A Study to Evaluate Various Combinations of Anti-HIV Medications to Treat Early HIV Infection
NCT ID: NCT00000919
Last Updated: 2012-06-07
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
COMPLETED
Clinical Phase
NA
Total Enrollment
900 participants
Study Classification
INTERVENTIONAL
Study Completion Date
2002-11-30
Brief Summary
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The purpose of this study is to compare the effectiveness of various combinations of anti-HIV drugs in HIV-positive men and women. Patients receive specific combinations of 3 or 4 of the following 6 drugs: didanosine (ddI), stavudine (d4T) efavirenz (EFV), nelfinavir (NFV), lamivudine (3TC), or zidovudine (ZDV).
Anti-HIV therapy is effective in preventing the spread of HIV in the body. However, patients often experience unpleasant side effects and have difficulties following the dosing schedule. This study looks for combinations of anti-HIV drugs ("cocktails") which will be the most effective with the fewest problems.
Anti-HIV therapy is effective in preventing the spread of HIV in the body. However, patients often experience unpleasant side effects and have difficulties following the dosing schedule. This study looks for combinations of anti-HIV drugs ("cocktails") which will be the most effective with the fewest problems.
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Detailed Description
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Highly active antiretroviral therapy, though effective in the suppression of HIV proliferation, is often complicated by difficulties with adherence and drug toxicity. Various combinations of highly active antiretroviral therapy exist; all have proved efficacious in related trials. The question addressed in this trial is which combination of antiretroviral "cocktails" provides the single greatest advantage in preventing the spread of HIV in the body. In effect, which therapy provides the greatest benefit with the fewest complications.
Step 1: Patients are randomized to 1 of 6 arms:
Arm A: didanosine (ddI), stavudine (d4T), efavirenz (EFV), and nelfinavir (NFV) placebo.
Arm B: ddI, d4T, EFV placebo, and NFV. Arm C: lamivudine (3TC)/zidovudine (ZDV), EFV, and NFV placebo. Arm D: 3TC/ZDV, EFV placebo, and NFV. Arm E: ddI, d4T, EFV, and NFV. Arm F: 3TC/ZDV, EFV, and NFV. Patients with virologic failure on 2 successive measurements or study-drug intolerance discontinue their randomized study therapy and proceed to Step 2. \[AS PER AMENDMENT 7/5/00: Patients must switch regimens as soon as possible after confirmation of virologic failure to prevent development of drug resistance.\]
Step 2:
Arm A: Patients receive treatment as in Arm D of Step 1. Arm B: Patients receive treatment as in Arm C of Step 1. Arm C: Patients receive treatment as in Arm B of Step 1. Arm D: Patients receive treatment as in Arm A of Step 1. Arms A, B, C, and D: Patients who fail Step 2 treatment proceed to Step 3. Arms E and F: Patients with virologic failure on Step 1 proceed immediately to Step 3.
Step 3 (salvage therapy):
Arm A, B, C, and D: Patients receive indinavir (IDV), amprenavir (APV), ddI, and hydroxyurea (HU).
\[AS PER AMENDMENT 7/5/00: Patients now receive treatment on Regimen 1, 2, 3, 4, 5, or 6. Regimen 1 consists of IDV, ritonavir (RTV), ddI, and HU. Regimen 2 consists of APV, RTV, ddI, and HU. Regimen 3 consists of IDV, RTV, abacavir (ABC), and 3TC/ZDV. Regimen 4 consists of APV, RTV, ABC, and 3TC/ZDV. Regimen 5 consists of IDV, RTV, ABC, d4T, and 3TC. Regimen 6 consists of APV, RTV, ABC, d4T, and 3TC.\] Arm E: Patients receive IDV, APV, and 3TC/ZDV. \[AS PER AMENDMENT 7/5/00: Patients now receive treatment on Regimen 7 or 8. Regimen 7 consists of IDV, RTV, and 3TC/ZDV. Regimen 8 consists of APV, RTV, and 3TC/ZDV.\] Arm F: Patients receive IDV, APV, ddI, and d4T. \[AS PER AMENDMENT 7/5/00: Patients now receive treatment on Regimen 9 or 10. Regimen 9 consists of IDV, RTV, ddI, and d4T. Regimen 10 consists of APV, RTV, ddI, and d4T.\] \[AS PER AMENDMENT 7/5/00: Patients already enrolled in Step 3 before site registration to Version 4.0 of this protocol have the option of receiving 1 of the appropriate new Step 3 regimens as outlined above or staying on their originally assigned Step 3 therapy.\] \[AS PER AMENDMENT 3/21/01: If virologic failure on Step 1 or 2 is confirmed, then HIV-1 RNA genotype resistance testing (in real-time, if possible) is performed. Patients receive 1 of the Step 3 drug regimens based on the results of the resistance testing.\] Patients may co-enroll in metabolic, pharmacologic, immunologic, or adherence substudies.
