Duration of efficacy of treatment of latent tuberculosis infection in HIV-infected adults.
BACKGROUND
Treatment of latent infection is needed to protect HIV-infected individuals against tuberculosis. A previous report addressed short-term efficacy of three regimens in HIV-infected adults. We now report on long-term efficacy of the study regimens.


METHODS
Three daily self-administered regimens were compared in a randomized placebo-controlled trial in 2736 purified protein derivative (PPD)-positive and anergic HIV-infected adults. PPD-positive subjects were treated with isoniazid (INH) for 6 months (6H), INH plus rifampicin for 3 months (3HR), INH plus rifampicin and pyrazinamide for 3 months (3HRZ), or placebo for 6 months. Anergic subjects were randomized to 6H or placebo.


RESULTS
6H initially protected against tuberculosis in PPD-positive individuals; however, benefit was lost within the first year of treatment. Sustained benefit was observed in persons receiving 3HR and 3HRZ. In a Cox regression analysis, the adjusted relative risk for tuberculosis compared with placebo was 0.67 [95% confidence interval (CI), 0.42-1.07] for 6H, 0.49 (95% CI, 0.29-0.82) for 3HR, and 0.41 (95% CI, 0.22-0.76) for 3HRZ. When the rifampicin-containing regimens were combined, the adjusted relative risk for tuberculosis compared with placebo was 0.46 (95% CI, 0.29-0.71). Among anergic subjects, a modest degree of protection with 6H was present (adjusted relative risk, 0.61; 95% CI, 0.32-1.16). Treatment of latent tuberculosis infection had no effect on mortality.


CONCLUSIONS
Six months of INH provided short-term protection against tuberculosis in PPD-positive HIV-infected adults. Three month regimens including INH plus rifampicin or INH, rifampicin and pyrazinamide provided sustained protection for up to 3 years.
Johnson
J L
JL
Division of Infectious Diseases, Department of Medicine, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, Ohio 44106-4984, USA.
Okwera
A
A
Hom
D L
DL
Mayanja
H
H
Mutuluuza Kityo
C
C
Nsubuga
P
P
Nakibali
J G
JG
Loughlin
A M
AM
Yun
H
H
Mugyenyi
P N
PN
Vernon
A
A
Mugerwa
R D
RD
Ellner
J J
JJ
Whalen
C C
CC
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D015994:Incidence; D007538:Isoniazid / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification; D011718:Pyrazinamide / Q000494:pharmacology / Q000627:therapeutic use; D012293:Rifampin / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014374:Tuberculin Test; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology
D000995:Antitubercular Agents; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin