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This study examined the effects of specific psychosocial factors on the progression of HIV infection in 200 HIV-1 seropositive but asymptomatic men and women. At baseline, participants' disease status was determined, and they were administered self-report assessments of coping style, social support and loneliness. Participants were classified at 6 and 12 month follow-ups as progressed or unchanged, compared to their baseline status. In logistic regression analyses, higher baseline Type C coping scores (indicating emotional inexpressiveness and decreased recognition of needs and feelings) significantly predicted progression at 6 months (p<0.01) and 12 months (p<0.02), but only among participants classified at baseline as CDC-A2 (between 200-499 CD4 cells/mm3). In participants originally classified as CDC-A1 (CD4 cell counts > 500/mm3), no psychosocial variable showed any significant relationship. Results emphasize the need to consider the disease context, as well as the interaction between biological and psychological factors in contributing to disease progression. [ABSTRACT FROM AUTHOR]

Reports global developments related to AIDS immunology as of August 1999. Role of cell cycle regulation during HIV infection; Examination of DNA content of circulating lymphocytes obtained from HIV-1 infected persons; Differentiation of classic autoimmune thrombocytopenia with immune complex-associated thrombocytopenia in systemic lupus.

Eighty-seven seropositive subjects with HIV (human immunodeficiency virus) infection together with 20 normal controls with no history of any illness were investigated for the presence of circulating immune complexes (CIC) by the conglutinin binding assay (KgBA) and further studied for isotype characterization of CIC. Six out of 87 patients showing very high values for immune complexes (CIC) were studied for the presence of free antigen. In 3 out of 6 (1, IVc1;1, III: 1, IVa) we could detect by ultracentrifugation analysis the presence of specific HIV (p15) anti-HIV (anti-pl5) and gp41-anti-gp4l CIC. Evidence in favour of this finding is supported by: (1) the presence of specific CIC (pl5-anti-pl5 or gp4)-anti-gp41) seen only at pH 7.2; (2) the apparent presence of free antigen and specific HIV antibodies were only at pH 4.0. The relevance of this finding lies in the attempt to explain the occurrence of false seronegativity seen occasionally in symptomatic patients. Thus, the presence of CIC might perhaps interfere in the routine assay (i.e. ELISA) making the diagnosis difficult. All these considerations will have to be taken into account in the future handling of this disease. [ABSTRACT FROM AUTHOR]

Abstract Background The optimal therapeutic strategies for patients presenting with advanced disease at HIV-1 diagnosis are as yet incompletely defined. Methods All patients presenting at two outpatient clinics in 2000-2009 with an AIDS-defining clinical condition or a CD4+ T cell count < 200/μL at HIV-1 diagnosis were analyzed for the presence of combined immunovirological response, defined by the concomitant presence of an absolute number of CD4+ T cells > 200 cells/μL and a plasma HIV-1 RNA copy number < 50/mL after 12 months of HAART. Results Among 102 evaluable patients, first-line regimens were protease inhibitors [PI]-based in 78 cases (77%) and efavirenz-based in 24 cases (23%). The overall response rate was 65% (95% CI: 55-74), with no differences by gender, age, nationality, route of transmission, hepatitis virus coinfections, presence of AIDS-defining clinical events, baseline HIV-1 viral load, or type of regimen (response rates with PI-based and efavirenz-based therapy: 63% and 71%, respectively, p = 0.474). Response rate was significantly better with higher baseline CD4+ T cell counts (78% with CD4+ ≥ 100/μL, compared to 50% with CD4+ < 100/μL; odds ratio: 3.5; 95% CI: 1.49-8.23, p = 0.003). Median time on first-line antiretroviral therapy was 24 months (interquartile range: 12-48). Switch to a second line treatment occurred in 57% of patients, mainly for simplification (57%), and was significantly more common with PI-based regimens [adjusted hazard ratios (AHR) with respect to efavirenz-based regimens: 3.88 for unboosted PIs (95% CI: 1.40-10.7, p = 0.009) and 4.21 for ritonavir-boosted PI (95%CI 1.7-10.4, p = 0.002)] and in older subjects (≥ 50 years) (AHR: 1.83; 95% CI: 1.02-3.31, p = 0.044). Overall mortality was low (3% after a median follow up of 48 months). Conclusions Our data indicate that a favorable immunovirological response is possible in the majority of naive patients presenting at HIV-1 diagnosis with AIDS or low CD4+ T cell counts, and confirm that starting HAART with a more compromised immune system may be associated with a delayed and sometimes partial immune recovery. Simpler regimens may be preferable in this particular population.