Step 1: Patients are randomized to 1 of 6 arms:
Arm A: didanosine (ddI), stavudine (d4T), efavirenz (EFV), and nelfinavir (NFV) placebo.
Arm B: ddI, d4T, EFV placebo, and NFV. Arm C: lamivudine (3TC)/zidovudine (ZDV), EFV, and NFV placebo. Arm D: 3TC/ZDV, EFV placebo, and NFV. Arm E: ddI, d4T, EFV, and NFV. Arm F: 3TC/ZDV, EFV, and NFV. Patients with virologic failure on 2 successive measurements or study-drug intolerance discontinue their randomized study therapy and proceed to Step 2. \[AS PER AMENDMENT 7/5/00: Patients must switch regimens as soon as possible after confirmation of virologic failure to prevent development of drug resistance.\]
Step 2:
Arm A: Patients receive treatment as in Arm D of Step 1. Arm B: Patients receive treatment as in Arm C of Step 1. Arm C: Patients receive treatment as in Arm B of Step 1. Arm D: Patients receive treatment as in Arm A of Step 1. Arms A, B, C, and D: Patients who fail Step 2 treatment proceed to Step 3. Arms E and F: Patients with virologic failure on Step 1 proceed immediately to Step 3.
Step 3 (salvage therapy):
Arm A, B, C, and D: Patients receive indinavir (IDV), amprenavir (APV), ddI, and hydroxyurea (HU).
\[AS PER AMENDMENT 7/5/00: Patients now receive treatment on Regimen 1, 2, 3, 4, 5, or 6. Regimen 1 consists of IDV, ritonavir (RTV), ddI, and HU. Regimen 2 consists of APV, RTV, ddI, and HU. Regimen 3 consists of IDV, RTV, abacavir (ABC), and 3TC/ZDV. Regimen 4 consists of APV, RTV, ABC, and 3TC/ZDV. Regimen 5 consists of IDV, RTV, ABC, d4T, and 3TC. Regimen 6 consists of APV, RTV, ABC, d4T, and 3TC.\] Arm E: Patients receive IDV, APV, and 3TC/ZDV. \[AS PER AMENDMENT 7/5/00: Patients now receive treatment on Regimen 7 or 8. Regimen 7 consists of IDV, RTV, and 3TC/ZDV. Regimen 8 consists of APV, RTV, and 3TC/ZDV.\] Arm F: Patients receive IDV, APV, ddI, and d4T. \[AS PER AMENDMENT 7/5/00: Patients now receive treatment on Regimen 9 or 10. Regimen 9 consists of IDV, RTV, ddI, and d4T. Regimen 10 consists of APV, RTV, ddI, and d4T.\] \[AS PER AMENDMENT 7/5/00: Patients already enrolled in Step 3 before site registration to Version 4.0 of this protocol have the option of receiving 1 of the appropriate new Step 3 regimens as outlined above or staying on their originally assigned Step 3 therapy.\] \[AS PER AMENDMENT 3/21/01: If virologic failure on Step 1 or 2 is confirmed, then HIV-1 RNA genotype resistance testing (in real-time, if possible) is performed. Patients receive 1 of the Step 3 drug regimens based on the results of the resistance testing.\] Patients may co-enroll in metabolic, pharmacologic, immunologic, or adherence substudies.
