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Introduction: Globally, lung cancer remains the leading cause of malignancy-related death in men and women. There is increasing evidence that the risk for lung cancer in people living with human immunodeficiency virus (PLHIV) is higher than that of the general population. Given the high burden of PLHIV and lung cancer in Southern Africa, we aimed to compare the characteristics of PLHIV and HIV-negative lung cancer patients with regards to demographics, cell type, performance status, and tumour stage at presentation. Methods: All patients who presented to a large tertiary hospital over a 7-year period with a confirmed tissue diagnosis of primary lung cancer were included in a prospective registry. The patient demographics, HIV status, as well as the patients' performance status according to the Eastern Cooperative Oncology Group (ECOG) were documented. Results: The cohort consisted of 1,805 patients (mean age 60.0 years) of which 1,129 were male. In total, 133 were PLHIV and 1,292 were confirmed HIV-negative, while the remaining were categorised as HIV-unknown. PLHIV with lung cancer were found to be younger than the HIV-negative group (mean [±SD] 54.6 [9.3] versus 60.3 [10.1], p < 0.001). Notably, not a single PLHIV was diagnosed with resectable non-small cell lung cancer (NSCLC), and only 7 of 133 (6.5%) had potentially curable disease NSCLC (up to stage IIIB) compared to 240 of 1292 HIV-negative patients (27.7%, p < 0.001). Conclusion: PLHIV with lung cancer were diagnosed at a significantly younger age and were significantly less likely to have curable NSCLC at presentation. [ABSTRACT FROM AUTHOR]