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Lung cancer screening with low-dose computed tomography (LDCT) of high-risk groups in the general population is recommended by several authorities. This may not be feasible in people living with HIV (PLWHIV) due to higher prevalence of nodules. We therefore assessed the prevalence of positive computed tomography (CT) images and lung cancers in PLWHIV.The Copenhagen comorbidity in HIV infection (COCOMO) study is an observational, longitudinal cohort study. Single-round LDCT was performed with subsequent clinical follow-up (NCT02382822).Outcomes included histology-proven lung cancer identified by LDCT and positive CT images (noncalcified nodules) in the entire cohort and in the high-risk group (>50 years of age and >30 pack-years). We also assessed the procedures and adverse events, and clinical factors associated with a positive CT image.LDCT was performed in 901 patients, including 113 at high risk for lung cancer. A positive image was found in 28 (3.1% of the entire cohort and 9.7% of the high-risk group). Nine patients (all in the high-risk group) had invasive procedures undertaken with no serious adverse events. Lung cancer (stages IA, IIA, and IIIA) was diagnosed in three patients from the high-risk group (2.7%). CD4+ cell count less than 500 cells/μl and CD4+ nadir less than 200 cells/μl were each independently associated with increased odds of a positive image odds ratio 2.32 [95% confidence interval: 1.01–5.13, P = 0.04] and odds ratio 2.63 [95% confidence interval: 1.13–6.66, P = 0.03].Randomized LDCT screening trials in PLWHIV are nonexistent, but these findings are comparable with screening rounds from the general population in terms of prevalence of lung cancer and positive CT images.