A Study of Abacavir Plus Indinavir Sulfate Plus Efavirenz in HIV-Infected Patients

• Status: Completed
• Trial end date: 1999-09-01
• Target enrollment: 0
• Participant gender: All

Summary

To compare the virologic response between abacavir (ABC, 1592U89) regimens (drug vs. placebo) and between the 2 dosing regimens (BID vs. TID) with respect to the proportion of patients with plasma HIV RNA levels below the limit of detection [AS PER AMENDMENT 8/27/97: < 500 copies/ml at week 16]. To evaluate the safety and tolerance of the study arms. [AS PER AMENDMENT 3/10/99: During the extension period, compare the time to detectable viremia (2 consecutive plasma HIV RNA levels greater than or equal to 500 copies/ml) between ABC and placebo.] Therapeutically, there is a need to explore potent alternative therapy for patients who have received, or are currently receiving, a double nucleoside analog combination including lamivudine (3TC), a regimen that was proven to be clinically inferior to indinavir (IDV) when combined with zidovudine/3TC in study ACTG 320. In order to produce and maintain a maximal antiviral response, all patients in this study will receive 2 or 3 potent, new agents; ABC, a nucleoside analog, EFV, a non-nucleoside reverse transcriptase inhibitor (NNRTI), and IDV, a protease inhibitor. Virologically, the major question this protocol seeks to answer is how prior 3TC exposure in a dual nucleoside regimen influences the response to subsequent treatment. It is unclear whether it is best to add a protease inhibitor either 1) an NNRTI at 1 of 2 doses, or 2) an NNRTI at 1 of 2 doses plus a new nucleoside analog to achieve plasma HIV RNA levels that are below the limits of detection.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Abacavir; Efavirenz; Indinavir

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• Chemoprophylaxis for Pneumocystis carinii pneumonia is required for all patients who have a CD4 cell count <= 200 cells/mm3.

• Topical and/or oral antifungal agents are permitted except for oral ketoconazole.

• Treatment, maintenance or chemoprophylaxis with approved agents for opportunistic infections as clinically indicated, except for rifabutin.

• All antibiotics as clinically indicated.

• Systemic corticosteroid use for <= 21 days for acute problems is permitted as medically indicated; chronic systemic corticosteroid use is not permitted, unless it is within physiologic replacement levels.

• Recombinant erythropoietin and granulocyte colony-stimulating factor are permitted as medically indicated.

• Regularly prescribed medications such as antipyretics, analgesics, allergy medications (except for terfenadine (Seldane) and astemizole (Hismanal)), antidepressants, sleep medications, oral contraceptives, megestrol acetate, testosterone or any other medications are permitted as medically indicated.

NOTE:

• Due to the possibility that EFV or ABC may alter the effectiveness of oral contraceptives or depo-progesterone, oral contraceptives or depo-progesterone must not be used as the sole form of birth control. [AS PER AMENDMENT 8/7/98: adequate birth control is hormonal plus barrier method or two barrier methods].

• Alternative therapies such as vitamins, acupuncture, and visualization techniques will be permitted. Herbal medications should be avoided. Patients should report the use of these therapies; alternative therapies will be recorded. [AS PER AMENDMENT 8/7/98: Due to the likelihood of IDV increasing the concentrations of sildenafil (Viagra) when coadministered, it is suggested that subjects who use viagra take the lowest dose (25 mg, i.e., half the typical dose).]

Both NIAID ACTG 320 participants and non-ACTG 320 patients must have:

• Documented HIV-1 infection.

• Written informed consent from parent or legal guardian for those patients < 18 years old.

Non-ACTG 320 patients must have:

• Documented CD4 cell count <= 200 cells/mm3 at the time of initiation of ZDV (or d4T) plus 3TC therapy [AS PER AMENDMENT 12/17/97:

• Documented CD4 cell count <= 250 cells/mm3 within 3 months of initiation of ZDV (or d4T) plus 3TC therapy].

Prior Medication:

Required:

For ACTG 320 patients:

• Patients must have participated in ACTG 320 with original randomization to the double-nucleoside combination arm, and maintenance of that treatment (on-study/on-treatment in ACTG 320) until enrollment into ACTG 368.

For non-ACTG 320 patients:

• Greater than or equal to 3 months [2 months AS PER AMENDMENT 12/17/97] of therapy with ZDV (or d4T) + 3TC and receiving ZDV (or d4T) + 3TC at the time of entry.

Exclusion Criteria

Co-existing Condition:

Non-ACTG 320 patients with the following symptoms and conditions are excluded:

Malignancy that requires systemic therapy other than minimal Kaposi's sarcoma.

NOTE:

• Minimal Kaposi's sarcoma, defined as <= 5 cutaneous lesions and no visceral disease or tumor-associated edema, allowed, provided systemic therapy not required.

Non-ACTG 320 patients with the following prior conditions or symptoms are excluded:

• Unexplained temperature > 38.5 degrees C for 7 consecutive days.

• Chronic diarrhea defined as > 3 liquid stools per day persisting for 15 days, within 30 days prior to entry.

• Proven or suspected acute hepatitis within 30 days prior to entry, even if AST (SGOT) and ALT (SGPT) are <= 5 X ULN.

Concurrent Medication: Excluded:

• All antiretroviral therapies other then study medications.

• Rifabutin and rifampin.

• Investigational drugs without specific approval from the protocol chair.

• Systemic cytotoxic chemotherapy.

• Oral ketoconazole (Nizoral), terfenadine (Seldane), astemizole (Hismanal), cisapride (Propulsid), triazolam (Halcion), and midazolam (Versed).

• Caution should be taken in the consumption of alcoholic beverages with study medications.

• Itraconazole.

Prior Medication: Excluded: For ACTG 320 patients:

• Those who opted to receive open-label IDV while on ACTG 320, or if they switched to open label IDV during the study.

For non-ACTG 320 patients:

• Acute therapy for an infection or other medical illness within 14 days prior to entry.

• Prior protease inhibitor therapy.

• Prior NNRTI therapy (approved or experimental).

• Erythropoietin, G-CSF or GM-CSF within 30 days prior to entry.

• Interferons, interleukins or HIV vaccines within 30 days prior to entry.

• Any experimental therapy within 30 days prior to entry.

• Rifampin or rifabutin within 14 days prior to entry.