Abstract Background Chest computed tomography (CT) findings in well-treated people with HIV infection (PWH) remain poorly characterized. Methods Cross-sectional analysis examining interstitial chest CT findings in PWH (n = 754) and uninfected controls (n = 470). Results HIV infection was independently associated with 1.82 (95% CI, 1.18–2.88) and 5.15 (95% CI, 1.72–22.2) higher adjusted odds of any interstitial lung abnormality and findings suspicious for interstitial lung disease, respectively. Conclusions HIV infection was independently associated with interstitial lung abnormalities and findings suspicious for interstitial lung disease. Whether these abnormalities develop into more recognizable disease states over time is unknown but warrants further investigation.