Conditions
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HIV Infections
Study Design
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Primary Study Purpose
TREATMENT
Blinding Strategy
DOUBLE
Interventions
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Indinavir sulfate
Intervention Type
DRUG
Lamivudine/Zidovudine
Intervention Type
DRUG
Ritonavir
Intervention Type
DRUG
Hydroxyurea
Intervention Type
DRUG
Abacavir sulfate
Intervention Type
DRUG
Amprenavir
Intervention Type
DRUG
Nelfinavir mesylate
Intervention Type
DRUG
Efavirenz
Intervention Type
DRUG
Lamivudine
Intervention Type
DRUG
Stavudine
Intervention Type
DRUG
Zidovudine
Intervention Type
DRUG
Didanosine
Intervention Type
DRUG
Eligibility Criteria
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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:
\[Allowed with caution:
* AS PER AMENDMENT 7/5/00:
Alcoholic beverages.\]
\[Required: AS PER AMENDMENT 7/5/00:
* Chemoprophylaxis for Pneumocystis carinii pneumonia if CD4+ cell count is less than or equal to 200 cells/mm3.\]
\[Suggested as an alternative agent for chemoprophylaxis against Mycobacterium avium complex:
* Azithromycin.\]
\[Allowed: AS PER AMENDMENT 7/5/00:
* Topical and oral antifungal agents. Oral itraconazole may be administered concurrently with IDV if the dose of IDV is reduced to 600 mg every 8 hours.
* Treatment, maintenance, or chemoprophylaxis for opportunistic infections, as clinically indicated unless otherwise prohibited by the protocol.
* All antibiotics, as clinically indicated unless otherwise prohibited by the protocol.
* Systemic corticosteroid use for 21 days or less for acute problems, as medically indicated.
* Recombinant erythropoietin (rEPO, epoetin alfa, Epogen, epoetin beta, Marogen), granulocyte colony-stimulating factor (G-CSF, filgrastim, Neupogen), and granulocyte-macrophage colony-stimulating factor (GM-CSF, Regramostim).
* Regularly prescribed medications, such as antipyretics, analgesics, allergy medications, antidepressants, sleep medications, oral contraceptives, megestrol acetate (Megace), testosterone, or any other medications, as medically indicated unless otherwise prohibited by the protocol. NOTE: Due to the possibility that study medications may alter the effectiveness of oral contraceptives or depoprogesterone, these agents must not be used as the sole form of birth control, because the role of some study medications on the effectiveness of these methods has not yet been established.
* Alternative therapies, such as vitamins.
* Medications requiring low gastric pH if not administered at the same time as buffered ddI. Patients taking these agents should do so at least 2 hours before ddI.\]
* 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.
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.
Minimum Eligible Age
13 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Robert Shafer
Role: STUDY_CHAIR
Gregory Robbins
Role: STUDY_CHAIR
Locations
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Univ of Alabama at Birmingham
Birmingham, Alabama, United States
Site Status
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States
Site Status
UCLA CARE Ctr
Los Angeles, California, United States
Site Status
Willow Clinic
Menlo Park, California, United States
Site Status
Univ of California / San Diego Treatment Ctr
San Diego, California, United States
Site Status
San Francisco AIDS Clinic / San Francisco Gen Hosp
San Francisco, California, United States
Site Status
San Francisco Gen Hosp
San Francisco, California, United States
Site Status
Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
San Jose, California, United States
Site Status
Marin County Specialty Clinic
San Rafael, California, United States
Site Status