Abstract In HIV-1 infected patients, increase of liver enzymes may be mainly due to viral coinfections, alcohol intake, hepatotoxic drugs or autoimmune diseases. Three cases of aminotransferase elevation occurred during a phase of uncontrolled viral replication combined with a severe immunodeficiency and resolved by an effective HAART are described, focusing on the etio-pathogenetic role possibly played by HIV-1 infection.

Objective: To evaluate the association between increased epicardial fat thickness (EFT) and liver stiffness measurement (LSM), as assessed by elastography in people living with Human Immunodeficiency Virus type 1 (HIV-1) infection (PWH)., Methods: 91 PWH on effective antiretroviral treatment (ART) were enrolled. EFT was measured by transthoracic echocardiography. Liver steatosis was evaluated by ultrasound Hamaguchi criteria and LSM by elastography with Acoustic Radiation Force Impulse (ARFI) Tecnique. LSM ≥8 Kpa was suggestive of clinically relevant fibrosis., Results: Mean age was 54.3 years and 27.5% were women. EFT correlated with HIV-1 infection duration (rS 0.252, p = 0.016), age at study entry (rS 0.527, p < 0.001), BMI (rS 0.363, p < 0.001), waist circumference (rS 0.549, p < 0.001), HDL (rS -0.391, p < 0.001), triglycerides (rS 0.375, p < 0.001), Hamaguchi score (rS 0.279, p = 0.007), right lobe of the liver (rS 0.259, p = 0.014), Left ventricular mass/Body surface area (rS 0.220, p = 0.036).A LSM ≥8 Kpa was found in 20.9% of PWH, more commonly in those with EFT above the median >5.6 mm (30.4% vs 11.1%, p = 0.038). LSM significantly correlated with EFT (rS 0.274, p = 0.009), CD4+ cells (rS -0.320, p = 0.003) and nadir of CD4+ cells (rS -0.292, p = 0.007).In a subgroup (n = 53), an HOMA-IR index >2.33 identified increased EFT, (AUC 0.73, 95%CI 0.59-0.84, p = 0.001) while an HOMA-IR >3.27 predicted increased LSM (AUC 0.76, 95%CI 0.62-0.87, p = 0.005)., Conclusions: PWH with increased EFT have worse metabolic profile and a high proportion of clinically relevant fibrosis at ARFI elastography, despite normal liver function tests. The HOMA-IR index might be used to identify PWH with increased EFT and liver fibrosis., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The persistence of low human immunodeficiency virus type 1 (HIV-1) replication in individuals undergoing antiretroviral therapy (ART) still threatens their health. Previous findings have shown that microRNAs (miRNAs) could interfere with several steps of the viral life cycle. Herein, we set out to investigate the expression of miR-150, miR-223, miR-382, miR-324-5p, miR-33a-5p, miR-34a, and miR-132 in the whole peripheral blood mononuclear cell (PBMC) population from people living with HIV-1 showing different levels of viral suppression. Levels of PBMC-associated miRNAs were analyzed in 30 individuals with undetectable viremia (target not detected) and 30 individuals with detectable low-level viremia (1-200 copies/mL). In addition, 30 samples from treatment-naive (NAIVE) individuals were investigated. Results were compared to a control group of 28 HIV-negative donors. All miRNAs analyzed were strongly downregulated in the NAIVE population, either compared to the treated group or to controls. Stratification of ART-treated donors according to the therapeutic regimen showed the downregulation of miR-33a-5p in subjects treated with non-nucleoside reverse transcriptase inhibitors compared with those treated with protease inhibitors. Collectively, the present study shows that uncontrolled viral replication leads to profound miRNA deregulation while treated individuals, irrespective of the degree of viral suppression, and even the types of antiviral drugs seem to be specifically associated with miRNA expression profiles. These evidences suggest that virological suppression could be favored by miRNA modulation.

