18F-FDG PET/CT as a novel metabolic parameter for lung function impairment and or harmful inflammation during early treatment of pulmonary TB co-infected by HIV

294 Objectives: HIV infection dramatically increases TB risk. Antiretroviral therapy (ART) improves survival in HIV-infected adults with pulmonary TB but ART-mediated functional immune restoration may trigger the TB immune reconstitution inflammatory syndrome (TB-IRIS). No studies to our knowledge have evaluated the relationship between ART initiation, immune recovery, local lung inflammation, and longer term lung function in HIV/TB. We decided to use FDG PET-CT to test the hypothesis that robust ART-mediated immune recovery induces pulmonary inflammation and impairs lung function in HIV/TB co-infected adults. Methods: The Lung Function after TB-IRIS (LIFT-IRIS) Study is a prospective cohort study evaluating changes in lung function and pulmonary symptoms up to 48 weeks after ART initiation in adults with HIV and pulmonary TB. An imaging sub-study enrolling individuals agreeing to undergo FDG PET-CT scanning prior to (baseline) and 4 weeks after ART initiation was conducted. Early changes in lung function (forced expiratory volume in 1 second, or FEV1), symptoms and lung enhancement on FDG PET-CT at week 4 in these individuals are the primary focus of this abstract. The choice of 4 weeks as the primary follow-up point is based on evidence that dramatic changes in cellular immune responses occur by this time and are associated with clinical outcomes including TB-IRIS and survival in HIV/pulmonary TB. HIV-infected, ART naive adults 18-70 years old with CD4 counts <200 cells/l were initially enrolled but the protocol was later amended to include individuals with CD4 counts <500 cells/l. Participants needed to complete at least the baseline FDG PET-CT scan to be included in analyses of pulmonary total glycolytic activity (TGA). Lung function was measured by spirometry. Lung symptoms were assessed by the COPD Assessment Test (CAT) score (range, 0-40, with higher scores indicating worse symptoms). Results: 48 participants were included in the imaging cohort and 30 (63%) returned for a second FDG PET-CT approximately 4 weeks after ART initiation. Those who did not return for a second scan had slightly lower baseline CD4 counts [84 cells/µl (IQR 48 - 156) vs 112 cells/µl (IQR 48 - 294)] and higher CAT scores [median = 9 cells/µl (IQR 4 - 17) vs 6 cells/µl (IQR 3 - 13)]. Increases in lung TGA during the initial 4 weeks of ART tended to occur in subjects who developed an FEV1 decrease or worsening symptoms during this time. The median change in lung TGA was an increase of 0.1 log10 SUVs (IQR -0.1 - 0.5) among those with an FEV1 decrease from baseline to week 4 versus a decrease of 0.2 log10 SUVs in those without an FEV1 decrease (IQR -0.3 - 0.0; p=0.06). Similarly, the median change in log10 SUVs from baseline to week 4 among those with worsening CAT scores versus others was 0.3 (IQR -0.0 - 0.8) vs -0.2 (IQR -0.3 - 0.0), p=0.02. Participants with increasing lung TGA on ART had significantly greater increases in the frequency of PPD-specific CD4+ T cells expressing TNFα and IFNγ from baseline to week 4 post-ART. The most robust associations were between increase in lung TGA and increase in the frequency of PPD-specific CD4+ T cells expressing both cytokines following ART initiation (p<0.001). Conclusions: Our study indicates that greater lung inflammation on FDG PET-CT is associated with worse lung function and symptoms prior to ART initiation and that greater recovery of pathogen-specific CD4 cell function on ART is associated with increased pulmonary inflammation and decreased lung function in HIV-infected individuals with pulmonary TB. Although these findings should not contribute to delaying ART initiation in individuals with HIV/TB, our results should however stimulate interest in further evaluation of therapeutic interventions to decrease lung inflammation in TB. These results constitute a direct evidence of the clinical relevance for the use of F-18 FDG PET/CT in the treatment evaluation of TB associated with HIV.