Tuberculosis

Risk Factors for Tuberculosis among HIV Positive People in the US and Canada

Worldwide, tuberculosis (TB) is the leading cause of death for people with HIV/AIDS. TB is relatively uncommon in industrialized countries such as the U.S. and Canada, where it is largely concentrated among immigrants and the indigent.

Although HIV positive people with compromised immune function are at risk for TB as an opportunistic illness, TB screening is not routinely done prior to initiation of combination antiretroviral therapy (ART) in low-incidence settings.

As described in the September 15, 2011, Journal of Infectious Diseases, Timothy Sterling, Richard Moore, and fellow investigators with NA-ACCORD (North American AIDS Cohort Collaboration on Research and Design) looked at TB incidence after starting ART. Identifying factors associated with developing tuberculosis after ART initiation could help focus screening efforts on people most at risk, they suggested.

The researchers analyzed medical record data from 16 cohorts that together included nearly 38,000 people with HIV in the US and Canada who initiated combination ART between December 1995 and August 2009.

Most participants (77%) were men and the median age was 39 years; 43% were white, 38% were black, and 15% were Hispanic/Latino. At the time of ART initiation the median CD4 T-cell count was 207 cells/mm³, or just above the threshold for an AIDS diagnosis. 19% had a history of injection drug use.

Results

• A total of 145 out of 37,845 participants, or 0.38%, were diagnosed with TB after ART initiation.
• 20 patients were diagnosed with TB during the first 3 months after starting ART
• Risk of developing TB was highest soon after starting ART:
  • First 1 month: 254 cases per 100,000 person-years;
  • First 3 months: 215 cases per 100,000 person-years;
  • 5 years after ART initiation: 43 cases per 100,000 person-years.
• In a multivariate analysis, factors independently associated with higher TB risk included:
  • Baseline CD4 count < 200 cells/mm³;
  • Black, Hispanic/Latino, or other nonwhite race/ethnicity;
  • History of injection drug use.
• Higher baseline HIV viral load was associated with increased TB risk only during the first 3 months after starting ART.
• Male sex tended to be associated with increased risk, but the difference did not reach statistical significance.

Based on these findings, the study authors recommended, "Screening for active tuberculosis prior to [ART] initiation should be targeted to persons with baseline CD4 < 200 [cells]/mm³ or increased HIV-1 RNA, persons of nonwhite race or Hispanic ethnicity, history of injection drug use, and possibly male sex."

These findings indicate that the risk of developing TB falls rapidly after effective ART suppresses viral load and allows CD4 cell recovery; the risk of TB recurrence was also low after ART initiation (1.5%). Regular screening could enable HIV positive people at risk for -- or already infected with -- TB to start ART promptly, as well as TB prophylaxis or treatment as needed. 

Investigator affiliations: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Biostatistics, Harvard School of Public Health, Boston, MA; Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA; Department of Medicine, University of California, San Francisco, CA; Department of Medicine, Rush University Medical Center, Chicago, IL; Department of Medicine, University of Calgary, Alberta, Canada; Division of Research, Kaiser Permanente Northern California, Oakland, CA; Department of Medicine, University of Washington, Seattle, WA; Department of Medicine, McGill University, Montreal, Quebec, Canada; Department of Medicine, Case Western Reserve University, Cleveland, OH; Department of Internal Medicine, University of Alabama, Birmingham, AL; Department of Medicine, University of North Carolina, Chapel Hill, NC; National Institutes of Health, Bethesda, MD; BC Centre for Excellence and HIV/AIDS and Simon Fraser University, Vancouver, British Columbia, Canada; Department of Medicine, Yale University and VA Connecticut Healthcare System, New Haven, CT.

9/16/11

Reference

TR Sterling, B Lau, J Zhang, RD Moore, et al (for NA-ACCORD/IeDEA). Risk Factors for Tuberculosis after Highly Active Antiretroviral Therapy Initiation in the United States and Canada: Implications for Tuberculosis Screening. Journal of Infectious Diseases 204(6):893-901 (abstract). September 15, 2011.