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Lung cancer screening with chest computed tomography (CT) is beneficial in smokers aged 55 to 74 years. We studied the risks, benefits and feasibility of early lung cancer diagnosis with CT in HIV-infected smokers.French, multicentre, single round chest CT study in France, realized between February 2011 and June 2012.Patients were HIV-infected smokers at least 40 years, at least 20 pack-years, with a CD4+ T-lymphocyte nadir count below 350 cells/μl.Single chest CT with a proposed standardized workup algorithm of positive images.The outcome was the number of histologically proven lung cancers diagnosed by CT with a 2-year follow-up.Median age of the 442 included patients was 49.8 years, 81.6% were under 55 years, 84% were men, median smoking was 30 pack-years, median nadir and last CD4+ cell counts were 168 and 574 cells/μl, respectively, and 90% of patients had a plasma HIV RNA below 50 copies/ml. A positive image at baseline was reported in 94 (21%) patients, and 15 (3.4%) patients had 18 invasive procedures with no serious adverse events. Lung cancer was diagnosed in 10 patients (six at early stages), of which nine (2.0%, 95% confidence interval: 0.9–3.8) were CT detected, and eight in patients below 55 years.Early lung cancer diagnosis with CT in HIV-infected smokers was feasible, safe, and yielded a significant number of cancers. Lung cancer screening of HIV-infected smokers with an important history of immunodeficiency revealed a substantial number of cancers at younger ages than the targeted range in the general population.