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Incidence of Active Tuberculosis in HIV-Infected Adults and Mortality in Thailand
Nicolas Salvadori1, Suwalai Chalermpantmetagul1, Julie Figoni1, Suchart Thongpaen2, Ampaipith Nilmanat3, Patinun Chirawatthanaphan4, Pramual Thaingamsilp5, Tim R. Cressey1, Nicole Ngo-Giang-Huong1, Gonzague Jourdain1
1 Institut de Recherche Pour le Développement UMI 174-PHPT, Chiang Mai, Thailand. 2 Mahasarakham Hospital, Mahasarakham, Thailand. 3 Hat Yai Hospital, Hat Yai, Thailand. 4 Phaholpolpayuhasaena Hospital, Kanchanaburi, Thailand. 5 Kalasin Hospital, Kalasin, Thailand.
Background: Thailand is one of the 22 high tuberculosis (TB) burden countries listed by the WHO. We estimated the incidence of active TB in HIV-infected adults, investigated the association between characteristics at antiretroviral therapy (ART) initiation and TB diagnosis, and compared survival rates of adults with and without active TB in a large HIV cohort in Thailand.
Methods: ART-naïve adults who enrolled in the PHPT cohort (NCT00433030) between 1999 and 2012 were included in this analysis. Screening for active TB was based on interview, clinical examination, chest X-ray and sputum smear. Incidence was the number of new cases divided by that of person-years of follow-up (PY). Using incidence rate ratios (IRRs) from Poisson regression models, the association between sex, age, education level, BMI, HIV RNA load, CD4 count, period of enrollment and complete blood count parameters at ART initiation and TB diagnosis was assessed. Survival rates were estimated and compared using Kaplan-Meier method and log-rank test.
Results: At ART initiation, 1702 adults (82% female) had a median age (IQR) of 31.5 years (27.1-36.8), HIV RNA load 4.8 log10 copies/mL (4.1-5.2) and CD4 count 144 cells/mm3 (67-218). Median follow-up was 6.9 years (2.4-8.3). Overall incidence rate of active TB was 0.98/100 PY (95% CI 0.80-1.19) (99 cases). Incidence rates decreased with ART duration, from 5.4/100 PY within the first 6 months to 0.24/100 PY after 5 years. Median time until TB diagnosis was 7.4 months (1.4-28.4). Male gender (IRR 2.0) and BMI <18.5 kg/m2 (IRR 4.0) at ART initiation were significantly associated with TB diagnosis (p <0.001), but not age above median (IRR 0.8, p = 0.20). Adjusting for gender and age, TB diagnosis was associated with (all p <0.001): higher (above median) HIV RNA load (IRR 2.2) and neutrophils (IRR 2.2), and lower (below median) lymphocytes (IRR 2.2), CD4 count (IRR 2.7), hemoglobin (IRR 2.8) and hematocrit (IRR 2.7). Of the 99 adults with TB diagnosis, 29 died (median survival time after diagnosis: 2.9 months (IQR 1.1-8.9)). Cumulative survival rates after ART initiation were 87% at 1 year, 73% at 5 years and 67% at 10 years in adults with active TB, versus 97%, 95% and 92% in those without active TB (p <0.001).
Conclusions: Active TB is a major cause of death in this HIV cohort in Thailand as in many settings. Most reported predictors are available in many ART programs. They should be carefully considered to accelerate TB diagnosis and treatment in patients initiating ART.