A Clinical Algorithm to Identify HIV Patients at High Risk for Incident Active Tuberculosis: A Prospective 5-Year Cohort Study.
BACKGROUND
Predicting the risk of tuberculosis (TB) in people living with HIV (PLHIV) using a single test is currently not possible. We aimed to develop and validate a clinical algorithm, using baseline CD4 cell counts, HIV viral load (pVL), and interferon-gamma release assay (IGRA), to identify PLHIV who are at high risk for incident active TB in low-to-moderate TB burden settings where highly active antiretroviral therapy (HAART) is routinely provided.


METHODS
A prospective, 5-year, cohort study of adult PLHIV was conducted from 2006 to 2012 in two hospitals in Taiwan. HAART was initiated based on contemporary guidelines (CD4 count < = 350/μL). Cox regression was used to identify the predictors of active TB and to construct the algorithm. The validation cohorts included 1455 HIV-infected individuals from previous published studies. Area under the receiver operating characteristic (ROC) curve was calculated.


RESULTS
Seventeen of 772 participants developed active TB during a median follow-up period of 5.21 years. Baseline CD4 < 350/μL or pVL ≥ 100,000/mL was a predictor of active TB (adjusted HR 4.87, 95% CI 1.49-15.90, P = 0.009). A positive baseline IGRA predicted TB in patients with baseline CD4 ≥ 350/μL and pVL < 100,000/mL (adjusted HR 6.09, 95% CI 1.52-24.40, P = 0.01). Compared with an IGRA-alone strategy, the algorithm improved the sensitivity from 37.5% to 76.5%, the negative predictive value from 98.5% to 99.2%. Compared with an untargeted strategy, the algorithm spared 468 (60.6%) from unnecessary TB preventive treatment. Area under the ROC curve was 0.692 (95% CI: 0.587-0.798) for the study cohort and 0.792 (95% CI: 0.776-0.808) and 0.766 in the 2 validation cohorts.


CONCLUSIONS
A validated algorithm incorporating the baseline CD4 cell count, HIV viral load, and IGRA status can be used to guide targeted TB preventive treatment in PLHIV in low-to-moderate TB burden settings where HAART is routinely provided to all PLHIV. The implementation of this algorithm will avoid unnecessary exposure of low-risk patients to drug toxicity and simultaneously, reduce the burden of universal treatment on the healthcare system.
Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Section of Infectious Diseases, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Susan Shin-Jung
SS
Lee
Department of Infection Control and Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan; Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Hsi-Hsun
HH
Lin
Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Section of Infectious Diseases, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Hung-Chin
HC
Tsai
National Health Research Institute, Zhu-nan, Taiwan.
Ih-Jen
IJ
Su
Centers for Disease Control, Ministry of Health and Welfare, Taipei, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
Chin-Hui
CH
Yang
Division of Infectious Diseases, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
Hsin-Yun
HY
Sun
Division of Infectious Diseases, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
Chien-Chin
CC
Hung
Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Section of Infectious Diseases, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Cheng-Len
CL
Sy
Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Section of Infectious Diseases, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Kuan-Sheng
KS
Wu
Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Section of Infectious Diseases, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Jui-Kuang
JK
Chen
Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Section of Infectious Diseases, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Yao-Shen
YS
Chen
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
Chi-Tai
CT
Fang
D017088:AIDS-Related Opportunistic Infections / Q000209:etiology; D000328:Adult; D000368:Aged; D000465:Algorithms; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count / Q000379:methods; D005260:Female; D006678:HIV / Q000472:pathogenicity; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D015994:Incidence; D059425:Interferon-gamma Release Tests / Q000379:methods; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D013624:Taiwan; D014376:Tuberculosis / Q000209:etiology* / Q000821:virology*; D019562:Viral Load / Q000379:methods; D055815:Young Adult