 days within 2 years prior to study entry. Unintentional weight loss of > 10 pounds or > 10 percent of usual body weight within 2 years prior to study entry. Oral hairy leukoplakia at any time prior to study entry. Recurrent oral candidiasis unrelated to the use of antibiotics within 2 years prior to entry or unrelated to the use of antibiotics within the past 3 months. Herpes zoster within 2 years prior to study entry. Seizures within the past 6 months or currently requiring anticonvulsants for control. Current heart disease. Current psychological or emotional problems sufficient in the investigator's opinion to prevent adequate compliance with study therapy. Gout. Concurrent Medication: Excluded: Rifampin. Chemoprophylaxis for Pneumocystis carinii pneumonia other than aerosolized pentamidine. Intravenous pentamidine. Other antiretroviral agents, experimental medication, biological response modifiers, systemic corticosteroids, cimetidine, and ranitidine. Barbiturates. Oral acidifying agents. Patients with a history of any of the following are excluded: AIDS-defining opportunistic infection, advanced AIDS-related complex, or malignancy. Acute or chronic pancreatitis. Grade 2 or higher neuropathy based on the Neuropathy Targeted Symptom Questionnaire. Seizures. Zidovudine therapy for = or > 13 months. Heart disease. Psychological or emotional problems sufficient in the investigator's opinion to prevent adequate compliance with study therapy. Gout. Prior Medication: Excluded within 4 weeks of study entry: Antiretroviral agents, including ribavirin, HPA-23, rifampin, AL721. Excluded within 3 months of study entry: Significant course of immunomodulating agents, such as steroids (> 1 week), isoprinosine, thymic factors, or any other experimental drugs. Excluded within 30 days prior to study entry: Neurotoxic drugs. Excluded: Didanosine (ddI). Dideoxycytidine (ddC). Zidovudine (AZT) if received for > 13 months. Prior Treatment: Excluded within 3 months of entry: Other experimental therapy. History of recent alcohol abuse.

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NCT00000657

Inclusion Criteria Concurrent Medication: Allowed: Chronic suppressive therapy for herpes simplex virus, cytomegalovirus, Candida albicans, and Salmonella. Prophylactic therapy for Pneumocystis carinii pneumonia. Maintenance anticonvulsant therapy following a seizure in the context of the AIDS dementia complex. Isoniazid only if no acceptable alternative therapy is available. Judicious use of benzodiazepines, tricyclics, and other antidepressants is allowed but a stable dose level should be obtained prior to entry and maintained throughout the trial. In patients for whom it is medically necessary to initiate or alter therapy with these drugs during the initial 16 week study period, data will not be used in the study. Metronidazole for single courses of therapy not to exceed 14 days within consecutive 90-day intervals, the first of which begins at the initiation of the study. Erythropoietin for patients under the relevant Treatment IND. Symptomatic therapies (such as analgesics, antihistamines, antiemetics, antidiarrheal agents). Allowed but not encouraged: trimethoprim /sulfamethoxazole (T/S) or other sulfonamides. Patients must have the following: Screened for other causes of dementia. Stage 1, 2, or 3 AIDS dementia complex. Estimated premorbid IQ of at least 70. Anti-HIV antibody or HIV in blood and/or cerebrospinal fluid. If prior history of positive syphilis serology, should have been treated with appropriate course of antibiotics; if not, such treatment should be administered prior to pretreatment screening. Not have previously shown intolerance to zidovudine (AZT). Able (or parent and/or guardian able) to provide written consent. Allowed: Basal cell carcinoma, in situ carcinoma of the cervix, Kaposi's sarcoma without evidence of visceral involvement or not requiring systemic chemotherapy. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Grade 3 neuropathy, based on the Neuropathy Targeted Symptom. Questionnaire, or patients with any moderate abnormality indicative of peripheral neuropathy including stocking loss of sensation (to sharp pain, light touch, or vibration), distal extremity weakness (< 4/5), or absent ankle jerks. History of present or past acute or chronic pancreatitis. Active, symptomatic AIDS-defining opportunistic infection and requiring any ongoing maintenance therapy for confounding neurologic disease. Severe premorbid psychiatric illness including bipolar illness, schizophrenia, and electroconvulsive therapy. Previous neurological disease unrelated to HIV infection: multiple sclerosis, documented stroke, degenerative disease. Patients with chronic seizure disorders or head injury will only be excluded if the condition results in functional impairment or is likely to interfere with the evaluation. Concurrent or previous central nervous system infections or neoplasms as revealed by Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) scan or cerebrospinal fluid analysis (such as toxoplasmosis, primary or metastatic Central Nervous System (CNS) lymphoma, progressive multifocal leukoencephalopathy, cryptococcal or other fungal meningitis, tuberculous Central Nervous System (CNS) infections, and untreated neurosyphilis). Concurrent Medication: Excluded: Intravenous pentamidine. DHPG (Ganciclovir) should not be co-administered. Monoamine oxidase (MAO) inhibitors, phenothiazines, butyrophenones, barbiturates, amphetamines. Oral acidifying agents. Patients with the following are excluded: Neoplasms not specifically allowed. Grade 3 neuropathy. History of present or past acute or chronic pancreatitis. Active, symptomatic AIDS-defining opportunistic infection. Requiring any ongoing maintenance therapy for confounding neurologic disease. Conditions listed under Exclusion Co-existing Conditions. Prior Medication: Excluded within 30 days of study entry: Anti-HIV therapy other than zidovudine (AZT). Biologic response modifiers. Corticosteroids. Drugs toxic to peripheral nerves. Investigative drugs. Neurotoxic drugs. Excluded: Dideoxycytidine (ddC). Active alcohol or drug abuse or methadone maintenance sufficient, in the investigator's opinion, to prevent adequate compliance with study therapy and evaluations.

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NCT00000658

Inclusion Criteria Concurrent Medication: Required: PCP prophylaxis with Bactrim, aerosolized pentamidine, or dapsone. Allowed: ddI, except when patient is also taking allopurinol. Patients must have the following: Diagnosis of HIV seropositivity and non-Hodgkin's lymphoma. Ability to give informed consent and willingness to comply with all procedures and visit schedule. If between ages of 12 and 18 must receive care under direct supervision of a pediatric oncologist, and have consent of parent, guardian, or person with power of attorney. Participation in clinical trials of other antiretroviral agents is at the discretion of the investigator and individual patient. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Active opportunistic infection, excluding Mycobacterium avium complex, requiring antibiotic therapy. Another prior or current malignancy, excepting curatively treated cervical or basal cell carcinoma. Kaposi's sarcoma if rapidly progressive, with visceral involvement, or causing peripheral edema. Primary central nervous system lymphoma. Concurrent Medication: Excluded: Zidovudine (AZT) or any antiretroviral agent unless allowed by investigator. ddI is allowed except when also taking allopurinol. Systemic myelosuppressive drugs, including trimethoprim/sulfamethoxazole (T/S), pyrimethamine/sulfa, or ganciclovir. - Patients with the following are excluded: Active opportunistic infection, excluding Mycobacterium avium complex, requiring antibiotic therapy. Another prior or current malignancy, excepting curatively treated cervical or basal cell carcinoma. Kaposi's sarcoma if rapidly progressive, with visceral involvement, or causing peripheral edema. Primary central nervous system lymphoma. Prior Medication: Excluded: Immunomodulating agents within 2 weeks of study entry. Prior Treatment: Excluded: Chemotherapy. Radiation therapy as outlined in protocol.

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NCT00000659

Inclusion Criteria Concurrent Medication: Allowed: Nystatin or clotrimazole for suppression of oral thrush. Aerosolized pentamidine as chemoprophylaxis for Pneumocystis carinii pneumonia (PCP). Trimethoprim / sulfamethoxazole (TMP / SMX) for patients who are clinically and hematologically stable on TMP / SMX PCP prophylaxis. Patients must have the following: Diagnosis of AIDS or advanced AIDS related complex (ARC). CD4 cell count < 300 cells/mm3. Ability to understand and sign the consent form. Risk Behavior: Allowed: History of drug abuse with current abstinence or enrollment in a methadone treatment program. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Malignancies other than Kaposi's sarcoma. AIDS dementia which, in the opinion of the investigator, precludes patients from giving fully informed consent or from complying fully with the requirements of this protocol. Active infection with an opportunistic pathogen requiring ongoing therapy. Preexisting antibodies to rCD4. Concurrent Medication: Excluded: Investigational drugs. Antiretroviral agents such as dextran sulfate or AL721. Cytotoxic chemotherapy. Concurrent Treatment: Excluded: Radiation therapy. Patients with the following are excluded: Malignancies other than Kaposi's sarcoma. AIDS dementia which, in the opinion of the investigator, precludes patients from giving fully informed consent or from complying fully with the requirements of this protocol. Active infection with an opportunistic pathogen requiring ongoing therapy. Preexisting antibodies to rCD4. Prior Medication: Excluded: Zidovudine (AZT) for longer than 30 days or prior treatment with AZT for < 30 days if discontinued for toxicity due to AZT. Excluded within 30 days of study entry: Immunomodulators. Previous participation in any group of another part of this study. For example, patients treated in Part 1A of this study may not reenter the study to be treated in Part 2. Chemotherapy. Prior Treatment: Excluded within 30 days of study entry: Radiation therapy. Active use of illicit drugs or abuse of alcohol at time of protocol entry.

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NCT00000660

Inclusion Criteria Concurrent Medication: AMENDED: 04-21-91 Zidovudine (AZT) allowed after completing 8 weeks on the study. Patients on reduced doses of VP-16 must have tolerated at least 4 consecutive weeks at the reduced dose before starting AZT. Zidovudine will not be provided by the NIAID Clinical Product Research Repository. AMENDED: Zidovudine (AZT) allowed after completing 12 weeks on study. Allowed: Aerosolized pentamidine for Pneumocystis carinii pneumonia prophylaxis (PCP). Concurrent Treatment: Allowed: Local radiotherapy or laser therapy to cosmetically apparent, non-indicator lesions provided the dose to any one lesion does not exceed 300 rads and the total surface area of all lesions treated does not exceed 10 cm2. Risk Behavior: Allowed: All risk groups. Patients must: Have AIDS-related Kaposi's sarcoma. Be ineligible for protocols of higher priority at study center. Be willing to sign an informed consent or have guardian willing to sign. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Active opportunistic infection not specifically allowed. Concurrent neoplasm not specifically allowed. Significant neurologic, cardiac, or liver disease. Concurrent Medication: Excluded: Therapy with potentially myelosuppressive, hepatotoxic, or nephrotoxic drugs for an opportunistic infection. Patients with the following are excluded: Active opportunistic infection not specifically allowed. Ongoing therapy, including maintenance therapy, for an opportunistic infection with potentially myelosuppressive, hepatotoxic, or nephrotoxic drugs. Concurrent neoplasm not specifically allowed. Significant neurologic, cardiac, or liver disease. Prior Medication: Excluded: Biologic response modifiers or corticosteroids within 14 days prior to study entry. Cytotoxic chemotherapy within 30 days prior to study entry. Ribavirin within 6 weeks prior to study entry. Azidothymidine (AZT), alpha-interferon, didanosine (ddI), ganciclovir (DHPG), or any other antiretroviral drugs within 1 week prior to study entry. Prior Treatment: Excluded within 30 days prior to study entry: Radiation therapy with > 4000 rads. Total skin electron beam therapy.

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NCT00000661

Inclusion Criteria Concurrent Medication: Required: Stable prescribed dosage of zidovudine (AZT), = or > 500 mg/day. Allowed: Prophylaxis for Pneumocystis carinii pneumonia (PCP) with aerosolized pentamidine. Erythropoietin. Patients must be: HIV positive by ELISA and Western blot. Currently taking a stable prescribed dosage of 500 mg/day of zidovudine (AZT). Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Allergy to benzodiazepines or a previously documented intolerance to zidovudine (AZT) therapy of = or < 600 mg/day. Significant underlying medical condition that could impair continuous participation in study. Malabsorption syndrome (3 or more loose stools a day for at least 4 weeks associated with an unintentional weight loss of at least 10 percent of body weight). Concurrent Medication: Excluded: Oral contraceptives. Cytotoxic chemotherapy. Ganciclovir. Flucytosine. Probenecid. Opiates. Valproic acid. Sulfa drugs. Sucralfate. Dapsone. Rifampin. Antacids within 2 hours of zidovudine (AZT) dose. Isoniazid. Ketoconazole. Pyrimethamine. Clindamycin. Aspirin. Ibuprofen. Investigational drugs not specifically allowed. Patients with the following are excluded: Allergy to benzodiazepines or a previously documented intolerance to zidovudine (AZT) therapy of = or < 600 mg/day. Significant underlying medical condition that could impair continuous participation in study. Unable to take oral medication reliably. Prior Medication: Excluded within 30 days of study entry: Antiretroviral agents other than zidovudine (AZT).

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NCT00000662

Inclusion Criteria Concurrent Treatment: Allowed: Blood transfusions for hematologic toxicity. Criteria for children 3 months to less than 15 months of age: Patient must be HIV antibody-positive by repeated reactive screening test (e.g., ELISA) and positive confirmatory test (e.g., Western blot). OR If antibody-negative, patient must have two positive p24 antigen determinations performed at least one week apart or have had a positive HIV culture. Patients must meet two of the following criteria: Be HIV culture positive or p24 antigen positive. Have at least one of the Class P-2 symptoms (by CDC criteria). Be immunosuppressed defined as having: CD4+(T4) lymphocytes = or < 400 cells/mm3. Abnormal age adjusted immunoglobulin levels (IgG or IgA). Decreased helper/suppressor ratio < 1.0. Note: In general, abnormal values for any of the above lab tests should be confirmed in 2 measurements at least 1 week apart, and other clinical causes for these abnormalities should be ruled out. Criteria for children 15 months to 12 years of age: Patient must be HIV antibody-positive by repeated reactive screening test (e.g., ELISA) and positive confirmatory test (e.g., Western blot). OR If antibody-negative, patient must have two positive p24 antigen determinations performed at least one week apart or have had a positive HIV culture. Patients must meet one of the following criteria: Have at least one of the class P-2 symptoms (by CDC criteria). Be immunosuppressed defined as having CD4+(T4) lymphocytes = or < 400 cells/mm3, based on two measurements at least 1 week apart. Exclusion Criteria Co-existing Condition: Patients with known hypersensitivity to AZT are excluded. Patients with the following are excluded: Failure to meet inclusion criteria. Inability to obtain signed informed consent from a parent or legal guardian. Enrollment in another treatment protocol that expressly prohibits concomitant treatment with zidovudine (AZT). Enrollment in another clinical trial in which AZT is a treatment. Known hypersensitivity to AZT.

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NCT00000663

Inclusion Criteria Patients must have the following: HIV-1 infection, or if less than 15 months old, born to mother with HIV-1 infection. Legally qualified guardian with the ability to sign a written, informed consent form. Willingness to abstain from all other experimental therapy for HIV-1 infection during the first 12 weeks of the study period. Anticipated life expectancy of at least 3 months. Prior Medication: Allowed: Prophylactic anti-Pneumocystis carinii pneumonia (PCP) or antifungal therapy. Gamma globulin as prophylaxis for measles and varicella. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Past or present history of neurological abnormalities including withdrawal syndrome or seizures. Past or present history of any serious active opportunistic infection including Pneumocystis carinii pneumonia (PCP). Echocardiogram values > 2 standard deviations from normal. Hematologic, renal, or hepatic insufficiency. Concurrent Medication: Excluded: Zidovudine (AZT). Intravenous gamma globulin (IVIG) except as prophylaxis for measles and varicella. Cancer chemotherapy. Corticosteroids. Other known immunomodulatory agents. Other experimental therapy not specifically allowed. Patients with the following are excluded: Hematologic, renal, or hepatic insufficiency. Past or present history of any serious active opportunistic infection. Prior Medication: Excluded for a minimum of 3 weeks prior to study entry: Zidovudine (AZT). Intravenous gamma globulin (IVIG). Cancer chemotherapy. Immunomodulatory agents. Acyclovir and other experimental therapy. Risk Behavior: Excluded: Patients born to substance abusing mothers (including alcohol) during the pregnancy.

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NCT00000664

Inclusion Criteria Concurrent Medication: Allowed: Prophylactic pentamidine for Pneumocystis carinii pneumonia (PCP). Topical steroids. Patients must: Be HIV positive. Fit one of the zidovudine use groups listed in Disease Status. Be able to give informed consent. Allowed: Basal cell carcinoma of the skin, in situ carcinoma of the cervix, Kaposi's sarcoma. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Major organ allograft. Significant cardiac disease or central nervous system lesions. Known previous intolerance to zidovudine (AZT) at 500 mg/day. Active opportunistic infections. Score of > 0.5 on the ACTG AIDS dementia complex staging test. Any focal abnormality on neurologic exam. Concurrent Medication: Excluded: Chemotherapy, hormonal therapy, or other immunotherapy. Other investigational drugs, agents, or devices. Beta-blockers. Steroids other than topical. Antihypertensive medication other than diuretics. Concurrent Treatment: Excluded: Radiation therapy. Patients with the following are excluded: History of seizures. Concurrent neoplasms not specifically allowed. Concomitant conditions listed in Exclusion Co-existing Conditions. Prior Medication: Excluded within 30 days prior to study entry: Anti-HIV medication other than zidovudine (AZT). Immunomodulators. Systemic steroids. Interferons. Interleukins. Other chemotherapy. Prior Treatment: Excluded within 30 days prior to study entry: Radiation therapy. Excluded within 4 weeks prior to study entry: Groups B, C, D Transfusions. Active substance abuse.

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NCT00000665

Inclusion Criteria Concurrent Medication: Allowed: Topical anti-Herpesvirus agents. Zidovudine (AZT) for patients in deferral or foscarnet treatment groups: 100 mg every 4 hours. For patients on ganciclovir: 100 mg every 8 hours. Dideoxyinosine (ddI) and other antiretroviral available via expanded access programs, investigational triazoles, granulocyte-macrophage colony-stimulating factor, and erythropoietin to treat marrow toxicity. The use of other investigational drugs will be considered on a drug by drug basis. It is not recommended that patients receiving ganciclovir take AZT simultaneously. If AZT is prescribed for patients taking ganciclovir, it should be prescribed at reduced doses and discontinued if hematologic toxicity develops. Patients must have: Diagnosis of AIDS by CDC criteria or a documented HIV infection. Cytomegalovirus (CMV) retinitis that does not require surgical intervention diagnosed in one or both eyes by a SOCA-certified ophthalmologist. The means available for compliance with follow-up visits (including a caregiver if necessary). Must consent to study or consent of parent or guardian if less than 18 years of age. Willingness to take reduced dose of zidovudine (AZT) if dictated by treatment assignment. Willingness to discontinue other systemic treatments for Herpesvirus infections while receiving foscarnet or ganciclovir. Prior Medication: Allowed: Zidovudine (AZT). Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Sufficient media opacities to preclude fundus photographs in both eyes. Concurrent Medication: Excluded: Other systemic treatments for Herpesvirus infections. Other anti-cytomegalovirus therapy. Excluded with foscarnet: Parenteral pentamidine, amphotericin B, or aminoglycosides. Use of marrow toxic agents with ganciclovir and nephrotoxic agents with foscarnet is discouraged, and alternative treatment should be used whenever possible. Patients with the following are excluded: Sufficient media opacities to preclude fundus photographs in both eyes. Known or suspected allergy to one of the study medications. Prior Medication: Excluded: Foscarnet or ganciclovir used previously to treat cytomegalovirus (CMV) retinitis. Excluded within 14 days of study entry: CMV hyperimmunoglobulin or other anti-CMV agents. Excluded within the past 28 days: Anti-CMV therapy. Active intravenous drug or alcohol abuse, sufficient in the investigator's opinion to prevent adequate compliance with study therapy and follow-up.

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NCT00000666

Inclusion Criteria Concurrent Medication: Required: Prophylactic treatment for Pneumocystis carinii pneumonia with aerosolized pentamidine, dapsone, or trimethoprim / sulfamethoxazole. Allowed: Most medications not specifically excluded. Prior Medication: Allowed: Antivirals. Antiretrovirals. Patients: Must be HIV positive or have an AIDS-defining illness OR be at known risk for HIV infection and have a CD4 cell count < 200/mm3 and no other known immunosuppressive disease. Must have positive titer for Toxoplasma gondii. Must be or become a patient of a CPCRA physician. May participate in other clinical trials as long as there is no potential activity against Toxoplasma gondii or cross-toxicity among study drugs. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: History of ocular, pulmonary, or central nervous system (CNS) toxicity. CNS lesions. Neurologic deficits except peripheral neuropathy. Mild, moderate, severe, or end-stage AIDS dementia complex. Grade 3 or higher nausea and/or vomiting. Sensitivity to pyrimethamine. Concurrent Medication: Excluded: On-going therapy with clindamycin, fansidar, methotrexate, trimetrexate, spiramycin, azithromycin, clarithromycin, 566C80, and/or sulfa agents other than anti-PCP agents. Patients with the following are excluded: History of ocular, pulmonary, or central nervous system (CNS) toxicity. CNS lesions or history of CNS lesions. Neurologic deficits except peripheral neuropathy. Mild, moderate, severe, or end-stage AIDS dementia complex. Grade 3 or higher nausea and/or vomiting. Sensitivity to pyrimethamine.

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NCT00000667

Inclusion Criteria Concurrent Medication: Allowed: Acute use (< 14 days) of acyclovir for Herpes simplex virus infections or ketoconazole for symptomatic Candida infections. Patients must have the following: Asymptomatic HIV seropositivity. Patients with CD4 counts of 400 - 500 cells/mm3 must be informed of the recommended zidovudine (AZT) therapy and sign an informed consent statement declining AZT therapy. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Systemic symptoms other than lymphadenopathy thought to be due to HIV infection including: Fatigue/malaise of > 1 month duration that interferes with normal activities. Fever of > 100 degrees F persisting for > 15 in a 30-day interval without definable cause. Involuntary weight loss in excess of 10 pounds or > 10 percent of normal weight within a 6-month interval. Diarrhea (> 3 stools/day) persisting for more than 30 days without definable cause. Recurrent oral candidiasis. Multidermatomal herpes zoster. Biopsy proven hairy leukoplakia. Evidence of clinically significant central nervous system dysfunction as assessed by neurological exam. Concurrent Medication: Excluded: Antiretroviral agents of proven or potential efficacy. Any potential immunoenhancing or immunosuppressive drugs. Patients with the following are excluded: Known hypersensitivity to insect cells or baculovirus. Abnormal chest x-ray taken within 3 months of study entry. Systemic symptoms other than lymphadenopathy thought to be due to HIV infection as listed in the patient exclusion coexisting diseases or complications. Evidence of clinically significant central nervous system dysfunction as assessed by neurological exam. Unwilling or unable to give written informed consent. Prior Medication: Excluded within 90 days of study entry: Zidovudine (AZT). Didanosine (ddI). Any potential antiretroviral. Immunomodulating agents. Active substance abuse (either continuing daily alcohol abuse or intravenous drug use).

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NCT00000668

Inclusion Criteria Concurrent Medication: Allowed: Topical acyclovir. There are two groups of patients. Group A must have: Confirmation of HIV infection by HIV antibody testing, p24 antigen, or culture of HIV. A positive urine culture for cytomegalovirus (CMV) within 4 weeks of study entry. Not received prior ganciclovir therapy. Group B must have: A diagnosis of AIDS by CDC criteria. CMV retinitis diagnosed on funduscopic evaluation by an ophthalmologist. Completed 4 weeks of intravenous ganciclovir with an improvement or stabilization of retinitis. The course of therapy should include a minimum of 24 days total of intravenous ganciclovir. Patients in both groups must understand the nature of the study, agree to the tests required in the protocol, and must understand and sign an informed consent form approved by the appropriate Institutional Review Board (IRB) and by Syntex. Required: Group B: 4 weeks of intravenous ganciclovir which should include a minimum of 24 days total of intravenous ganciclovir. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Macular involvement due to cytomegalovirus (CMV) retinitis in both eyes. Active CMV retinitis in which there is progression. Presence of diarrhea or other clinically significant or uncontrolled gastrointestinal disease including persistent nausea and/or abdominal pain. Diarrhea is defined as > 3 unformed stools/day. Dementia or decreased mentation or other encephalopathic signs and symptoms which would interfere with the ability of the patient to follow the protocol, to take assigned dose regimen reliably, and to keep a daily record on a calendar. Significant CMV disease of other organs, including CMV gastroenteritis or CMV pneumonia. Concurrent Medication: Excluded: Any investigational drug. Acyclovir not specifically allowed. Any other nucleoside analog. Zidovudine (AZT). Probenecid. Aspirin. Patients with the following are excluded: Macular involvement due to cytomegalovirus (CMV) retinitis in both eyes. Active CMV retinitis in which there is progression. CMV end organ disease. Presence of diarrhea or other clinically significant or uncontrolled gastrointestinal disease including persistent nausea and/or abdominal pain. Diarrhea is defined as > 3 unformed stools/day. Dementia or decreased mentation or other encephalopathic signs and symptoms which would interfere with the ability of the patient to follow the protocol, to take assigned dose regimen reliably, and to keep a daily record on a calendar. Significant CMV disease of other organs, including CMV gastroenteritis or CMV pneumonia. Prior Medication: Excluded within 4 days of study entry: Antimetabolite. Interferon. Other nucleoside analog including zidovudine (AZT). Excluded for Group A: Ganciclovir or other anti-cytomegalovirus therapy.

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NCT00000669

Inclusion Criteria Concurrent Medication: Allowed: Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis if this drug is extended to children. Acute therapy not exceeding 7 days with oral or intravenous acyclovir for herpes simplex infections. Trimethoprim / sulfamethoxazole for Pneumocystis carinii infections during course of study at discretion of investigator after discussion with the sponsor. Symptomatic therapy with analgesics, antihistamines, antiemetics, antidiarrheal agents, or other supportive therapy as deemed necessary by the principal investigator. Patients must have: Diagnosis of AIDS as defined by CDC or meeting CDC P2 classification. Patients must be free of opportunistic infection or other serious bacterial, fungal, or parasitic infection at time of entry into study. Life expectancy > 6 months. Parent or guardian (and patient as applicable) able to give informed consent. Available for follow-up for at least 6 months. Allowed: Hemophilia. Exclusion Criteria Co-existing Condition: Children with the following are excluded: Chronic hematologic disorders unrelated to coagulation defects, hemoglobinopathies, or ITP. Intractable diarrhea. No venous access. History of seizures within previous 2 years or currently requiring anticonvulsants for control. Currently active heart disease as evidenced by a cardiac arrhythmia or other significant abnormality on routine electrocardiography (ECG) or shortening fraction of < 10 percent on echocardiogram. Renal disease. Any other clinical condition that in the opinion of the investigator makes the patient unsuitable for study. Concurrent Medication: Excluded: Antiretroviral drugs. Zidovudine (AZT). AL 721. Interferon. Corticosteroids. Immunomodulating drugs. Other systemic investigation agent. Ribavirin. Rifampin, barbiturates, or any other potent inducer or inhibitor of drug-metabolizing enzymes. Cytotoxic anticancer therapy. H-2 blockers. Intravenous ketoconazole. Immunoglobulin preparations. Children with the following are excluded: Chronic hematologic disorders unrelated to coagulation defects, hemoglobinopathies, or ITP. Intractable diarrhea. No venous access. History of seizures within previous 2 years or currently requiring anticonvulsants for control. Currently active heart disease as evidenced by a cardiac arrhythmia or other significant abnormality on routine electrocardiography (ECG) or shortening fraction of < 10 percent on echocardiogram. Renal disease. Any other clinical condition that in the opinion of the investigator makes the patient unsuitable for study. Renal disease. Prior Medication: Excluded: Any prior therapy which in the opinion of the investigator would make the patient unsuitable for study. Excluded within 2 weeks of study entry: Trimethoprim / sulfamethoxazole. Excluded within 1 month of study entry: Study drug or other antiretroviral drug or systemic investigational agent. Any agent known as a potent inducer or inhibitor of drug metabolizing enzymes. H-2 blockers. Ketoconazole. Immunoglobulin preparations. Excluded within 3 months of study entry: Ribavirin. Excluded: Zidovudine (AZT) for > 6 months. Cytotoxic anticancer therapy. Prior Treatment: Excluded within 4 weeks of study entry: Blood transfusion. Lymphocyte transfusions for immune reconstitution. Bone marrow transplant.

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NCT00000670

Inclusion Criteria Concurrent Medication: Allowed: Interferon. Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis. Concurrent Treatment: Allowed: Radiation for skin lesions. Patients with symptomatic HIV infection taking zidovudine (AZT) five or six times a day as therapy. Includes patients with AIDS who have history of cytologically confirmed Pneumocystis carinii pneumonia (PCP), patients with advanced AIDS related complex (ARC), and HIV antibody positive patients. Patients must be able to give written informed consent. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Allergy to probenecid. Any underlying medical condition sufficient, in the investigator's opinion, to prevent adequate compliance with study therapy. History of urinary tract urate stones or gout. Becoming acutely ill, unstable, or febrile. Concurrent Medication: Excluded: Methotrexate. Antiretroviral drugs. Ganciclovir. Amphotericin. Experimental drugs. Isoniazid. Pyrazinamide. Flucytosine. Intravenous pentamidine. Dapsone. Fansidar. Antineoplastic drugs not specifically allowed. Trimethoprim / sulfamethoxazole. Valproic acid. Opiates. Rifampin. Sulfonylureas. Concurrent Treatment: Excluded: Radiation not specifically allowed. Patients with the following are excluded: Allergy to probenecid. Any underlying medical condition sufficient, in investigator's opinion, to prevent adequate compliance with study therapy. History of urinary tract urate stones or gout. Becoming acutely ill, unstable, or febrile.

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NCT00000671

Inclusion Criteria Concurrent Medication: Required: Aerosolized pentamidine (300 mg every 4 weeks). Allowed: Chronic suppressive treatment for toxoplasmosis, Pneumocystis carinii pneumonia (PCP), cryptococcal meningitis, herpes simplex virus infection. Ganciclovir for patients developing cytomegalovirus (CMV) infection while in study. Erythropoietin for patients under the relevant treatment IND. Treatment of opportunistic infections with other than sulfonamide-containing regimens. Aspirin, acetaminophen, or non-steroidal anti-inflammatory agents is discouraged, but is permitted for as short a period of time as possible. Chronic use of trimethoprim - sulfamethoxazole or other sulfonamide preparations is not encouraged while on study. Patients must: Have had the diagnosis of AIDS or advanced AIDS related complex (ARC). Have received AZT therapy for at least 12 months, with a minimal daily dose of 500 mg/day and with no more than 60 days off AZT therapy within the 12 month period; medical records with documentation of AZT dosing must be provided. Provide informed consent (guardian as appropriate). Be available for follow-up for at least 6 months. Have the inclusion laboratory values within approximately 14 days of initiating therapy (except for CD4 cell counts). Patients whose AIDS-defining condition is Kaposi's sarcoma alone must have CD4 cell counts < 300 cells/mm3. Allowed: Positive blood culture for Mycobacterium avium or Cytomegalovirus. Prior history of toxoplasmosis, Herpes simplex, Cryptococcus, or Pneumocystis carinii pneumonia (PCP) requiring chronic suppressive therapy. Occasional premature atrial or ventricular contractions. Prior Medication: Required: Zidovudine (AZT) therapy for at least 12 months, with a minimal daily dose of 500 mg/day, and with no more than 60 days off AZT therapy within the 12-month period (documentation of AZT dosing must be provided). Allowed: Intralesional agents. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Psychological or emotional problems sufficient, in the investigator's opinion, to prevent adequate compliance with study therapy. AIDS-dementia complex = or > stage 2. Active AIDS defining opportunistic infections not specifically allowed. Intractable diarrhea. Grade 2 neuropathy, based on the Neuropathy Targeted Symptom Questionnaire, or any moderate abnormality indicative of peripheral neuropathy, particularly impaired sensation of sharp pain, light touch, or vibration in the lower extremities, distal extremity weakness, or distal extremity hyperreflexia. Prior history of acute pancreatitis within past 2 years or chronic pancreatitis. History of seizures within past 2 years or currently requiring anticonvulsants for control. History of past or current heart disease. Malignancy likely in the investigator's opinion to require cytotoxic chemotherapy during the expected course of this trial. Life expectancy < 3 months. Concurrent Medication: Excluded: Isoniazid (INH). Neurotoxic drugs. Oral acidifying agents. Patients with the following are excluded: Psychological or emotional problems sufficient, in the investigator's opinion, to prevent adequate compliance with study therapy. AIDS-dementia complex = or > stage 2. Active AIDS defining opportunistic infections not specifically allowed. Intractable diarrhea. Prior history of acute pancreatitis within past 2 years or chronic pancreatitis. History of seizures within past 2 years or currently requiring anticonvulsants for control. History of past or current heart disease. Malignancy likely in the investigator's opinion to require cytotoxic chemotherapy during the expected course of this trial. Life expectancy = or < 3 months. Previous participation in any study of ddI, ddC or d4T. Prior Medication: Excluded: Ganciclovir (DHPG). Excluded within 1 month of study entry: ddI and any other antiretroviral drug or investigational anti-HIV agent except for zidovudine (AZT). Interferons. Immunomodulating drugs. Cytotoxic agents not specifically allowed. Neurotoxic drugs. Excluded within 3 months of study entry: Ribavirin. Prior Treatment: Excluded within 14 days of study randomization: Blood transfusion. Active alcohol or drug abuse that is sufficient, in investigator's opinion, to prevent adequate compliance with study therapy.

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NCT00000672

Inclusion Criteria Concurrent Medication: Required: Aerosolized pentamidine (300 mg every 4 weeks). In the event of physiological intolerance, alternative PCP prophylaxis may be trimethoprim/sulfamethoxazole 1 DS tab per day or dapsone 50 - 100 mg per day. Allowed: Chronic suppressive treatment for toxoplasmosis, Pneumocystis carinii pneumonia (PCP), cryptococcal meningitis, herpes simplex virus, cytomegalovirus, coccidioidomycosis, and histoplasmosis (absorption of ketoconazole or dapsone may be inhibited if given at the same time as the buffered solution of ddI, and should be taken 2 hours before or 2 hours after taking ddI; oral acidifying agents are not allowed). Isoniazid is permitted only if no acceptable alternative therapy is available. Metronidazole may be used for single courses not to exceed 14 days within consecutive 90 day intervals, the first of which begins at the initiation of the study. Erythropoietin for patients under the relevant treatment IND. Intravenous acyclovir for short courses of therapy. Patients must: Have documented hematologic intolerance to zidovudine (AZT). Have the diagnosis of AIDS or advanced AIDS related complex (ARC). Have ended treatment for acute Pneumocystis carinii pneumonia (PCP) at least 2 weeks before study entry. Have previous intolerance on at least two courses of AZT therapy (one of which must have been at daily doses of 500 mg of AZT or less). Be able to provide informed consent (and/or guardian as appropriate). Be available for follow-up for at least 6 months. Have baseline laboratory values as measured within 7 days before initial drug dosing. Allowed: Development of new opportunistic infections during the study - patients remain in the protocol. Prior Medication: Required: Prior use and intolerance to zidovudine (AZT). Allowed: Intralesional agents. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Presence of Kaposi's sarcoma (KS) with known or suspected visceral disease or where KS requires chemotherapy. Active AIDS defining opportunistic infections not specifically allowed. Intractable diarrhea. Stage 2 AIDS-dementia complex. History of intolerance to aerosolized pentamidine. Grade 2 neuropathy, based on the Neuropathy Targeted Symptom Questionnaire, or any moderate abnormality indicative of peripheral neuropathy, particularly impaired sensation of sharp pain, light touch, or vibration in the lower extremities, distal extremity weakness, or distal extremity hyporeflexia. Prior history of acute or chronic pancreatitis. History of seizures within past 2 years or currently requiring anticonvulsants for control. Any other clinical conditions or prior therapy which, in the opinion of the investigator, would make the patient unsuitable for study or unable to comply with the dosing requirements. Concurrent Medication: Excluded: Isoniazid (INH). Patients with the following are excluded: Active AIDS-defining opportunistic infections not specifically allowed. Intractable diarrhea. AIDS-dementia complex = or > stage 2. History of intolerance to aerosolized pentamidine. Grade 2 neuropathy, based on the Neuropathy Targeted Symptom Questionnaire, or any moderate abnormality indicative of peripheral neuropathy, particularly impaired sensation of sharp pain, light touch, or vibration in the lower extremities, distal extremity weakness, or distal extremity hyporeflexia. Prior history of acute or chronic pancreatitis. History of seizures within past 2 years or currently requiring anticonvulsants for control. Any other clinical conditions or prior therapy which, in the opinion of the investigator, would make the patient unsuitable for study or unable to comply with the dosing requirements. Previous participation in any Phase I ddI study. Life expectancy < 6 months. Prior Medication: Excluded: Chronic therapy for cytomegalovirus infection with ganciclovir. ddI. d4T. ddC. Excluded within 2 weeks of study entry: Zidovudine (AZT). Excluded within 1 month of study entry: Therapy with any other antiretroviral drug or investigational agent not specifically allowed, including interferon and immunomodulating drugs. Ganciclovir. Neurotoxic drugs. Excluded within 3 months of study entry: Ribavirin. Cytotoxic anticancer therapy. Prior Treatment: Excluded within 2 weeks of study randomization: Transfusion. Active alcohol or drug abuse that is sufficient, in investigator's opinion, to prevent adequate compliance with study therapy.

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NCT00000673

Inclusion Criteria Concurrent Medication: Allowed: Zidovudine (AZT). AMENDED: 8/8/90 Other available antiretroviral therapy. Pneumocystis carinii pneumonia (PCP) prophylaxis, either systemic or local (aerosolized). Chemotherapy for Kaposi's sarcoma. Systemic therapy for intercurrent opportunistic infections. Acyclovir or other treatment of Herpes simplex virus (HSV) or Varicella zoster virus (VZV) infections. Systemic therapy deemed necessary for appropriate medical management. Patients must have AIDS and cytomegalovirus (CMV) retinitis in at least one eye, diagnosed by an ophthalmologist and verified by fundoscopy and fundus photography. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Contraindication to intravitreal injection, including obvious external infection and vitreous hemorrhage. Medical opacities of cornea, lens, and/or vitreous which precludes fundus photography. Concurrent Medication: Excluded: Prophylactic acyclovir at time of study entry. Other anticytomegalovirus (CMV) therapy, particularly systemic ganciclovir, foscarnet, or CMV hyperimmune globulin. Topical ophthalmic medications should be avoided. Cytomegalovirus (CMV) therapies and chronic acyclovir, including necessary therapies for an intercurrent opportunistic infection. Patients with the following are excluded: Contraindication to intravitreal injection, including obvious external infection and vitreous hemorrhage. Medical opacities of cornea, lens, and/or vitreous which precludes fundus photography.

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NCT00000674

Inclusion Criteria Concurrent Medication: Allowed: Erythropoietin. Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia (PCP). Immunoglobulin therapy. Alpha interferon. Patients entering study on isoniazid (INH) may continue INH therapy. Use of corticosteroids is discouraged. If corticosteroids are needed for the management of intracranial hypertension or cranial mass effect, use of dexamethasone is encouraged (4 g orally 4 times daily for 3 days and thereafter tapered over the next 10 to 14 days). Patients are admitted into the study if they have: Laboratory evidence of HIV infection or if they have an undetermined HIV infection status if they belong to a high-risk group for HIV infection. Either a definite or presumptive diagnosis of toxoplasmic encephalitis. Patient or appropriate family member, or legal designee must be able to understand and sign a written informed consent. Allowed: HIV encephalopathy. AMENDED: Allows patients who have relapsed. Patients with a previous diagnosis of toxoplasmic encephalitis based on histopathology or documented neuroradiological response to pyrimethamine and sulfonamides or pyrimethamine and clindamycin and who have relapsed toxoplasmic encephalitis. Relapse must be documented by definite progression of lesions or appearance of new lesions compatible with toxoplasmic encephalitis. Prior Medication: Allowed if liver enzymes stable for 6 weeks prior to study entry: Rifampin. Isoniazid. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Infections of the central nervous system. Malabsorption syndrome (3 or more loose stools a day for at least 4 weeks associated with an unintentional weight loss of at least 10 percent of body weight). History of sensitivity to the study medication. Malignancies requiring the use of cytotoxic chemotherapy. Coma. Diffuse central white matter lesions. Negative serology for Toxoplasma as performed at the Palo Alto Medical Foundation (unless biopsy is positive). Lymphoma of the central nervous system. Cerebral Kaposi's sarcoma. Hemorrhagic diathesis or active bleeding disorder. Concurrent Medication: Excluded: Erythromycin or other macrolides. Sulfonamides. Immunomodulators. Cytotoxic chemotherapy. Amphotericin. Dapsone. Rifamycins. Ganciclovir. Allopurinol. Antifolates. Azidothymidine and other antiretrovirals and investigational agents not specifically allowed. Folate supplements. Isoniazid (INH) therapy may not be started while on therapy. Concurrent Treatment: Excluded: Lymphocyte replacement. Patients with the following are excluded: Negative HIV antibodies by a federally licensed ELISA (as determined at or after study entry), unless there is documentation of a previously positive HIV culture or p24 antigen. Coma. Diffuse central white matter lesions. Negative serology for Toxoplasma as performed at the Palo Alto Medical Foundation (unless biopsy is positive). Lymphoma of the central nervous system. Cerebral Kaposi's sarcoma. Hemorrhagic diathesis or active bleeding disorder. Unable to take oral medications reliably. Any medical or social condition which, in the opinion of the investigator, would adversely affect either participation and/or compliance in this study. Prior Medication: Excluded: Treatment for toxoplasmic encephalitis.

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NCT00000675

Inclusion Criteria Patients must fulfill the following criteria: Diagnosis of AIDS or AIDS-related complex, according to CDC criteria, in previously documented HIV seropositive individuals. Failure to tolerate or respond to zidovudine (AZT) therapy for HIV infection or a decision to decline such therapy. Willingness to abstain from all other experimental therapy for HIV infection during study period. Life expectancy of at least 3 months. Patients must be able to sign a written informed consent form. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Serious active opportunistic infection or malignancies not specifically allowed. Concurrent Medication: Excluded: Oral or intravenous acyclovir for herpes. Zidovudine (AZT). Interferon. Corticosteroids. Nonsteroidal anti-inflammatory agents (NSAIDS). Intravenous acyclovir. Other known immunomodulatory agents. Other experimental therapy. Patients with the following are excluded: Serious active opportunistic infection or malignancies not specifically allowed. Prior Medication: Excluded within 4 weeks of study entry: Zidovudine (AZT). Chemotherapy. Immunomodulatory agents. Other experimental therapy.

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NCT00000676

Inclusion Criteria Concurrent Medication: Required: Zidovudine (AZT). Antipneumocystis prophylaxis. Allowed: Topical suppressive antifungal agents. Eligibility requirements are: Participation in NIAID ACTG 081. No history of systemic fungal infection, including esophageal or systemic candidiasis, cryptococcosis, histoplasmosis, coccidioidomycosis, blastomycosis, sporotrichosis, or aspergillosis. Willingness to sign an informed consent. Transaminases < 5 x upper limit of normal. Noncompliance will not be a reason for withdrawal of a patient from the study, unless patient refuses further treatment. Allowed: A history of oropharyngeal, vaginal or cutaneous candidiasis. Dermatophyte infections (i.e., tinea pedis) at entry but not active candida infection. Sites of suspected dermatophyte involvement other than the feet should have candida excluded by culture. Prior Medication: Allowed: Topical suppressive antifungal agents. Exclusion Criteria Co-existing Condition: Patients with the following conditions or diseases are excluded: History of systemic fungal infection, including esophageal or systemic candidiasis, cryptococcosis, histoplasmosis, coccidioidomycosis, blastomycosis, sporotrichosis, or aspergillosis. Active systemic fungal infection at time of enrollment. Active superficial fungal infection at time of entry. (Such patients may be treated with topical antifungal agents and may be randomized if they are in clinical remission 14 days after completion of such therapy.) Concurrent Medication: Excluded: Amphotericin B. Fluconazole. Itraconazole. SCH 39304. Other systemic antifungals. Patients with the following are excluded: Previous or currently active systemic fungal infection. History of allergy or intolerance to imidazole or azoles. Positive serum cryptococcal antigen titer at any dilution. Requiring multi-agent therapy for tuberculosis or for symptomatic Mycobacterium avium infection.

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NCT00000677

Inclusion Criteria Concurrent Medication: Allowed: Currently approved antiviral therapy. Maintenance therapy for cytomegalovirus retinitis or toxoplasmosis. Rifampin. Isoniazid. Dilantin or barbiturates if investigator agrees to rigorously monitor anticonvulsant drug levels. Coumarin-type anticoagulants if investigator agrees to rigorously monitor prothrombin time. Prophylactic treatment for Pneumocystis carinii pneumonia (PCP). Concurrent Treatment: Allowed: Local radiotherapy for mucocutaneous Kaposi's sarcoma. Prior Medication: Allowed: Amphotericin B, up to 1 mg/kg, during the previous 7 days. Patients must be HIV positive by 2 methodologies and have either primary cryptococcal meningitis with no prior anti-cryptococcal therapy or relapsed disease after prior therapy. Prior therapy for cryptococcal meningitis is limited to approved drugs. Written informed consent either from patient or patient's parent or legal guardian is required. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: History of hypersensitivity to imidazole or azole compounds. Central nervous system disease. Acute opportunistic infection. Underlying conditions that in the opinion of the investigator could preclude assessment of response. Concurrent Medication: Excluded: Systemic antifungal drugs other than study drug. Any investigational drug other than treatment IND drugs. Oral hypoglycemic agents. Oral contraceptives. Cytotoxic chemotherapy. Patients with the following are excluded: Unable to take oral medications. Concurrent central nervous system disease which in opinion of investigator would interfere with assessment of response. Concurrent acute opportunistic infection requiring therapy (patients who develop an acute opportunistic infection after initiation of study medication may remain on study medication). Prior Medication: Excluded within 7 days of study entry: Amphotericin B, > 1 mg/kg.

