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The immune factors associated with impaired SARS-CoV-2 vaccine response in elderly people are mostly unknown. We studied individuals older than 60 and younger than 60 years, who had been vaccinated with SARS-CoV-2 BNT162b2 mRNA, before and after the first and second dose. Aging was associated with a lower anti–RBD IgG levels and a decreased magnitude and polyfunctionality of SARS-CoV-2–specific T cell response. The dramatic decrease in thymic function in people > 60 years, which fueled alteration in T cell homeostasis, and their lower CD161+ T cell levels were associated with decreased T cell response 2 months after vaccination. Additionally, deficient DC homing, activation, and TLR-mediated function, along with a proinflammatory functional profile in monocytes, were observed in the > 60-year-old group, which was also related to lower specific T cell response after vaccination. These findings might be relevant for the improvement of the current vaccination strategies and for the development of new vaccine prototypes., This work was supported by the Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía grants CV20-85418 and P20_00906 and by research contracts DOC-01659 and DOC-00963, as well as by Consejería de Salud, Junta de Andalucía research contract RH-0037-2020 and Instituto de Salud Carlos III CP19/00159, FI17/00186, FI19/00083, PI19/01127, and CM20/00243 from Fondos FEDER. ERM was supported by the Spanish Research Council (CSIC). We thank all the community volunteers, participants from the IBiS, Chema Niño, and the nursing staff from Virgen del Rocío University Hospital who have taken part in this project. We also thank Alicia Gutierrez and Esperanza Muñoz for reviewing the manuscript. In memoriam Silvio Manuel Pérez Martín.

Background There are several regimens for starting antiretroviral treatment, but it remains unknown whether either of them is more advantageous regarding the time course and magnitude of human immunodeficiency virus (HIV) RNA decay in semen. Objective To evaluate the differential effect of different antiretroviral drug families on viral kinetics in seminal plasma (SP) of treatment-naive HIV-infected patients. Methods Phase II, randomized, open-label study in which participants were randomized 1:1:1 to receive tenofovir-disoproxil fumarate (DF) plus emtricitabine, and either cobicistat-boosted elvitegravir (EVGcobi), rilpivirine (RPV), or ritonavir-boosted darunavir (DRVrtv). The primary endpoint was the proportion of participants with undetectable HIV-RNA in SP at week 12. HIV type 1 (HIV-1) RNA was measured in paired SP and blood plasma (BP) at baseline and after 1, 2, 4, 6, 8, 12, 18, and 24 weeks. Elvitegravir (EVG), RPV, and darunavir (DRV) concentrations were quantified by the liquid chromatography-tandem mass spectrometry method. Results In SP, the HIV-RNA decay rate with RPV was as fast as with EVGcobi; by week 12, all participants in the RPV and the EVGcobi groups reached an undetectable viral load but only 58.3% in the DRVrtv arm (P = .003). The highest SP/BP drug concentration ratio was for EVG (0.43), followed-up by RPV (0.19), and DRV (0.10). For both EVG and RPV, the SP concentrations exceeded >2-fold the protein binding-adjusted EC90 for wild-type HIV-1; for DRV, only 33.7% of the SP showed concentrations above the protein binding-adjusted EC90. Conclusions In SP, both RPV and EVGcobi, associated to tenofovir-DF and emtricitabine, behave similarly and achieve an undetectable viral load much faster than DRVrtv. Registration European Medical Agency (No. EudraCT: 2014-001348-39).