Impact of antiretroviral therapy on the incidence of tuberculosis: the Brazilian experience, 1995-2001.
BACKGROUND
The human immunodeficiency virus (HIV) fuels tuberculosis (TB) epidemics. In controlled clinical trials, antiretroviral therapy (ART) reduces TB incidence in HIV-infected patients. In this study we determine if, under programmatic conditions, Brazil's policy of universal ART access has impacted TB incidence among HIV-infected patients.


METHODS
We abstracted clinical information from records of HIV-infected patients managed in the public sector in 11 Brazilian states between 1/1/1995 and 12/31/2001. Case ascertainment (TB and HIV) utilized guidelines (with added stringency) published by Brazil's Ministry of Health. We determined TB incidence and hazards ratio (HR) for ART-naïve and ART-treated [including highly active ART (HAART)] patients employing Cox proportional hazards analysis.


RESULTS
Information from 463 HIV-infected patients met study criteria. The median age of the study population was 34 years, 70% were male, and mean follow-up to primary endpoints--TB, death, and last clinic visit--was 330, 1059, and 1125 days, respectively. Of the 463 patients, 76 (16%) remained ART-naïve. Of the patients who never received HAART (n = 157) 81 were treated with ART non-HAART. Of the patients who received any ART (n = 387), 306 were treated with HAART (includes those patients who later switched from ART non-HAART to HAART). Tuberculosis developed in 39/463 (8%) patients. Compared to HAART- and ART non-HAART-treated patient groups, TB incidence was 10- (p<0.001) and 2.5-fold (p = 0.03) higher in ART-naïve patients, respectively. The median baseline absolute CD4+ T-lymphocyte count for patients who developed TB was not significantly different from that of patients who remained TB free. In multivariate analysis, the incidence of TB was statistically significantly lower in HAART-treated [HR 0.2; 95% (CI 0.1, 0.6); p<0.01] compared to ART naïve patients. A baseline CD4+ T-lymphocyte count <200 cells/mm(3) [HR 2.5; (95% CI 1.2, 5.4); p<0.01], prior hospitalization [HR 4.2; (95% CI 2.0, 8.8); p<0.001], prior incarceration [HR 4.1; 95% CI 1.6, 10.3); p<0.01], and a positive tuberculin skin test [HR 3.1; (95% CI 1.1, 9.0); p = 0.04] were independently and positively associated with incident TB.


CONCLUSIONS
In this population-based study we demonstrate an 80% reduction in incident TB, under programmatic conditions, in HAART-treated HIV-infected patients compared to ART-naïve patients.
Miranda
Abraham
A
The Global AIDS Program, United States Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
Morgan
Meade
M
Jamal
Leda
L
Laserson
Kayla
K
Barreira
Draurio
D
Silva
Guida
G
Santos
Joseney
J
Wells
Charles
C
Paine
Patricia
P
Garrett
Denise
D
D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000453:epidemiology*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001938:Brazil / Q000453:epidemiology; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D008297:Male; D016016:Proportional Hazards Models; D014376:Tuberculosis / Q000150:complications / Q000453:epidemiology*