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NCT00000678

Inclusion Criteria Concurrent Medication: Required: Aerosolized pentamidine will be given, as tolerated for all patients, for Pneumocystis carinii pneumonia prophylaxis at a dose of 300 mg once every 4 weeks. Allowed maintenance treatment with: Pyrimethamine (= or < 75 mg/day). Sulfadiazine (< 4 gl/day). Amphotericin (1 mg/kg/day up to 5 days). Fluconazole (400 mg/day). Ketoconazole (400 mg/day). Acyclovir (up to 12.4 mg/kg q8h IV for zoster or up to 4000 mg/day will be allowed PO with precautions - nausea and vomiting possible with doses > 1000 mg/day). Ganciclovir (6 mg/kg/day). Medications for tuberculosis or Mycobacterium avium for patients who have recovered from toxoplasmosis, cryptococcosis, candidiasis, herpes virus infections, cytomegalovirus infections, tuberculosis, or Mycobacterium avium intracellulare. Erythropoietin and megace as needed. Isoniazid if patient has no peripheral neuropathy at study entry and is taking pyridoxine at least 50 mg/day concomitantly. Phenytoin if patient has no peripheral neuropathy at study entry and has been stable on the drug for at least 3 months. Patients must have had Pneumocystis carinii pneumonia (PCP) and no other AIDS defining opportunistic infection present when zidovudine (AZT) therapy was first initiated. Patients must have: Advanced AIDS related complex (ARC). Antibody to HIV by federally licensed ELISA and confirmed by Western blot analysis. Ability to give conformed consent. Exclusion Criteria Co-existing Condition: Patients are excluded who: Have had zidovudine (AZT) therapy interrupted for > 30 consecutive days at any time during AZT therapy or have been off AZT for > 90 days total. Have had AZT therapy interrupted for "recurrent" grade 4 toxicity, defined as > one episode of the same grade 4 toxicity after dose interruption or attenuation. Have visceral or extensive Kaposi's sarcoma requiring therapy or any other malignancy requiring therapy. Have a history of peripheral neuropathy. Concurrent Medication: Excluded: Other experimental medications, including foscarnet, ribavirin, and fluconazole (prior to IND approval). Other antiretroviral agents, biologic modifiers or corticosteroids. Drugs that can cause peripheral neuropathy including phenytoin (under conditions not specifically allowed), hydralazine, metronidazole, nitrofurantoin, vincristine, cisplatinum, dapsone, disulfiram, and diethyldithiocarbamate. Patients with the following are excluded: History of peripheral neuropathy or moderate to severe peripheral neuropathy as defined by the combination of signs or symptoms of peripheral neuropathy and findings indicative of peripheral neuropathy on the standardized neurologic exam. Active opportunistic infection. Participation in another research treatment study. Prior Medication: Excluded: Dideoxycytidine (ddC). Didanosine (ddI). Active substance or alcohol abuse.

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NCT00000679

Inclusion Criteria Concurrent Medication: Allowed: Aerosolized pentamidine (300 mg once every 4 weeks) for Pneumocystis carinii pneumonia (PCP) prophylaxis. Neuroleptics, benzodiazepines, or antidepressants if patient has been stable with chronic treatment > 1 month. Low dose benzodiazepines or low dose antidepressants. Drugs that are unlikely to cause increased toxicity with either study drug and are unlikely to cause peripheral neuropathy. Drugs with little nephrotoxicity, hepatotoxicity, or cytotoxicity that the patient has been taking and tolerating well. Acyclovir (up to 600 mg/kg/day) for up to 21 days. Ketoconazole (up to 400 mg/day) Nystatin. Low-dose acetaminophen or nonsteroidal anti-inflammatory agents. Isoniazid if patient has no evidence of peripheral neuropathy at entry and if patient takes 50 mg/day pyridoxine concomitantly with isoniazid. Allowed with interruption of study medication for up to 21 days per episode and for a total of 42 days for the study: Drugs that could cause serious additive toxicity when coadministered with either study medication for treatment of an acute intercurrent illness or opportunistic infection, including: Acyclovir (< 600 mg/day), fluconazole, systemic pentamidine, foscarnet, pyrimethamine, triple sulfa, ansamycin, ganciclovir, trimethoprim / sulfamethoxazole. Patients must have a diagnosis of AIDS or advanced AIDS related complex (ARC). At least 20 percent of the patients must have a consistently positive serum HIV p24 antigen (= or > 70 pg/ml) as defined by the Abbott HIV antigen test, on two separate occasions at least 72 hours apart. Patients found at screening to have a temperature > 38.5 degrees C should be evaluated for the possibility of an occult opportunistic or bacterial infection or neoplasm. If this complete evaluation reveals an infection, they can be entered. If this evaluation is unrevealing, they may be entered after evaluation is completed but while mycobacterial cultures are still pending. Patients with a history of unexplained temperatures > 38.5 degrees C should be evaluated as above and/or be afebrile (temperature < 38.0 degrees C) for 2 weeks prior to study entry. Allowed: Kaposi's sarcoma not specifically excluded, basal cell carcinoma of the skin or in situ carcinoma of the cervix. Current positive venereal disease research label (VDRL) and fluorescent treponemal antibody (FTA) if treated as for asymptomatic neurosyphilis. Prior Medication: Allowed: Drugs that cause peripheral neuropathy and drugs that could cause significant increased toxicity with zidovudine (AZT) or dideoxycytidine (ddC) including experimental drugs if therapy with these drugs is completed and patient is stable for 14 days. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Active AIDS defining opportunistic infection or other active intercurrent illness is excluded if ongoing treatment requires the use of excluded concomitant medication. Patients with symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to entry into the study, or with current neoplasms not specifically allowed. Severe AIDS dementia complex defined by a score of < 23 on the Mini-Mental State Exam. Signs, symptoms, or history of peripheral neuropathy. Significant cardiac disease, defined as history of ventricular arrhythmias requiring medication, prior myocardial infarct, or history of angina or ischemia changes on ECG (electrocardiography). Requiring > 2 weeks of acyclovir therapy at > 600 mg/day. Current positive venereal disease research label (VDRL) and fluorescent treponemal antibody (FTA) not specifically allowed. Significant liver disease. Concurrent Medication: Excluded: Drugs that cause peripheral neuropathy: chloramphenicol, cisplatinum, iodoquinol, dapsone, phenytoin, disulfiram, ethionamide, glutethimide, gold, hydralazine, ribavirin, metronidazole, vincristine, nitrofurantoin. Drugs that could cause significant increased toxicity with zidovudine (AZT) or dideoxycytidine (ddC), including experimental drugs not specifically allowed. Drugs that could cause seizures or changes in mental status or neurological examination. Concurrent Treatment: Excluded: Transfusion dependency. Patients with the following are excluded: Active AIDS defining opportunistic infection or other active intercurrent illness if ongoing treatment requires use of excluded concomitant medication. Symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to study entry, or current neoplasms not specifically allowed. Severe AIDS dementia complex defined by a score of < 23 on the Mini-Mental State Exam. Signs, symptoms, or history of peripheral neuropathy. Unwilling or unable to sign informed consent. Prior Medication: Excluded: Zidovudine (AZT), dideoxycytidine (ddC), or any other antiretroviral nucleoside analog. Excluded within 90 days of study entry: Any experimental drug including fluconazole, ganciclovir, foscarnet, erythropoietin, or ribavirin. Excluded within 90 days of study entry: Drugs that have caused significant nephrotoxicity or significant hepatotoxicity. Drugs that could cause peripheral neuropathy including phenytoin, hydralazine, metronidazole, and nitrofurantoin. Systemic corticosteroids or immunomodulators including interferon and interleukin. Prior Treatment: Excluded within 30 days of study entry: Radiation therapy. Active substance or alcohol abuse.

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NCT00000680

Inclusion Criteria Concurrent Medication: Required: Zidovudine (AZT) during treatment and for 20 weeks after the last infusion unless medically contraindicated. Allowed: Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis. Oral antibiotics for PCP prophylaxis if hematologically stable on that regimen for at least 30 days prior to study entry. Patients must have the following: Positive HIV antibody test by federally licensed ELISA. Positive HIV culture or plasma p24 antigen. CDC Group IV severe AIDS-related complex (ARC) or AIDS. Must have been on zidovudine (AZT) at least 6 weeks prior to infusion and agree to continue this medication during the study and for 20 weeks after the last infusion unless medically contraindicated. Allowed: Kaposi's sarcoma. Exclusion Criteria Co-existing Condition: AMENDED: Pulmonary diseases that require treatment. AMENDED: Significant central nervous system disease including AIDS dementia, psychiatric disabilities, or seizure disorders. AMENDED: Symptomatic HIV CNS infections or symptoms compatible with HIV encephalopathy. Original design: Patients with the following conditions or symptoms are excluded: Active bacterial or opportunistic infection that requires treatment. Neoplasms not specifically allowed, basal cell carcinoma of the skin, or in-situ carcinoma of the cervix. Clinically significant cardiac (= or > class II, New York Heart Association) or peripheral vascular disease that requires treatment. Hemorrhagic diathesis including hemophilia or active bleeding disorder. Concurrent Medication: Excluded: Antineoplastic therapy. Medication required for treatment of active cardiac disease. Cardiac glycosides. Antiarrhythmics. Antianginal agents. Anticoagulants. Thrombolytic agents. Vasodilators. Excluded within 30 days of study entry: Antiretroviral agents not specifically allowed. Corticosteroids. Acyclovir. Excluded within 60 days of study entry: Biological response modifiers. Patients with the following are excluded: Unable to give properly informed consent by reason of impaired mentation. Diseases and conditions specified elsewhere in the protocol. Required: Zidovudine (AZT) for at least 6 weeks prior to infusion. Risk Behavior: Excluded: Active substance abuse.

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NCT00000681

Inclusion Criteria Concurrent Medication: Allowed: Non-steroidal agents such as acetaminophen for drug-related fevers. Pentamidine inhalation prophylaxis for Pneumocystis carinii pneumonia (PCP) in patients with a prior history or a T4 count < 200 cells/mm3. Antiemetics for nausea, vomiting. Symptomatic treatment for grades 1 and 2 oral toxicity. Toxicity grades according to NIAID Recommendations for Grading Acute and Subacute Toxic Effects (Adults). Patients must have newly diagnosed biopsy-proven advanced AIDS-related Kaposi's sarcoma. Exclusion Criteria Concurrent Medication: Excluded: Systemic steroids for > 1 week in any 30 days. All known marrow-suppressive agents. Any other investigational drugs. Patients will be excluded from the study for the following reasons: The presence of other active malignancies except basal cell carcinoma of the skin and in situ uterine cancer. Alteration of mental status that may not permit compliance with the protocol. Symptomatic sensory or motor neuropathy. History of myocardial infarction or significant arrhythmias. Class III/IV functional capacity in cardiac patients. Prior Medication: Excluded: Cytotoxic chemotherapy. Excluded within 1 week of study entry: Therapy for Kaposi's sarcoma, including interferons, immunomodulators, antiretroviral agents. Patients may not have any of the following diseases or symptoms: Allergy to bleomycin. The presence of other active malignancies except basal cell carcinoma of the skin and in situ uterine cancer. Alteration of mental status that may not permit compliance with the protocol. Symptomatic sensory or motor neuropathy. History of myocardial infarction or significant arrhythmias. Class III/IV functional capacity in cardiac patients. Concurrent serious infections, such as Pneumocystis carinii pneumonia (PCP), toxoplasma brain abscess, cytomegalovirus (CMV) retinitis or colitis, cryptococcal meningitis, and symptomatic Mycobacterium avium- intracellulare (MAI).

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NCT00000682

Inclusion Criteria Required: Prior zidovudine (AZT) therapy for 9 months. Concurrent Medication: Allowed: Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP) with aerosolized pentamidine of 300 mg every 4 weeks through the Respirgard II nebulizer. Maintenance treatment with pyrimethamine, sulfadiazine, amphotericin, fluconazole, ketoconazole, acyclovir, or inhaled pentamidine for subjects who have recovered from toxoplasmosis, cryptococcosis, candidiasis, herpes infection, or PCP. Dapsone for PCP. Pyrimethamine-sulfadoxine for toxoplasmosis. Ganciclovir (DHPG) for maintenance only for cytomegalovirus (CMV) retinitis. Note: Any approved medications can be used to treat an opportunistic infection. All concurrent medications should be kept to a minimum and recorded. Patients must be positive for HIV by ELISA test and must have been receiving zidovudine (AZT) therapy for at least 9 months and have received AZT within 90 days prior to entry into the study. Patients may be transfusion dependent as long as no more than 3 units of blood are needed in a 21-day period and the hemoglobin does not fall below 6.4 g/dl on two consecutive occasions despite the transfusions. Exclusion Criteria Concurrent Medication: Excluded: Antiretroviral study medications other than zidovudine (AZT) and biologic response modifiers. Corticosteroids and chronic aspirin. Cimetidine. Flurazepam. Indomethacin. Ranitidine. Probenecid. Other experimental medications. Patients will be excluded from the study for the following reasons: Removal from zidovudine (AZT) during treatment on ACTG protocol 002 for recurrent grade 4 toxicity. Removal from prior dideoxycytidine (ddC) therapy for peripheral neuropathy = or > grade 3. Visceral or extensive Kaposi's sarcoma requiring therapy or another malignancy requiring therapy. Toxicity grades according to NIAID Recommendations for Grading Acute and Subacute Toxic Effects (Adults). Prior Medication: Excluded: Antiretroviral study medications other than zidovudine (AZT) and biologic response modifiers. Patients may not have visceral or extensive Kaposi's sarcoma requiring therapy or another malignancy requiring therapy.

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NCT00000683

Inclusion Criteria Patients must demonstrate the following clinical and laboratory findings: Normal history and physical examination. Normal chest X-ray (optional). Normal urinalysis. Negative ELISA. Negative Western blot test. Negative HIV culture. No evidence of smallpox vaccination. Note: As an operational definition, an individual can be considered "vaccinia naive" only if no scar is observable and the patient claims and/or has evidence of not being vaccinated. If the patient does not know his/her history, it should be presumed that he/she was vaccinated. Exclusion Criteria Patients will be excluded from the study for the following reasons: Appearance of or serologic or clinical evidence of HIV infection. Appearance of or serologic or clinical evidence of clinically active viral infections, including mononucleosis, Epstein-Barr virus, cytomegalovirus which may affect HIV immunocompetence. Syphilis, gonorrhea, or any other sexually transmitted diseases including chlamydia or pelvic inflammatory disease in the last 6 months. History of immunodeficiency or chronic illness. Evidence of depression. History of positive PPD (tuberculosis exposure). Positive syphilis serology. Positive for circulating Hepatitis B antigen. Eczema, active or within the past year. Household contact with someone who is pregnant. Household contact with children less than 12 months old. Household contact with anyone with eczema. Household contact with anyone with immunodeficiencies. Vaccinia immunity. Note: Current PPD test is required only if Merieux skin reaction to the tuberculin antigen is positive. If the patient does not know his/her vaccine history, it should be presumed that he/she was vaccinated. Prior Treatment: Excluded within 1 year of study entry: Treatment for psychiatric problems. Excluded within 6 months of study entry: Blood transfusions or cryoprecipitates. Patients may not have any of the following diseases or symptoms: Appearance of or serologic or clinical evidence of HIV infection. Appearance of or serologic or clinical evidence of clinically active viral infections, including mononucleosis, Epstein-Barr virus, cytomegalovirus which may affect HIV immunocompetence. Syphilis, gonorrhea, or any other sexually transmitted diseases including chlamydia or pelvic inflammatory disease in the last 6 months. History of immunodeficiency or chronic illness. Evidence of depression. Eczema, active or within the past year. High risk behavior for human immunodeficiency virus (HIV) infection, including: Any history of intravenous drug use. Syphilis, gonorrhea, or any other sexually transmitted diseases including chlamydia or pelvic inflammatory disease in the last 6 months. More than 2 sexual partners or sexual contact with a high-risk partner in the last 6 months.

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NCT00000684

Inclusion Criteria Concurrent Medication: Allowed: Acetaminophen. Patients must have: - Clinically documented AIDS or AIDS-related complex (ARC) defined as CDC group IVA or history of any of the findings that define CDC group IV subgroup C-2: oral candidiasis, oral hairy leukoplakia, multidermatomal herpes zoster, recurrent nontyphoidal Salmonella bacteremia, or nocardiosis. Prior Medication: Allowed: Acetaminophen. Exclusion Criteria Concurrent Treatment: Excluded: Intramuscular injections. Patients will be excluded from the study for the following reasons: Acute illness requiring hospitalization or antiviral drug therapy for treatment. Volunteers who have taken any antiviral medications, anticoagulants, antiplatelet medications, or any nonsteroidal anti-inflammatory drugs, except acetaminophen, within 2 weeks of study entry, or those who anticipate the need for such medication during the study. Positive stool guaiac at screening. Disorders of coagulation or any known contraindication to anticoagulation, including but not limited to gastrointestinal or other serious bleeding, major trauma or surgery within the past 2 months, stroke or suspicion of central nervous system (CNS) bleeding, Kaposi sarcoma (with or without proven gastrointestinal involvement), and any known CNS lesions that might be prone to bleed. Allergy to dextran sulfate or heparin. Acute or asymptomatic HIV infection. Prior Medication: Excluded: Antiviral medications. Anticoagulants. Antiplatelet medications. Any nonsteroidal anti-inflammatory drugs (except acetaminophen). Prior Treatment: Excluded: Hospitalization for acute illness. Patients may not have any of the following diseases or symptoms: Allergy to dextran sulfate or heparin. Acute or asymptomatic HIV infection. Acute illness requiring hospitalization. Chronic anemia requiring transfusion within the past month. Disorders of coagulation or any known contraindication to anticoagulation, including but not limited to gastrointestinal or other serious bleeding, major trauma or surgery within the past 2 months, stroke or suspicion of central nervous system (CNS) bleeding, Kaposi's sarcoma, and any known CNS lesions which might be prone to bleed.

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NCT00000685

Inclusion Criteria Concurrent Medication: Allowed: Symptomatic therapy such as analgesics, antihistamines, antiemetics, antidiarrheal agents, or other supportive therapy. Aerosolized pentamidine. Discouraged: - Sucralfate or antacids. However if these medications are essential for the patient's management, they should not be given within 8 hours before or 2 hours after the scheduled pharmacokinetic study. - Concurrent Treatment: Allowed: Blood transfusions. Patients must have HIV infection with renal insufficiency and acceptable hepatic and hematologic function. They must have been on dialysis treatment for at least 3 months. Prior Medication: Allowed: Cytotoxic chemotherapy for local mucocutaneous lesions. Aerosolized pentamidine. Exclusion Criteria Concurrent Medication: Excluded: Ongoing therapy for opportunistic infections, including systemic maintenance therapy which cannot be discontinued for the duration of the study, such as amphotericin B or ganciclovir. H-2 blockers. Zidovudine (AZT). Other antiretroviral agents or other experimental therapy. Discouraged: - Sucralfate or antacids. However, if these medications are essential for the patient's management, they should not be given within 8 hours before or 2 hours after the scheduled pharmacokinetic study. - Patients will be excluded from the study for the following reasons: Presence of active opportunistic infections. Severe malabsorption syndrome (persistent diarrhea greater than 4 weeks duration with = or > 4 loose stools per day accompanied by = or > 10 percent unintentional weight loss. Acute illness, febrile or unstable, 48 hours prior to the first pharmacokinetic study. Known sensitivity to zidovudine or thymidine-type agents. Diabetes mellitus requiring treatment. Prior Medication: Excluded: - Treatment for diabetes mellitus. Excluded within 72 hours of study entry: H-2 blockers. Zidovudine (AZT). Excluded within 2 weeks of study entry: Other antiretroviral agents or other experimental therapy. Rifampin or rifampin derivatives. Probenecid. Dilantin. Methadone. Oral contraceptives. Barbiturates. Significant hepatotoxic agents or valproic acid. TMP / SMX. Dapsone. Fansidar. Excluded within 30 days of study entry: - Cytotoxic chemotherapy. Prior Treatment: Excluded within 30 days of study entry: Radiation therapy for local mucocutaneous lesions. Risk Behavior: Active drug or alcohol use which might interfere with the study objectives. Note: Alcohol consumption is prohibited 48 hours prior to the first pharmacokinetic study and during the study. Tobacco smoking is not excluded although tobacco use will be quantified. Patients may not have any of the following diseases or symptoms: Presence of active opportunistic infections. Severe malabsorption syndrome (persistent diarrhea greater than 4 weeks duration with = or > 4 loose stools per day accompanied by = or > 10 percent unintentional weight loss. Acute illness, febrile or unstable, 48 hours prior to the first pharmacokinetic study. Diabetes mellitus.

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NCT00000686

Inclusion Criteria Patients must have: Diagnosis of AIDS or AIDS related complex (ARC). Previous intolerance to daily doses of up to 1200 mg of zidovudine (AZT) demonstrated by a decrease in hemoglobin levels of 2 - 8.5 g/dl or AZT-related depression of neutrophils of 200 - 750 cells/mm3. Ability to provide informed consent. Prior Medication: Allowed: Zidovudine (AZT). Exclusion Criteria Co-existing Condition: Patients with the following are excluded: AIDS-defining opportunistic infection on enrollment. Intractable diarrhea. History of seizures within past 2 years or currently requiring anticonvulsants for control. Any other clinical conditions or prior therapy which in the opinion of the investigator would make the patient unsuitable for study or unable to comply with the dosing requirements. Concurrent Medication: Excluded: Systemic maintenance or chemoprophylaxis for opportunistic infection (includes dapsone, acyclovir). Systemic therapy with this or any other antiretroviral drug (except zidovudine (AZT)) or investigational drug. Ribavirin. Cytotoxic anticancer therapy. Any agent known as a potent inducer or inhibitor of drug-metabolizing enzymes (includes rifampin and barbiturates). Trimethoprim / sulfamethoxazole (TMP / SMX). Patients with the following are excluded: AIDS-defining opportunistic infection on enrollment. Intractable diarrhea. History of seizures within past 2 years or currently requiring anticonvulsants for control. Any other clinical conditions or prior therapy which in the opinion of the investigator would make the patient unsuitable for study or unable to comply with the dosing requirements. Prior Medication: Excluded within 2 weeks of study entry: Any agent known as a potent inducer or inhibitor of drug-metabolizing enzymes (includes rifampin and barbiturates). Excluded within 1 month of study entry: Systemic therapy with this or any other antiretroviral drug (except zidovudine (AZT)) or investigational drug. Excluded within 3 months of study entry: Ribavirin. Cytotoxic anticancer therapy. Active alcohol or drug abuse sufficient in investigator's opinion to prevent adequate compliance with study therapy.

All

NCT00000687

Inclusion Criteria Concurrent Medication: Allowed: Inhalation pentamidine for the prevention of Pneumocystis carinii pneumonia (PCP) at a dose of 300 mg once every 4 weeks. AMENDED: Trimethoprim - sulfamethoxazole or dapsone only if on the maintenance phase of the study. Concurrent Treatment: Allowed: Blood transfusions. Patients must have a positive antibody to HIV by any federally licensed ELISA test. All lab tests must be within 7 days of entry into the study. Exclusion Criteria Concurrent Medication: Excluded: Other antiretroviral agents. Immunomodulators. Corticosteroids. Cytotoxic chemotherapy. Aspirin. H2 blockers. Barbiturates and myelosuppressive drugs should be particularly avoided as they may interfere with the metabolism or enhance the toxicities of either zidovudine or interferon alfa-2a. Other experimental medications. Concurrent Treatment: Excluded: Radiation therapy. Patients with prior experience of Grade 4 toxicity to zidovudine therapy will be excluded from the study. Prior Medication: Excluded: Interferon therapy. Excluded within 30 days of study entry: Immunomodulators. Corticosteroids. Cytotoxic chemotherapeutic agents. Excluded within 14 days of study entry: Zidovudine (AZT). Prior Treatment: Excluded within 30 days of study entry: Blood transfusions. Radiation therapy. Patients may not have any of the following diseases or symptoms: Active opportunistic infection associated with AIDS. Significant neurologic disease associated with AIDS, as manifested by motor abnormalities including impaired rapid eye movement or ataxia, motor weakness in the lower extremities, sensory deficit consistent with a peripheral neuropathy, bladder or bowel incontinence. Internal organ involvement with Kaposi's sarcoma, i.e., nonnodal visceral Kaposi's sarcoma, excluding minimal gastrointestinal disease of less than 5 lesions. Tumor-associated edema. Current neoplasm other than Kaposi's sarcoma. Significant cardiac disease, including a recent history of myocardial infarction or significant current cardiac arrhythmias. Active drug or alcohol abuse.

