Human T-Lymphotropic Virus type 1c subtype proviral loads, chronic lung disease and survival in a prospective cohort of Indigenous Australians

• Published in: PLoS neglected tropical diseases Vol. 12; no. 3; p. e0006281
• Main Authors: Einsiedel, Lloyd, Pham, Hai, Wilson, Kim, Walley, Rebecca, Turpin, Jocelyn, Bangham, Charles, Gessain, Antoine, Woodman, Richard J.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.03.2018; Public Library of Science (PLoS)
• Subjects: Adult; Adults; Aged; Alcohol use; Australia - epidemiology; Biology and life sciences; Bronchiectasis; Bronchiectasis - epidemiology; Bronchiectasis - ethnology; Bronchiectasis - virology; Bronchiolitis - epidemiology; Bronchiolitis - ethnology; Bronchiolitis - virology; Bronchitis; Bronchitis - epidemiology; Bronchitis - ethnology; Bronchitis - virology; Bronchopneumonia; Chronic Disease - epidemiology; Chronic infection; Cohort Studies; Cohorts; Complications; Complications and side effects; Computed tomography; Death; Diabetes; Disease-Free Survival; Diseases; Epidemiology; Fatalities; Female; Funding; Health risks; Hematology; Hospitals; HTLV-I infections; HTLV-I Infections - epidemiology; HTLV-I Infections - ethnology; HTLV-I Infections - mortality; HTLV-I Infections - virology; Human T-lymphotropic virus 1 - classification; Human T-lymphotropic virus 1 - genetics; Human T-lymphotropic virus 1 - isolation & purification; Human T-lymphotropic virus 1 - physiology; Humans; Infections; Infectious diseases; Inflammation; Inflammatory diseases; Leukemia; Leukocytes; Life Sciences; Lung diseases; Lung Diseases - diagnostic imaging; Lung Diseases - epidemiology; Lung Diseases - ethnology; Lung Diseases - virology; Lungs; Lymphocytes; Lymphoma; Male; Medical prognosis; Medicine and Health Sciences; Middle Aged; Mortality; Native peoples; Patient outcomes; Peripheral blood; Prognosis; Prospective Studies; Proviruses - isolation & purification; Proviruses - physiology; Risk; Risk Factors; Survival; Tomography; Tomography, Emission-Computed; Tropical diseases; Viral Load; Virology; Viruses; Australia; United Kingdom > UK; Alice Springs Northern Territory Australia
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0006281

The Human T-Lymphotropic Virus type 1c subtype (HTLV-1c) is highly endemic to central Australia where the most frequent complication of HTLV-1 infection in Indigenous Australians is bronchiectasis. We carried out a prospective study to quantify the prognosis of HTLV-1c infection and chronic lung disease and the risk of death according to the HTLV-1c proviral load (pVL). 840 Indigenous adults (discharge diagnosis of bronchiectasis, 154) were recruited to a hospital-based prospective cohort. Baseline HTLV-1c pVL were determined and the results of chest computed tomography and clinical details reviewed. The odds of an association between HTLV-1 infection and bronchiectasis or bronchitis/bronchiolitis were calculated, and the impact of HTLV-1c pVL on the risk of death was measured. Radiologically defined bronchiectasis and bronchitis/bronchiolitis were significantly more common among HTLV-1-infected subjects (adjusted odds ratio = 2.9; 95% CI, 2.0, 4.3). Median HTLV-1c pVL for subjects with airways inflammation was 16-fold higher than that of asymptomatic subjects. There were 151 deaths during 2,140 person-years of follow-up (maximum follow-up 8.13 years). Mortality rates were higher among subjects with HTLV-1c pVL ≥1000 copies per 105 peripheral blood leukocytes (log-rank χ2 (2df) = 6.63, p = 0.036) compared to those with lower HTLV-1c pVL or uninfected subjects. Excess mortality was largely due to bronchiectasis-related deaths (adjusted HR 4.31; 95% CI, 1.78, 10.42 versus uninfected). Higher HTLV-1c pVL was strongly associated with radiologically defined airways inflammation and with death due to complications of bronchiectasis. An increased risk of death due to an HTLV-1 associated inflammatory disease has not been demonstrated previously. Our findings indicate that mortality associated with HTLV-1c infection may be higher than has been previously appreciated. Further prospective studies are needed to determine whether these results can be generalized to other HTLV-1 endemic areas.