Trial Information

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 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.]