Cohort profile: PRESTIGIO, an Italian prospective registry-based cohort of people with HIV-1 resistant to reverse transcriptase, protease and integrase inhibitors.

PURPOSE: The PRESTIGIO Registry was established in 2017 to collect clinical, virological and immunological monitoring data from people living with HIV (PLWH) with documented four-class drug resistance (4DR). Key research purposes include the evaluation of residual susceptibility to specific antiretrovirals and the validation of treatment and monitoring strategies in this population. PARTICIPANTS: The PRESTIGIO Registry collects annual plasma and peripheral blood mononuclear cell samples and demographic, clinical, virological, treatment and laboratory data from PLWH followed at 39 Italian clinical centres and characterised by intermediate-to-high genotypic resistance to ≥1 nucleoside reverse transcriptase inhibitors, ≥1 non-nucleoside reverse transcriptase inhibitors, ≥1 protease inhibitors, plus either intermediate-to-high genotypic resistance to ≥1 integrase strand transfer inhibitors (INSTIs) or history of virological failure to an INSTI-containing regimen. To date, 229 people have been recorded in the cohort. Most of the data are collected from the date of the first evidence of 4DR (baseline), with some prebaseline information obtained retrospectively. Samples are collected from the date of enrollment in the registry. FINDINGS TO DATE: The open-ended cohort has been used to assess (1) prognosis in terms of survival or development of AIDS-related or non-AIDS-related clinical events; (2) long-term efficacy and safety of different antiretroviral regimens and (3) virological and immunological factors predictive of clinical outcome and treatment efficacy, especially through analysis of plasma and cell samples. FUTURE PLANS: The registry can provide new knowledge on how to implement an integrated approach to study PLWH with documented resistance to the four main antiretroviral classes, a population with a limited number of individuals characterised by a high degree of frailty and complexity in therapeutic management. Given the scheduled annual updates of PLWH data, the researchers who collaborate in the registry can send study proposals at any time to the steering committee of the registry, which evaluates every 3 months whether the research studies can be conducted on data and biosamples from the registry and whether they are aimed at a better understanding of a specific health condition, the emergence of comorbidities or the effect of potential treatments or experimental drugs that may have an impact on disease progression and quality of life. Finally, the research studies should aim to be inclusive, innovative and in touch with the communities and society as a whole. TRIAL REGISTRATION NUMBER: NCT04098315.

Sexually transmitted infections in people with multidrug-resistant HIV.

Retrospective, cohort analysis including people with four-class drug-resistant HIV. Bacterial sexually transmitted infections (STIs) had an incidence of 1.3/100-person-years-of-follow-up (PYFU) in men (3.5/100-PYFU in MSM) whereas no STIs were diagnosed in women. The occurrence of STIs in this fragile population might be related to the achievement of good HIV infection control; however, given the remaining risk of virological failure and possible transmission of a multidrug-resistant virus, STI prevention counselling and HIV viremia monitoring should be prioritized.

Increasing incidence and prevalence of metabolic syndrome in people living with HIV during the COVID-19 pandemic.

Introduction: The aim of this study was to analyze the impact of COVID-19 pandemic restrictions on the prevalence and incidence of metabolic syndrome (MS), and to identify predictors of new MS cases in people living with HIV (PLWH). Methods: This cohort study included PLWH followed at the IRCCS San Raffaele, Milan, Italy, with at least one body mass index (BMI) determination during the pre-pandemic period (1 December 2018 to 29 February 2020) and the pandemic period (1 March 2020 to 31 May 2021). MS diagnosis was based on NCEP ATP III 2005 criteria. Univariable Poisson regression model was used to compare MS incidence rates. Univariable mixed linear models estimated the crude mean change in metabolic parameters during each time period. Multivariable Cox proportional hazards model was used to assess risk factors for MS. Results: This study included 1,564 PLWH, of whom 460 and 1,104 were with and without a diagnosis of MS, respectively, at the beginning of the pre-pandemic period, with an overall prevalence of MS of 29.4%. During the pre-pandemic period, 528/1,564 PLWH had MS, with a prevalence of 33.8% (95%CI = 31.5%-36.1%), while during the pandemic period, the number of PLWH with a diagnosis of MS increased to 628/1,564, with a prevalence of 40.2% (95%CI 37.8%-42.6%; McNemar's test: p < 0.0001). Similarly, the MS incidence rate increased from 13.7/100 person-years of follow-up (PYFU; 95%CI = 11.7-16.0) in the pre-pandemic period to 18.5/100 PYFU (95%CI = 16.2-21.1) in the pandemic period (p = 0.004), with 201 subjects developing MS during the pandemic period. In addition, we observed a significant increase in the crude mean change during the pandemic period compared with the pre-pandemic period for: total cholesterol, LDL cholesterol, plasma glucose, blood pressure, and atherosclerotic cardiovascular disease (ASCVD) risk score. Finally, after adjustment for HIV risk factors, HBV, HCV, ART duration, duration of virologic suppression and use of INSTIs, age [adjusted hazard ratio (AHR) per 3 years older = 1.12 (95%CI = 1.08-1.17)], sex [AHR female vs. male = 0.62 (95%CI = 0.44-0.87)] and CD4+ cell count [AHR per 100 cells/µL higher = 1.05 (95%CI = 1.01-1.09)] were associated with the risk of MS. Conclusion: The COVID-19 pandemic affected the metabolic profile of PLWH and increased the prevalence and incidence of MS.