All

NCT00000688

Inclusion Criteria Concurrent Medication: Allowed: Zidovudine (AZT) for patients in delayed treatment group and not receiving ganciclovir. Didanosine (ddI) may be continued or initiated in any patient during the study. Topical acyclovir. Topical ophthalmics. Aerosolized pentamidine. Patients must have: AIDS as defined by the CDC criteria or have had confirmation of HIV infection by ELISA, p24 antigen assay, or culture of HIV. Retinal lesions greater than 1500 microns from edge of optic disc outside major temporal vascular arcades, and greater than 3000 microns from fovea. Understanding of study provisions, and willingness to sign informed consent form approved by the appropriate Institutional Review Board and Syntex. Life expectancy of at least 4 months. Exclusion Criteria Co-existing Condition: Patients with ocular conditions requiring immediate surgical correction are excluded. Concurrent Medication: Excluded during first 4 weeks of ganciclovir treatment: Zidovudine (AZT). Excluded: Other investigational drugs and antimetabolites, alkylating agents, nucleoside analogs (topical ophthalmics are permitted), acyclovir, interferon, foscarnet (non-nucleoside pyrophosphate analog), cytomegalovirus (CMV) hyperimmune globulin, and cytokines. Patients with the following are excluded: Immediately sight-threatening retinitis (= or < 1500 microns from edge of optic disc, or inside major temporal vascular arcades, or = or < 3000 microns from the fovea). Ocular media opacities (corneal, lenticular, or vitreal) preventing ophthalmologic and photographic retinal assessment. Demonstrated hypersensitivity to acyclovir. Prior Medication: Excluded: - Previous treatment with anti-cytomegalovirus therapy.

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NCT00000689

Inclusion Criteria Patients must have: Positive HIV antibody by ELISA with Western blot confirmation, or positive HIV culture or serum p24 antigen capture assay, or prior diagnosis of AIDS by the CDC surveillance criteria. Pathological diagnosis of large cell (cleaved or non-cleaved), immunoblastic, or small non-cleaved lymphoma, stage I, II, III, or IV. If displaying systemic ("B") symptoms, evaluation for concurrent opportunistic infections as follows: Buffy coat for Mycobacterium intracellulare-avium (MAI) and cytomegalovirus (CMV) cultures; serum cryptococcal antigen; some measure of pulmonary function to exclude Pneumocystis carinii pneumonia including chest x-ray and either gallium scan, blood gases, or DLCO; stool culture and special stains for Salmonella, Isospora belli, cryptosporidium, CMV, and MAI in patients with diarrhea; computerized tomography (CT) scan or magnetic resonance imaging (MRI) of brain, or lumbar puncture for India ink, acid-fast bacilli smear, cryptococcal antigen, or fungal/mycobacterial culture. Bone marrow involvement is permitted if the patient meets the hematologic criteria above. Patients who have central nervous system (CNS) involvement at diagnosis or who are diagnosed during treatment will receive cranial radiotherapy: - The total dose of 2400 rads will be delivered at a rate of 200 rads/day to the mid plane employing parallel opposing, lateral whole brain fields. The lower border of the field will encompass C2 to cover the meninges. Patients will be treated 5 days/week, Monday through Friday, until the total prescribed dose has been completed. Radiation will begin as soon as possible after documentation of lymphomatous disease in the CNS. If a second course of treatment is required, the 2400 rads is well within whole brain tolerance for normal tissues (4500-5000 rads). Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Acute bacterial or opportunistic infection. Second primary cancer other than Kaposi's sarcoma, non-melanoma skin cancer, or carcinoma in-situ of the cervix. Primary central nervous system (CNS) lymphoma. Concurrent Medication: Excluded: Patients receiving prophylactic or maintenance therapy for bacterial or opportunistic infections, with the exception of those receiving Fansidar (sulfadoxine / pyrimethamine) for Pneumocystis carinii pneumonia prophylaxis. Antiretroviral agents. Immunomodulators. Patients with the following are excluded: Acute bacterial or opportunistic infection. Second primary cancer other than Kaposi's sarcoma, non-melanoma skin cancer, or carcinoma in-situ of the cervix. Primary central nervous system (CNS) lymphoma. Prior Medication: Excluded: Prior therapy for lymphoma. Excluded within 1 week of study entry: Antiretroviral agents and immunomodulators. Prior Treatment: Excluded: Prior therapy for lymphoma.

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NCT00000690

Exclusion Criteria Co-existing Condition: Volunteers with any of the following are excluded: Disorders of coagulation or disorders of plasma lipids. Allergy to dextran sulfate, other sulfates, other dextrans. Concurrent Medication: Excluded: Volunteers who anticipate need for medication during study. Volunteers with any of the following are excluded: Disorders of coagulation or disorders of plasma lipids. Allergy to dextran sulfate, other sulfates, other dextrans. Prior Medication: Excluded within 2 weeks of study entry: Any medication. Risk Behavior: Excluded: Ingestion of alcohol within 48 hours prior to study. History of recent drug or alcohol abuse. Disorders of coagulation or disorders of plasma lipids. Allergy to dextran sulfate, other sulfates, other dextrans. Volunteers selected are: In good general health as determined by screening history, physical examination, and laboratory panel within established limits of normal for hospital laboratory. Consenting volunteers. Available for 6 days of continuous hospitalization.

Male

NCT00000691

Inclusion Criteria Concurrent Medication: Allowed: Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis. Oral antibiotics if patient is hematologically stable on that regimen for at least 30 days prior to study entry. Therapy with vancomycin. Drug therapy for Kaposi's sarcoma if patient is hematologically stable for at least 30 days prior to study entry. Initiate or resume zidovudine (AZT) in 2nd week of foscarnet maintenance therapy at dose of 100 or 200 mg q4h at investigator's discretion. Initiate or continue erythropoietin therapy via the treatment IND mechanism. Initiate or continue therapy with investigational triazoles for disseminated fungal infections. Caution should be used in concurrent use of foscarnet and ciprofloxacin, as such use has appeared to exacerbate renal failure in one patient. Prior Medication: Allowed: Oral antibiotics if patient is hematologically stable on that regimen for at least 30 days prior to study entry. Drug therapy for Kaposi's sarcoma if patient is hematologically stable for at least 30 days prior to study entry. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Corneal, lens, or vitreous opacification that precludes examination of the fundi. Clinically significant pulmonary or neurologic impairment, including intubation or coma. Karnofsky performance status = or < 50. Concurrent Medication: Excluded: Immunomodulators. Biologic response modifiers. Investigational agents (other than erythropoietin and investigational triazoles). Ganciclovir. Didanosine (ddI). Systemic acyclovir. CMV hyperimmune serum / globulin. Interferons. Nephrotoxic agents including aminoglycosides, amphotericin B, parenteral pentamidine. Caution should be used in the concurrent use of foscarnet and ciprofloxacin, as such use has appeared to exacerbate renal failure in one patient. Patients with the following are excluded: Corneal, lens, or vitreous opacification that precludes examination of the fundi. Clinically significant pulmonary or neurologic impairment, including intubation or coma. Unwilling or unable to suspend zidovudine treatment until 2nd week of foscarnet maintenance therapy. Prior Medication: Excluded: Foscarnet for cytomegalovirus retinitis. Systemic acyclovir. Immunomodulators. Biologic response modifiers. Investigational agents (other than erythropoietin and investigational triazoles). AIDS patients with active cytomegalovirus (CMV) retinitis who cannot be treated with ganciclovir. At least one pending CMV culture from both blood (buffy-coat) and urine must be obtained prior to study entry. Patients must be able to give informed consent. Patients with a history of a seizure disorder or central nervous system mass lesion will be included.

All

NCT00000692

Inclusion Criteria Concurrent Medication: Allowed: Aerosolized pentamidine. Nystatin. Clotrimazole. Topical acyclovir. Concurrent Treatment: Allowed: Blood transfusions for = or > grade 3 hemoglobin toxicity. Exclusion Criteria Co-existing Condition: Patients with the following conditions will be excluded: Clinical significant diarrhea (> 3 stools per day for > 7 days without definable cause). Active opportunistic infection, requiring ongoing therapy, at time of enrollment. Any malignancy besides Kaposi's sarcoma, basal cell carcinoma, or squamous cell carcinoma unless the squamous cell carcinoma requires ongoing therapy. Neurologic disease including dementia, peripheral neuropathy, myelopathy (CDC category IVb). Concurrent Medication: Excluded: Antimetabolites. Alkylating agents. Drugs with known hepatic or bone marrow toxicity. Patients with significant organ dysfunction will be excluded. Prior Medication: Excluded: Antimetabolites. Alkylating agents. Excluded within 30 days of study entry: Any investigational medication. Drugs with anti-HIV activity. Excluded within 90 days of study entry: Ribavirin treatment. Excluded within 6 months of study entry: Cancer chemotherapy. Prior Treatment: Excluded within 6 months of study entry: Radiation therapy. Patients must demonstrate the following clinical and laboratory findings: AIDS or advanced AIDS related complex (ARC), according to Centers for Disease Control (CDC) category IV, excluding neurologic disease in IVb. Ability to understand the terms of study participation. Current use of illicit drugs or abuse of alcohol.

All

NCT00000693

Inclusion Criteria Prior Medication: Required: Patients must have successfully completed remission induction therapy with ganciclovir (minimum of 14 days of therapy) for acute cytomegalovirus (CMV) retinitis within the preceding 48 hours. Patients who show no evidence of progressive disease are considered to have met criteria for successful induction. Amended to allow: Investigational triazoles. Human recombinant erythropoietin (Eprex). Other investigational non-antiviral therapies offered through treatment IND. Patients must: Have HIV infection as determined by a commercially licensed ELISA test confirmed by a licensed Western blot Have salvageable vision (corrected acuity of 20/100 or better) in at least one eye. Be capable of signing an informed consent. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Known or suspected allergy to one of the study medications. Inability to maintain adequate hydration status. Concurrent Medication: Excluded: Concurrent therapy with nephrotoxic agents. Systemic therapy for another opportunistic infection. Systemic prophylaxis for Pneumocystis carinii pneumonia (PCP). Probenecid. Patients are advised that validity of this trial may be jeopardized by use of other potentially antiviral or immunomodulating treatments. Patients with the following are excluded: Known or suspected allergy to one of the study medications. Inability to maintain adequate hydration status. Prior Medication: Excluded within 2 weeks of study entry: Steroids. Cytotoxic or immunosuppressive drugs. Investigational agents. (Amended to now allow these.) Immunomodulatory drugs (except ganciclovir). Prior Treatment: Excluded within 2 weeks of study entry: Radiotherapy. Risk Behavior: Excluded: History of unreliable drug intake and inability to cooperate in the testing procedures. Unwilling or unable to give informed consent or unwilling to sign approved consent form.

All

NCT00000694

Inclusion Criteria Concurrent Medication: Allowed: Prophylaxis for Pneumocystis carinii pneumonia (PCP) with aerosolized pentamidine. Ibuprofen, not to exceed 1600 mg/day, for fever or analgesia. Biopsy-proven Kaposi's sarcoma confined to the skin, lymph nodes, or non-nodular lesions of the hard palate. Positive antibody to HIV confirmed by any federally licensed ELISA test kit. Patients must be able to give informed consent. Allowed: Basal cell carcinoma. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Prior or concurrent opportunistic infection or B symptoms (unexplained fever, night sweats, > 10 percent involuntary weight loss or diarrhea persisting > 2 weeks). Visceral (non-nodal) Kaposi's sarcoma including extensive oral lesions. Severe (> 2+) tumor-associated edema. Concurrent neoplasia (excluding basal cell carcinoma). Significant cardiac disease (New York Heart Association class III or IV) or history of myocardial infarction o significant cardiac arrhythmias. Dementia (= or > stage 2). Concurrent Medication: Excluded: Any systemic chemoprophylaxis not specifically allowed. Aspirin and acetaminophen. Nonsteroidal anti-inflammatory agents not specifically allowed. Corticosteroids. Barbiturates. Other antiviral agents, immunotherapy, hormonal therapy, chemotherapy directed at treatment of viral infection or malignancy. Other investigational agents. Concurrent Treatment: Excluded: Radiation therapy directed at treatment of viral infection or malignancy. Patients with the following are excluded: Prior or concurrent opportunistic infection or B symptoms (unexplained fever, night sweats, > 10 percent involuntary weight loss or diarrhea persisting > 2 weeks). Visceral (non-nodal) Kaposi's sarcoma including extensive oral lesions. Severe (> 2+) tumor-associated edema. Concurrent neoplasia (excluding basal cell carcinoma). Significant cardiac disease (New York Heart Association class III or IV) or history of myocardial infarction or significant cardiac arrhythmias. Dementia (= or > stage 2). Prior Medication: Excluded: Interferon alpha-2b. Granulocyte-macrophage colony-stimulating factor (GM-CSF). Prior grade 3 or grade 4 toxicity during AZT therapy. Excluded within 30 days of study entry: Zidovudine (AZT). Corticosteroids. Biologic response modifiers. Cytotoxic chemotherapy. Antiretroviral agents. Toxicity grades according to NIAID Recommendations for Grading Acute and Subacute Toxic Effects (Adults). Prior Treatment: Excluded within 30 days of study entry: Requirement for red blood cell transfusions within 30 days of study entry. Radiation therapy. Active drug or alcohol abuse.

All

NCT00000695

Inclusion Criteria Concurrent Treatment: Allowed: Local radiotherapy or laser therapy to cosmetically apparent Kaposi's lesions, provided the dose to any one lesion does not exceed 3000 gray and the total surface area of all lesions treated does not exceed 10 cm2 during the course of the trial. Patients must demonstrate the following clinical and laboratory findings: Positive for HIV by federally licensed ELISA test. Acceptable bone marrow function. Acceptable renal function. Acceptable hepatic function. Exclusion Criteria Concurrent Medication: Excluded: Other potentially antiretroviral compounds. Patients will be excluded from the study for the following reasons: Concurrent, active opportunistic infections requiring therapy. Extensive Kaposi's sarcoma with more than 100 cutaneous lesions, requiring systemic chemotherapy, prior treatment with more than one chemotherapy regimen, excluding intralesional therapy, or symptomatic visceral Kaposi's sarcoma. Evidence of clinically significant cardiac dysfunction (New York Heart Association grade III or IV). History of malignant neoplasms other than nonmelanomatous skin cancer or cancer in situ of the cervix. Proteinuria of 2+ or greater and/or 24-hour urine protein of greater than 1. Prior Medication: Excluded: More than one chemotherapy regimen for Kaposi's sarcoma. Any interferon preparation or zidovudine (AZT). Excluded within 30 days of study entry: Other immunomodifiers. Acyclovir. Other investigational drugs. Excluded within 60 days of study entry: Cytotoxic therapy. Patients may not have any of the following diseases or symptoms: Development of an AIDS-defining opportunistic infection, other than oral thrush or localized zoster. Non-Kaposi's sarcoma, AIDS-defining malignancy.

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NCT00000696

Inclusion Criteria Concurrent Medication: Allowed: Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP), as aerosolized pentamidine. Ibuprofen. Acute therapy (7 days) with oral acyclovir. Acute therapy with ketoconazole. Patients must have: A diagnosis of AIDS related complex as well as defined symptoms within 12 months of study entry in the absence of concurrent illness or conditions other than HIV infection. Estimated life expectancy of at least 12 weeks. Positive serum p24 antigen > 70 pg/ml. Patients may have received prior zidovudine (AZT) and / or interferon alpha therapy, provided that: The total duration of treatment was < 6 months. Patients treated > 12 weeks but < 6 months should have received continuous therapy (no more than 14 consecutive days or 21 total days off during the treatment period). For patients treated = or < 12 weeks, continuous treatment means < 7 days off total during the treatment period. For all patients, a washout period of = or > 4 weeks must have elapsed prior to study entry. Treatment did not result in a major adverse reaction attributable to AZT or IFN-A2a such that rechallenge at a randomly assigned dosage level would be precluded. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Acquired immunodeficiency syndrome (AIDS) as defined by opportunistic infections. Significant cardiac (New York Heart Association Class 3 or 4), hepatic, renal, or neurologic disorder. Concurrent neoplasm other than basal cell carcinoma or in situ carcinoma of the cervix. Significant neurological disorder which impairs the patient's ability to give or receive informed consent or reduces the patient's performance status to the extent that protocol requirements and self-administration of drug cannot be accurately completed. Concurrent Medication: Excluded: All concomitant medications should be kept to a minimum. Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP), other than aerosolized pentamidine. Other antiretroviral agents. Experimental medications. Biologic response modifiers. Systemic corticosteroids. Cimetidine. Ranitidine. Aspirin, acetaminophen, and nonsteroidal anti-inflammatory agents with the exception of ibuprofen. Barbiturates. Cardiac glycosides, antiarrhythmics, or vasodilators. Systemic treatment for an active infection, including pulmonary tuberculosis. Concurrent Treatment: Excluded: Systemic treatment for an active infection, including pulmonary tuberculosis. Patients with the following will be excluded from the study: AIDS as defined by opportunistic infections, Kaposi's sarcoma, or other AIDS defining neoplasms, HIV dementia complex, or HIV wasting disease. HIV constitutional disease. Any one of the following: Fever of > 38.5 degrees persisting for > 1 month. Involuntary weight loss of = or > 10 lbs or 10 percent of body weight. Diarrhea defined as = or > 2 liquid stools per day persisting for at least a total of 14 days without definable cause. Significant cardiac (New York Heart Association Class 3 or 4), hepatic, renal, or neurologic disorder. Concurrent neoplasm other than basal cell carcinoma or in situ carcinoma of the cervix. Significant neurological disorder which impairs the patient's ability to give or receive informed consent or reduces the patient's performance status to the extent that protocol requirements and self-administration of drug cannot be accurately completed. Prior AZT or IFN-A2a therapy for = or > 6 months. Previous major adverse reaction to AZT or IFN-A2a. Prior Medication: Excluded: Prior zidovudine (AZT) or interferon therapy for = or > 6 months. Excluded within 4 weeks of study entry: Any antiretroviral agent, Cytotoxic chemotherapy, or immunomodulator, including corticosteroids. Excluded within 30 days of study entry: Anti-infectives or agents likely to produce hematologic side effects (e.g., trimethoprim / sulfamethoxazole). Excluded: Cardiac glycosides, antiarrhythmics, or vasodilators. Active substance abuse.

All

NCT00000697

Inclusion Criteria Concurrent Medication: Allowed if hematologically stable on that regimen for at least 30 days prior to study entry: Oral antibiotics. Chemotherapy for Kaposi's sarcoma. Acyclovir for outbreaks of herpes simplex or shingles. Zidovudine (AZT), either initiated or continued, by patients randomized to both treatment arms. AZT given concurrently with foscarnet may be administered at a dose of 100 or 200 mg every 4 hours (q4h) at the investigator's discretion. Patients randomized to the delayed treatment arm may initiate or continue AZT administration at a dose of 100 or 200 mg q4h at the investigator's discretion. AZT may not be administered during the first 3 weeks of foscarnet therapy. Patients randomized to immediate therapy may begin or resume AZT when they enter the 2nd week of maintenance therapy (week 4 of the 10-week study period), if their hemoglobin is = or > 8 g/dl and absolute neutrophil count is = or > 1000 cells/mm3 at that time. Caution should be used in the concurrent use of foscarnet and ciprofloxacin, as such use has appeared to exacerbate renal failure in one patient. Patients must have active AIDS-related cytomegalovirus (CMV) retinitis as identified by its characteristic ophthalmoscopic appearance and verified by fundus photography. Patients must also demonstrate one of the following clinical and/or laboratory findings: Treatment with ganciclovir (DHPG) resulting in dose-limiting toxicity (absolute neutrophil count (= polymorphonuclear leukocytes plus bands) < 500 cells/mm3 or platelets < 25000 platelets/mm3) occurring on = or > two documented occasions at least 7 days apart while receiving up to a maximum induction regimen of 10 mg/kg/day or a maintenance regimen of up to 5 mg/kg/day. Neutropenia should not be the result of zidovudine (AZT) treatment. Ineligibility for DHPG therapy because of baseline neutropenia (absolute neutrophil count < 500 cells/mm3) or thrombocytopenia (platelets < 25000 platelets/mm3) documented on = or > 2 occasions at least 7 days apart. Baseline myelosuppression should not be the result of ongoing therapy with either prescription drugs, including AZT, or over-the-counter medications. Prior Medication: Allowed: Zidovudine (AZT), according to protocol stipulations. Prophylaxis therapy for Pneumocystis carinii pneumonia (PCP). Chemotherapy for Kaposi's sarcoma. Exclusion Criteria Co-existing Condition: Patients with any of the following diseases or symptoms are excluded: An immediately sight-threatening lesion in a salvageable eye (i.e., patients who have a cytomegalovirus (CMV) lesion that is within 1500 microns of the optic disc or fovea in an eye with correction vision of 20/100 or better). Corneal, lens or vitreous opacification which precludes examination of the fundi of either eye. Any clinically significant pulmonary or neurologic impairment (i.e., patients who are intubated or comatose), although patients with a history of a seizure disorder or a central nervous system (CNS) mass lesion may be enrolled. Concurrent Medication: Excluded: Systemic acyclovir as preventive therapy for herpes infection. Any nephrotoxic agent. Specifically excluded are aminoglycosides, amphotericin B, and parenteral pentamidine. A patient who requires such therapy must be temporarily discontinued from study therapy; if nephrotoxic therapy is given for > 7 days, the patient will be permanently withdrawn from study therapy. Other anti-cytomegalovirus (CMV) therapy, specifically ganciclovir, CMV hyperimmune serum/globulin, interferons, and immunomodulators. Patients will be excluded from the study if they are unwilling or unable to suspend zidovudine (AZT) treatment during the first 3 weeks of the study period (1) if randomized to the immediate treatment arm, or (2) when crossed-over from the delayed treatment arm to foscarnet therapy because of retinitis progression. Prior Medication: Excluded: Foscarnet for cytomegalovirus (CMV) retinitis. Excluded within 7 days of study entry: Immunomodulators. Investigational agents other than ganciclovir.

All

NCT00000698

Inclusion Criteria Concurrent Medication: Allowed: Aerosolized pentamidine prophylaxis for Pneumocystis carinii pneumonia. Topical ophthalmics. Topical acyclovir. Concurrent Treatment: Allowed: Hemodialysis for patients with renal impairment. Patients must have: Diagnosis of AIDS and immediately sight-threatening cytomegalovirus retinitis. Prior Medication: Allowed: Zidovudine. Prior therapy for retinitis. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: Non-immediately sight-threatening cytomegalovirus retinitis. Concurrent Medication: Excluded: Systemic investigational agents such as antimetabolites, alkylating agents, nucleoside analogs, acyclovir sodium (Zovirax). Interferon. Cytokines. Foscarnet (non-nucleoside pyrophosphate analog). Ganciclovir may be withheld for up to 21 days for an acute course with an investigational or toxic therapy or oral / IV acyclovir. Patients with the following are excluded: Non-immediately sight-threatening cytomegalovirus retinitis.

