To describe characteristics and prognosis of patients with suboptimal immunological response to combined antiretroviral therapy (CART). Using data from a multicenter cohort study, we selected patients who initiated CART and showed suboptimal CD4-T cell response (defined as < 50 cells/L increase) after 1 year of therapy, despite sustained virological suppression. Characteristics of those patients were compared with subjects who showed optimal immunological response. Of 650 patients with virological suppression, 108 (16.6%) showed suboptimal CD4-T cell response. Independent predictors of suboptimal response were previous injection drug use (OR, 1.85; 95% CI, 1.12-2.98) and age at CART initiation (OR, 1.04 per year increase; 95%CI, 1.01-1.06). Hepatitis C virus coinfection was not associated with impaired inmunological response. As compared with patients with optimal immunological response, those with suboptimal response had a higher mortality rate (3.22 versus 0.71 per 100 person-years; p=.001), but a similar rate of new AIDSdefining events. In patients with sustained virological suppression with CART, previous injection drug use, but not hepatitis C virus coinfection, and older age at initiation of therapy were associated with suboptimal CD4 T-cell responses. Patients with suboptimal response had a higher mortality over time, mainly due to diseases other than AIDS-defining events.

To analyse the role of thymic function and its association with cellular immunosenescence markers in patients with low-level CD4 T cell repopulation, despite complete HIV RNA replication control on highly active antiretroviral therapy (HAART). Cellular immunosenescence markers comparing patients with CD4 T cell counts ≤250 cells/mm³ for ≥48 weeks (n = 11) and patients with a CD4 T cell count ≥500 cells/mm³ (n = 11) were investigated. Both groups were also compared with 11 healthy volunteers of similar age. Naive CD4 T cell counts, β- and δ-T cell rearrangement excision circles, recent thymic emigrants, replicative senescence marker, cell activation, and rate of apoptosis were analysed. The Mann–Whitney U-test was used to compare parameters between both low-level and high-level CD4 T cell repopulation groups, and healthy volunteers. Our results showed a lower thymic activity in patients with low-level CD4 T cell repopulation, leading to a decline in CD4 T cell production. On the other hand, a higher activation along with a higher replicative senescence of CD4 T cells contributed to a higher rate of apoptotic CD4 T cells in this group of patients. We propose a model with several different related mechanisms involved in premature immune senescence in HIV-infected patients with low-level CD4 repopulation on HAART. The understanding of such different mechanisms could help find effective strategies to prevent immune decay.

Chronic and systemic inflammatory alterations occur in HIV-infected patients and elderly uninfected subjects and in both scenarios these alterations are associated with the development of chronic morbidities and mortality. However, whether the levels of inflammatory alterations in untreated HIV-infected patients and elderly individuals are similar is unknown. Moreover, whether long-term antiretroviral therapy normalizes inflammatory alterations compared with HIV-uninfected persons of different age is not known. We analysed soluble inflammatory levels [high-sensitivity C-reactive protein, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8 and IL-17] in a cohort of viraemic HIV-infected patients compared with (i) age-matched, (ii) elderly and (iii) non-survivor elderly, uninfected healthy controls. We longitudinally analysed the effect of long-term 48 and 96 week suppressive combined antiretroviral therapy (cART) on the soluble inflammatory levels compared with those found in control subjects. Baseline IL-6 and IL-8 levels were at similar or lower concentrations in untreated patients compared with healthy elderly individuals. However, TNF-α and IFN-γ levels broadly exceeded those found in survivors and non-survivor elderly individuals. Long-term suppressive cART normalized most of the inflammatory markers, with the exception of TNF-α levels, which persisted as high as those in elderly non-survivor controls. Chronic inflammatory alterations associated with HIV infection are maintained at a different level from those of ageing. The persistent alteration of TNF-α levels in HIV-infected patients might cause tissue damage and have implications for developing non-AIDS-defining illnesses, even when HIV replication is long-term controlled by cART.

(1) Background: The serum ferritin cut-off to define absolute iron deficiency is not well-established. The aim of the present study was to determine a clinically relevant ferritin threshold by using early serum biomarkers of iron deficiency such as hepcidin and the soluble transferrin receptor; (2) Methods: Two hundred and twenty-eight asymptomatic subjects attending a hospital as outpatients between 1st April 2020 and 27th February 2022 were selected. Iron metabolism parameters as part of the blood analysis were requested by their doctor and included in the study. Then, they were classified into groups according to their ferritin levels and iron-related biomarkers in serum were determined, quantified, and compared between ferritin score groups and anemic subjects. (3) Results: Serum ferritin levels below 50 ng/mL establish the point from which the serum biomarker, the soluble transferrin receptor to hepcidin ratio (sTfR/Hep ratio), begins to correlate significantly with ferritin levels. (4) Conclusion: Ferritin levels ≤ 50 ng/mL are indicative of early iron deficiency; hence, this should be considered as a clinically relevant cut-off for iron deficiency.