Higher human T-cell leukaemia virus type 1 (HTLV-1) proviral load is associated with end-stage kidney disease in Indigenous Australians: Results of a case-control study in central Australia.

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.

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

BACKGROUND: 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). METHODOLOGY/PRINCIPAL FINDINGS: 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). CONCLUSION/SIGNIFICANCE: 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.