San Mateo AIDS Program / Stanford Univ
Stanford, California, United States
Site Status
Stanford Univ Med Ctr
Stanford, California, United States
Site Status
Harbor UCLA Med Ctr
Torrance, California, United States
Site Status
Univ of Colorado Health Sciences Ctr
Denver, Colorado, United States
Site Status
Georgetown Univ Hosp
Washington D.C., District of Columbia, United States
Site Status
Howard Univ
Washington D.C., District of Columbia, United States
Site Status
Univ of Miami School of Medicine
Miami, Florida, United States
Site Status
Emory Univ
Atlanta, Georgia, United States
Site Status
Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr
Atlanta, Georgia, United States
Site Status
Univ of Hawaii
Honolulu, Hawaii, United States
Site Status
Northwestern Univ Med School
Chicago, Illinois, United States
Site Status
Cook County Hosp
Chicago, Illinois, United States
Site Status
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, United States
Site Status
Indiana Univ Hosp
Indianapolis, Indiana, United States
Site Status
Division of Inf Diseases/ Indiana Univ Hosp
Indianapolis, Indiana, United States
Site Status
Methodist Hosp of Indiana / Life Care Clinic
Indianapolis, Indiana, United States
Site Status
Univ of Iowa Hosp and Clinic
Iowa City, Iowa, United States
Site Status
Charity Hosp / Tulane Univ Med School
New Orleans, Louisiana, United States
Site Status
Tulane Med Ctr Hosp
New Orleans, Louisiana, United States
Site Status
Tulane Univ School of Medicine
New Orleans, Louisiana, United States
Site Status
State of MD Div of Corrections / Johns Hopkins Univ Hosp
Baltimore, Maryland, United States
Site Status
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, United States
Site Status
Boston Med Ctr
Boston, Massachusetts, United States
Site Status
Beth Israel Deaconess - West Campus
Boston, Massachusetts, United States
Site Status
Univ of Minnesota
Minneapolis, Minnesota, United States
Site Status
St Louis Regional Hosp / St Louis Regional Med Ctr
St Louis, Missouri, United States
Site Status
Univ of Nebraska Med Ctr
Omaha, Nebraska, United States
Site Status
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, United States
Site Status
Beth Israel Med Ctr
New York, New York, United States
Site Status
Manhattan Veterans Administration / New York Univ Med Ctr
New York, New York, United States
Site Status
Chelsea Ctr
New York, New York, United States
Site Status
Cornell Univ Med Ctr
New York, New York, United States
Site Status
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States
Site Status
Mount Sinai Med Ctr
New York, New York, United States
Site Status
Columbia Presbyterian Med Ctr
New York, New York, United States
Site Status
St Mary's Hosp (Univ of Rochester/Infectious Diseases)
Rochester, New York, United States
Site Status
Univ of Rochester Medical Center
Rochester, New York, United States
Site Status
Univ of North Carolina
Chapel Hill, North Carolina, United States
Site Status
Carolinas Med Ctr
Charlotte, North Carolina, United States
Site Status
Duke Univ Med Ctr
Durham, North Carolina, United States
Site Status
Moses H Cone Memorial Hosp
Greensboro, North Carolina, United States
Site Status
Akron City Hospital
Akron, Ohio, United States
Site Status
Univ of Cincinnati
Cincinnati, Ohio, United States
Site Status
Univ of Kentucky Lexington
Cincinnati, Ohio, United States
Site Status
Case Western Reserve Univ
Cleveland, Ohio, United States
Site Status
MetroHealth Med Ctr
Cleveland, Ohio, United States
Site Status
Ohio State Univ Hosp Clinic
Columbus, Ohio, United States
Site Status
Milton S Hershey Med Ctr
Hershey, Pennsylvania, United States
Site Status
Philadelphia Veterans Administration Med Ctr
Philadelphia, Pennsylvania, United States
Site Status
Univ of Pennsylvania at Philadelphia