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and heterologous immunization approaches implemented worldwide for booster doses call for diversified vaccine portfolios. GRAd-COV2 is a gorilla adenovirus-based COVID-19 vaccine candidate encoding prefusion-stabilized spike. The safety and immunogenicity of GRAd-COV2 is evaluated in a dose- and regimen-finding phase 2 trial (COVITAR study, ClinicalTrials.gov: NCT04791423) whereby 917 eligible participants are randomized to receive a single intramuscular GRAd-COV2 administration followed by placebo, or two vaccine injections, or two doses of placebo, spaced over 3 weeks. Here, we report that GRAd-COV2 is well tolerated and induces robust immune responses after a single immunization; a second administration increases binding and neutralizing antibody titers. Potent, variant of concern (VOC) cross-reactive spike-specific T cell response peaks after the first dose and is characterized by high frequencies of CD8s. T cells maintain immediate effector functions and high proliferative potential over time. Thus, GRAd vector is a valuable platform for genetic vaccine development, especially when robust CD8 response is needed., Competing Interests: Declaration of interests S. Capone, R. Camerini, R.D., F.G., S. Battella, A.M.C., G.P., S. Colloca, and A.F. are full employees of ReiThera Srl. S. Colloca and A.F. are founders and shareholders of Keires AG. S. Colloca is named inventor of the patent application no. 20183515.4 titled “GORILLA ADENOVIRUS NUCLEIC ACID- AND AMINO ACID-SEQUENCES, VECTORS CONTAINING SAME, AND USES THEREOF.” L.V. is full employee of Exom, the CRO in charge of the COVITAR study management. S.L.C. received honoraria from Gilead, ViiV, GSK, Janssen, and MSD, has participated on the advisory boards of Gilead, ViiV, GSK, Janssen, and MSD, and has received support for attending meetings from Gilead. M. Lichtner received honoraria and support for attending meetings from Gilead, MSD, and ViiV, participated on the advisory boards of ViiV, Abbvie, and MSD, and received grants through the institution from Gilead and Abbvie. R. Carsetti was a member of the COVITAR study steering committee. C.I. received financial support from Exom for statistical analysis of the COVITAR study., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) is a recommended once-daily single-tablet regimen for the treatment of people living with HIV (PLWH). We aimed to assess efficacy, safety, and tolerability of BIC/FTC/TAF among PLWH, with a specific focus on people older than 55 years., Methods: We recruited an observational retrospective real-life cohort, including all PLWH who underwent a therapeutic switch to BIC/FTC/TAF, independently from the previous treatment regimen (the BICTEL cohort). Longitudinal nonparametric analyses and linear models were built., Results: After 96 weeks of follow-up, 164 PLWH were included, with 106 older than 55. Both the intention-to-treat and the per-protocol analysis showed low rates of virologic failure, independent of the pre-switch anchor drug. At week 96, a significant increase in CD4 + T cell count and in CD4 + /CD8 + ratio was observed, inversely correlated with baseline immune status. Fasting serum lipid profile, total body weight, BMI, and hepatic function were not affected by the switch, without new onset of metabolic syndrome or weight gain. Compared to baseline, we observed a renal function worsening which is worthy of further follow-up., Conclusion: BIC/FTC/TAF is an effective, safe, and well-tolerated switching strategy for PLWH, especially among those older than 55.

Chronic immune activation has a significant role in HIV-1 disease pathogenesis and CD4+ T-cell depletion. The causes of chronic inflammation and immune activation are incompletely understood, but they are likely multifactorial in nature, involving both direct and indirect stimuli. Possible explanations include microbial translocation, coinfection, and continued presence of competent replicating virus. In fact, long-term viral suppression treatments are unable to normalize elevated markers of systemic immune activation. Furthermore, high levels of pro-inflammatory cytokines increase susceptibility to premature aging of the immune system. The phenomenon of "inflammaging" has begun to be evident in the last decades, as a consequence of increased life expectancy due to the introduction of cART. Quality of life and survival have improved substantially; however, PLWH are predisposed to chronic inflammatory conditions leading to age-associated diseases, such as inflammatory bowel disease, neurocognitive disorders, cardiovascular diseases, metabolic syndrome, bone abnormalities, and non-HIV-associated cancers. Several approaches have been studied in numerous uncontrolled and/or randomized clinical trials with the aim of reducing immune activation/inflammatory status in PLWH, none of which have achieved consistent results.

