Health outcomes and social determinants in people living with HIV in Sweden : insights from the COVID-19 era and beyond

<jats:p>&lt;p dir="ltr"&gt;People with HIV (PWH) experience improved health and quality of life in the era of contemporary antiretroviral treatment (ART), and their life expectancy in high- income countries approaches that of people without HIV. However, disparities remain. PWH have been shown to face an increased risk and earlier onset of age- related comorbidities, even with access to effective ART and viral suppression. The comorbidity burden has been attributed in part to long-term effects of life- long ART and to residual low-grade inflammation and immune dysfunction that persist despite ART. Furthermore, PWH in high-income countries such as Sweden have lower socioeconomic status, including lower education and income, and approximately 60% are migrants. These social determinants are themselves associated with a higher risk of age-related comorbidities and may contribute to the excess risk observed among PWH. The extent to which these social factors contribute, however, has been less well studied and is important to clarify in order to target interventions effectively.&lt;/p&gt;&lt;p dir="ltr"&gt;The overall aim of the thesis was to investigate the risk of comorbidities, with a focus on COVID-19 and type 2 diabetes mellitus (T2DM), in PWH compared with people without HIV. Through linkage of Swedish nationwide registers across four studies, these outcomes were examined in virtually the entire adult Swedish population or a sample of it, while accounting for demographics, socioeconomic factors, and underlying comorbidities.&lt;/p&gt;&lt;p dir="ltr"&gt;Study I assessed the risk of severe COVID-19 (intensive care admission or mortality) among individuals hospitalised with COVID-19 by HIV status during the first phase of the pandemic (February 2020 to October 2021). In total, 64,815 individuals were hospitalised with COVID-19, of whom 121 were PWH. Odds ratios (OR) were estimated using logistic regression. The unadjusted OR of severe COVID-19 was lower among PWH compared with people without HIV (OR 0.60, 95% CI 0.34-0.94), whereas adjustment for age and sex showed no significant difference (adjOR 0.70, 95% CI 0.43-1.26). These findings added to the evidence that PWH with access to ART, viral suppression, and a high CD4+ T-cell count did not have a higher risk of severe COVID-19 than people without HIV. The lower unadjusted OR was largely explained by PWH being younger at admission, possibly reflecting a different clinical threshold for admission rather than a true difference in COVID-19 severity.&lt;/p&gt;&lt;p dir="ltr"&gt;Study II investigated the risk of COVID-19 hospitalisation following confirmed SARS-CoV-2 infection in PWH (n=1,348) compared with people without HIV (n=1,669,389) between January 2021 and February 2023. Analyses were categorised by vaccination status and by pandemic period (pre-Omicron, Omicron during public testing, and Omicron after public testing) and ORs were estimated using logistic regression. Among those unvaccinated or vaccinated with only two doses, unadjusted ORs were significantly increased in PWH compared with people without HIV, but not after adjustment for age, sex, month of SARS-CoV-2 infection, income, migrant status, and comorbidities. No significant differences were observed among those vaccinated with at least three doses. During Omicron and public testing, PWH had significantly increased adjusted odds of hospitalisation compared with people without HIV. Taken together, the risk of COVID-19 hospitalisation in PWH was overall similar to that of people without HIV, although temporal variations were observed and may reflect differences in testing patterns by HIV status.&lt;/p&gt;&lt;p dir="ltr"&gt;Study III estimated the risk ratio (RR) of SARS-CoV-2 vaccination uptake across doses 1-5 using modified Poisson regression, among individuals alive and resident in Sweden at the start of vaccination, comparing PWH (n=7,668) with people without HIV (n=8,168,340). People with HIV were divided into two groups based on COVID-19 vaccination prioritisation: non-vulnerable PWH and clinically vulnerable PWH. In both groups, PWH had lower unadjusted 3-dose uptake (non- vulnerable: RR 0.90, 95% CI 0.88-0.91); however, after adjustment, particularly for country of birth, PWH had higher uptake (non-vulnerable: adjRR 1.17, 95% CI 1.15-1.19). This pattern did not persist among individuals aged ≥65 years, where 5-dose uptake was lower among non-vulnerable PWH (adjRR 0.91, 95% CI 0.85- 0.96). Taken together, PWH had lower vaccination uptake than people without HIV, although it was mainly explained by the higher proportion of PWH born outside Sweden. At the same time, the higher adjusted uptake among PWH underscores that frequent healthcare contact that comes with living with HIV facilitates vaccination, however the same advantage did not appear to extend to older PWH. This further suggests that public health measures addressing vaccination uptake should be directed at migrant populations rather than at PWH.