BackgroundThe 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).Methodology/Principal findings840 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).Conclusion/SignificanceHigher 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.

Case series suggest that human T‐cell leukaemia virus type 1 (HTLV‐1) is associated with kidney disease; however, little is known about the impact of proviral load (PVL). The present study was commenced to determine whether higher HTLV‐1 PVL is associated with end stage kidney disease (ESKD) in Indigenous Australians. A case‐control study was conducted in Alice Springs Hospital (ASH), 1 July 2007 to 30 November 2015. Cases included all 80 Indigenous adults (>17 years) with HTLV‐1c and ESKD, matched 1:1 by sex to controls with HTLV‐1 who had no renal disease or other recognised disease associations of HTLV‐1, and were recruited during the same period. The association between PVL and ESKD was assessed using logistic regression. Median (IQR) HTLV‐1c PVL for subjects with ESKD (6.86, IQR (3.35, 8.23) log copies per 105 peripheral blood leukocytes (PBL) (ie, 0.95; IQR, 0.03; 3.70% PBL) was significantly higher than that of the asymptomatic group (3.47; IQR (−0.04, 6.61) log copies per 10 5 PBL (ie, 0.01; IQR, 0.00; 0.52% PBL) (asymptomatic vs ESKD, P (ranksum) < .001). Major factors associated with ESKD were diabetes (adjusted odds ratio [aOR], 21.80; 95% CI, 4.84, 98.22; P < .001), hypertension (aOR, 4.16; 1.11, 15.64; P = .03), remote residence (aOR, 5.34; 95% CI, 1.17, 27.29; P = .03) and HTLV‐1c PVL greater than or equal to 100 copies per 10 5 PBL (aOR, 3.67; 95% CI, 1.36, 9.92; P = .01). Higher HTLV‐1c PVL are strongly associated with inflammatory diseases. The high HTLV‐1c PVL reported here may have clinical implications for people with HTLV‐1 who require haemodialysis. Longitudinal studies are required to determine whether this association is causal.