HIV and vicarious stigma in a cohort of people living with HIV in Italy: What happens when the stigma is fueled by healthcare providers?

Vicarious stigma shows how indirect stigmatizing experiences can lead people living with HIV (PLWH) to feel discriminated against. We enrolled 350 PLWH, who were administered a 17-item questionnaire to investigate a subjective experience of stigma experienced in the hospital care setting. We found that at least once 215 PLWH (61.4%) did not want the HIV exemption indicated on the prescription for a specialist medical visit, 232 PLWH (66.3%) never used their HIV-related exemption to make a specialist medical visit, 230 PLWH (65.7%) avoided undergoing a medical assessment outside the infectious disease clinics and 241 patients (68.9%) felt unwelcome during a specialist medical visit. Moreover, 241 patients (61.1%) had heard at least once stories of health workers who did not want to touch PLWH, 213 patients (60.9%) had heard stories at least once of PLWH who had been mistreated by hospital staff, 180 patients (51.4%) had at least once heard stories about PLWH being refused treatment and services and 257 patients (73.4%) had at least once heard stories about health workers talking publicly about PLWH. This is a little explored area, especially regarding the vicarious stigma faced by PLWH. Our findings indicate the importance of combating HIV-related stigma for the wellbeing of PLWH.

Efficacy of Lamivudine Plus Dolutegravir vs Dolutegravir-Based 3-Drug Regimens in People With HIV Who Are Virologically Suppressed.

Background: Lamivudine + dolutegravir maintenance dual therapy (DT) could be less effective than 3-drug therapy (TT) in the context of resistance-associated mutations to nucleoside reverse transcriptase inhibitors (NRTIs). The ARCA database was queried to test this hypothesis with a trial emulation strategy. Methods: People with HIV taking 2 NRTIs plus a protease inhibitor or a non-NRTI who switched to DT or dolutegravir-based TT were followed up from the first HIV RNA <50 copies/mL (baseline) to virologic failure (VF; ie, 2 consecutive HIV RNA ≥50 copies/mL or 1 HIV RNA ≥200 copies/mL). Those switching to DT within 6 months were assigned to the treatment arm and all other patients to the control arm. Each participant was also cloned, assigned to the opposite strategy, and censored at the time of deviation from that strategy. Using inverse probability of censoring weight Cox regression models, we calculated hazard ratios of VF for DT vs TT stratified for the presence of resistance-associated mutations. Results: Overall 626 people were analyzed: 204 with DT and 422 with TT (73% men; mean age, 44 years). Ten and 31 VFs occurred with DT and TT, respectively, over a median 5.8 years. When compared with a fully active TT, the DT had similar efficacy (adjusted hazard ratio, 0.88; 95% CI, .29-2.61; P = .812) when full susceptibility was confirmed at historical genotype. When previous M184V/I was present in both groups, the risk of VF was higher for DT vs TT but was not statistically significant (adjusted hazard ratio, 3.06; 95% CI, .45-20.84; P = .252). Conclusions: DT was not associated with a significantly higher risk of VF than dolutegravir-based TT.

Treatment of Aorto-iliac and Infrainguinal Vascular Infections with a Prefabricated Bovine Pericardial Graft.