Treatment success of rescue regimens after dual therapy failure in people living with HIV in a real-life setting.

OBJECTIVES: Few data on management of two-drug regimen (2DR) failure in people living with HIV (PLWH) are available. METHODS: Retrospective study of treatment-experienced PLWH on a 2DR who experienced virological failure (VF) [two consecutive viral loads (VLs) ≥50 copies/mL, single VL ≥1000 copies/mL, or antiretroviral therapy (ART) switch after single VL ≥50 copies/mL with previous blips] or discontinuation for toxicity (baseline). Integrase strand transfer inhibitor (INSTI)-based [one INSTI plus one nucleoside reverse transcriptase inhibitor (NRTI) (n = 78) or one non-NRTI (n = 20)] or boosted protease inhibitor (PI/b)-based [one PI/b plus one NRTI (n = 116) or one INSTI (n = 12)] 2DRs were included. Probabilities of treatment success (TS), VF and discontinuation for any other cause of rescue regimens were estimated by Kaplan-Meier curves. A stepwise Cox model was performed to assess predictors of TS. RESULTS: Overall, 226 PLWH were evaluated: at baseline, 144 individuals discontinued 2DR for toxicity and 82 had VF [median viraemia 81 (63-212) copies/mL]; 171 switched therapy (49.7% to triple regimen, 40.9% to different 2DR), while 55 (exclusively with VF) maintained failing regimens. Probabilities of 12- and 24-month TS were 75.6% and 64.7%, respectively. Higher TS probabilities were observed in individuals who switched ART at 2DR failure (P = 0.003) and PLWH who discontinued 2DR for toxicity (P = 0.008). Therapy switch was the only predictor of TS (P = 0.002). CONCLUSIONS: Overall probability of rescue regimens' TS introduced after 2DR failure is good. Prompt ART switch after 2DR failure is advisable.

Inflammation burden score in multidrug-resistant HIV-1 infection.

OBJECTIVES: Four-class drug-resistant (4DR) people living with HIV (PLWH) are a fragile population with a high burden of disease. No data on their inflammation and T-cell exhaustion markers are currently available. METHODS: Inflammation, immune activation and microbial translocation biomarkers were measured through ELISA in 30 4DR-PLWH with HIV-1 RNA ≥ 50 copies/mL, 30 non-viremic 4DR-PLWH and 20 non-viremic non-4DR-PLWH. Groups were matched by age, gender and smoking habit. T-cell activation and exhaustion markers were assessed by flow cytometry in 4DR-PLWH. An inflammation burden score (IBS) was calculated from soluble marker levels and associated factors were estimated through multivariate regression. RESULTS: The highest plasma biomarker concentrations were observed in viremic 4DR-PLWH, the lowest ones in non-4DR-PLWH. Endotoxin core immunoglobulin G showed an opposite trend. Among 4DR-PLWH, CD38/HLA-DR and PD-1 were more expressed on CD4+ (p = 0.019 and 0.034, respectively) and CD8+ (p = 0.002 and 0.032, respectively) cells of viremic compared to non-viremic subjects. An increased IBS was significantly associated with 4DR condition, higher values of viral load and a previous cancer diagnosis. CONCLUSIONS: Multidrug-resistant HIV infection is associated with a higher IBS, even when viremia is undetectable. Therapeutic approaches aimed to reduce inflammation and T-cell exhaustion in 4DR-PLWH need to be investigated.

