A Study to Evaluate Various Combinations of Anti-HIV Medications to Treat Early HIV Infection
HIV Infections
About this trial
This is an interventional treatment trial for HIV Infections focused on measuring HIV Protease Inhibitors, Reverse Transcriptase Inhibitors, Anti-HIV Agents, Viral Load
Eligibility Criteria
Inclusion Criteria Concurrent Medication: [Required: AS PER AMENDMENT 7/5/00: Chemoprophylaxis for Pneumocystis carinii pneumonia if CD4+ cell count is less than or equal to 200 cells/mm3.] [Suggested as an alternative agent for chemoprophylaxis against Mycobacterium avium complex: Azithromycin.] [Allowed: AS PER AMENDMENT 7/5/00: Topical and oral antifungal agents. Oral itraconazole may be administered concurrently with IDV if the dose of IDV is reduced to 600 mg every 8 hours. Treatment, maintenance, or chemoprophylaxis for opportunistic infections, as clinically indicated unless otherwise prohibited by the protocol. All antibiotics, as clinically indicated unless otherwise prohibited by the protocol. Systemic corticosteroid use for 21 days or less for acute problems, as medically indicated. Recombinant erythropoietin (rEPO, epoetin alfa, Epogen, epoetin beta, Marogen), granulocyte colony-stimulating factor (G-CSF, filgrastim, Neupogen), and granulocyte-macrophage colony-stimulating factor (GM-CSF, Regramostim). Regularly prescribed medications, such as antipyretics, analgesics, allergy medications, antidepressants, sleep medications, oral contraceptives, megestrol acetate (Megace), testosterone, or any other medications, as medically indicated unless otherwise prohibited by the protocol. NOTE: Due to the possibility that study medications may alter the effectiveness of oral contraceptives or depoprogesterone, these agents must not be used as the sole form of birth control, because the role of some study medications on the effectiveness of these methods has not yet been established. Alternative therapies, such as vitamins. Medications requiring low gastric pH if not administered at the same time as buffered ddI. Patients taking these agents should do so at least 2 hours before ddI.] Vaccinations, if administered at least 2 weeks prior to an HIV RNA viral load evaluation. [Allowed with caution: AS PER AMENDMENT 7/5/00: Oral ketoconazole with IDV. Medications that interact with PIs as substrates, inhibitors, or inducers, including, but not limited to: allopurinol, alprazolam, amitriptyline, atorvastatin, bupropion, carbamazepine, cerivastatin, chlorpheniramine, chlorpromazine, chlorzoxazone, cimetidine, clarithromycin, clofibrate, clorazepate, clozapine, codeine, dapsone, desipramine, diazepam, diltiazem, disopyramide, encainide, erythromycin, estazolam, estrogens and progesterones, fluoxetine, flurazepam, fluvastatin, glucocorticoids, hypericum perforatum (St. John's wort), imipramine, isoniazid, itraconazole, ketoconazole, labetalol, lamotrigine, lidocaine, lovastatin, mexiletine, morphine, naloxone, nefazodone, nifedipine, nortriptyline, opioids, oxazepam, pentazocine, phenobarbital, phenytoin, promethazine, propofol, propranolol and other beta blockers, sildenafil, simvastatin, temazepam, T3 (thyroid hormone), warfarin, valproic acid, and zolpidem. Drugs with high protein-binding properties, nephrotoxic drugs, and opiate agonists (e.g., methadone or buprenorphine).] NOTE: Refer to package insert for potential drug interactions with IDV, RTV, NFV, or APV that may require therapeutic drug monitoring and/or adjustment of concomitant medications.] [Allowed with extreme caution: AS PER AMENDMENT 7/5/00: ddI, as clinically indicated in patients with known risk factors, including, but not limited to, alcohol abuse, morbid obesity, hypertriglyceridemia, cholelithiasis, endoscopic retrograde cholangiopancreatography, use of medications known to cause pancreatitis (e.g., pentamidine) and use of medications known or thought to increase exposure to ddI (e.g., HU, allopurinol).] Concurrent Treatment: [Allowed: AS PER AMENDMENT 7/5/00: Acupuncture and visualization techniques.] Patients must have: HIV infection, as documented by any licensed ELISA test kit and confirmed by either Western blot, HIV culture, HIV antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA at any time prior to study entry. Plasma HIV-1 RNA of 500 