BACKGROUND: The use of biological grafts provides acceptable mid- and long-term results in native or prosthetic vascular infections. Several reports describe the successful use of bovine pericardium in case of vascular infections, mainly as a large patch to be sutured as a tubular graft. Recently, a novel prefabricated bovine pericardium graft (Biointegral Surgical No-React® Inc, Mississauga, ON, Canada) has been introduced in clinical practice with promising results. In this study, we report our preliminary experience utilizing Biointegral Surgical graft in case of native and or prosthetic aorto-iliac and infrainguinal infection. METHODS: We retrospectively analyzed data from 20 patients with native or prosthetic aorto-iliac and infrainguinal infection who underwent in situ reconstruction (ISR) with a Biointegral Surgical No-React bovine pericardium prosthesis between October 2020 and February 2023 at the Vascular Surgery Unit of the Fondazione Policlinico Universitario Gemelli - IRCCS in Rome, Italy. All patients followed a standardized protocol including postoperative anticoagulation and long-term intravenous antibiotics. RESULTS: The indication for surgery was: mycotic aortic aneurysm in 4 patients (20%), graft infection after abdominal aortic repair in 11 patients (55%), peripheral graft infection in 5 patients (25%). Complete excision of the infected aorta or prosthetic graft, surgical debridement and ISR were performed in all patients. Hospital mortality rate was 5% (n = 1) and graft-related mortality of 0%. During follow-up (median 13 months, range 6-34 months), reinfection was 5.2% and primary graft patency 94.7%. CONCLUSIONS: The use of prefabricated bovine pericardial grafts represents a promising option for the treatment of native and prosthetic aorto-iliac and infrainguinal infections. The application of this biological graft with a standardized postoperative protocol has been associated with a satisfactory patency and reinfection rate without increased bleeding complications.

The association between stigma and wellbeing in an Italian cohort of PLWH: The role of social support and personal factors.

Our aim was to assess the association between different types of stigma and physical, behavioural and emotional wellbeing, and to evaluate whether these associations were mediated by the level of social support, age, education, sex and time from HIV diagnosis in an Italian cohort of people living with HIV (PLWH). We enrolled 96 PLWH and had them complete a cross-sectional online survey that included the "HSS-12", the "SF-12" and the "DASS-21". We performed linear regression analyses to explore the associations between the HSS-12 scores and cART adherence, viral load, SF-12 and DASS-21 scores, and a mediation analysis to identify mediators in the significant associations. We showed that higher level of depression and worse perception of mental health were significantly associated with higher HSS-12 "personalised stigma" (p = .009, p = .020) "disclosure concerns" (p = .012, p = .039), "concerns about public attitudes" (p =.007, p = .005) and "negative self-image" scores; (p < .001, p = .001); worse perception of physical health status was associated with higher HSS-12 "personalised stigma" scores (p = .018); higher level of anxiety and stress were associated with higher "negative self-image" scores (0.001 and p < .001). The association between higher HSS-12 "negative self-image" and higher levels of depression, anxiety and stress were mediated by lower age (a*b = +0.10; a*b = +0.12; a*b = +0.11). This study may have important implications for clinical practice as it contributes to understanding the characteristics and consequences of HIV-related stigma in a population of PLWH with excellent viroimmunological status and therapeutic adherence.

Atypical ductal hyperplasia on vacuum-assisted breast biopsy: a scoring system to predict the risk of upgrade to malignancy.

RATIONALE AND OBJECTIVES: Our multicentric study analysed clinical, radiologic and pathologic features in patients with atypical ductal hyperplasia (ADH) diagnosed with vacuum-assisted biopsy (VAB), to identify factors associated with the risk of upgrade, to develop a scoring system to support decision making. MATERIALS AND METHODS: Patients with ADH on VAB under stereotactic/tomosynthesis guidance (2012-2022) were eligible. Inclusion criteria were availability of surgical histopathological examination of the entire lesion or radiologic follow-up (FUP) ≥ 24 months. VAB results were compared with surgical pathological results or with imaging FUP evolution to assess upgrade. A backward stepwise linear regression was used to identify predictors of upgrade. The discriminatory power of the model was calculated through the area under the receiver operating curve (ROC-AUC); the Hosmer-Lemeshow test was used to assess model calibration. The points system was developed based on the selected risk factors, and the probability of upgrade associated with each point total was determined. RESULTS: 112 ADH lesions were included: 91 (91/112, 81.3%) underwent surgical excision with 20 diagnosis of malignancy, while 21 (21/112, 18.7%) underwent imaging FUP with one interval change (mean FUP time 48 months). Overall upgrade rate was 18.7% (21/112). Age, menopausal status, concurrent breast cancer, BIRADS classification and number of foci of ADH were identified as risk factors for upgrade. Our model showed an AUC = 0.85 (95% CI 0.76-0.94). The points system showed that the risk of upgrade is < 2% when the total score is ≤ 1. CONCLUSION: Our scoring system seemed a promising easy-to-use decision support tool for management of ADH, decreasing unnecessary surgeries, reducing patients' overtreatment and healthcare costs.