Philadelphia, Pennsylvania, United States
Site Status
Univ of Pittsburgh Med Ctr
Pittsburgh, Pennsylvania, United States
Site Status
Julio Arroyo
West Columbia, South Carolina, United States
Site Status
Univ of Texas Galveston
Galveston, Texas, United States
Site Status
Univ of Washington
Seattle, Washington, United States
Site Status
Azienda Ospedaliera Umberto I
Ancona, , Italy
Site Status
Ospedale S Orsola
Bologna, , Italy
Site Status
Spedali Civili - Carosi
Brescia, , Italy
Site Status
Spedali Civili Cadeo
Brescia, , Italy
Site Status
Archispedale S Anna
Ferrara, , Italy
Site Status
Universita di Genova
Genova, , Italy
Site Status
Ospedale Luigi Cacco Moroni
Milan, , Italy
Site Status
Ospedale Luigi Sacco Cargnel
Milan, , Italy
Site Status
Azienda Ospedaliera di Parma
Parma, , Italy
Site Status
IRCCS Policlinico S Matteo Filice
Pavia, , Italy
Site Status
IRCCS Policlinico S Matteo Minoli
Pavia, , Italy
Site Status
Archispedale S Maria Nuova
Reggio Emilia, , Italy
Site Status
Universita di Roma - Delia
Roma, , Italy
Site Status
Ospedale Civile Maggiore
Verona, , Italy
Site Status
Univ of Puerto Rico
San Juan, , Puerto Rico
Site Status
Azienda USL di Piacenza
, ,
Site Status
Francesco Leoncini
, ,
Site Status
Countries
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United States
Italy
Puerto Rico
References
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Smeaton LM, DeGruttola V, Robbins GK, Shafer RW. ACTG (AIDS Clinical Trials Group) 384: a strategy trial comparing consecutive treatments for HIV-1. Control Clin Trials. 2001 Apr;22(2):142-59. doi: 10.1016/s0197-2456(00)00126-4.
Reference Type
BACKGROUND
Dube MP, Zackin R, Tebas P, et al. Prospective study of regional body composition in antiretroviral-naive subjects randomized to receive zidovudine+lamivudine or didanosine+stavudine combined with nelfinavir, efavirenz, or both: A5005s, a substudy of ACTG 384. Antiviral Ther. 2002;7:L18. Abstract 27.
Reference Type
BACKGROUND
Smith PF, Robbins G, Shafer R, Wu H, Yu S, Hirsch M, Merigan T, Morse GD, ACTG 384 Study Team. Effect of Efavirenz on the Pharmacokinetics of Nelfinavir and M8 in Naïve, HIV-infected Patients Receiving Long-term HAART Therapy. 10th Conference on Retroviruses and Oppurtunistic Infections. Feb 2003. Abstract 148.
Reference Type
BACKGROUND
Shafer RW, Smeaton LM, Robbins GK, De Gruttola V, Snyder SW, D'Aquila RT, Johnson VA, Morse GD, Nokta MA, Martinez AI, Gripshover BM, Kaul P, Haubrich R, Swingle M, McCarty SD, Vella S, Hirsch MS, Merigan TC; AIDS Clinical Trials Group 384 Team. Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med. 2003 Dec 11;349(24):2304-15. doi: 10.1056/NEJMoa030265.
Reference Type
RESULT
Robbins GK, De Gruttola V, Shafer RW, Smeaton LM, Snyder SW, Pettinelli C, Dube MP, Fischl MA, Pollard RB, Delapenha R, Gedeon L, van der Horst C, Murphy RL, Becker MI, D'Aquila RT, Vella S, Merigan TC, Hirsch MS; AIDS Clinical Trials Group 384 Team. Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med. 2003 Dec 11;349(24):2293-303. doi: 10.1056/NEJMoa030264.
Reference Type
RESULT
Reynolds NR, Testa MA, Marc LG, Chesney MA, Neidig JL, Smith SR, Vella S, Robbins GK; Protocol Teams of ACTG 384, ACTG 731 and A5031s. Factors influencing medication adherence beliefs and self-efficacy in persons naive to antiretroviral therapy: a multicenter, cross-sectional study. AIDS Behav. 2004 Jun;8(2):141-50. doi: 10.1023/B:AIBE.0000030245.52406.bb.
Reference Type
RESULT
Hulgan T, Haas DW, Haines JL, Ritchie MD, Robbins GK, Shafer RW, Clifford DB, Kallianpur AR, Summar M, Canter JA. Mitochondrial haplogroups and peripheral neuropathy during antiretroviral therapy: an adult AIDS clinical trials group study. AIDS. 2005 Sep 2;19(13):1341-9. doi: 10.1097/01.aids.0000180786.02930.a1.