copies/ml or more, confirmed by the Roche Amplicor assay only and performed within 60 days [AS PER AMENDMENT 5/5/99: 70 days] of study entry by any certified laboratory. Inclusion laboratory parameters, documented within 14 days prior to study entry (see lab values). [AS PER AMENDMENT 9/9/99: Co-enrollment on ACTG A5005s (Metabolism Substudy) is required for patients enrolling under Version 3.0 of ACTG 384.] Risk Behavior: [Allowed with caution: AS PER AMENDMENT 7/5/00: Alcoholic beverages.] Exclusion Criteria Co-existing Condition: Patients with the following condition are excluded: AIDS-related malignancy other than minimal Kaposi's sarcoma. Concurrent Medication: [Excluded: AS PER AMENDMENT 7/5/00: Chronic systemic corticosteroids. For Steps 1 and 2, all antiretroviral therapies other than study medications. For step 3, contact the team to discuss potential addition or substitution with off-study antiretroviral medications. Investigational drugs without specific approval from the study chairs. Neurotoxic and pancreatotoxic drugs. Systemic cytotoxic chemotherapy. Amiodarone, astemizole, bepridil, cisapride, cholestyramine, ergot and ergot derivatives, flecainide, ganciclovir, interferon alfa, midazolam (unless used for sedation on ACTG 723), pimozide, propafenone, propoxyphene, quinidine, ribavirin, rifampin, sucralfate, terfenadine, and triazolam. Rifabutin for patients on RTV in Step 3 and for patients on Steps 1 and 2 because of the contradictory effects of EFV and NFV on plasma rifabutin levels. If a patient on Step 1 or 2 requires treatment with rifabutin after coming on the study, the team must be notified. Alpha tocopherol (vitamin E) supplementation since vitamin E is contained in the soft gelatin capsule formulation of APV. ddI concurrently with IV pentamidine. Herbal medications.] Patients with the following prior conditions are excluded: Pancreatitis within 3 years of study entry. Current peripheral neuropathy grade 2 or greater or history of peripheral neuropathy grade 3 or greater. Documented or suspected acute hepatitis within 30 days prior to study entry. Unexplained temperature above 38.5 C for any 7 days or chronic diarrhea (defined as more than 3 liquid stools per day persisting for more than 15 days) within 30 days prior to study entry. Any previous hypersensitivity to study drugs or their components. Prior Medication: Excluded: Receipt within 30 days of erythropoietin, G-CSF, or GM-CSF. Treatment within 14 days of study entry with any of the following: amiodarone, astemizole, cisapride, ergot or ergot derivatives, ketoconazole, midazolam, propoxyphene, quinidine, rifampin, terfenidine, or triazolam. Prior antiretroviral therapy for 7 days or more, including protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), and nonnucleoside reverse transcriptase inhibitors (NNRTIs). [AS PER AMENDMENT 5/5/99: Systemic ketoconazole or itraconazole, intravenous pentamidine, and rifabutin are prohibited. Midazolam is allowed for sedation in patients participating on ACTG 723.] Any vaccination within 14 days prior to study entry. Any immunomodulator or investigational therapy within 30 days prior to study entry. [AS PER AMENDMENT 5/5/99: 6. Rifabutin is discouraged.] Prior Treatment: Excluded: Acute therapy for an infection or other medical illness within 14 days prior to study entry. [AS PER AMENDMENT 5/5/99: Acute therapy for a serious infection or other serious medical illness that is potentially life-threatening and requires systemic therapy and/or hospitalization within 14 days of study entry. Patients with Pneumocystis carinii pneumonia must have completed acute therapy at least 7 days prior to entry and be clinically stable. Patients with other serious infection or serious medical illness who must continue chronic therapy must have completed at least 14 days of therapy prior to entry and be clinically stable. Patients with all other infections or medical illnesses must have completed therapy, or at least 14 days of maintenance therapy, prior to entry and be clinically stable (restrictions do not apply to oral and vaginal candidiasis, mucocutaneous herpes simplex infection, and minor skin conditions).] Risk Behavior: Excluded: Possible current substance abuse that could prevent compliance with the study medication.