Reporting a single case of cystic echinococcosis in retroperitoneal mass of uncertain origin.

Echinococcal disease (hydatid disease (HD) is an endemic parasitosis caused by Echinococcus granulosus in the larval stage, and it is typically due to the production of unilocular cystic lesions, usually involving the liver for the majority of patients and the lungs in 25%, but also any other organs can be potentially involved in developing echinococcal disease. We report a case of extrahepatic, retroperitoneal echinococcal disease, caused by Echinococcus granulosus. The patient underwent a surgical removal of the abdominal mass, revealed by abdominal ultrasound and computerized tomography scanning, and in the founded clinical and radiological suspicion of echinococcal disease, multiple bioptical samples were sent for microbiological analysis and albendazole therapy was started; Echinococcus granulosus protoscolices were found on the bioptical sample, and the diagnosis was successfully confirmed. According to the current parasitology literature on echinococcal disease, extrahepatic localization, although rare, can be found, and it should be considered in the differential diagnosis of an abdominal mass when epidemiological risk factors and anamnestic data are present, regardless of the usual site of the disease.

Ventilator-associated pneumonia (VAP) and pleural empyema caused by multidrug-resistant Acinetobacter baumannii in HIV and COVID 19 infected patient: A case report.

We analyzed the case of a 49-year-old woman with HIV infection off-therapy with poor viro-immunological compensation, not vaccinated for SARS-COV-2, hospitalized for lobar pneumonia and severe COVID19-related respiratory failure in intensive care unit (ICU). The hospitalization was complicated by bacteraemic ventilator-associated pneumonia (VAP) caused by multidrug-resistant Acinetobacter baumannii (MDR-AB) isolated on pleural fluid culture, treated with colistin and cefiderocol for about 3 weeks. The molecular research of MDR-AB on transtracheal aspirate was negative following this therapy. The aim is to show the safety, efficacy and tolerability of colistin-based combination therapy with cefiderocol for Acinetobacter baumannii infection in HIV-infected patient.

Toxoplasmosis mimicking CMV chorioretinitis in newly diagnosed PLWH: a case report.

Background: cytomegalovirus (CMV) retinitis, cerebral and ocular toxoplasmosis are common infections in patients with acquired immunodeficiency syndrome (AIDS). Material and methods: this is a case of a 46-year-old female with previous Kaposi's sarcoma, diagnosed with an HIV infection two weeks prior to hospitalization. Blood test at diagnosis showed a CD4+ count of 77 cell/µL and HIV-RNA 3.758.745 copies/mL. Therapy with bictegravir/emtricitabine/tenofovir alafenamide fumarate was started and clinical, viroimmunological and microbiological investigations were performed. Results: the patient went to our hospital for the onset of left occipito-parietal headache and blurred vision. Brain CT and MRI were performed which did not show focal lesions or vascular alterations. Syphilis serology was negative, Toxoplasma gondii serology showed positive IgG and negative IgM, serum CMV-DNA was 31.184 IU/mL. Eye fundus evidenced intraretinal hemorrhages, fluorescein angiography and computed optical tomography documented cottony exudates, retinal hemorrhages and vitreous involvement. Therapy with valganciclovir was initiated for suspicion of CMV retinitis. About a month later, the patient reported blurred vision for which she was re-admitted. Ocular fundus showed a cottony lesion near the macula. Molecular test on vitreous body was positive for Toxoplasma gondii, while on cerebrospinal fluid it was negative; in addition, an MRI of the brain with contrast medium was performed which showed an area of altered hyperintense signal compatible with a diagnosis of Toxoplasma gondii uveitis and neurotoxoplasmosis. Therapy with pyrimethamine and clindamycin (allergy for sulfonamide reported by the patient) was started. Allergy counseling was performed with the execution of allergy tests (patch test) with negative result; therefore the administration of clindamycin was replaced with sulfadiazine. A month following the start of anti-toxoplasma therapy, there was a clinical and radiological improvement. Conclusions: despite progressive developments in the management of PLWH, in this case two different kind of opportunistic infection are found in a late-presenter patient. In particular, two aspects can be highlighted. The first one is that, in the setting of an highly impaired immune system, clinical presentation can be deceptive and more than one opportunistic infection can be observed together in the same patient. The second aspect is that after starting antiretroviral therapy, a rapid improvement of viro-immunologic parameters has been documented, probably leading to an immune reconstitution inflammatory syndrome (IRIS).