Reference Type
RESULT
Smith PF, Robbins GK, Shafer RW, Wu H, Yu S, Hirsch MS, Merigan TC, Park JG, Forrest A, Fischl MA, Morse GD; ACTG 384-5006 Team. Pharmacokinetics of nelfinavir and efavirenz in antiretroviral-naive, human immunodeficiency virus-infected subjects when administered alone or in combination with nucleoside analog reverse transcriptase inhibitors. Antimicrob Agents Chemother. 2005 Aug;49(8):3558-61. doi: 10.1128/AAC.49.8.3558-3561.2005.
Reference Type
RESULT
Haas DW, Smeaton LM, Shafer RW, Robbins GK, Morse GD, Labbe L, Wilkinson GR, Clifford DB, D'Aquila RT, De Gruttola V, Pollard RB, Merigan TC, Hirsch MS, George AL Jr, Donahue JP, Kim RB. Pharmacogenetics of long-term responses to antiretroviral regimens containing Efavirenz and/or Nelfinavir: an Adult Aids Clinical Trials Group Study. J Infect Dis. 2005 Dec 1;192(11):1931-42. doi: 10.1086/497610. Epub 2005 Nov 1.
Reference Type
RESULT
Gandhi RT, Spritzler J, Chan E, Asmuth DM, Rodriguez B, Merigan TC, Hirsch MS, Shafer RW, Robbins GK, Pollard RB; ACTG 384 Team. Effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy in HIV-1-positive subjects: results from ACTG 384. J Acquir Immune Defic Syndr. 2006 Aug 1;42(4):426-34. doi: 10.1097/01.qai.0000226789.51992.3f.
Reference Type
RESULT
Marc LG, Testa MA, Walker AM, Robbins GK, Shafer RW, Anderson NB, Berkman LF; ACTG Data Analysis Concept Sheet Study Team. Educational attainment and response to HAART during initial therapy for HIV-1 infection. J Psychosom Res. 2007 Aug;63(2):207-16. doi: 10.1016/j.jpsychores.2007.04.009.
Reference Type
RESULT
Li B, Veturi Y, Verma A, Bradford Y, Daar ES, Gulick RM, Riddler SA, Robbins GK, Lennox JL, Haas DW, Ritchie MD. Tissue specificity-aware TWAS (TSA-TWAS) framework identifies novel associations with metabolic, immunologic, and virologic traits in HIV-positive adults. PLoS Genet. 2021 Apr 26;17(4):e1009464. doi: 10.1371/journal.pgen.1009464. eCollection 2021 Apr.
Reference Type
DERIVED
Lok JJ, Hunt PW, Collier AC, Benson CA, Witt MD, Luque AE, Deeks SG, Bosch RJ. The impact of age on the prognostic capacity of CD8+ T-cell activation during suppressive antiretroviral therapy. AIDS. 2013 Aug 24;27(13):2101-10. doi: 10.1097/QAD.0b013e32836191b1.
Reference Type
DERIVED
Lok JJ, Bosch RJ, Benson CA, Collier AC, Robbins GK, Shafer RW, Hughes MD; ALLRT team. Long-term increase in CD4+ T-cell counts during combination antiretroviral therapy for HIV-1 infection. AIDS. 2010 Jul 31;24(12):1867-76. doi: 10.1097/QAD.0b013e32833adbcf.
Reference Type
DERIVED
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
11343
Identifier Type: REGISTRY
Identifier Source: secondary_id
AACTG A5005s
Identifier Type: -
Identifier Source: secondary_id
AACTG A5006s
Identifier Type: -
Identifier Source: secondary_id
AACTG A5007s
Identifier Type: -
Identifier Source: secondary_id
AACTG A5031s
Identifier Type: -
Identifier Source: secondary_id
AACTG 731
Identifier Type: -
Identifier Source: secondary_id
ACTG 384
Identifier Type: -
Identifier Source: org_study_id
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