A Phase II Study of the Prolongation of Virologic Success (ACTG 372A) and Options for Virologic Failure (ACTG B/C/D) in HIV-Infected Subjects Receiving Indinavir in Combination With Nucleoside Analogs: A Rollover Study for ACTG 320

Inclusion Criteria

Inclusion Criteria

Concurrent Medication:

Required:

- Chemoprophylaxis for Pneumocystis carinii pneumonia for all patients with a CD4 cell
count of 200 cells/mm3 or less.

Allowed:

- Treatment, maintenance, or chemoprophylaxis, including topical and/or oral antifungal
agents unless otherwise excluded by the protocol.

- All antibiotics as clinically indicated, unless otherwise excluded in the protocol.

- Systemic corticosteroid use for 21 days or less for acute problems as medically
indicated. Chronic corticosteroid use is not permitted, unless it is within
physiologic replacement levels. Study team must be contacted in these instances.

- rEPO and G-CSF as medically indicated.

- Regularly prescribed medications such as [AS PER AMENDMENT 06/29/98: alternative,
FDA-approved antiretrovirals not supplied by the study] [AS PER AMENDMENT 12/27/01:
or unapproved antiretrovirals available by expanded access (when permanently
discontinued from randomized study treatment)], antipyretics, analgesics, allergy
medications, antidepressants, sleep medications, oral contraceptives, megestrol
acetate, testosterone, or any other medications not otherwise excluded by the
protocol, as medically indicated.

- [AS PER AMENDMENT 12/27/01: Supplemental and] alternative therapies such as vitamins,
acupuncture, and visualization techniques.

Recommended as an alternative agent for chemoprophylaxis against Mycobacterium avium
complex for patients randomized to EFV in Group B or D:

- clarithromycin or azithromycin.

Patients must have:

- HIV-1 infection as documented by any licensed ELISA test kit and confirmed by either
a 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.

Non-ACTG patients:

- Documented CD4 cell count of 200 cells/mm3 or less at the time of initiation of ZDV
(or d4T) plus 3TC plus IDV.

- Signed, informed consent from a parent or legal guardian for patients under 18 years
of age.

Prior Medication:

Required:

Non-ACTG 320 patients:

- At least 3 months prior therapy with ZDV (or d4T) plus 3TC plus IDV and continued
receipt of ZDV (or d4T) plus 3TC plus IDV until enrollment. IDV and 3TC must have
been initiated concurrently.

ACTG patients:

- Randomization to the ZDV (or d4T) plus 3TC plus IDV combination arm or receipt of
open-label prior to unblinding and maintenance of that treatment as participation in
ACTG 320.

Group D:

- Prior NNRTI-exposure.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions and symptoms are excluded:

- Unexplained temperature above 38.5 C for any 7 days or chronic diarrhea, defined as
more than 3 liquid stools per day persisting for 15 days, within 30 days prior to
study treatment.

- AIDS-related malignancy, other than minimal Kaposi's sarcoma that requires systemic
chemotherapy. Minimal Kaposi's sarcoma is defined as 5 or fewer cutaneous lesions and
no visceral disease or tumor-associated edema that does not require systemic therapy.

- Documented or suspected acute hepatitis within 30 days prior to study entry,
irrespective of laboratory values.

Concurrent Medication:

Excluded:

- All antiretroviral therapies other than study [AS PER AMENDMENT 06/16/99: provided]
medications, [AS PER AMENDMENT 06/16/99: unless approved by the protocol chairs] [AS
PER AMENDMENT 12/27/01: while on original randomized treatment.]

- Rifabutin and rifampin.

- Investigational agents without specific approval from the protocol chair.

- Systemic cytotoxic chemotherapy.

- Oral ketoconazole and itraconazole. NOTE: Itraconazole may be permitted for Group B
and Group D patients if fluconazole is not an option.

- Terfenadine, astemizole, cisapride, triazolam, midazolam, amiodarone, quinine, ergot
derivatives, isotretinoin, [AS PER AMENDMENT 12/27/01: pimozide, St.John's Wort, and
milk thistle.]

- [AS PER AMENDMENT 12/27/01: Concomitant use of lovastatin or simvastatin is not
recommended because of potential drug interactions. Pravastatin or atorvastatin may
be used after consultation with the Study Team.]

To be avoided:

- Herbal medications.

Prior Medication:

Excluded:

- Any prior protease inhibitor therapy other than indinavir.

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

- Any experimental therapy within 30 days prior to study entry.

- Rifampin, rifabutin, ketoconazole, or itraconazole within 14 days of study entry.

Non-ACTG patients:

- Acute therapy for an infection or other medical illness within 14 days prior to study
therapy.

- NNRTI therapy prior to study entry (with the exception of Group D).

- Recombinant erythropoietin (rEPO), granulocyte colony-stimulating factor (G-CSF,
filgrastim), or granulocyte-macrophage colony-stimulating factor (GM-CSF,
sargramostim) within 30 days prior to study entry.

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