All

NCT00000699

Inclusion Criteria It must be possible to culture HIV from peripheral blood lymphocytes on 2 consecutive screenings within 2 months of starting treatment. Concurrent Medication: Allowed: Systemic medications not listed in the Exclusion Concurrent Medications field considered necessary for the patient's medical management and which would not interfere with the study may be used, but such use must be documented. Exclusion Criteria Concurrent Medication: Excluded: Systemic steroids. Cytotoxic immunosuppressive medications. Any systemic experimental anti-HIV drug such as dideoxycytidine (ddC), foscarnet, ribavirin, isoprinosine, or zidovudine (AZT). Any other medication felt to be immunomodulatory or felt to exhibit significant hepatotoxicity or hematologic or renal toxicity by study investigators. Prior Medication: Excluded within 6 weeks of study entry: Systemic steroids. Cytotoxic immunosuppressive medications. Any systemic experimental anti-HIV drug such as dideoxycytidine (ddC), foscarnet, ribavirin, isoprinosine, or zidovudine (AZT). Any other medication felt to be immunomodulatory or felt to exhibit significant hepatotoxicity or hematologic or renal toxicity by study investigators. Current active infections, known cardiac disease, or prior history of one of the following: Gout, uric acid urolithiasis, uric acid nephrolithiasis, or renal dysfunction. Neoplasms: Other than locally treated basal or squamous carcinoma. Cardiovascular: Myocardial infarction, cardiac arrhythmia, cardiomyopathy, or congestive heart failure. Past or current history of CDC-defined AIDS including HIV encephalopathy and HIV wasting syndrome. Constitutional symptoms (CDC Group IV-A), neurologic symptoms (CDC Group IV-B), or any prior or current non-AIDS defining secondary infectious disease (CDC Group IV-C2). Grade 1 impairment on 2 or more items in the ACTG Micro Neuro-AIDS Assessment. Active drug or alcohol abuse.

All

NCT00000700

Inclusion Criteria Concurrent Medication: Allowed: All concomitant medication to minimum and record. Any approved medications can be used to treat an opportunistic infection. Dapsone may be used for Pneumocystis carinii pneumonia (PCP). Pyrimethamine - sulfadoxine may be used for toxoplasmosis. Ganciclovir for cytomegalovirus may be used for maintenance only. Prophylactic therapy for PCP. Concurrent Treatment: Allowed: Local, limited radiation therapy to isolated Kaposi's sarcoma lesions provided total area is < 5 x 5 cm and a 6-MeV electron beam or 90 kV x-ray = or < 3000 rads total is used. Patients must have: HIV seropositivity as confirmed by any federally licensed ELISA test kit. Allowed: Malignancy in past which has been in complete remission for 1 year without therapy. Exclusion Criteria Co-existing Condition: Patients with active opportunistic infections will be excluded. Concurrent Medication: Excluded: Aspirin on a regular basis or beyond 72 hours without contacting investigator. Cimetidine. Flurazepam. Indomethacin. Ranitidine. Probenecid. Patients with the following are excluded: Status post-Pneumocystis carinii pneumonia with symptomatic visceral Kaposi's sarcoma (KS) or progression of KS within the month prior to study entry. Other concurrent neoplasms other than basal cell carcinoma of the skin. Requiring blood transfusions > once per month. Last transfusion cannot have been given within 7 days of entry. Active substance abuse. Unwilling to sign informed consent or to be followed at medical center where enrolled for duration of study and follow-up if necessary. Prior Medication: Excluded within 2 weeks of study entry: Treatment for acute Pneumocystis carinii pneumonia (PCP). Excluded within 30 days of study entry: Other antiretroviral agents, immunomodulating agents, or corticosteroids. Prior Treatment: Excluded within 30 days of study entry: Radiation therapy or cytotoxic chemotherapy for Kaposi's sarcoma. Required: Patients must be at least 2 weeks post- therapy status for acute Pneumocystis carinii pneumonia (PCP).

All

NCT00000701

Inclusion Criteria Concurrent Treatment: Allowed: Nutritional support not exceeding 120 calories/kg/day (hyperalimentation or dietary supplements including vitamin, folate, iron supplements). Exclusion Criteria Co-existing Condition: Children with the following conditions are excluded: Asymptomatic with T-lymphocyte deficiency. Asymptomatic viremic patients or those not meeting definition criteria of AIDS related complex (ARC) or AIDS. Clinical evidence of active infection of acute nature or active significant or clinically apparent opportunistic infection at time of entry into study. Hemoglobinopathy including sickle cell anemia. Congenital infections such as toxoplasmosis or herpes simplex virus infection in the first month after birth or cytomegalovirus infection in the first 6 months after birth. Children with the following conditions are excluded: Asymptomatic with T-lymphocyte deficiency. Asymptomatic viremic patients or those not meeting definition criteria of AIDS related complex (ARC) or AIDS. Clinical evidence of active infection of acute nature or active significant or clinically apparent opportunistic infection at time of entry into study. Hemoglobinopathy including sickle cell anemia. Congenital infections such as toxoplasmosis or herpes simplex virus infection in the first month after birth or cytomegalovirus infection in the first 6 months after birth. Prior Medication: Excluded: Suramin. Ribavirin. HPA 23. Phosphonoformate. Ansamycin. Interleukin 2. Interferon. Excluded within 30 days of study entry: All cytolytic chemotherapeutic agents, immunomodulating agents including steroids and immunoglobulin preparations. Antivirals (acyclovir, ganciclovir). Prior Treatment: Excluded within 4 weeks of study entry: Lymphocyte transfusions for immune reconstitution. Excluded within 3 months of study entry: Bone marrow transplant. Child who is seropositive for HIV antibody or has HIV viremia and presents with one or more of following clinical criteria and at least one of the laboratory criteria may be considered an ARC patient for purpose of study: Clinical criteria: Persistent oral candidiasis despite appropriate therapy. Wasting syndrome characterized by failure to thrive and malnutrition. Recurrent or chronic unexplained diarrhea. Lymphadenopathy (more than 1 cm) at 2 or more noncontiguous sites. Hepatomegaly with or without splenomegaly. Encephalopathy with loss of developmental milestones and cortical atrophy present on computed tomography (CT) examination. Recurrent bacterial infections (bacteremia, pneumonia, septic arthritis, meningitis). Cutaneous anergy as defined by lack of delayed cutaneous hypersensitivity to selected antigens. Laboratory criteria: Hypergammaglobulinemia (IgG or IgA) defined as immunoglobulin values exceeding the maximum age-adjusted level. Decreased number of total T-lymphocytes (2 SD from mean). Absolute depression in T-helper cells to less than 500/mm3. Depressed (equal to or more than 2 SD from normal mean) in vitro mitogen response to at least one antigen. One positive HIV culture within 3 months of study entry into the study or blood obtained and culture pending. Life expectancy greater than 6 months. Ambulatory and free of opportunistic infection at time of entry. Reliably diagnosed disease at least moderately indicative of underlying cellular immunodeficiency and no known cause of underlying cellular immunodeficiency or other reduced resistance reported to be associated with that disease. Disease accepted as sufficiently indicative of underlying cellular immunodeficiency by CDC. In absence of these opportunistic diseases, a histologically confirmed diagnosis of chronic lymphoid interstitial pneumonitis will be considered indicative of AIDS unless test(s) for HIV are negative.

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NCT00000702

Inclusion Criteria Concurrent Medication: Allowed: Aspirin, in modest doses. Ibuprofen, in modest doses. Maintenance antibiotic therapy posttherapy for an AIDS-defining opportunistic infection. Concurrent Treatment: Allowed: Blood transfusion if cardiovascular status is compromised. Exclusion Criteria Active substance abuse. Co-existing Condition: Patients with the following conditions will be excluded: Concurrent or previous central nervous system infections or neoplasms. Active AIDS-defining opportunistic infection. Severe premorbid psychiatric illness. Confounding neurological disease. Concurrent neoplasms. Concurrent Medication: Excluded: Maintenance methadone or naltrexone. Acetaminophen. Mood- or central nervous system-altering drugs. Zidovudine for Pneumocystis carinii pneumonia (PCP). Acyclovir. Rifampin or derivatives. Drugs with antiretroviral activity. Experimental agents. The following patients will be excluded from the study: Patients requiring ongoing therapy for an AIDS-defining opportunistic infection. Patients with a history of Mycobacterium avium intracellulare infection. Patients with a history of Pneumocystis carinii pneumonia infection. Patients with a daily temperature of 38 degrees C or more for 1 month. Prior Medication: Excluded: Zidovudine (AZT). Excluded within 14 days of study entry: Systemic anti-infectives. Excluded within 30 days of study entry: Immunomodulators and biologic response modifiers. Any investigational agent. Cytotoxic chemotherapy for Kaposi's sarcoma. Prior Treatment: Excluded: Radiation therapy. Patients must demonstrate the following clinical and laboratory findings: No currently active AIDS-defining opportunistic infections. One negative blood culture for Mycobacterium avium intracellulare within 4-6 weeks prior to study entry. Constitutionally well without persistent fever. Less than 25 Kaposi's sarcoma lesions and less than 10 new lesions during the 30 days prior to study entry. Patients may have stable or indolently progressive mucocutaneous Kaposi's sarcoma. Characteristic clinical symptoms and signs of AIDS dementia complex. Abnormalities on 2 or more of 7 neuropsychological motor tests in the Neurological Screening Battery. Estimated premorbid IQ equal to or greater than 70 (+ or - 5), which is consistent with completion of sixth grade.

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NCT00000703

Inclusion Criteria Concurrent Medication: Allowed: Ibuprofen. Standard antiemetic agents. Ganciclovir therapy for sight- or life-threatening Cytomegalovirus infection. Zidovudine and methotrexate may be resumed during ganciclovir maintenance phase. Exclusion Criteria Co-existing Condition: The following patients will be excluded from the study: Patients with recurrent infection that may interfere with the planned protocol. Patients with a second active tumor other than nonmelanomatous skin cancer or Kaposi's sarcoma. Patients with stage IE primary central nervous system lymphoma. Concurrent Medication: Excluded: Corticosteroids. Aspirin. Acetaminophen. Nonsteroidal anti-inflammatory drugs, except ibuprofen. Chemotherapy for infection associated with neutropenia. Zidovudine (AZT) for infection associated with neutropenia. Investigational therapies, except ganciclovir therapy for sight- or life-threatening cytomegalovirus infection. AZT and methotrexate will be suspended during induction therapy with ganciclovir. The following patients will be excluded from the study: Patients with recurrent infection that may interfere with the planned protocol. Patients with a second active tumor other than nonmelanomatous skin cancer or Kaposi's sarcoma. Patients with stage IE primary central nervous system lymphoma. Prior Medication: Excluded: Zidovudine (AZT). Excluded within 2 weeks of study entry: Immunomodulating agents. Antiretroviral therapy prior to diagnosis of lymphoma. Patients must demonstrate the following clinical and laboratory findings: Any stage of the disease, including stage I. Newly diagnosed, previously untreated high-grade lymphoma. Presence of measurable tumor parameter(s). Adequate hepatic, renal, and bone marrow function.

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NCT00000704

Inclusion Criteria Concurrent Medication: Allowed: Aspirin, acetaminophen, and nonsteroidal anti-inflammatory agents. Acute therapy (7 days) with oral acyclovir. Acute therapy with ketoconazole. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Negative antigen test within 2 weeks of starting therapy. Significant malabsorption (> 10 percent weight loss within past 3 months with serum carotene < 75 IU/ml or vitamin A < 75 IU/ml). Significant cardiac, liver, or neurologic disease. For group A: Opportunistic infection or malignancy fulfilling definition of AIDS, or with concurrent neoplasm other than basal cell carcinoma of the skin or in situ carcinoma of the cervix. For group B: Active opportunistic infection, symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to study entry, or with concurrent neoplasms other than KS, basal cell carcinoma of the skin, or in situ carcinoma of the cervix. Concurrent Medication: Excluded: Acyclovir therapy. Chemoprophylaxis for Pneumocystis carinii pneumonia. Other antiretroviral agents, biologic modifiers, or systemic corticosteroids. Other experimental medications, sedatives, and barbiturates. Group B: Therapy and/or prophylaxis for AIDS-defining opportunistic infection, antineoplastic therapy. Concurrent Treatment: Excluded: - Transfusion dependency (requiring 2 units of blood more than once per month). Patients with history of idiopathic thrombocytopenia purpura are excluded. Prior Medication: Excluded within 30 days of study entry: Biologic modifiers or corticosteroids. Excluded within 90 days of study entry: Antiretroviral agents. Prior Treatment: Excluded within 2 weeks of study entry: Transfusion. Inclusion criteria are: Consistently positive HIV antigen as defined by Abbott HIV antigen test. This demonstration will be seen on two occasions, each separated by at least 72 hours, the last of which must be within 2 weeks of starting therapy. HIV antigen titer must be = or > 100 pg. Positive antibody to HIV confirmed by any federally licensed enzyme-linked immunosorbent assay (ELISA) test kit. The following conditions are allowed: - Basal cell carcinoma of the skin or in situ carcinoma of the cervix. Active substance abuse.

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NCT00000705

Inclusion Criteria You may be eligible for this study if you: Are HIV-positive. Have a bleeding disorder such as hemophilia A or B, a lack of factor VIII (a blood clotting factor), or severe von Willebrand's disease. Will be available for follow-up for at least a year. Are at least 12 years old (consent of parent or guardian required if under 18). Are willing to use an effective method of birth control during the study. Exclusion Criteria You will not be eligible for this study if you: Have a life-threatening opportunistic (AIDS-related) infection or AIDS-related symptoms. Have taken certain drugs within 30 days prior to study entry including chemotherapy and interferon. Are taking acetaminophen or drugs containing acetaminophen. Are pregnant or breast-feeding.

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NCT00000706

Inclusion Criteria Patients must: Have symptomatic HIV infection. Be taking zidovudine (AZT), 100 or 200 mg, 5 or 6 x/day. Allowed: History of Pneumocystis carinii pneumonia (PCP). Advanced AIDS related complex (ARC). HIV antibody positive with an absolute CD4 lymphocyte count of < 200 cells/mm3 before study entry. Exclusion Criteria Co-existing Condition: Patients with any of the following conditions are excluded: Glucose-6-phosphate dehydrogenase deficiency. Allergy to sulfa drugs, probenecid, or quinine. Concurrent Medication: Excluded: - Other drugs that might influence the metabolism or renal excretion of zidovudine (AZT).

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NCT00000707

Inclusion Criteria Concurrent Treatment: Allowed during aerosolization: Metaproterenol or albuterol to treat bronchospasm. Patients must have: HIV infection confirmed by ELISA, HIV culture, or p24 antigenemia. Suspected subclinical Pneumocystis carinii infection as detected by > 10 percent change in lung volumes and/or diffusing capacity indicative of progressive restrictive disease as detected by monthly screening pulmonary function tests (PFT's). Patients will be afebrile and have no respiratory signs or symptoms of clinical disease. Morphologic confirmation of pneumocysts will be determined by bronchoalveolar lavage (BAL) performed 24 hours after the initial aerosol inhalation. If the BAL is negative for pneumocysts, the patient will be withdrawn from this protocol and will be followed per the screening PFT protocol at Stony Brook. Diagnostic bronchoscopy and BAL must be performed within 2 weeks of detection of > 10 percent change in PFTs. Ability and willingness to sign informed consent. Prior Medication: Allowed: Primary prophylaxis with agents active against Pneumocystis carinii pneumonia (PCP), but no more than 5 patients may have received prior prophylaxis with aerosolized pentamidine. Zidovudine. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: History of Pneumocystis carinii pneumonia (PCP). Development of respiratory signs and/or symptoms in the interval between detection of pulmonary function test (PFT) abnormality and the time of initial aerosol deposition. Dyspnea, cough, or bronchospasm that prevents cooperation with aerosol administration. History of a major adverse reaction to pentamidine defined by absolute neutropenia, < 750 polymorphonuclear leukocytes plus bands; thrombocytopenia, < 40000 platelets; creatinine rise, > 3.0 mg/dl; liver function abnormalities, SGOT or SGPT > 5 x normal; hypoglycemia, < 50 mg/dl; rash, exfoliative or mucositis; cough, unremitting cough or bronchospasm uncontrolled by bronchodilator preventing > 50 percent of dose delivered for > 2 days. Concurrent Medication: Excluded: Zidovudine. Patients unable to cooperate with aerosol administration are excluded. Prior Medication: Excluded: - Another antiprotozoal regimen for this episode. Unable to complete therapy or follow-up for social reasons in the opinion of the investigator.

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NCT00000708

Inclusion Criteria Concurrent Medication: Allowed: Immunosuppressant therapy. Cyclosporin plasma concentrations should be monitored and appropriate dosage adjustments made when used with amphotericin B or fluconazole. Antiviral therapy. Prophylaxis for Pneumocystis carinii pneumonia. Treatment of intercurrent opportunistic infection as long as no investigational agent, or approved agent for an investigational indication, is used. Antipyretics, hydrocortisone, or meperidine to prevent or ameliorate side effects associated with amphotericin B. Concurrent Treatment: Allowed: - Radiation therapy for mucocutaneous Kaposi's sarcoma. Patients must have: Written informed consent obtained from the patient or from the patient's legal guardian. One of the following: (1) Tentative identification of Cryptococcus neoformans in culture of lumbar cerebrospinal fluid (CSF). Results of baseline cultures need not be available when therapy is begun, but therapy is discontinued if the baseline CSF culture is later found to be negative for C. neoformans, or (2) Clinical and CSF findings (cell count, protein, glucose) compatible with cryptococcal meningitis plus one of the following: (a) Positive CSF India ink examination, (b) Culture or biopsy evidence of extraneural cryptococcal infection, (c) Positive serum of CSF cryptococcal antigen test, or increase in titer for previously treated patients with suspected relapse, or (d) Biopsy evidence of central nervous system cryptococcal infection. Treatment status of either no prior systemic antifungal therapy for cryptococcosis or relapse after prior therapy. The success of prior therapy must have been documented by negative CSF culture at the end of therapy. Prior Medication: Allowed within 4 weeks of study entry: - Successful prior therapy for cryptococcosis, but no more than 1 mg/kg/week amphotericin B. Allowed: Immunosuppressant therapy. Antiviral therapy. Prophylaxis for Pneumocystis carinii pneumonia. Exclusion Criteria Co-existing Condition: Excluded: Acute or chronic meningitis based on any etiology other than cryptococcosis. History of allergy to or intolerance of imidazoles, or amphotericin B. Moderate or severe liver disease defined as any one or more of the following: SGOT or SGPT > 5 x upper limit of normal, total bilirubin > 2.5 mg/dl, prothrombin time > 5 seconds over control, or alkaline phosphatase > 2 x upper limit of normal. Comatose patients. Concurrent Medication: Excluded: Drugs with low therapeutic ratios that undergo hepatic metabolism may not be used with fluconazole until possible drug interactions have been clarified. Coumarin-type anticoagulants. Oral hypoglycemics. Barbiturates. Immunostimulants. Investigational drugs or approved (licensed) drugs for investigational indications. Systemic antifungal agent other than the assigned study drug. Concurrent Treatment: Excluded: Lymphocyte replacement. Prior Medication: Excluded within 4 weeks of study entry: More than 1 mg/kg/week amphotericin B. Patients unlikely to survive more than 2 weeks.

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NCT00000709

Inclusion Criteria Concurrent Medication: Allowed: Prophylactic therapy for Pneumocystis carinii pneumonia (PCP); aerosol pentamidine is the preferred method. Maintenance anticonvulsant therapy following a seizure in the context of the AIDS dementia complex. Patients taking anticonvulsants should have their anticonvulsant blood levels measured prior to starting zidovudine (AZT) or with changes in AZT dosage. Phenytoin, carbamazepine, and valproic acid. Judicious use of benzodiazepams. For analgesia or fever, modest doses of aspirin, Tylenol, or ibuprofen. Use of major mood or central nervous system altering drugs is discouraged and should be documented. Patients with the following are included: An estimated pre-illness IQ = or > 70. A general neurodiagnostic evaluation before entry which will include a computerized tomographic (CT) scan or magnetic resonance imaging (MRI) scan and a lumbar puncture. Stable or indolently progressive mucocutaneous Kaposi's sarcoma with < 25 lesions and onset of < 10 new lesions during the 30-day period prior to study entry. Chronic seizure disorders requiring anticonvulsant therapy as long as the seizures are not associated with a fixed neurologic deficit. A blood HIV culture and p24 antigen capture assay at the time of the lumbar puncture. A second p24 antigen assay on study entry. Informed consent form must be signed by the patient, legal guardian, or parent. Active substance abuse that would limit a patient's cooperation or evaluation. Exclusion Criteria Co-existing Condition: Patients with the following will be excluded from the study: Active, symptomatic AIDS-associated opportunistic infections requiring ongoing maintenance therapy. Persistent fever, active persistent diarrhea, or continued severe weight loss. Severe premorbid psychiatric illness. Confounding neurologic disease or deficit. Concurrent or previous central nervous system infections or neoplasms. Concurrent active neoplasms other than basal cell carcinoma of the skin and mucocutaneous Kaposi's sarcoma. Concurrent Medication: Excluded: Major psychotropic medication including tricyclic antidepressants, MAO inhibitors, phenothiazines, butyrophenones, barbiturates, or amphetamines. Cimetidine. Ranitidine. Probenecid. Indomethacin. Acyclovir (ACV) prophylaxis for recurrent Herpes simplex. Patients with the following will be excluded from the study: Active, symptomatic AIDS-associated opportunistic infections requiring ongoing maintenance therapy. Persistent fever, active persistent diarrhea, or continued severe weight loss. Severe premorbid psychiatric illness. Confounding neurologic disease or deficit. Concurrent or previous central nervous system infections or neoplasms. Concurrent active neoplasms other than basal cell carcinoma of the skin and mucocutaneous Kaposi's sarcoma. Prior Medication: Excluded within 2 weeks of study entry or for greater than 2 weeks of therapy: Zidovudine (AZT). Patients must not have previously exhibited toxic reaction to AZT. Excluded within 30 days of study entry: Immunomodulators and biologic response modifiers, including systemic steroids. Any investigational agent. Cytotoxic chemotherapy for Kaposi's sarcoma. Prior Treatment: Excluded within 30 days of study entry: Radiation therapy. Excluded within 2 weeks of study entry: Blood transfusion.

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NCT00000710

Inclusion Criteria Concurrent Medication: Recommended: Allopurinol for consistent occurrence of hyperuricemia observed with 2',3'-dideoxyinosine (ddI) administration. Allowed: Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis. Oral acyclovir for herpes simplex infections provided ddI dosing is suspended during this time. Ketoconazole for patients not responding to any other therapy and after consultation with the sponsor. Symptomatic therapy such as analgesics, antihistamines, antiemetics, antidiarrheal agents, or other supportive therapy may be administered as deemed necessary by the principal investigator. Aspirin rather than acetaminophen for fever. Patients with the following will be included: An absence of life-threatening opportunistic infection on enrollment. A life expectancy less than 6 months. Available for follow-up for at least 6 months. Able to provide informed consent. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Intractable diarrhea. No venous access. A history of or propensity for seizure disorders. A history of past or current heart disease or other significant abnormality on routine EKG. Concurrent Medication: Excluded: Adenine deaminase inhibitors. Trimethoprim / sulfamethoxazole for Pneumocystis carinii pneumonia (PCP) infections. Antibiotics. Acetaminophen for therapy of fever. Patients with the following are excluded: Intractable diarrhea. A life expectancy less than 6 months. No venous access. A history of or propensity for seizure disorders. A history of past or current heart disease or other significant abnormality on routine EKG. Prior Medication: Excluded: Any agent known as a potent inducer or inhibitor of drug-metabolizing enzymes. Excluded within 2 weeks of study entry: Trimethoprim / sulfamethoxazole. Excluded within 1 month of study entry: Any antiretroviral drug. Investigational agents. 2',3'-didanosine. AL721. Interferons. Immunomodulating drugs. Excluded within 3 months of study entry: Ribavirin. Cytotoxic agents. Risk Behavior: Excluded: Active alcohol or drug abuse sufficient in the investigator's opinion to prevent adequate compliance.