Clinical presentation of human monkeypox virus infection during the 2022 outbreak: descriptive case series from a large italian Research Hospital.

BACKGROUND: In May 2022, a new case of Monkeypox Virus (MPX) was reported in a non-endemic area, the United Kingdom, and since then, the number of confirmed cases in Europe has been increasing until WHO, on May 10 2023, declared that MPOX is no longer a public health emergency of international concern. We aimed to describe the clinical and microbiological characteristics of sixteen patients with a confirmed diagnosis of MPX followed by a single Italian clinical centre, the Fondazione Policlinico Universitario Agostino Gemelli, between May 20 and August 30. MATERIALS AND METHODS: A prospective observational study has been conducted, collecting microbiological samples during the time of the infection, as well as epidemiological and clinical data of the patients. All patients provided written informed consent. RESULTS: During clinical practice, 16 individuals presenting with consistent symptoms tested positive for MPX on a polymerase chain reaction. All patients were men having sex with men (MSM). The most frequent clinical presentation was a vesicular erythematous cutaneous rash, mainly distributed on the genital and perianal area, but also regarding limbs, face, neck, chest and back in some of the patients. Systemic symptoms, such as fever or lymphadenopathy, involved eight patients. The symptom most frequently reported by patients was pruritus in the area of the vesicles. Thirteen patients also reported pain. Nine patients were HIV-1 coinfected, but no significant differences have been observed compared to other cohort patients. The median time between the onset of symptoms and the healing was 19.5 days (IQR 14.0-20.3). CONCLUSIONS: Our cohort of patients presented a mild manifestation of the disease with no complications and no need for antiviral therapy nor hospitalization. This population seems different from the ones reported in the literature during the previous outbreaks in endemic areas in epidemiological data and clinical manifestations but also from a cohort of patients described in the literature from the 2022 outbreak, suggesting the importance for healthcare workers to keep in mind the possibility of an MPX infection in the differential diagnosis of patients presenting with consistent symptoms, even in non-endemic areas, to ensure efficient isolation of the patient for infection control purposes and effective management of the infection preventing the development of MPOX-related complications.

Blood telomere length gain in people living with HIV switching to dolutegravir plus lamivudine versus continuing triple regimen: a longitudinal, prospective, matched, controlled study.

BACKGROUND: Blood telomere length (BTL) is a validated biomarker of aging. ART reduces immunosenescence and has benefits in terms of BTL in people living with HIV (PLWH). However, it has also been observed that ART containing NRTIs, such as tenofovir or abacavir, which are potent inhibitors of human telomerase activity in vitro, might negatively affect BTL. Here we investigated the effects on BTL 1 year after switching to a dual therapy (DT) with dolutegravir + lamivudine versus maintaining a standard triple therapy (TT) with a two-NRTI backbone and an anchor drug. METHODS: This was a longitudinal, prospective, matched, controlled study that included virologically suppressed adults on stable three-drug ART who either switched at baseline (BL) to DT or maintained TT. The DT and TT groups were 1:1 matched for age, sex, years since HIV diagnosis, years on ART and anchor drug. BTL was assessed by a monochrome multiplex qPCR at BL and after 48 weeks (W48). RESULTS: We enrolled 120 PLWH, i.e. 60 participants in each group. At BL, the BTL means were comparable between the two groups (P = 0.973). At W48, viro-immunological status was stable and an overall increase in the mean BTL was observed, i.e., +0.161 (95%CI, 0.054-0.268) (P = 0.004). However, the within-group analysis showed a significant mean BTL gain in the DT group (P = 0.003) but not in the TT group (P = 0.656). CONCLUSIONS: In this setting of virologically suppressed PLWH, simplifying to dolutegravir + lamivudine was associated with a higher gain in BTL than maintaining triple therapy after the 1 year follow-up. These findings suggest that as a simplification strategy dolutegravir + lamivudine might have a positive effect on BTL.

