Clinical trial NCT00000895: A Study to Learn More About MAC Disease and the Use of Anti-HIV Drugs in Patients With Advanced HIV Infection
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mycobacterium Avium-intracellulare Infection
HIV Infections
Keywords: AIDS-Related Opportunistic Infections
Mycobacterium avium-intracellulare Infection
HIV-1
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
Mycobacterium avium Complex
Bacteremia
Nevirapine
HIV Protease Inhibitors
Risk Factors
RNA, Viral
Reverse Transcriptase Inhibitors
Nelfinavir
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

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

Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Univ of Southern California / LA County USC Med Ctr
state: California
city: San Diego
country: United States
facility: Univ of California / San Diego Treatment Ctr
state: California
city: Stanford
country: United States
facility: Stanford Univ Med Ctr
state: California
city: Washington
country: United States
facility: Howard Univ
state: District of Columbia
city: Miami
country: United States
facility: Univ of Miami School of Medicine
state: Florida
city: Atlanta
country: United States
facility: Emory Univ
state: Georgia
city: Chicago
country: United States
facility: Northwestern Univ Med School
state: Illinois
city: Chicago
country: United States
facility: Cook County Hosp
state: Illinois
city: Chicago
country: United States
facility: Rush Presbyterian - Saint Luke's Med Ctr
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ Hosp
state: Indiana
city: Indianapolis
country: United States
facility: Division of Inf Diseases/ Indiana Univ Hosp
state: Indiana
city: Buffalo
country: United States
facility: SUNY / Erie County Med Ctr at Buffalo
state: New York
city: New York
country: United States
facility: Beth Israel Med Ctr
state: New York
city: New York
country: United States
facility: Bellevue Hosp / New York Univ Med Ctr
state: New York
city: New York
country: United States
facility: St Vincent's Hosp / Mem Sloan-Kettering Cancer Ctr
state: New York
city: Rochester
country: United States
facility: Univ of Rochester Medical Center
state: New York
city: Cincinnati
country: United States
facility: Univ of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve Univ
state: Ohio
city: Columbus
country: United States
facility: Ohio State Univ Hosp Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Univ of Pennsylvania at Philadelphia
state: Pennsylvania
city: West Columbia
country: United States
facility: Julio Arroyo
state: South Carolina
city: Dallas
country: United States
facility: Univ of Texas Southwestern Med Ctr of Dallas
state: Texas
city: Dallas
country: United States
facility: Univ of Texas, Southwestern Med Ctr of Dallas
state: Texas
city: Galveston
country: United States
facility: Univ of Texas Galveston
state: Texas
city: Seattle
country: United States
facility: Univ of Washington
state: Washington
Study officials:
name: Rob Roy MacGregor
role: STUDY_CHAIR
name: David Perlman
role: STUDY_CHAIR
References:
citation: MacGregor RR, Hafner R, Wu JW, Murphy RL, Perlman DC, Bermudez LE, Inderlied CB, Picker LJ, Wallis RS, Andersen JW, Mahon LF, Koletar SL, Peterson DM; ACTG Protocol 341 Team. Clinical, microbiological, and immunological characteristics in HIV-infected subjects at risk for disseminated Mycobacterium avium complex disease: an AACTG study. AIDS Res Hum Retroviruses. 2005 Aug;21(8):689-95. doi: 10.1089/aid.2005.21.689.