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NCT00000711

Inclusion Criteria Concurrent Medication: Allowed: Modest doses of acetaminophen, aspirin, or non-prescription doses of ibuprofen may be used with caution for fever control and mild analgesia. Prolonged use more than 72 hours is not advised without dose supervision. All patients should have a documented history of positive HIV antibody by ELISA test. Patients should qualify for zidovudine (AZT) treatment for the following reasons: Patients with a prior episode of cytologically confirmed Pneumocystis carinii pneumonia (PCP). Patients with a prior episode of any AIDS-defining opportunistic infection and less than 200 T4 cells. Patients with advanced ARC as defined by mucocutaneous candidiasis and/or unexplained weight loss and less than 200 T4 cells and fever more than 100 degrees F of more than 3 weeks duration; clinical diagnosis of hairy leukoplakia; herpes zoster infection within 3 months of entry; or unexplained diarrhea. All patients must have received at least 8 weeks of AZT prior to enrollment and must not have required a dose adjustment for the previous 4 weeks. Patients must be willing to sign an informed consent statement. Required: Zidovudine (AZT) for at least 8 weeks. Exclusion Criteria Co-existing Condition: The following patients will be excluded: Patients receiving zidovudine (AZT) while enrolled in another protocol. Patients with other life-threatening and uncontrolled opportunistic infection. Patients with evidence of lymphoma or neoplasm other than indolent Kaposi's sarcoma. Dementia that would prevent giving appropriate informed consent. Concurrent Medication: Excluded: Acetaminophen or products containing acetaminophen. Drugs that are nephrotoxic, are cytotoxic, or decrease blood cell number or function may increase the risk of toxicity. Probenecid may inhibit excretion of zidovudine (AZT). Some experimental nucleoside analogs should be avoided. The following patients will be excluded: Patients receiving zidovudine (AZT) while enrolled in another protocol. Patients with other life-threatening and uncontrolled opportunistic infection. Patients with evidence of lymphoma or neoplasm other than indolent Kaposi's sarcoma. Dementia that would prevent giving appropriate informed consent. Prior Medication: Excluded within 8 weeks of study entry: Prior systemic therapy with an antimetabolite, cytotoxic drug, interferon, immunomodulator, corticosteroid, or nucleoside analog other than zidovudine.

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NCT00000712

Inclusion Criteria Concurrent Medication: Allowed: Methadone maintenance. Therapies available through expanded access or treatment IND programs unless specifically excluded. Allowed within 30 days of study entry: Systemic steroids only if given for treatment of Pneumocystis carinii pneumonia. Recommended: PCP prophylaxis. Patient must have: Recovered from first episode of histologically proven Pneumocystis carinii pneumonia (PCP) or microbiologically proven AIDS-defining opportunistic infection as defined in Centers for Disease Control HIV classification group IV. C-1. Study entry must be within 120 days of AIDS-defining diagnosis. Written documentation of positive antibody to HIV by any federally licensed ELISA test kit. This test should be confirmed by another method, for example, Western blot, radioimmunoassay (RIA), HIV culture. Patients cannot be transfusion dependent (requiring blood transfusion more than once per month). The last transfusion must be > 2 weeks before entry. AMENDED 90-08-27 to include HIV positive patients with CD4+ count < 200 cells/mm3. Prior Medication: Allowed: Zidovudine (AZT) for < 365 days prior to study entry. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Symptomatic visceral or progressive Kaposi's sarcoma (KS) (defined by > 10 new lesions in the 30 days prior to entry). Other concurrent neoplasms other than basal cell carcinoma of skin (patients who have been in complete remission for 1 year for a malignancy may be enrolled). Malabsorption as defined by persistent diarrhea > 6 stools/day for > 4 weeks. Patients whose sole AIDS-defining condition is constitutional disease as defined in CDC's HIV group IV-A or neurologic disease as defined in CDC's HIV group IV-B or AIDS-associated malignancies as defined in CDC's HIV group IV-C. Concurrent Medication: Excluded: Acyclovir (ACV) prophylaxis or frequent (> once per month) repeated courses of ACV therapy for herpes simplex virus infection. Any concomitant medicine unless required. Systemic therapy/prophylaxis/maintenance for AIDS-defining opportunistic infection other than prophylaxis for Pneumocystis carinii pneumonia (PCP). Acetaminophen for > 72 hours. Cimetidine. Flurazepam. Indomethacin. Ranitidine. Probenecid (if receiving AZT). Rifampin. Rifampin-related drugs. Patients with the following are excluded: Active opportunistic infections. Symptomatic visceral or progressive Kaposi's sarcoma (KS) (defined by > 10 new lesions in the 30 days prior to entry). Other concurrent neoplasms other than basal cell carcinoma of skin (patients who have been in complete remission for 1 year for a malignancy may be enrolled). Malabsorption as defined by persistent diarrhea > 6 stools/day for > 4 weeks. Patients whose sole AIDS-defining condition is constitutional disease as defined in CDC's HIV group IV-A or neurologic disease as defined in CDC's HIV group IV-B or AIDS-associated malignancies as defined in CDC's HIV group IV-C. Prior Medication: Excluded: Zidovudine (AZT) for > 365 days prior to study entry. Excluded within 14 days of study entry: Systemic acyclovir (ACV) therapy. Excluded within 30 days of study entry: Antiretroviral therapy (other than AZT per above). Immunomodulating agents. Biologic response modifiers. Excluded within 60 days of study entry: Ribavirin. Prior Treatment: Excluded within 30 days of study entry: Cytotoxic chemotherapy or radiation therapy for Kaposi's sarcoma. Active substance abuse that would impair compliance with study procedure.

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NCT00000713

Inclusion Criteria Concurrent Medication: Allowed: Short-course therapy (7 days) with oral acyclovir or ketoconazole. Patients must have: Evidence of HIV infection as measured by a confirmed positive antibody test. A confirmed or pending HIV blood culture, and serum p24 antigen test. The ELISA test confirmed by a licensed Western blot analysis if they are asymptomatic. Exclusion Criteria Concurrent Medication: Excluded: Aspirin or acetaminophen beyond 72 hours without contacting investigator. Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP). Patients with the following are excluded: AIDS. AIDS related symptoms or with advanced ARC and < 200 CD4 cells/mm3 and at least two of the following: Weight loss in excess of 10 lbs or 10 percent of body weight within a 6-month interval. Temperature > 38.5 degrees C with or without night sweats, persisting for more than 14 consecutive days or more than 15 days in a 30-day interval. Diarrhea defined as = or > 3 liquid stools per day, persisting for more than 30 days without definable cause. Recurrent oral candidiasis as documented by morphology or by response to antifungal therapy. Patients cannot have active oral candidiasis at the time of entry into the study; they must be free of candidiasis from baseline 1 to enrollment. Multidermatomal herpes zoster within the past 2 years. Hairy leukoplakia within the past 3 years. Prior Medication: Excluded within 14 days of study entry: Other biologic response modifiers. Corticosteroids. Systemic antibiotics. Excluded within 30 days of study entry: Other antiretroviral agents. Excluded within 60 days of study entry: Ribavirin. Zidovudine. Concurrent neoplasms other than basal cell carcinoma of the skin. Active drug or alcohol abuse.

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NCT00000714

Inclusion Criteria Concurrent Medication: Allowed: Noninvestigational therapies as needed. Maintenance therapy with investigational triazoles such as itraconazole and SCH 39304. High-dose corticosteroids (exceed physiologic replacement doses) including oral prednisone 40 mg bid for 5 days, 40 mg daily for 5 days and then 20 mg daily for the remainder of PCP therapy. Same dose for methylprednisolone. Concurrent Treatment: Allowed: Any ventilatory support, antihypertensive agents, invasive monitoring, and other necessary medical intervention, according to his/her medical status, personal wishes, and the judgment of his/her physician. Patients must have: HIV seropositivity. Diagnosis of Pneumocystis carinii pneumonia (PCP). Serious intolerance to trimethoprim / sulfamethoxazole (TMP / SMX) therapy defined as follows: Platelets < 50000 platelets/mm3. Neutrophil count (polys plus bands) = or < 500 cells/mm3 on at least two occasions = or > 12 hours apart. Mucocutaneous reaction - blistering rash, mucosal involvement, generalized maculopapular eruption, or intolerable pruritus. Hepatitis demonstrated by transaminase elevation > 5 times the upper limit of normal, or = or > 300 IU if baseline is abnormal. Drug fever with daily temperature = or > 103 degrees F beginning after the 5th day of treatment persisting for at least 3 days and not responsive to antipyretic therapy, with no other discernible cause. Any other severe or life-threatening adverse reaction to TMP / SMX which, in the investigator's opinion, makes continued or recurrent treatment with TMP / SMX inadvisable as determined on a case-by-case basis. Serious intolerance to pentamidine therapy defined as follows: Platelets < 50000 platelets/mm3. Neutrophil count (polys plus bands) = or < 500 cells/mm3 on at least two occasions = or > 12 hours apart. Serum creatinine > 3.0 mg/dl. Systolic blood pressure < 90 mm requiring supportive therapy. Symptomatic hypoglycemia with blood glucose < 40, or hyperglycemia requiring therapy. Pancreatitis with laboratory confirmation (abnormal amylase and/or lipase). Any other severe or life-threatening adverse reaction to pentamidine, which, in the investigator's opinion, makes continued or recurrent treatment with pentamidine inadvisable as determined on a case-by-case basis. Informed consent by patient or legal guardian. Prior Medication: Required: Trimethoprim / sulfamethoxazole and pentamidine therapies. Prior Medication: Allowed: Myelosuppressive or nephrotoxic agents including zidovudine. History of high-risk behavior for HIV infection - homosexual or bisexual men, intravenous drug abusers, recipients of HIV-infected blood products, or sexual partners of persons in these groups may be admitted without proof of HIV infection. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: History of Type I hypersensitivity (i.e., urticaria, angioedema, or anaphylaxis), exfoliative dermatitis, or other life-threatening reactions due to trimetrexate. Patients with a less severe adverse reaction may be enrolled if, in the opinion of the investigator, these adverse effects do not prohibit rechallenge with the drug. Concurrent Medication: Excluded: Myelosuppressive or nephrotoxic agents including zidovudine and ganciclovir. Investigational therapies. Patients with the following are excluded: History of Type I hypersensitivity (i.e., urticaria, angioedema, or anaphylaxis), exfoliative dermatitis, or other life-threatening reactions due to trimetrexate. Patients with a less severe adverse reaction may be enrolled if, in the opinion of the investigator, these adverse effects do not prohibit rechallenge with the drug.

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NCT00000715

Inclusion Criteria Prior Medication: Allowed: Zidovudine (AZT), but must be suspended during study medication. Unequivocal diagnosis of Pneumocystis carinii pneumonia established by morphologic confirmation of three or more typical Pneumocystis carinii organisms in sputum, bronchoalveolar lavage fluid, or lung tissue obtained by transbronchial or open-lung biopsy within 3 days before or after randomization. If morphologic confirmation is not possible prior to therapy, patients may be randomized if the investigator believes there is a high suspicion of PCP based on clinical presentation. If morphologic diagnosis cannot be established within 5 days of randomization, the patient will be withdrawn from study therapy. Resting (A-a) DO2 less than 30 torr on room air at all ACTG sites except San Francisco General Hospital. Non-ACTG sites will enter patients up to a resting (A-a) DO2less than 55 mmHg on room air. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Dyspnea, cough, bronchospasm, or other reasons causing inability to cooperate with aerosol administration. History of major adverse reaction to pentamidine or sulfonamide-containing preparation defined as: Absolute neutropenia of 750 or less PMN + bands cells/mm3. Thrombocytopenia below 40000 platelets/mm3. Rise in creatinine: To more than 3.0 mg/dl. Liver function abnormalities: SGOT or SGPT greater than 5 x upper limit of normal. Hypoglycemia below 50 mg/dl. Rash: Exfoliative or mucositis. Cough: Unremitting or bronchospasm uncontrolled by bronchodilator preventing more than 50 percent of delivered dose for more than 2 days. Concurrent Medication: Excluded: Other drugs for the treatment or prevention of AIDS or Pneumocystis carinii pneumonia. Zidovudine (AZT). Patients with the following are excluded: Dyspnea, cough, bronchospasm, or other reasons causing inability to cooperate with aerosol administration. History of major adverse reaction to pentamidine or sulfonamide-containing preparation defined as: Absolute neutropenia of 750 or less PMN + bands cells/mm3. Thrombocytopenia lower than 40000 platelets/mm3. Rise in creatinine: To greater than 3.0 mg/dl. Liver function abnormalities: SGOT or SGPT greater than 5 x upper limit of normal. Hypoglycemia less than 50 mg/dl. Rash: Exfoliative or mucositis. Cough: Unremitting or bronchospasm uncontrolled by bronchodilator preventing more than 50 percent of delivered dose for more than 2 days. Prior Medication: Excluded within 14 days of study entry: Systemic steroids higher than adrenal replacement doses. Excluded within 6 weeks of study entry: Another antiprotozoal regimen for this episode, whether therapeutic or prophylactic. Sulfamethoxazole / trimethoprim. Pyrimethamine. Sulfadoxine / pyrimethamine. Pentamidine. Eflornithine.

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NCT00000716

Inclusion Criteria Concurrent Medication: Allowed: Amphotericin B and antituberculosis chemotherapy. Children who have advanced lymphocytic interstitial pneumonitis (LIP) who are steroid dependent may remain on such therapy. Secondary prophylaxis for Pneumocystis carinii pneumonia (PCP) with careful monitoring for possible toxicity due to combination therapy with zidovudine (AZT). Concurrent Treatment: Allowed: Blood transfusions for hematologic toxicity. Immunoglobulin therapy for development of = or > 3 serious bacterial infections while receiving zidovudine. A serious bacterial infection includes septicemia (not catheter related), pneumonia, meningitis, bone or joint infection, or abscess of the body cavity or internal organ. The pathogen must be one of the following organisms: Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Streptococcus group B, Pseudomonas aeruginosa, Hemophilus influenzae B, and Pneumococcus. Laboratory documentation of the pathogen is required. Patients must comply with the following: Life expectancy of more than 6 months. Children must have laboratory evidence of HIV infections as demonstrated by either a positive viral culture or detectable serum p24 antigen or repeated positive test for HIV antibody determined by a federally licensed ELISA test and confirmed by Western blot. Children under 15 months of age, who are thought to have acquired HIV through perinatal transmission and whose only laboratory evidence of HIV infection is a positive antibody test, must also have increased immunoglobulin levels and decreased absolute number of CD4+ cells or a decreased helper/suppressor ratio. AIDS: Must have clinical evidence of HIV infection as demonstrated by the presence of one or more of the indicator diseases as defined in the CDC Surveillance definition for AIDS. (NOTE: Children with lymphocytic interstitial pneumonitis are excluded unless they meet at least one of the following conditions: an additional AIDS-defining opportunistic infection, recurrent serious bacterial infection, HIV encephalopathy, wasting syndrome, or meet the definition of AIDS related complex (ARC). ARC: Children who present with at least one of the first three clinical findings and one of any other listed below within 2 months of entry or who present with two of the first three symptoms listed: <= 500 CD4 cells/mm3 within 4 weeks of entry, persistent (>= 2 months) or recurrent oral candidiasis despite therapy, diarrhea (defined as >= 3 loose stools per day) that is either persistent or recurrent, hepatomegaly, splenomegaly, cardiomyopathy, nephropathy manifested by nephrotic syndrome without evidence of renal failure, 2 or more episodes of herpes stomatitis within a 1-year period, or 2 or more episodes of recurrent herpes zoster or chronic zoster (defined as = or > 30 days duration regardless of therapy). Written informed consent from a parent or guardian. Exclusion Criteria Co-existing Condition: Patients with the following will be excluded: Any active or chronic opportunistic infection at time of entry requiring acute therapy with experimental agents or agents which may affect zidovudine (AZT) toxicity or safety, nor serious bacterial, fungal, or parasitic infections requiring parenteral therapy at the time of entry. Concurrent Medication: Concomitant medications should be kept to a minimum. Excluded: Chronic use of drugs that are metabolized by hepatic glucuronidation, such as acetaminophen. Acute therapy for active or chronic opportunistic infection with experimental agents or agents which may affect zidovudine (AZT) toxicity. Parenteral therapy for serious bacterial, fungal, or parasitic infections. Prophylaxis for Pneumocystis carinii pneumonia (PCP) for children who have not had a previous episode of PCP, oral candidiasis, or otitis media. Immunoglobulin therapy. Note: Immunoglobulin therapy may be administered to children who develop = > 3 serious bacterial infections while receiving AZT. Children with lymphocytic interstitial pneumonitis (LIP) as their only clinical sign of HIV infection will be excluded from the study. Children with any of the following laboratory findings within 2 weeks of entry will be excluded: A total bilirubin > 3 times Upper Limit of Normal (ULN). SGOT > 5 x Upper Limit of Normal in the presence of an age-adjusted abnormal bilirubin. Creatinine clearance < 50 ml/min/1.73 m2. White blood cells < 2000 cells/mm3. Neutrophils < 800 cells/mm3. Hematocrit < 24 percent. Hemoglobin < 8.0 g /dl. Children who will be unable to be followed by their original study center for the 24 weeks of the study will be excluded. Prior Medication: Excluded within 2 weeks of study entry: Any other experimental therapy or drugs which cause prolonged neutropenia or significant nephrotoxicity. Excluded within 4 weeks of study entry: Immunomodulating agents including steroids, interferon, isoprinosine, and interleukin-2. Excluded within 2 months of study entry: Other antiretroviral agents. Note: Children with advanced lymphocytic interstitial pneumonitis (LIP) who are steroid dependent may remain on such therapy. Prior Treatment: Excluded within 4 weeks of study entry: Immunoglobulin. Lymphocyte transfusions for immune reconstitution. Excluded within 3 months of study entry: Bone marrow transplant. Active alcohol or drug abuse.

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NCT00000717

Inclusion Criteria Concurrent Medication: Allowed: Oral antiemetics. Patients must have the following for inclusion: HIV positive by ELISA, p24 antigen or culture. Pneumocystis carinii pneumonia (PCP). Patients must have an (A-a) DO2 < 40 mmHg on room air. Willingness to sign an informed consent. Prior Medication: Allowed: - Prophylaxis for Pneumocystis carinii pneumonia (PCP) with agents other than clindamycin and primaquine. Exclusion Criteria Concurrent Medication: Excluded: Hematotoxic therapy, including zidovudine (AZT) or ganciclovir. Patients with the following are excluded: History of allergy to clindamycin, lincomycin, or related drugs; or to primaquine or related drugs. Positive screen for G6PD deficiency, known NAD methemoglobin reductase deficiency, and/or known hemoglobin M abnormality. Concomitant conditions defined in Patient Exclusion Co-Existing Conditions. Any medical or social situation which, in the opinion of the investigator, would adversely affect participation in the study. Note: Patients may be enrolled while G6PD screen is pending, but must be withdrawn if results are not known within 5 days after entry. Prior Medication: Excluded within 14 days of study entry: Systemic steroids at doses exceeding physiologic replacement or other investigational agents. Excluded within 6 weeks of study entry: Prior institution of any antiprotozoal therapy for the current episode of Pneumocystis carinii pneumonia or prophylaxis. Patients must not have any of the following symptoms or diseases: History of allergy to clindamycin, lincomycin, or related drugs; or to primaquine or related drugs. Positive screen for G6PD deficiency, known NAD methemoglobin reductase deficiency, and/or known hemoglobin M abnormality. Diarrhea, defined as = or > 3 watery stools per day. Severe nausea and vomiting or other medical condition, such as ileus, that precludes oral therapy. Ventilator dependence or (A-a) DO2 = > 30 mm Hg. Any medical or social situation which, in the opinion of the investigator, would adversely affect participation in the study. Note: Patients may be enrolled while G6PD screen is pending, but must be withdrawn if results are not known within 5 days after entry.

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NCT00000718

Inclusion Criteria Concurrent Medication: Encouraged though not required: Inhaled pentamidine as prophylaxis for Pneumocystis carinii pneumonia (PCP). Allowed: AL-721 use is discouraged but not prohibited. Use of aspirin, acetaminophen, and nonsteroidal anti-inflammatory agents should be minimized, with continuous use for > 72 hours discouraged. Acute therapy (7 days) with oral acyclovir. Acute therapy with ketoconazole. Concurrent Treatment: Allowed: Up to 4 units of packed red blood cells for hemoglobin toxicity. All patients must have the following: A consistently positive serum HIV p24 antigen = or > 70 pg/ml, defined by the Abbott HIV antigen test, on two occasions. The tests must be within 1 month of study entry, separated by at least 72 hours, and the last must be within 2 weeks of starting therapy. Any negative antigen test during the period will exclude the patient from the study. A positive antibody to HIV confirmed by any federally licensed ELISA test kit. Patients in group A must have AIDS related complex (ARC) as defined by the documented presence of at least one of the following: Recurrent oral candidiasis. Hairy leukoplakia. History of herpes zoster. Temperature > 38.5 degrees C with or without night sweats, persisting for > 14 consecutive days or > 15 days in a 30-day interval prior to study entry. Weight loss of > 15 lbs. or 10 percent of body weight noted in a 120-day period prior to study entry. Diarrhea defined as = or > 3 liquid stools per day, persisting for > 30 days prior to study entry without definable cause. Patients in group B must have CDC-defined AIDS not requiring systemic maintenance chemotherapy. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Transfusion dependence requiring 2 units of blood more than once per month. Significant malabsorption (> 10 percent weight loss within the past 3 months with serum carotene < 75 IU/ml or vitamin A < 74 IU/ml). Significant cardiac or liver disease. Significant neurologic abnormalities defined by any one of the following: A significant abnormality on the ddC Neuropathy Targeted Symptom Questionnaire defined as a symptom score > 4 (moderate severity) in any one of six categories or a score > 2 (mild severity) in any two of six categories. Moderate abnormalities on standardized neurologic exam. Any severe abnormality (a value = or > 4.0) on standardized 4-arm quantitative sensory testing of vibration threshold. Diabetes, renal failure, or alcoholism. Dose-limiting or transfusion-requiring toxicity during a previous course of zidovudine therapy. History of idiopathic thrombocytopenic purpura. Requirement for prolonged acyclovir therapy. Patients in group A must not have the following: Opportunistic infection or malignancy fulfilling the CDC definition of AIDS. Neoplasms other than basal cell carcinoma of the skin or in situ carcinoma of the cervix. Patients in group B must not have the following: Active opportunistic infection or AIDS-defining opportunistic infection requiring ongoing systemic therapy and/or prophylaxis other than inhaled pentamidine for Pneumocystis carinii pneumonia prophylaxis. Symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to study entry. Concurrent neoplasms other than KS, basal cell carcinoma of the skin or in situ carcinoma of the cervix. Concurrent Medication: Excluded: Neurotoxic drugs. Prolonged acyclovir therapy. Antineoplastic therapy. Systemic therapy and/or prophylaxis for an AIDS-defining opportunistic infection, other than inhaled pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis. Other antiretroviral agents, immunomodulators, or systemic corticosteroids. Other experimental medication. Concurrent Treatment: Excluded: Transfusion dependency (requiring 2 units of blood more than once per month). Prior Medication: Excluded: Antiretroviral agents within 60 days of study entry. Biologic modifiers or corticosteroids within 30 days prior to study entry. Dideoxycytidine (ddC). Prior Treatment: Excluded: Blood transfusion within 2 weeks of entry. Any negative HIV p24 antigen test during the month prior to entry will exclude the patient from the study. Active drug or alcohol abuse.

