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BackgroundWhether people living with HIV (PLWH) are at greater risk of acquiring SARS-CoV-2 infection is currently unknown. Prospective serologic studies may allow seroincidence analyses, where all infections are accurately identified. Because of this, we evaluated the incidence of and associated factors with SARS-CoV-2 infection in PLWH in Southern Spain.MethodsThis was a prospective cohort study including PLWH from a University Hospital in Southern Spain. Patients were enrolled if 1) they had attended as outpatients our Unit from August 1st, 2019 to February 8th, 2020; 2) had two subsequent evaluations from February 9th, 2020 to February 15th, 2021. Serum antibodies against SARS-CoV-2 were determined in baseline and intra-pandemic samples.Results710 PLWH were included in the study. Of them, 46 [6.5%, 95% confidence interval (95% CI): 4.8%-8.5%] patients developed SARS-CoV-2 infection. Between May 18th and November 29th, 2020, the rate of seroconversion was 5.3% (95% CI: 3.1%-9%) for the general population in the area of Seville and 2.3% (95% CI: 1.3%-3.6%) for PLWH in this study (p=0.001). After multivariate analysis, adjusted by age and sex, active tobacco smoking was the only factor independently associated with lower risk of SARS-Cov-2 infection (Incidence rate ratio 0.35, 95% CI: 0.18-0.68, p=0.002).ConclusionsThe incidence of SARS-CoV-2 infection among PLWH in Southern Spain during the ongoing pandemic was lower than that reported for the general population in the same area. Tobacco smoking was the only factor independently associated with a lower risk of incident SARS-CoV-2 infection.SummaryThe incidence of SARS-CoV-2 infection among people living with HIV is lower than that of general population in Southern Spain. Active tobacco smoking could be associated with a lower risk of developing COVID-19.