Discontinuation of Mycobacterium avium complex prophylaxis in patients with antiretroviral therapy-induced increases in CD4+ cell count. A randomized, double-blind, placebo-controlled trial. AIDS Clinical Trials Group 362 Study Team.
BACKGROUND
Patients infected with HIV who experience increases in CD4(+) cell counts are at reduced risk for opportunistic infections. However, the safety of discontinuing prophylaxis against Mycobacterium avium complex has been uncertain.


OBJECTIVE
To compare the rate of M. avium complex infection in patients with increased CD4(+) cell counts who receive azithromycin and those receiving placebo.


METHODS
Randomized, double-blind, placebo-controlled trial.


METHODS
29 university-based clinical centers in the United States.


METHODS
643 HIV-1-infected patients with a previous CD4(+) cell count less than 0.05 x 10(9) cells/L and a sustained increase to greater than 0.10 x 10(9) cells/L during antiretroviral therapy.


METHODS
Azithromycin, 1200 mg once weekly (n = 321), or matching placebo (n = 322).


METHODS
Mycobacterium avium complex cultures, CD4(+) cell counts, and clinical evaluations for AIDS-defining illnesses and bacterial infections were done every 8 weeks. Plasma HIV-1 RNA levels were measured at 16-week intervals.


RESULTS
During follow-up (median, 16 months), 2 cases of M. avium complex infection were reported among the 321 patients assigned to placebo (incidence rate, 0.5 event per 100 person-years [95% CI, 0.06 to 1.83 events per 100 person-years]) compared with no cases among the 322 patients assigned to azithromycin (CI, 0 to 0.92 events per 100 person-years), resulting in a treatment difference of 0.5 event per 100 person-years (CI, -0.20 to 1.21 events per 100 person-years) for placebo versus azithromycin. Both cases were atypical in that M. avium complex was localized to the vertebral spine. Patients receiving azithromycin were more likely than those receiving placebo to discontinue treatment with the study drug permanently because of adverse events (8% vs. 2%; hazard ratio, 0.24 [CI, 0.10 to 0.57]).


CONCLUSIONS
Prophylaxis against Mycobacterium avium complex can safely be withdrawn or withheld in adults with HIV infection who experience increases in CD4(+) cell count while receiving antiretroviral therapy.
Currier
J S
JS
University of California, Los Angeles, CARE Center, 10833 LeConte Avenue, Room BH-412 CHS, Los Angeles, CA 90095, USA. jscurrier@mednet.ucla.edu
Williams
P L
PL
Koletar
S L
SL
Cohn
S E
SE
Murphy
R L
RL
Heald
A E
AE
Hafner
R
R
Bassily
E L
EL
Lederman
H M
HM
Knirsch
C
C
Benson
C A
CA
Valdez
H
H
Aberg
J A
JA
McCutchan
J A
JA
D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control*; D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019380:Anti-HIV Agents / Q000627:therapeutic use; D017963:Azithromycin / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D015269:Mycobacterium avium Complex; D015270:Mycobacterium avium-intracellulare Infection / Q000517:prevention & control*; D010919:Placebos; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D010919:Placebos; D012367:RNA, Viral; D017963:Azithromycin