Sites / Locations
- Univ of Alabama at Birmingham
- Univ of Southern California / LA County USC Med Ctr
- UCLA CARE Ctr
- Willow Clinic
- Univ of California / San Diego Treatment Ctr
- San Francisco AIDS Clinic / San Francisco Gen Hosp
- San Francisco Gen Hosp
- Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
- Marin County Specialty Clinic
- San Mateo AIDS Program / Stanford Univ
- Stanford Univ Med Ctr
- Harbor UCLA Med Ctr
- Univ of Colorado Health Sciences Ctr
- Georgetown Univ Hosp
- Howard Univ
- Univ of Miami School of Medicine
- Emory Univ
- Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr
- Univ of Hawaii
- Northwestern Univ Med School
- Cook County Hosp
- Rush Presbyterian - Saint Luke's Med Ctr
- Indiana Univ Hosp
- Division of Inf Diseases/ Indiana Univ Hosp
- Methodist Hosp of Indiana / Life Care Clinic
- Univ of Iowa Hosp and Clinic
- Charity Hosp / Tulane Univ Med School
- Tulane Med Ctr Hosp
- Tulane Univ School of Medicine
- State of MD Div of Corrections / Johns Hopkins Univ Hosp
- Harvard (Massachusetts Gen Hosp)
- Boston Med Ctr
- Beth Israel Deaconess - West Campus
- Univ of Minnesota
- St Louis Regional Hosp / St Louis Regional Med Ctr
- Univ of Nebraska Med Ctr
- SUNY / Erie County Med Ctr at Buffalo
- Beth Israel Med Ctr
- Manhattan Veterans Administration / New York Univ Med Ctr
- Chelsea Ctr
- Cornell Univ Med Ctr
- Mem Sloan - Kettering Cancer Ctr
- Mount Sinai Med Ctr
- Columbia Presbyterian Med Ctr
- St Mary's Hosp (Univ of Rochester/Infectious Diseases)
- Univ of Rochester Medical Center
- Univ of North Carolina
- Carolinas Med Ctr
- Duke Univ Med Ctr
- Moses H Cone Memorial Hosp
- Akron City Hospital
- Univ of Cincinnati
- Univ of Kentucky Lexington
- Case Western Reserve Univ
- MetroHealth Med Ctr
- Ohio State Univ Hosp Clinic
- Milton S Hershey Med Ctr
- Philadelphia Veterans Administration Med Ctr
- Univ of Pennsylvania at Philadelphia
- Univ of Pittsburgh Med Ctr
- Julio Arroyo
- Univ of Texas Galveston
- Univ of Washington
- Azienda Ospedaliera Umberto I
- Ospedale S Orsola
- Spedali Civili - Carosi
- Spedali Civili Cadeo
- Archispedale S Anna
- Universita di Genova
- Ospedale Luigi Cacco Moroni
- Ospedale Luigi Sacco Cargnel
- Azienda Ospedaliera di Parma
- IRCCS Policlinico S Matteo Filice
- IRCCS Policlinico S Matteo Minoli
- Archispedale S Maria Nuova
- Universita di Roma - Delia
- Ospedale Civile Maggiore
- Univ of Puerto Rico
- Azienda USL di Piacenza
- Francesco Leoncini