A Study to Learn More About MAC Disease and the Use of Anti-HIV Drugs in Patients With Advanced HIV Infection

Pathogenesis of MAC Disease in Advanced HIV-1-Infected Subjects and the Impact of Highly-Active Antiretroviral Treatment (HAART) on Immune Functions Relevant for MAC and Other Opportunistic Infections

The purpose of this study is to determine if infection with Mycobacterium avium complex (MAC) occurs in other parts of the body before it is found in the blood. This study also evaluates the relationships between the amount of HIV in the blood, immune system functions, and the presence of MAC infection.

HIV-positive patients are at risk for MAC infection because their immune systems have been weakened by HIV. It is hoped that aggressive treatment with anti-HIV drugs may improve their immune systems enough to prevent against MAC.

The intent of this study is to define more precisely the natural history and immunopathogenesis of MAC disease in the HIV-infected population. It is suggested that MAC disease in AIDS patients results both from specific immunologic deficiencies caused by HIV infection of the host and as a result of specific mycobacterial virulence properties. Therefore, aggressive antiretroviral drug treatment of HIV-infected patients at risk for DMAC due to specific immune deficiencies will improve these immune functions in such a manner as to resist DMAC.

A total of 85 patients will be stratified at baseline into one of three groups:

Group I - 40 patients at high risk for MAC infection are neither followed beyond baseline nor receive study treatment.

Group II - 15 patients with DMAC, i.e., newly diagnosed MAC-bacteremic patients with no more than 72 hours prior treatment for MAC, receive individualized regimen of HAART for 48 weeks: nelfinavir (NEV), nevirapine (NVP), and nucleoside reverse transcriptase inhibitor(s) as per primary physician. Patients are evaluated through clinical, microbiologic, and virologic assessments, and intensive immunologic evaluations at Weeks 12, 24, and 48.

Group III - 30 asymptomatic HIV-infected patients are further stratified (15 patients/stratum) by CD4 count (less than or equal to 50 cells/mm3 or 100-250 cells/mm3). Patients in Group III follow the same HAART regimen and evaluations as Group II patients and continue evaluations for up to 48 weeks, if an acceptable response is found within 12 weeks of entry. Patients in Stratum 1 of Group III receive MAC prophylaxis with azithromycin once weekly with follow-up evaluations as in Group II. Patients in Group III that have a positive MAC blood or bone marrow culture at any time during the study will, from that point on, follow the same schedule of evaluations as patients in Group II.

[AS PER AMENDMENT 11/3/98: Up to 100 evaluable patients will now be studied. Group 2 is now modified to include up to an additional 15 evaluable patients with known MAC bacteremia and less than or equal to 7 days prior MAC treatment who are unable to commit to long-term follow-up (Group 2b); these patients will undergo only baseline evaluations. Group 2a consists of 15 evaluable patients with known MAC bacteremia and less than or equal to 7 days of prior MAC treatment who are willing and able to enter the follow-up phase.]

Inclusion Criteria

You may be eligible for this study if you:

• Are HIV-positive.
• Have a CD4 count under 50 cells/mm3 or between 100 and 250 cells/mm3 within 30 days of study entry.
• Have at least one symptom (e.g., fever, diarrhea, or weight loss) suggestive of MAC infection.
• Have MAC infection with 7 days or less of MAC treatment.
• Have an HIV blood level greater than 10,000 copies/ml within 30 days of study entry.
• Are 18 years of age or older.

Exclusion Criteria

You will not be eligible for this study if you:

• Have any active infection (except for MAC in Group 2 patients) or any cancer.
• Are unable to follow an acceptable anti-HIV drug regimen (Groups 2 and 3).
• Are pregnant or breast-feeding.