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NCT00000719

Inclusion Criteria Concurrent Medication: Allowed: Aerosolized pentamidine at prophylactic doses, but its use is discouraged in persons without a history of Pneumocystis carinii pneumonia (PCP). Acyclovir for acute disseminated zoster. Maintenance doses of pyrimethamine, amphotericin, and pentamidine are allowed for patients who recover from toxoplasmosis, cryptococcosis, or pneumocystosis acquired after study entry. Patients included in the study must have HIV infection confirmed by ELISA test and must have a documented history of at least 4 weeks of zidovudine (AZT) treatment. While hemoglobin at the start of AZT therapy must have been = or > 9.5 g/dl and granulocyte count = or > 1200 cells/mm3 at the start of AZT therapy, hematologic toxicity due to a reduced dose of AZT will be defined as: Hematologic toxicity must have occurred during a period when AZT was administered at = or < 600 mg/day for at least 2 weeks. There must have been no evidence of a cause for toxicity other than HIV infection and AZT use. Hematologic intolerance may have consisted of hemoglobin toxicity, granulocyte toxicity, or both. Recovery from hematologic toxicity must be manifested by the presence of a granulocyte count of > 1000 cells/mm3 and a hemoglobin of > 9.5 g/dl. without transfusions during the preceding 4 weeks. Patients must also have no significant bilateral symptoms of peripheral neuropathy, although all patients may have any degree of stable unilateral neurologic deficit. Up to 24 patients may have certain moderate bilateral abnormalities of peripheral neuropathy. AZT may not have been administered within 14 days prior to entering the study. Prior Medication: Required: A documented history of at least 4 weeks of zidovudine treatment which resulted in hematologic toxicity at reduced dose. Allowed but discouraged: A1-721. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Known active AIDS opportunistic infections. Known mycobacteremia, although cultures may be pending at the time of enrollment. Symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to entry into the study or with concurrent neoplasms other than KS, basal cell carcinoma of the skin or in situ carcinoma of the cervix. Significant malabsorption as manifested by steatorrhea with greater than 10 percent weight loss within the last 3 months. Diabetes. Concurrent Medication: Excluded: Experimental medications. Aspirin. Acetaminophen. Nonsteroidal anti-inflammatory agents should be minimized, with continuous use for > 72 hours discouraged. Chronic suppressive anti-infective therapy other than inhaled pentamidine and neurotoxic drugs should be avoided. Continuous therapy for > 7 days of acyclovir is prohibited except for the acute treatment of disseminated herpes zoster infection. Patients with the following are excluded: Known mycobacteremia, although cultures may be pending at the time of enrollment. Symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to entry into the study or with concurrent neoplasms other than KS, basal cell carcinoma of the skin or in situ carcinoma of the cervix. Significant malabsorption as manifested by steatorrhea with greater than 10 percent weight loss within the last 3 months. Diabetes. Known active AIDS opportunistic infections. Patients must also have no significant bilateral symptoms of peripheral neuropathy, although all patients may have any degree of stable unilateral neurologic deficit. Up to 24 patients may have certain moderate bilateral abnormalities of peripheral neuropathy. AZT may not have been administered within 14 days prior to entering the study. Prior Medication: Excluded within 30 days of study entry: Any antiretroviral agents except zidovudine (AZT). Discouraged: A1-721. Pentamidine at prophylactic doses in persons without a history of Pneumocystis carinii pneumonia (PCP). Active substance and/or alcohol abuse.

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NCT00000720

Inclusion Criteria Concurrent Medication: Allowed: Benadryl and/or acetaminophen may be given before and during intravenous immunoglobulin (IVIG) infusion in patients demonstrating mild reactions during infusion. Acetaminophen for short-term fever and pain. Zidovudine (AZT). Steroids. Oral or systemic (swish and swallow) nystatin. Maintenance therapy for fungal disease or tuberculosis. Prophylaxis for a previous episode of Pneumocystis carinii pneumonia (PCP) including the use of trimethoprim / sulfamethoxazole (TMP / SMX). The dosage is specified as TMP 75 mg/m2 twice daily 3 times a week and SMX 375 mg/m2 twice daily 3 times a week. Recommended: Children with AIDS and / or CD4 count = or < 500 cells/mm3 should receive primary PCP prophylaxis as described. Concurrent Treatment: Allowed: Blood transfusion for hemoglobin < 8 g/dl and hematocrit < 24 percent or bone marrow suppression. Supplemental oxygen with a prestudy PaO2 < 70 mmHg. Children must have one or more of the indicator diseases of AIDS; however, there must be an absence of acute opportunistic infection and an absence of bacterial infection requiring treatment at the time of entry into the study. Children with lymphoid interstitial proliferation (LIP) are excluded from enrollment unless they have had additional AIDS-defining opportunistic infections, meet ARC criteria, have had two or more serious bacterial infections in the 12 months prior to study entry, have evidence of HIV encephalopathy, or are currently on supplemental oxygen and steroids with a pre-treatment PaO2 < 70 mm Hg. Children with concurrent LIP and ARC are eligible for inclusion. Thrombocytopenia is an exclusion except if it is HIV-associated. Children randomized prior to their 13th birthday are eligible. All lab values must be within 4 weeks of study entry. Prior Medication: Allowed: Zidovudine (AZT). Exclusion Criteria Co-existing Condition: Patients with the following will be excluded: Lymphoid interstitial proliferation (LIP) not requiring steroids and supplemental oxygen or with other lymphoproliferative diseases as their sole clinical evidence of HIV infection. Known hypersensitivity to immunoglobulin. Active HIV thrombocytopenia requiring IVIG therapy. Concurrent Medication: Excluded: Chronic acetaminophen. Drugs that are metabolized by hepatic glucuronidation should not be used for more than 24 hours without notifying the study physician. Antibacterial prophylaxis for otitis, sinusitis, or urinary tract infection. Prophylaxis treatment for Pneumocystis carinii pneumonia (PCP) prior to the first episode of laboratory-documented PCP. Immunoglobulin (IVIG) therapy required for active HIV thrombocytopenia. Patients with the following will be excluded: Lymphoid interstitial proliferation (LIP) not requiring steroids and supplemental oxygen or with other lymphoproliferative diseases as their sole clinical evidence of HIV infection. Known hypersensitivity to immunoglobulin. Active HIV thrombocytopenia requiring IVIG therapy. Inability to establish or maintain intravenous access. Lack of parental or guardian authorization for intravenous access. Prior Medication: Excluded within 4 weeks of study entry: Any other experimental therapy. Other antiretroviral agents. Drugs which cause prolonged neutropenia or significant nephrotoxicity. Immunoglobulins. Immunomodulating agents. Active alcohol or drug abuse.

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NCT00000721

Inclusion Criteria Concurrent Medication: Allowed: Nystatin or clotrimazole for suppression of oral thrush. Aerosolized pentamidine for Pneumocystis prophylaxis in Group A patients. Trimethoprim / sulfamethoxazole for Pneumocystis prophylaxis in patients who are hematologically stable on trimethoprim / sulfamethoxazole. Patients must have: Group A: AIDS and symptoms defined in disease status. Group B: AIDS related complex (ARC) and symptoms defined in disease status. Exclusion Criteria Co-existing Condition: Patients with the following disease or conditions are excluded: Malignancies other than Kaposi's sarcoma. AIDS dementia. Opportunistic infections requiring ongoing therapy except oral thrush suppression with nystatin or clotrimazole or Pneumocystis prophylaxis in Group A patients. Significant organ system dysfunction including: Granulocytopenia with a granulocyte count < 1000 cells/mm3. Thrombocytopenia - < 75000 platelets/mm3. Anemia with a hemoglobin < 9.5 g/dl. Renal dysfunction - creatinine > 2 mg/dl. Hepatic dysfunction with enzymes or bilirubin > 3 x upper limit of normal. Patients with the following are excluded: Preexisting antibodies to rCD4. Malignancies other than Kaposi's sarcoma. AIDS-dementia complex. Opportunistic infections requiring ongoing therapy. Significant organ system dysfunction. Inability to sign voluntarily the consent form. Prior Medication: Excluded: Recombinant soluble CD4 protein (rCD4). Excluded within 30 days of study entry: Immunomodulatory therapy or agent with anti-HIV activity. Chemotherapy. Prior Treatment: Excluded within 30 days of study entry: Radiotherapy. Active illicit drug use or alcohol abuse at time of entry.

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NCT00000722

Inclusion Criteria Prior Medication: Allowed: Prophylaxis for Pneumocystis carinii pneumonia (PCP); zidovudine. Unequivocal diagnosis of Pneumocystis carinii pneumonia (PCP) established by morphological confirmation of three or more typical Pneumocystis carinii organisms in bronchoalveolar lavage fluid, obtained immediately following the initial inhalation of radiolabeled aerosol. Resting (A-a) DO2 < 30 torr on room air or resting (A-a) DO2 = or < 55 torr on room air with a serious intolerance to trimethoprim / sulfamethoxazole (TMP / SMX), defined as one or more of the following: Platelets < 50000 platelets/mm3 or absolute neutrophil count (polys plus bands) = or < 500 cells/mm3 on at least two occasions = or > 12 hours apart. Blistering rash, mucosal involvement, generalized maculopapular eruption, or intolerable pruritus. Transaminase > 5 x ULN or = or > 300 IU if baseline is abnormal. Daily temperature = or > 103 degrees F beginning after the 5th day of treatment and persisting for at least 3 days and not responsive to antipyretic therapy, with no other discernible cause. Any other severe or life-threatening adverse reaction to TMP / SMX that, in the investigator's opinion, makes continued or recurrent treatment with TMP / SMX inadvisable (approved on a case-by-case basis by the NIAID clinical monitor). Exclusion Criteria Co-existing Condition: Patients with the following conditions or diseases are excluded: Dyspnea, cough, bronchospasm, or other reasons causing inability to cooperate with aerosol administration. History of major adverse reaction to pentamidine. Patients with the following conditions or diseases are excluded: Dyspnea, cough, bronchospasm, or other reasons causing inability to cooperate with aerosol administration. History of major adverse reaction to pentamidine. Prior Medication: Excluded: Other antiprotozoal regimens. Excluded within 14 days of entry: Systemic steroids > adrenal replacement doses

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NCT00000723

Inclusion Criteria Patient must have negative titers for toxoplasmosis or other infectious etiology for CNS disease. Prior Medication: Allowed: Zidovudine may be continued per protocol specifications. Exclusion Criteria Pathologic diagnosis of lymphoma in central nervous system (CNS) must be confirmed but no previous treatment is allowed. In participating institutions where CNS biopsies cannot be obtained, the patient may be considered eligible if space-occupying lesions have been demonstrated on computerized tomography or magnetic resonance imaging with negative titers for toxoplasmosis or negative response to empiric therapy for intracerebral toxoplasmosis and negative workup for other infectious etiology of CNS disease. Co-existing Condition: Patients with the following are excluded: Positive titers for toxoplasmosis. Positive titers for other infectious etiology of CNS disease. Acute intercurrent infection. A second active tumor other than nonmelanomatous skin cancer or Kaposi's sarcoma. Lymphomatous meningitis alone without a mass lesion in the brain. Concurrent Medication: Excluded: Acetaminophen, nonsteroidal anti- inflammatory agents, and corticosteroids other than dexamethasone. Prior Medication: Excluded: Acetaminophen, nonsteroidal anti-inflammatory agents, and corticosteroids other than dexamethasone. Excluded within 2 weeks of study entry: Immunomodulating agents. Excluded within 30 days of study entry: Any investigational agent.

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NCT00000724

Inclusion Criteria Concurrent Medication: Allowed: Antihypertensive agents. Concurrent Treatment: Allowed: Blood products. Ventilatory support. Prior Medication: Required: At least 7 days trimethoprim / sulfamethoxazole or parenteral pentamidine. Allowed: Myelosuppressive or nephrotoxic agents including zidovudine, but must be discontinued during trial. No improvement in ventilatory status, defined as no change or a decrease in arterial or alveolar difference ((A-a) DO2) in the 72 hours prior to entry. (A-a) DO2 should be determined on room air, or receiving an FiO2 of 100 percent for 10 minutes via a tightly fitting non-rebreathing mask, or at an FiO2 of 100 percent for 10 minutes if the patient is being ventilated. Intolerance to TMP / SMX is defined as one or more of the following: Platelets < 50000 platelets/mm3 or absolute neutrophil count (polys + bands) = or < 500 cells/mm3 on at least two occasions = or > 12 hours apart. Blistering rash, mucosal involvement, generalized maculopapular eruption or intolerable pruritus. Transaminase > 5 x ULN or = or > 300 IU if baseline abnormal. Daily temperature = or > 103 degrees F beginning after the 5th day of treatment and persisting for at least 3 days and not responsive to antipyretic therapy, with no other discernible cause. Any other severe or life-threatening adverse reaction to TMP / SMX that, in the investigator's opinion, makes continued or recurrent treatment with TMP / SMX inadvisable (approved on a case-by-case basis by the NIAID clinical monitor). Intolerance to pentamidine is defined as one or more of the following: Platelets < 50000 platelets/mm3 or absolute neutrophil count (polys + bands) < 550 cells/mm3 on at least two occasions = or > 12 hours apart. Serum creatinine > 3.0 mg/dl. Systolic blood pressure < 90 mm requiring supportive therapy. Symptomatic hypoglycemia with blood glucose = or < 40 or hyperglycemia requiring therapy. Pancreatitis with laboratory confirmation (abnormal amylase and/or lipase). Any other severe or life-threatening adverse reaction to pentamidine that, in the investigator's opinion, makes continued or recurrent treatment with pentamidine inadvisable (approved on a case-by-case basis by the NIAID clinical monitor). Exclusion Criteria Co-existing Condition: Patients with the following are excluded: History of Type I hypersensitivity (i.e., urticaria, angioedema, or anaphylaxis), exfoliative dermatitis, or other life-threatening reactions due to trimetrexate. Patients with less severe adverse reactions may be enrolled if, in the opinion of the investigator, they do not prohibit rechallenge with the drug. Concurrent Medication: Excluded: Myelosuppressive or nephrotoxic agents. Other investigational drugs including high-dose steroids (exceeding physiologic replacement doses). Patients with the following are excluded: History of Type I hypersensitivity (i.e., urticaria, angioedema, or anaphylaxis), exfoliative dermatitis, or other life-threatening reactions due to trimetrexate. Patients with less severe adverse reactions may be enrolled if, in the opinion of the investigator, they do not prohibit rechallenge with the drug.

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NCT00000725

Inclusion Criteria Patients must have biopsy-proven AIDS-associated Kaposi's sarcoma. Evidence of HIV infection as manifested by a positive antibody test. Exclusion Criteria Active drug or alcohol abuse. Co-existing Condition: Excluded are patients with: Active opportunistic infections requiring ongoing therapy. Excluded within 90 days of study entry: Must be off therapy for Pneumocystis carinii pneumonia (PCP) unless recovered. Clinically significant cardiac disease, including a history of myocardial infarction or arrhythmia. Concurrent neoplasms other than basal cell carcinoma of the skin. Known hypersensitivity to polymycin B or neomycin. Excluded are patients with: Active opportunistic infections requiring ongoing therapy. Excluded within 90 days of study entry: Must be off therapy for Pneumocystis carinii pneumonia (PCP) unless recovered. Clinically significant cardiac disease, including a history of myocardial infarction or arrhythmia. Concurrent neoplasms other than basal cell carcinoma of the skin. Known hypersensitivity to polymycin B or neomycin. Prior Medication: Excluded: Interferon. Zidovudine (AZT). Excluded within 30 days of study entry: Any biologic modifiers, corticosteroids, cytotoxic chemotherapeutic agents. Other drugs which can cause neutropenia or significant nephrotoxicity. Rifampin or rifampin derivatives, or systemic anti-infectives. Excluded within 90 days of study entry: Other antiviral agents. A history of Pneumocystis carinii pneumonia (PCP) completed treatment. Prior Treatment: Excluded within 30 days of study entry: Radiation therapy.

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NCT00000726

Exclusion Criteria Concurrent Medication: Excluded: Acyclovir. Zidovudine (AZT). Any potentially nephrotoxic agent, especially aminoglycosides, pentamidine, or amphotericin B. Prior Medication: Excluded: Ganciclovir. Foscarnet. Excluded within 7 days of study entry: Any potentially nephrotoxic agent. Excluded within 14 days of study entry: Cytomegalovirus hyperimmune globulin in therapeutic doses. Immunomodulators. Biologic response modifiers. Investigational agents. Amphotericin B maintenance for a systemic mycosis. Known allergy to foscarnet. Active AIDS-defining opportunistic infection other than cytomegalovirus (CMV) including systemic mycosis, pulmonary or neurologic impairment (comatose). Patient must be diagnosed as having: AIDS CDC Group IV.C. Cytomegalovirus (CMV) retinitis as identified by its characteristic ophthalmoscopic appearance and verified by fundus photography. One pending culture for CMV from blood and urine prior to study entry.

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NCT00000727

Inclusion Criteria Patients must fulfill the following criteria: Randomization within 10 weeks of completing therapy for Pneumocystis carinii pneumonia (PCP). Ability to tolerate oral and aerosolized therapy at the time of randomization. Life expectancy > 4 months. Concurrent Medication: Allowed: Inhaled bronchodilators for cough and bronchospasm related to aerosolized pentamidine treatment. Aspirin at modest doses. Ibuprofen at modest doses. Acetaminophen at modest doses. Erythropoietin for management of anemia. Allowed to treat opportunistic infections while on study: Acyclovir. Ketoconazole. Amphotericin B. Nystatin. Clotrimazole. Also allowed: Ganciclovir (DHPG) for maintenance therapy of life-threatening or sight-threatening cytomegalovirus retinitis (CMV retinitis) infection only. Zidovudine (AZT) must be discontinued during the acute induction phase of treatment and will be restarted when maintenance therapy is introduced. Concurrent Treatment: Allowed: Local radiation therapy for Kaposi's sarcoma. Prior Medication: Allowed: Primary prophylactic therapy prior to Pneumocystis carinii pneumonia (PCP) episode. Risk Behavior: Allowed: Patients maintained in a methadone maintenance program per local investigator's judgment. Exclusion Criteria Active drug or alcohol abuse which would impair performance as a study subject. Concurrent Medication: Excluded: Famotidine. Any medications suspected of interference with the metabolism of zidovudine. Flurazepam. Chronic probenecid. Phenobarbital. Phenytoin. Experimental therapies, except as noted. Chronic oral bronchodilators should not be started in patients in order to maintain them on aerosolized pentamidine after they have exhibited pulmonary toxicity. Prior Medication: Excluded for the 30 patients who will undergo pharmacokinetic studies: Zidovudine (AZT) at any time. Excluded within 7 days of study entry for the 30 patients who will undergo pharmacokinetic studies: Trimethoprim / sulfamethoxazole. Pyrimethamine / sulfadoxine. Aerosolized pentamidine. Excluded: Pentamidine by any route for the original infection. Prophylactic therapy for Pneumocystis carinii pneumonia (PCP) between the discontinuation of acute treatment and study entry. Prior Treatment: Excluded within 2 weeks of study entry: Transfusions of blood or red blood cells. Patients may not have any of the following symptoms or diseases: Known treatment-limiting hypersensitivity to sulfonamides, trimethoprim, pyrimethamine, pentamidine, or zidovudine (AZT), especially but not limited to, exfoliative dermatitis, erythema multiforme, and Stevens-Johnson syndrome. Development of severe hypoglycemia (serum glucose < 50 mg/dl with pentamidine therapy). History of neoplasms other than basal cell carcinoma of the skin or carcinoma in situ of the cervix, or mucocutaneous Kaposi's sarcoma. Known visceral Kaposi's sarcoma. Known glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

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NCT00000728

Inclusion Criteria Detectable HIV nucleic acid in patient peripheral blood mononuclear leukocytes (PBML's) by the gene amplification technique. A positive antibody to HIV confirmed by any federally licensed ELISA test kit. Concurrent Medication: Allowed: Medications without which there might be significant risk, such as seizures, loss of diabetic control or respiratory embarrassment. Necessary topical agents including topical acyclovir. Diuretics for significant fluid retention only. Concurrent Treatment: Allowed: Blood transfusions for anemia if hematocrit falls below 25 percent. Exclusion Criteria Active drug or alcohol abuse. Co-existing Condition: Patients with the following will be excluded: Grade 1 impairment on two or more items in the ACTG Micro Neuro AIDS assessment. Concurrent neoplasms other than basal cell carcinoma of the skin or in situ carcinoma of the cervix. Major organ allograft. Significant cardiac disease or central nervous system lesions. Patients with hemophilia should be evaluated and treated under the hemophilia protocol. Concurrent Medication: Excluded: Inderal or vasoactive hypertensive medication. Non-essential medications including pain medications. Excluded are: Patients with an opportunistic infection or malignancy fulfilling the definition of AIDS. Patients with AIDS related complex, defined as: 1. Weight loss in excess of 15 lbs. or 10 percent of body weight noted in a 2-year period prior to entry into the study. 2. Temperature greater than 38.5 degrees C with or without night sweats, persisting for more than 14 consecutive days or more than 15 days in a 30-day interval during a 2-year period prior to entry into the study. 3. Diarrhea defined as = or > 3 liquid stools per day, persisting for more than 30 days during a 2-year period prior to entry into the study without a definable cause. 4. Herpes zoster during the past 2 years. 5. Oral candidiasis or biopsy-proven hairy leukoplakia during the last 2 years. 6. Active substance abuse. Prior Medication: Excluded: Zidovudine (AZT). Excluded within 30 days of study entry: Antiretroviral agents. Biologic response modifiers. Corticosteroids. Excluded within 60 days of study entry: Ribavirin.

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NCT00000729

Inclusion Criteria Concurrent Medication: Allowed: Aerosolized pentamidine for secondary Pneumocystis carinii pneumonia (PCP) prophylaxis. Short course therapy with oral acyclovir (ACV) = or < 7 days. Short course therapy with ketoconazole = or < 7 days for patients who are not responding to any other therapy. Flurazepam. Diphenhydramine. Prior Medication: Allowed: Systemic therapy, prophylaxis or maintenance for an AIDS-defining opportunistic infection. Patients with any of the following findings may be included: Asymptomatic HIV patients with or without lymphadenopathy. Patients with AIDS as defined by the CDC surveillance case definitions. Patients with past or present mild to moderate signs or symptoms consistent with HIV infection. p24 antigen in the serum = or > 60 pg/ml. Exclusion Criteria Co-existing Condition: Patients with the following will be excluded: Ongoing systemic therapy / prophylaxis / maintenance for an AIDS-defining opportunistic infection. Symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to entry into the study, or with concurrent neoplasms other than KS or basal cell carcinoma of the skin or in situ carcinoma of the cervix. Cytomegalovirus (CMV) retinitis. AIDS dementia. Concurrent Medication: Excluded: Antiretrovirals. Immunomodulatory agents. Corticosteroids Other systemic antiviral or antimicrobial agents. Experimental medications. Excluded on chronic basis and discouraged for > 72 hours: Acetaminophen. Narcotics. Aspirin. Concurrent Treatment: Excluded: Transfusion dependency or requirement of 2 units of blood more than once per month. Patients with the following will be excluded: Ongoing systemic therapy / prophylaxis / maintenance for an AIDS-defining opportunistic infection. Symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to entry into the study, or with concurrent neoplasms other than KS or basal cell carcinoma of the skin or in situ carcinoma of the cervix. Cytomegalovirus (CMV) retinitis. AIDS dementia. Prior Medication: Excluded within 30 days of study entry: Antiretroviral agents (except ribavirin). Immunomodulatory agents. Excluded within 60 days of study entry: Ribavirin. The last blood transfusion cannot have been given within 2 weeks of entry. Active substance abuse which could impair compliance with the protocol.