HIV viral load monitoring during monkeypox virus infection among people with HIV.

OBJECTIVES: Aims of this study were to assess the characteristics of Mpox among people with HIV (PWH) and describe the change of some immune-virological parameters during Mpox virus infection. DESIGN: Case series of PWH diagnosed with Mpox between May and July 2022 at the Infectious Diseases Unit of San Raffaele Scientific Institute, Milan, Italy. METHODS: Real-time PCR was used to detect Mpox virus on oropharyngeal, cutaneous, genital and rectal swabs, plasma, seminal fluids, and urines. The values of the CD4 + lymphocytes and HIV-RNA were assessed both at Mpox diagnosis and after Mpox virological clearance and were compared to those prior to Mpox. The relationship between the symptoms clinical duration of Mpox and the CD4 + cell count at diagnosis was assessed with Spearman's correlation coefficient. RESULTS: Overall, 28 PWH on antiretroviral therapy with Mpox were evaluated. HIV-RNA did not substantially change at Mpox infection with respect to previous virological profile ( P  = 0.721). However, at time of Mpox diagnosis, we observed a detectable HIV-RNA (196 copies/ml) in one individual previously undetectable (HIV-RNA < 20 copies/ml) and an increase to 1.220 copies/ml in a previously viremic subject (HIV-RNA = 263 copies/ml). No significant differences in CD4 + cell count were found before and at time of Mpox diagnosis ( P  = 0.151) and a higher CD4 + cell count at Mpox diagnosis was marginally related to a lower duration of Mpox symptoms ( r  = -0.341, P  = 0.068). CONCLUSIONS: Among PWH, we advise monitoring HIV viral load at Mpox diagnosis and during follow-up, as well as providing counseling on the results, due to the important individual and community implications.

Disseminated Mycobacterium chimaera infection favoring the development of Kaposi's sarcoma: a case report.

BACKGROUND: Disseminated Mycobacterium chimaera infection is an emerging disease in people undergone to cardiothoracic surgery, which need to be suspected also with atypical presentations. CASE PRESENTATION: We report the case of a 74-year-old man with fever of unknown origin, purple nodules on both feet and a history of open-heart surgery. Imaging investigations showed an abscess near aortic bioprosthesis but screening for endocarditis resulted negative and pyrexia did not respond to antibiotic therapy. A biopsy of cutaneous lesions showed HHV8-related Kaposi's sarcoma, so bone marrow biopsy was executed with evidence of HHV8 localization. Bone marrow and urine mycobacterial cultures resulted positive for M. chimaera and a specific antimicrobial therapy was started, with apyrexia after 7 weeks. CONCLUSIONS: M. chimaera infection should be always investigated as a possible etiology of fever of unknow origin in people with a history of open-heart surgical intervention, even with negative mycobacterial blood cultures. The possible role of disseminated infection in inducing immunodepression with the occurrence of other opportunistic diseases (such as Kaposi's sarcoma) cannot be excluded.

Prevalence of peri-implantitis in a sample of HIV-positive patients.

OBJECTIVES: This study aimed to assess the prevalence of peri-implantitis in human immunodeficiency virus (HIV)-positive patients and the presence of a possible correlation between the immunological profile and serological values, of peri-implantitis, and of possible differences between all-on-4 and single crown/bridge prostheses. SUBJECTS AND METHODS: This retrospective study included 58 adult HIV-positive patients (222 implants) with either all-in-4 prostheses or single crowns/bridges on at least one dental implant loaded for more than a year who were followed for 3 year (mean follow-up). Data pertaining to the probing pocket depth (PPD), bleeding on probing, and immunological and systemic profile were collected. RESULTS: Patients with single crown/bridge implant rehabilitation showed higher prevalence of peri-implantitis (34%) than patients with all-on-4 rehabilitation (0%) (p = 0.012). Patients with all-on-4 rehabilitation were significantly older than those with single crowns/bridges (p = 0.004). Patients with peri-implantitis had implants for a significantly longer duration than those without (p = 0.001), implying that the probability of peri-implantitis increases as the age of implant increases. CONCLUSIONS: The prevalence of peri-implantitis was 26% in the HIV-positive patients population. No correlation was found between patients' immunological and serological factors and peri-implantitis. The most important risk factor for peri-implantitis and mucositis was implant age.