Two-Drug Regimen Containing Darunavir: Metabolic Evaluation of an Old Dual Therapy.

Regimens containing darunavir are one of the first one with two drugs that demonstrated good efficacy as a simplification strategy. We wanted to describe the characteristics of patients followed in our center on a dual therapy regimen containing darunavir evaluating the metabolic aspects during follow-ups. We collected data from 208 patients switching to lamivudine plus darunavir with either ritonavir or cobicistat between 2010 and 2019. In all patients we found an increase in low-density lipoprotein (LDL), with no rising in creatinine, total cholesterol, or triglycerides. Twenty-five patients reached 120 weeks of follow-up. In these patients, no significant metabolic changes were described without concomitant treatment with drugs for dyslipidemia. These regimens seem to be more tolerable in metabolic profile compared with the data concerning three-drug therapies, leading only to a slight increase in LDL. The main reason for discontinuation was for a single-tablet therapy. None of the patients started treatment for dyslipidemia.

Characteristics of mental health interventions in a cohort of Italian PLWH over the last five years: impact of HIV disease and outbreak of COVID-19 pandemic.

Evidence accumulated during past years confirm that people living with HIV (PLWH) still have to deal with comorbidities and chronic complications that can increase physical and psychological issues and can affect daily functioning, quality of life and mental health. Moreover, during the COVID-19 pandemic PLWH proved to be a population at increased risk of psychological distress. We explored the ongoing issues and the characteristics of the mental health interventions for which a cohort of Italian PLWH interacted with a psychologist over the past five years. We analysed a dataset that included 61 PLWH who underwent a psychological intervention between 2018 and 2022. We compared different frequencies in characteristics of mental health interventions according to different demographic and clinical variables, psychopathological symptoms and time of the request for intervention. We showed that psychopathological symptoms most frequently reported by patients were anxiety (55.7%), and depression (49.2%). Furthermore, we reported that most our patients undertook occasional psychological support meetings (31%), sought an intervention after the outbreak of the COVID-19 pandemic (62.3%) and complained about disclosure issues (48.5%). Disclosure issues were mainly reported by younger PLWH (p = 0.002) with a shorter disease (p = 0.031) and treatment history (p = 0.032), and higher interpersonal sensitivity (p = 0.042). It seems fundamental to integrate psychological interventions into the care of PLWH, to give particular attention to PLWH with risky demographic, clinical and mental health factors and to pay special attention to emergency conditions (such as the COVID-19 pandemic) and the most widespread issues to create ad hoc interventions.

Changes in Metabolic Profile in PLWHIV Switching to Doravirine-Based Regimen.

Thanks to the modern ARV regimens and the fact that the morbidity and mortality of metabolic syndrome increases with age, clinicians are continuously researching effective and safe antiretroviral regimens with low impact on the lipid profile. Doravirine (DOR) is the latest non-nucleoside reverse-transcriptase inhibitor (NNRTI) that shows long-term safety and tolerability and a favorable lipid profile. The aim of this study is to assess the impact of DOR-based three-drug regimens on the lipid profile in clinical practice. We retrospectively analyzed a cohort of 38 treatment-experienced, virologically suppressed people living with HIV (PLWH) switching to this regimen, following the eligibility criteria. We carried out comparison analysis of immunological and metabolic parameters between baseline and 48 weeks of follow up. In our cohort of treatment-experienced, virologically suppressed PLWH, three-drug regimens with DOR showed good efficacy and a positive profile on lipid metabolism at 48 weeks of follow up.