&lt;/p&gt;&lt;p dir="ltr"&gt;Study IV assessed the risk of severe renal events, cardiovascular events, and all- cause mortality following a T2DM diagnosis in PWH (n=350) compared with people without HIV (n=311,668) between 2010 and 2024. Hazard ratios (HR) were estimated using Cox proportional hazards models adjusted for quintiles of a propensity score based on age, sex, migrant status, comorbidities, and socioeconomic status. A significantly increased risk of major adverse kidney events among PWH compared with people without HIV (adjHR 2.04, 95% CI 1.57- 2.65) was found. No significant differences were observed for major adverse cardiovascular events or all-cause mortality in multivariable models. The renal signal persisted across several sensitivity analyses, however, correction for the known benign serum creatinine increase associated with bictegravir, cobicistat, dolutegravir, and rilpivirine attenuated the estimate and did not remain statistically significant (adjHR 1.32, 95% CI 0.90-1.94). Although detailed exploration of ART was limited by the few events among PWH, these findings highlight the importance of closer monitoring and careful management of renal risk factors in PWH with T2DM and warrant further research to clarify this association.&lt;/p&gt;&lt;p dir="ltr"&gt;Study I-IV collectively highlight that the previously observed increased comorbidity risk among PWH may be shaped not only by biological vulnerability and ART, but also by social determinants and differences in healthcare access and monitoring. Consequently, the excess comorbidity burden among PWH may be meaningfully reduced by addressing sociodemographic disparities, optimising comorbidity management, and strengthening preventive care, while further research continues to explore the underlying mechanisms and improve risk prediction.&lt;/p&gt;&lt;h3 dir="ltr"&gt;List of scientific papers&lt;/h3&gt;&lt;p dir="ltr"&gt;I. &lt;b&gt;Killander Möller I,&lt;/b&gt; Gisslen M, Wagner P, Sparen P, Carlander C. COVID-19 hospitalization outcomes in adults by HIV status; a nation-wide register-based study. HIV Med 2023;24(10):1045-55.&lt;br&gt;&lt;a href="https://doi.org/10.1111/hiv.13515" target="_blank" rel="noreferrer"&gt;https://doi.org/10.1111/hiv.13515&lt;br&gt;&lt;br&gt;&lt;/a&gt;&lt;/p&gt;&lt;p dir="ltr"&gt;II. &lt;b&gt;Killander Möller I,&lt;/b&gt; Hedberg P, Wagner P, Lindahl H, Nyström S, Blixt L, et al. Risk of COVID-19 hospitalisation by HIV-status and SARS- CoV-2 vaccination status during pre- and post-Omicron era in a national register-based cohort study in Sweden. Infect Dis (Lond). 2024;57(2): 178-191.&lt;br&gt;&lt;a href="https://doi.org/10.1080/23744235.2024.2405582" target="_blank" rel="noreferrer"&gt;https://doi.org/10.1080/23744235.2024.2405582&lt;br&gt;&lt;br&gt;&lt;/a&gt;&lt;/p&gt;&lt;p dir="ltr"&gt;III. &lt;b&gt;Killander Möller I,&lt;/b&gt; Hedberg P, Wagner P, Sparén P, Gisslén M, Nauclér P, et al. Sociodemographic factors influencing SARS-CoV-2 vaccination uptake in people with and without HIV: Insights from a Swedish Nationwide cohort. Vaccine. 2025;62:127580.&lt;br&gt;&lt;a href="https://doi.org/10.1016/j.vaccine.2025.127580" target="_blank" rel="noreferrer"&gt;https://doi.org/10.1016/j.vaccine.2025.127580&lt;br&gt;&lt;br&gt;&lt;/a&gt;&lt;/p&gt;&lt;p dir="ltr"&gt;IV. &lt;b&gt;Killander Möller I,&lt;/b&gt; Wagner P, Brännström J, Bäckdahl T, Elvstam O, Gisslen M, et al. Renal and Cardiovascular Complications Following Type 2 Diabetes Mellitus in People With and Without HIV: Data from Cohort Study on Morbidity and HIV in Sweden (COSMOHS) between 2010-2024. Clin Infect Dis. 2026;82(6):e1252-e1261.&lt;br&gt;&lt;a href="https://doi.org/10.1093/cid/ciag261" target="_blank" rel="noreferrer"&gt;https://doi.org/10.1093/cid/ciag261&lt;/a&gt;&lt;/p&gt;</jats:p>