OA-451 Spirometry, diffusion capacity, absolute lung volumes and PET/CT findings upon completion of tuberculosis treatment – preliminary findings of StatinTB/ExtendTB trial

<h3>Background</h3> Morbidity and mortality rates after successful completion of a six-month course of tuberculosis (TB) treatment remain elevated. Persistent lung inflammation (PLI) on 18F-FDG-PET/CT has been associated with TB relapse and may also lead to post-TB lung disease (PTLD). <h3>Methods</h3> The ongoing EDCTP-funded StatinTB trial (RIA2017T-2004; NCT04147286) evaluates safety/efficacy of 40 mg atorvastatin to reduce PLI after TB treatment in HIV-/HIV+ adults measured by 18F-FDG-PET/CT with extended total follow-up of 96 weeks (ExtendTB, NIH-funded). We report findings at time of enrolment into StatinTB/ExtendTB of the first 106 participants. Participants with clinical response to TB treatment and a negative sputum culture for TB at 16 weeks were screened after completing 24 weeks of treatment for drug-sensitive TB. Complete pulmonary function and PLI were measured using EasyOne Pro®Lab and PET/CT. PLI was defined as total lung glycolysis (TLG)≥50 SUVbw*mL. StatinTB/ExtendTB are conducted according to ICH-GCP. <h3>Results</h3> Of the 106 participants (32% women) aged 32.5±7.0 years who underwent PET/CT, 20.8% were HIV+, 57.5% smokers, 28.3% had previous TB; 13.2% reported ongoing cough, 3.8% chest pain and 8.5% shortness of breath. PLI was present in 49.1% of participants (mean TLG of 209±161 SUVbw*mL). Diffusing capacity of the lung for carbon monoxide (DLCO) was consistently reduced in participants with PLI (DLCO%Pred 73.4% vs. 93.7%; p=0.0002) as was FVC%Pred (82.1% vs. 94.9%; p=0.0004); FEV1%Pred was 82.1% vs 94.9%, p=0.0004. After accounting for other variables including HIV and smoking, every one percent increase in DLCO%Pred remained independently associated with a decrease of 4.7 SUVbw*mL of TLG (p=0.017). <h3>Conclusion</h3> PTLD is present in half of participants. Impaired DLCO is associated with PLI in adults after completing a 24-week treatment regimen for drug-sensitive TB. This highlights the need for treatment optimisation during and after TB treatment to reduce PTLD with persistent lung inflammation.