Differences in the Long-term Impact of the COVID-19 Pandemic on the Mental Health and Professional Quality of Life of Resident and Specialist Physicians.

BACKGROUND: The COVID-19 pandemic created an extremely difficult situation for healthcare workers (HCWs) worldwide. We aimed to compare the mental health and professional quality of life of residents and specialist physicians in a cohort of Italian HCWs caring for patients with COVID-19 about two years after the start of the COVID-19 pandemic. METHODS: In November 2021, an online survey investigating the emotional states of depression, anxiety, stress, compassion satisfaction and compassion fatigue was administered to HCWs (N= 78) at the Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome. RESULTS: Our findings suggest that from 5 to 20% of our cohort of HCWs still showed the effects of the adverse psychological impact of the pandemic and more than half of them experienced medium levels of compassion fatigue as well as a medium level of compassion satisfaction. Our results also show that those with fewer years of clinical practice might be at greater risk of burnout (p= 0.021), anxiety and stress symptoms (both ps= 0.027) and might develop a lower level of compassion satisfaction (p=0.018). Moreover, the factors that potentially contribute to poor mental health, compassion fatigue and compassion satisfaction seem to differ between residents and specialist physicians. CONCLUSIONS: This overview presents one of the first pictures of the long-term effects of the pandemic on the mental health and professional quality of life of an Italian sample of HCWs. Moreover, it also helps identify professionals who are most in need of support and emphasises the importance of improving the psychological and professional wellbeing of these individuals especially during a pandemic-like crisis with long lasting effects.

Efficacy of Dolutegravir versus Darunavir in Antiretroviral First-Line Regimens According to Resistance Mutations and Viral Subtype.

BACKGROUND: Dolutegravir (DTG)-based first-line regimens have shown superior efficacy versus darunavir (DRV)-based ones in randomized trials. We compared these two strategies in clinical practice, particularly considering the role of pre-treatment drug resistance mutations (DRMs) and of the HIV-1 subtype. MATERIALS AND METHODS: The multicenter Antiretroviral Resistance Cohort Analysis (ARCA) database was queried to identify HIV-1-positive patients starting a first-line therapy with 2NRTIs plus either DTG or DRV between 2013 and 2019. Only adult (≥18 years) patients with a genotypic resistance test (GRT) prior to therapy and with HIV-1 RNA ≥1000 copies/mL were selected. Through multivariable Cox regressions, we compared DTG- versus DRV-based regimens in the time to virological failure (VF) stratifying for pre-treatment DRMs and the viral subtype. RESULTS: A total of 649 patients was enrolled, with 359 (55.3%) and 290 (44.7) starting DRV and DTG, respectively. In 11 months of median follow-up time, there were 41 VFs (8.4 in 100 patient-years follow-up, PYFU) and 15 VFs (5.3 per 100 PYFU) in the DRV and DTG groups, respectively. Compared with a fully active DTG-based regimen, the risk of VF was higher with DRV (aHR 2.33; p = 0.016), and with DTG-based regimens with pre-treatment DRMs to the backbone (aHR 17.27; p = 0.001), after adjusting for age, gender, baseline CD4 count and HIV-RNA, concurrent AIDS-defining event and months since HIV diagnosis. Compared with patients harboring a B viral subtype and treated with a DTG-based regimen, patients on DRV had an increased risk of VF, both in subtype B (aHR 3.35; p = 0.011), C (aHR 8.10; p = 0.005), CRF02-AG (aHR 5.59; p = 0.006) and G (aHR 13.90; p < 0.001); DTG also demonstrated a reduced efficacy in subtypes C (versus B, aHR 10.24; p = 0.035) and CRF01-AE (versus B; aHR 10.65; p = 0.035). Higher baseline HIV-RNA and a longer time since HIV diagnosis also predicted VF. CONCLUSIONS: In line with randomized trials, DTG-based first-line regimens showed an overall superior efficacy compared with DRV-based regimens. GRT may still play a role in identifying patients more at risk of VF and in guiding the choice of an antiretroviral backbone.