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NCT00000730

Inclusion Criteria Concurrent Medication: Allowed: physiologic replacement doses of steroids. Pneumocystis carinii pneumonia (PCP) in patient who is HIV positive by ELISA, HIV culture, or p24 antigenemia, or is a member of a risk group for HIV infection. Failed at least 4 but not > 14 full days' therapy with either sulfamethoxazole/trimethoprim (SMX/TMP) or parenteral pentamidine. Patients must have received therapy with only one of the two conventional agents prior to enrollment. Patients in whom an unequivocal diagnosis of this episode of PCP has been or can be established by morphologic confirmation of three or more typical Pneumocystis carinii organisms in sputum, bronchoalveolar lavage fluid, or lung tissue obtained by transbronchial or open lung biopsy within 15 days prior to study entry. Patients in whom no significant improvement in arterial-alveolar oxygen pressure (defined as a decrease of at least 15mm Hg) is observed in the 24 hours prior to entry. Patient is willing to have maximal medical support, including pressors, invasive monitoring, and/or mechanical ventilation, during at least the first 7 days of protocol therapy if such support is necessary. Continuation of maximal medical support beyond 7 days is at discretion of investigator and patient. Patients with history of hypersensitivity less severe than type I may be enrolled if, in opinion of investigator, these adverse effects do not prohibit rechallenge with the drug. Prior Medication: Required: At least 4 full days but no greater than 14 full days of parenteral and/or oral therapy with sulfamethoxazole/trimethoprim (SMX/TMP) or pentamidine. Allowed: Zidovudine (AZT). Exclusion Criteria Co-existing Condition: Excluded: Patients with history of type I hypersensitivity (urticaria, angioedema, anaphylaxis), exfoliative dermatitis, or other life-threatening reaction secondary to trimetrexate, sulfamethoxazole/trimethoprim, or pentamidine. Presence of any process that, in the opinion of investigator, would be adversely and seriously affected by steroid therapy. Failure to meet inclusion criteria. Concurrent Medication: Excluded: Zidovudine (AZT). Myelosuppressive agents. Nephrotoxic agents. AZT may be resumed at completion of study. Excluded: Patients with history of type I hypersensitivity (urticaria, angioedema, anaphylaxis), exfoliative dermatitis, or other life-threatening reaction secondary to trimetrexate, sulfamethoxazole/trimethoprim, or pentamidine. Presence of any process that, in the opinion of investigator, would be adversely and seriously affected by steroid therapy. Failure to meet inclusion criteria. Prior Medication: Excluded within 4 days of study entry: Any other investigational agent. Excluded within 14 days of study entry: Steroids (other than physiologic replacement doses).

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NCT00000731

Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Severe ongoing opportunistic infection including Pneumocystis carinii pneumonia (PCP), cryptococcal or toxoplasmosis meningoencephalitis, disseminated herpes simplex or herpes zoster. A demonstrated prior sensitivity or an experience of significant adverse effects during prior therapy with the drug to be used in the study. Significant diarrhea at entry ( > 1 watery stool/day). Patients with the following are excluded: Severe ongoing opportunistic infection including Pneumocystis carinii pneumonia (PCP), cryptococcal or toxoplasmosis meningoencephalitis, disseminated herpes simplex or herpes zoster. A demonstrated prior sensitivity or an experience of significant adverse effects during prior therapy with the drug to be used in the study. Significant diarrhea at entry ( > 1 watery stool/day). AIDS related complex (ARC) defined as presence of any one of the following within 12 months prior to entry and absence of a concurrent illness or condition other than HIV infection to explain the findings: Fever of > 38.5 degrees C persisting for longer than 3 weeks. Involuntary weight loss of > 15 lbs. or > 10 percent of baseline noted in a 120-day period prior to evaluation. History of diarrhea (> 2 liquid stools per day) persisting for longer than 1 month but not occurring at entry. History of clinical diagnosis of oral candidiasis or hairy leukoplakia. Patients who have AIDS-defined opportunistic infections or tumors. Patients eligible for zidovudine under the labeling. A positive HIV antibody test. Exceptions will be made for patients with a previously positive HIV antibody test with progressive disease and patients where virus isolation has been made. A life expectancy of at least 3 months. Patients with stable Kaposi's sarcoma, mild herpes infections, mild or stable depression, asymptomatic or mild cytomegalovirus or Epstein-Barr virus infection, or a hepatitis B virus carrier state will be acceptable for study. Inability to abstain from alcohol or any other drug, including nonprescription medications, during the study period.

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NCT00000732

Inclusion Criteria Prior Medication: Allowed: Zidovudine (AZT) for patients with AIDS. AIDS related complex (ARC). The presence of any one of the following findings within 12 months prior to entry and the absence of a concurrent illness or conditions other than HIV infection to explain the findings: Fever of > 38.5 C degrees persisting for longer than 3 weeks. Involuntary weight loss of > 15 lbs. or > 10 percent of baseline noted in a 120-day period prior to evaluation. Diarrhea (> 2 liquid stools per day) persisting for longer than 1 month. History of clinical diagnosis of oral candidiasis or hairy leukoplakia. Patients who have AIDS-defining opportunistic infections or tumors. Patients eligible for AZT under the labeling. A positive HIV antibody test. Exceptions will be made for patients with a previously positive HIV antibody test with progressive disease and patients where virus isolation has been made. A life expectancy of at least 3 months. Patient with stable Kaposi's sarcoma, mild herpes infection, mild or stable depression, asymptomatic or mild cytomegalovirus or Epstein-Barr virus infection, or a hepatitis B virus carrier state will be acceptable for study. Exclusion Criteria Concurrent Medication: Excluded: Phenytoin. Prior Medication: Excluded within 30 days of study entry: Other antiretroviral agents. Patient has any severe ongoing opportunistic infections including Pneumocystis carinii pneumonia (PCP), cryptococcal or toxoplasmosis meningoencephalitis, disseminated herpes simplex or herpes zoster. Patient has significant diarrhea at entry ( > 1 watery stool per day). Patient has demonstrated prior sensitivity or has experienced significant adverse effects during prior therapy with the drugs to be used in the study. Cannot abstain from alcohol or any other drugs during the study.

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NCT00000733

Inclusion Criteria Patients must be asymptomatic according to the following criteria: Normal neurologic exam. No unintentional weight loss of greater than 10 lbs. or more than 10 percent of usual body weight within 2 years prior to entering the study. No unexplained temperature above 38 degrees C on more than 5 consecutive days or on more than 10 days in any 30 days in the 2 years prior to expected entry into the study. No unexplained diarrhea defined by equal to or more than 3 liquid stools per day persisting more than 7 days within 2 years prior to expected entry into the study. No active hepatitis of any form. In addition, patients must not have previously had AIDS or an AIDS related illness. Exclusion Criteria Co-existing Condition: Excluded: Temperature of greater than 37.8 degrees C. Development of an AIDS-defining opportunistic infection. Unexplained diarrhea defined by equal to or more than 3 liquid stools per day. Active hepatitis of any form. Patients who have had oral candida infection documented by morphology, or by response to antifungal therapy, or oral hairy leukoplakia, or herpes zoster infection within 2 years of anticipated study entry at any time will be excluded. Patients with a prior history of a malignancy other than cutaneous basal cell carcinomas or cervical carcinoma in situ and patients with a significant chronic underlying medical illness that would impair continuous participation in the study will be excluded. Prior Medication: Excluded within 90 days of study entry: Immunomodulators. Active alcohol or drug abuse sufficient in the investigator's opinion to prevent adequate compliance with the study therapy.

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NCT00000734

Inclusion Criteria Prior Medication: Allowed: Zidovudine (AZT) for patients with AIDS. AIDS related complex (ARC). The presence of any one of the following findings within 12 months prior to entry and the absence of a concurrent illness or condition other than HIV infection to explain the findings: Fever of > 38.5 degrees C persisting for longer than 3 weeks. Involuntary weight loss of > 15 lbs. or > 10 percent of baseline noted in a 120-day period prior to evaluation. Diarrhea (> 2 liquid stools per day) persisting for longer than 1 month. History of clinical diagnosis of oral candidiasis or hairy leukoplakia. Patients who have AIDS-associated opportunistic infections or tumors. Patients eligible for AZT under the labeling. A positive HIV antibody test. Exceptions will be made for patients with a previously positive HIV antibody test with progressive disease and patients where virus isolation has been made. Patient with stable Kaposi's sarcoma, mild herpes infection, mild or stable depression, asymptomatic or mild cytomegalovirus or Epstein-Barr virus infection, or a hepatitis B virus carrier state will be acceptable for study. A life expectancy of at least 3 months. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Severe ongoing opportunistic infections including Pneumocystis carinii pneumonia (PCP), cryptococcal or toxoplasmosis meningo-encephalitis, disseminated herpes simplex or herpes zoster. Significant diarrhea at entry ( > 1 watery stool per day). Concurrent Medication: Excluded: Phenytoin. Prior Medication: Excluded within 30 days of study entry: Other antiretroviral agents or immunomodulating agents. Patient has demonstrated prior sensitivity or has experienced significant adverse effects during prior therapy with the drugs to be used in the study. Patient cannot abstain from alcohol or any other drugs, including nonprescription medication, during the study period.

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NCT00000735

Inclusion Criteria Hemophiliacs are included. Patients must have: Consistently positive serum HIV p24 antigen (= or > 70 pg/ml) defined by the Abbott HIV antigen test. This demonstration must be seen on two occasions, each separated by at least 72 hours, the last of which must be within 2 weeks of starting therapy. Positive HIV antibody test. Prior Medication: Allowed: Acyclovir for short course (7 days). Ketoconazole for short course (7 days). Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis. Trimethoprim / sulfamethoxazole for PCP prophylaxis. Exclusion Criteria Co-existing Condition: Patients with AIDS encephalopathy as a sole indicator are excluded. Patients with AIDS encephalopathy as a sole indicator are excluded. Prior Medication: Excluded: Other experimental medication. Antineoplastic therapy. Amphotericin B. Ganciclovir. Excluded within 14 days of study entry: Biologic modifiers. Corticosteroids. Excluded within 30 days of study entry: Other antiretroviral agents. Excluded within 60 days of study entry: Ribavirin. Active drug or alcohol abuse.

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NCT00000736

Inclusion Criteria Patients must: Be HIV seropositive and asymptomatic. Have normal neurologic exam as defined by the Micro Neuro-AIDS assessment. Concurrent Medication Required: Prophylaxis for Pneumocystis carinii pneumonia (PCP). Aerosolized pentamidine is preferred but if not possible, Trimethoprim / sulfamethoxazole 1 DS tablet per day or Dapsone 50 - 100 mg per day is allowed. Exclusion Criteria Active drug or alcohol abuse sufficient to prevent adequate compliance with study therapy in the investigator's opinion. Co-existing Condition: Patients with the following diseases or conditions are excluded: Hemophilia. Oral candida infection documented by morphology or by response to antifungal therapy within 2 years of study entry. Oral hairy leukoplakia at any time prior to study entry. Herpes zoster infection (including single dermatome infection) within 2 years of study entry. Active diarrhea as defined by 3 or more liquid stools per day. Temperature > 37.8 degrees C. Grade 1 impairment on two or more items (mild AIDS dementia complex) in the ACTG Micro Neuro-AIDS Assessment. Prior history of malignancy other than cutaneous basal cell carcinomas or cervical carcinoma in situ. Patients with the following are excluded from entry: AIDS or AIDS-related complex defining symptoms. Significant, chronic underlying medical illnesses which would impair continuous participation in this 3-year clinical trial. Hemophilia. Prior Medication: Excluded: Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP). Other experimental medications. Excluded within 60 days of study entry: Antiretroviral drugs or immunomodulators (biologic response modifiers). Excluded within 120 days of study entry: Systemic corticosteroids. Prior Treatment: Excluded within 3 months of study entry: Blood transfusion.

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NCT00000737

Inclusion Criteria Concurrent Medication: Allowed: Zidovudine (AZT), didanosine (ddI), and dideoxycytidine (ddC). If initiating new antiretroviral therapy, patient must have been on a stable dose for at least 4 weeks prior to study entry. Maintenance or suppressive therapy with any of the following, provided patient has been on a stable dose for at least 1 week prior to study entry: Ganciclovir or foscarnet for CMV retinitis. Fluconazole, amphotericin B, or flucytosine for cryptococcosis. Amphotericin B for disseminated histoplasmosis. Pyrimethamine, sulfadiazine, dapsone, or clindamycin for toxoplasmosis. Amikacin, clarithromycin, clofazimine, ethambutol, ciprofloxacin, or rifampin for disseminated Mycobacterium avium complex. Isoniazid, rifampin, ethambutol, or pyrazinamide for M. tuberculosis. Any of the following provided patient is on a stable dose for at least 1 week prior to study entry: Trimethoprim-sulfamethoxazole, aerosolized pentamidine, or dapsone for Pneumocystis carinii prophylaxis. Clotrimazole troches, nystatin suspension, ketoconazole, or fluconazole for oral candidiasis. Oral acyclovir for mucocutaneous herpes simplex. Narcotic analgesics, tranquilizers, sedative-hypnotics, or anticholinergic agents provided patient is on a stable dose for at least 1 week prior to study entry. Patients must have: HIV infection. HIV-wasting syndrome and anorexia. Life expectancy of at least 4 months. Ability to tolerate oral therapy, feed themselves, and have access to as much food as they desire with no dietary restrictions. Prior Medication: Allowed: Prior zidovudine (AZT), didanosine (ddI), and dideoxycytidine (ddC). Prior maintenance or suppressive therapy for certain opportunistic infections, as follows: Ganciclovir or foscarnet for CMV retinitis. Fluconazole, amphotericin B, or flucytosine for cryptococcosis. Amphotericin B for disseminated histoplasmosis. Pyrimethamine, sulfadiazine, dapsone, or clindamycin for toxoplasmosis. Amikacin, clarithromycin, clofazimine, ethambutol, ciprofloxacin, or rifampin for disseminated Mycobacterium avium complex. Isoniazid, rifampin, ethambutol, or pyrazinamide for M. tuberculosis. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: Major, acute opportunistic infections. Active neoplasms other than Kaposi's sarcoma or localized skin carcinoma. Diabetes, congestive heart failure, clinical ascites, or uncontrolled hypertension. Persistent grade 3/4 diarrhea. Impaired oral intake, such as occurs with Candida esophagitis or severe mouth ulcers. Clinically significant cardiac arrhythmias. Requirement for anticonvulsants for seizure disorder. Concurrent Medication: Excluded: Marijuana use. Anabolic steroids. Anticonvulsants for seizure disorders. Alcohol or barbiturates. Patients with the following prior conditions are excluded: Diagnosis of a major, acute opportunistic infection within 2 months prior to study entry. Hospitalization within 2 weeks prior to study entry. History of hypersensitivity reactions to megestrol acetate, dronabinol, or sesame oil (a component of the dronabinol capsules). History of thromboembolic events. History of psychiatric disorder other than depression. Prior Medication: Excluded: Prior dronabinol. Megestrol acetate within 2 months prior to study entry. Marijuana within 1 month prior to study entry. Anabolic steroids within 3 months prior to study entry. Current drug or alcohol abuse (patients with a history of occasional marijuana use are eligible provided they have abstained from its use for 1 month prior to study entry and agree to refrain from marijuana use for the study period).

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NCT00000738

Inclusion Criteria Concurrent Medication: Allowed: Alternative or additional antiretroviral agents if on a stable dose for 8 weeks prior to study entry. Isoniazid. Anticonvulsants. Benzodiazepines and antidepressants (provided dose is stable prior to study entry). Symptomatic therapies (e.g., analgesics, antihistamines, antiemetics, and antidiarrheal agents). Maintenance therapy with clarithromycin, azithromycin, amikacin, ethambutol, clofazimine, ciprofloxacin, and rifampin for disseminated Mycobacterium avium infection. Maintenance therapy for opportunistic infections (e.g., PCP, MAI, CMV). Patients must have: Documented HIV infection. HIV-Associated Motor / Cognitive Complex. Acceptable neurological and neuropsychological impairment scores. Estimated premorbid IQ of 70 or greater, consistent with completion of the sixth grade or ability to read at the sixth grade level. Current ability to read and comprehend a newspaper or history of such ability will satisfy this criterion for patients whose formal education stopped before the sixth grade. For patients who are illiterate, ability to make change from a dollar for a combined purchase of two items or the history of such ability will satisfy this criterion. In the absence of a functional definition, an age-correlated scaled score of > 5 on the Vocabulary Subtest of the WAIS-R or WISC-R may be used to establish IQ. Ability to provide written informed consent. Prior Medication: Required: AZT for at least 12 weeks prior to study entry or any other approved antiretroviral agent (i.e., ddI or ddC) for at least 8 weeks prior to study entry, except in antiretroviral-intolerant patients who must be off antiretrovirals for at least 4 weeks. Exclusion Criteria Co-existing Condition: Patients with the following symptoms and conditions are excluded: Active symptomatic AIDS-defining opportunistic infection (maintenance therapy for opportunistic infections, e.g., Pneumocystis carinii pneumonia, Mycobacterium avium infection, and cytomegalovirus, is permitted). Neoplasms other than basal cell carcinoma, in situ carcinoma of the cervix, or Kaposi's sarcoma without evidence of visceral involvement or that do not require systemic chemotherapy. Confounding neurological disorders, including the following: a) neurologic disease unrelated to HIV infection (such as multiple sclerosis, documented stroke, degenerative disease); b) chronic seizure disorders or head injuries if the condition results in functional impairment or is likely to interfere with evaluations; c) central nervous system (CNS) infections or neoplasms (such as toxoplasmosis, primary or metastatic CNS lymphoma, progressive multifocal leukoencephalopathy, cryptococcal or other fungal meningitis, tuberculous CNS infections, or untreated neurosyphilis). Severe premorbid psychiatric illness including bipolar illness, schizophrenia, and depression requiring electroconvulsive therapy. Major depression likely to interfere with evaluation or protocol compliance. Concurrent Medication: Excluded: Major psychotropic medication, including MAO inhibitors, phenothiazines, butyrophenones, barbiturates, or amphetamines (unless a stable dose is maintained for 30 days prior to study entry). Any ongoing maintenance therapy for confounding neurological disorders. Patients with the following prior conditions are excluded: Confounding neurological disorders defined in the "Exclusion Co-existing Conditions" field. Prior Medication: Excluded: Investigative drugs within 30 days prior to study entry. Confounding calcium channel antagonists (such as nifedipine, verapamil, diltiazem, and related drugs) within 4 weeks prior to study entry. Active alcohol or drug abuse.

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NCT00000739

Inclusion Criteria Concurrent Medication: Allowed: Rifampin and rifampin derivatives for up to 1 week during the study. Rifabutin or other drugs that could alter dapsone metabolism (if prescribed by the child's primary care physician). Patients must have: Evidence of HIV infection. PER AMENDMENT 11/16/95: Children who require prophylaxis. (Was written - Risk of developing PCP.) Known intolerance to TMP / SMX. Consent of parent or guardian. Patients entering this study may be co-enrolled in other ACTG pediatric studies. Exclusion Criteria Co-existing Condition: Patients with the following symptoms and conditions are excluded: Glucose-6-phosphate dehydrogenase deficiency. Known allergy to dapsone. Concurrent Medication: Excluded: Rifampin, rifampin derivatives, or oxidant drugs for more than 1 week. Patients with the following prior conditions are excluded: Serious or life-threatening reactions to TMP / SMX (e.g., anaphylaxis, Stevens-Johnson syndrome, hypotension) that would contraindicate therapy with sulfa drugs. Prior Medication: Excluded: Prior dapsone. Rifampin, rifampin derivatives, or oxidant drugs within 1 week prior to study entry. TMP / SMX within 7 days prior to study entry (and toxicity must be clearly resolving). Prior Treatment: Excluded: RBC transfusion within 4 weeks prior to study entry.

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NCT00000740

Inclusion Criteria Patients must have: HIV antibody positive. CD4 cell counts less than 500/mm3. Adequate general health. No significant deterioration in performance status within the past month. Prior treatment with a stable regimen of antiretroviral medication for at least 4 weeks prior to study. Prior Medication: Required: Stable regimen of antiretroviral medication for at least 4 weeks prior to study entry. Allowed: Aerosolized pentamidine for PCP prophylaxis. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: Intercurrent infection. Clinically significant abnormality on EKG. Known hypersensitivity to quinolines. Known hemoglobin M abnormality. Known NADH methemoglobin reductase deficiency. Positive test for G6PD deficiency. Fever. Prior Medication: Excluded: Other systemic medication (other than AZT, ddC, ddI, methadone, acyclovir, and NSAIDs) within 3 days prior to study entry.

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NCT00000741

Inclusion Criteria Concurrent Medication: Allowed: Recombinant erythropoietin and any FDA-approved cytokine for management of anemia. Antiretroviral agents. Patients must have: Documented HIV infection. PCP. No more than 36 hours of prior primary therapy for confirmed or presumed PCP. Prior Medication: Allowed: Up to 35 hours of primary therapy for confirmed or presumed PCP. Exclusion Criteria Co-existing Condition: Patients with the following symptoms and conditions are excluded: Demonstrated intolerance to steroids. Requirement for steroids at greater than physiological doses for other medical conditions.

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NCT00000742

Inclusion Criteria Concurrent Medication: Allowed: PCP prophylaxis with aerosolized pentamidine, trimethoprim / sulfamethoxazole or dapsone. Clotrimazole troches or nystatin oral suspension for oral candidiasis. Acyclovir (up to 1000 mg/day) for herpes lesions. Patients must have: HIV infection documented by serologic tests or HIV culture OR prior diagnosis of AIDS by established CDC criteria. CD4 counts = or < 500 cells/mm3 on two evaluations. Part II only: No prior therapy with antiretroviral or immunomodulating agents (e.g., AZT, ddI, ddC, interferon). Exclusion Criteria Co-existing Condition: Patients with the following symptoms and conditions are excluded: Acute medical problems at time of study entry (including active opportunistic infections such as active cryptococcosis, Pneumocystis carinii, herpes zoster, histoplasmosis, or CMV, or nonopportunistic diseases including liver disease, renal disease, orthostatic hypotension, hypertension, lymphoma). Current diagnosis of malignancy for which systemic therapy would be required during the study. Concurrent Medication: Excluded: Any other investigational drugs. Phenobarbital, phenytoin, ketoconazole, rifampin, cimetidine, beta blockers, chronic anti-acid therapy, antiarrhythmic agents or other medications known to affect cardiac conduction or seizure threshold. Cytotoxic chemotherapy. Patients with the following prior conditions are excluded: History of cardiovascular disease including conduction disturbances, arrhythmias, atherosclerotic heart disease, or valvular heart disease. History of CNS disease such as seizure disorder, AIDS Dementia Complex, Progressive Multifocal Leukoencephalopathy, or any other active neurological disorder. History of active or chronic gastrointestinal disorders such as chronic diarrhea (> 4 weeks duration), constipation, unexplained abdominal pain (such as irritable bowel syndrome), or other GI motility disorders. History of hypercholesterolemia requiring medication or serum cholesterol = or > 300. Part I patients only: History of inability to tolerate zidovudine (200 mg q 8 hours). Part III patients only: History of pancreatitis or > grade 2 peripheral neuropathy. Prior Medication: Excluded: Cytotoxic chemotherapy within 1 month prior to study entry. Part II only: prior therapy with antiretroviral or immunomodulatory agents (including but not limited to AZT, ddI, ddC, and interferon). Current use of alcohol or illicit drugs.

Male