Patients with frailty are considered to be at greater risk to get severe infection from SARS-CoV-2. One of the most effective strategies is vaccination. In our study we evaluated both the humoral immune response elicited by the vaccination at different time points, and the T -cell response in terms of interferon (IFN)-γ production in frail patients and healthy donors. Fifty-seven patients (31 patients undergoing hemodialysis and 26 HIV positive subjects) and 39 healthcare workers were enrolled. All participants received two doses of the mRNA vaccine BNT162b2. Healthcare workers showed a significantly higher antibody titer than patients twenty-one days after the first dose (p < 0.001). From the same time point we observed for both groups a decay of the antibody levels with a steeper slope of decline in the patients group. Regarding T -cell response the only significant difference between non-reactive and reactive subjects was found in median antibody levels, higher in the responders group than in non-responders. The healthcare workers seem to better respond to the vaccination in terms of antibodies production; the lack of T -cell response in about 50% of the participants seems to suggest that in our study population both humoral and cell-mediated response decline over time remarking the importance of the booster doses, particularly for frail patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Objectives: Systemic sclerosis (SSc) patients are at risk for a severe disease course during SARS-CoV-2 infection either due to comorbidities or immunosuppression. The availability of SARS-CoV-2 vaccines is crucial for the prevention of this hard-to-treat illness. The aim of this study is to assess the humoral response after mRNA vaccination against SARS-CoV-2 in SSc patients., Method: Seropositivity rate and serum IgG levels were evaluated 1 month (t1) and 3 months (t3) after the second dose of vaccine in a cohort of SSc patients and healthy controls (HC). Differences were made with Student's or Mann-Whitney's t-test and with the chi-square or Fisher exact test. Logistic regression model including immunosuppressive treatments (corticosteroids, CCS; mycophenolate mofetil, MMF; methotrexate, MTX; rituximab, RTX) was built to assess the predictivity for seropositivity., Results: The seropositivity rate was similar in 78 SSc patients compared to 35 HC at t1 but lower at t3. SSc patients had lower serum IgG levels than HC at t1 but not at t3. SSc patients treated with immunosuppressive therapy showed both a lower seropositive rate (t1, 90.3% vs 100%; t3, 87.1% vs 97.9%; p < 0.05) and serum IgG levels than untreated patients both at t1 [851 BAU/ml (IQR 294-1950) vs 1930 BAU/ml (IQR 1420-3020); p < 0.001] and t3 [266 BAU/ml (IQR 91.7-597) vs 706 BAU/ml (IQR 455-1330); p < 0.001]. In logistic regression analysis, only MTX was significant [OR 39.912 (95% CI 1.772-898.728); p < 0.05]., Conclusions: SSc patients treated with MTX had a lower serological response to mRNA vaccine, and even low doses of CCS can adversely affect antibody titer and vaccination response. Key Points • SSc patients are able to produce vaccine-induced antibodies after mRNA vaccination. • In SSc patients, clinical characteristics of disease did not influence seropositivity rate. • In SSc patients, even low doses of CCS can adversely affect antibody titer and vaccination response. • In SSc patients, MTX treatment is mainly associated with reduced seropositivity and lower serum IgG levels., (© 2022. The Author(s).)

Objective: to assess the influence of SARS-CoV-2 mRNA vaccine on B-cell phenotypes in systemic sclerosis (SSc)., Methods: peripheral blood B-cell subpopulations were evaluated before (t1) and 3 months (t3) after the second dose of vaccine in 28 SSc patients. Peripheral blood B-cell subpopulations were evaluated in 21 healthy controls (HCs) only at t1. Anti-spike IgG levels were evaluated at t3 in both cohorts., Results: SSc patients presented higher naive, double-negative, and CD21 low B cells compared to HCs. IgM-memory and switched-memory B cells were lower in SSc patients than HCs. No differences in anti-spike IgG levels after vaccination were observed between SSc patients and HCs. Anti-spike IgG levels after vaccination were lower in SSc patients with increased CD21 low B cells at baseline compared to SSc patients with normal CD21 low B cells. A positive correlation was found between IgG levels and naive B cells. A negative linear correlation was shown between IgG levels and IgM-memory, switched-memory, double-negative, and CD21 low B cells., Conclusions: SARS-CoV-2 mRNA vaccine response is normal in SSc patients not undergoing immunosuppressive therapy. The normal number of naive B cells is a positive marker of antibody response. The increased percentage of CD21 low B cells represents a negative marker of antibody response.