Reduced probability of improving viro-immunological state in subjects with vertical transmission of HIV reaching adult age: A multicenter retrospective cohort study.

INTRODUCTION: Young adults with vertical transmission (VT) of human immunodeficiency virus (HIV) represent a fragile population. This study evaluates factors associated with viro-immunological outcome of these patients. METHODS: We performed a multicenter study including HIV-infected subjects with VT ≥ 18 years old from six Italian clinics. Subjects were observed from birth to death, lost to follow-up, or last visit until December 31, 2019. Condition of "optimal viro-immunological status" (OS) was defined as the simultaneous presence of HIV ribonucleic acid (RNA) < 50 copies/mL, CD4+ > 500 cells/mm3 , and CD4+/CD8+ ratio ≥ 1. RESULTS: A total of 126 subjects were enrolled. At 18 years of age, 52/126 (44.4%) had HIV-RNA > 50 copies/mL, 47/126 (38.2%) had CD4+ < 500/mm3 , and 78/126 (67.2%) had CD4+/CD8+ < 1; 28 subjects (23.7%) presented in the condition of OS. Having a CD4+/CD8+ ratio ≥ 1 at 18 years of age was related with an increased probability of shift from suboptimal viro-immunological status (SOS) to OS (HR: 7.7, 95% confidence interval [CI]: 4.23-14.04), and a reduced risk of shift from the OS to the SOS (HR: 0.49, 95% CI: 0.26-0.92). Acquired immunodeficiency syndrome (AIDS) diagnosis significantly reduced the probability of shift from a viro-immunological SOS to OS (HR: 0.09, 95% CI: 0.03-0.30). Subjects who had not achieved an OS at 18 years of age had an increased risk of discontinuation of combination antiretroviral therapy (cART, p = .019). CONCLUSIONS: Only a small proportion of subjects with VT of HIV reached the adult age with "OS". Transition to the adult care with a compromised viro-immunological condition represents a negative driver for future optimal infection control, with a higher risk of discontinuation of cART and a reduced probability to improve the immunological status later in the years.

New insight of human-IgH 3'regulatory regions in immunoglobulins switch.

BACKGROUND: Several studies in animal models have demonstrated the role of the 3' Regulatory Region (3'RR) in the B cell maturation in mammals. In healthy humans, the concentration of each class of circulating immunoglobulins (Igs) has stable but different levels, due to several control mechanisms that also involve a duplicated version of the 3'RR on the chromosome 14 (chr14). The classes' equilibrium can be altered during infections and in other pathological conditions. MATERIAL AND METHODS: We studied the concentrations of IgA, IgM, IgG classes and IgG subclasses in a cohort of 1235 people having immunoglobulin concentrations within normal range to determine the presence of any correlation between the Igs serum concentrations, age and ratio among Ig classes and IgG subclasses in healthy humans. Furthermore, we assessed the concentrations of IgE and the allelic frequency of 3'RR1 hs1.2 enhancer in a group of 115 subjects with high levels of circulating IgE due to acute exacerbation of allergic asthma and in a control group of 118 healthy subjects. RESULTS: In both children and adult subjects, the concentrations of the four IgG subclasses decreased from IgG1 to IgG4. Furthermore, the 3'RR1 enhancer hs1.2 alleles contribute to the control of the IgG subclasses levels, but it does not affect the IgE levels. CONCLUSION: The 3'RR1 controls IgG and IgE through different mechanisms, only in the IgG case involving the hs1.2 alleles. Thus, considering the IgH constant genes loci on the chromosome 14 and the multiple steps of switch that rearrange the whole region, we found that in humans the classes of Igs are modulated by mechanisms involving a complex interaction and transition between 3'RR1 and 3'RR2, also in physiological conditions.