Investigating seroprevalence of IgG antibodies against Monkeypox Virus (MPXV) in a cohort of people living with HIV (PLWH) in Rome, during the 2022 outbreak: Moving beyond traditional at-risk populations.

BACKGROUND: High incidence mpox rates suggest asymptomatic individuals may contribute to virus transmission. We undertook this study to assess the seroprevalence of IgG anti-MPXV in a cohort of asymptomatic PLWH, to analyze the size of the phenomenon of asymptomatic infections. MATERIALS AND METHODS: From October 2022 to March 2023 we serially collected serum samples from PLWH attending our Clinic. IgG against MPXV have been assessed on stored cryopreserved samples with an ELISA. Only people with no previous reported vaccine against smallpox or mpox nor previous clinical manifestations consistent with a mpox diagnosis were included. RESULTS: 285 PLWH were included. Twenty-one participants tested positive for IgG anti MPXV (7.37 %, 95 % CI 4.62-11.0). Seropositivity was predominant in male (15/285, 71.4) with a small fraction of female (6/285,28.6 %) and PWID (1/285,4.8 %). CONCLUSIONS: Our findings suggest the possibility of an asymptomatic course of the mpox infection even in populations beyond traditional high-risk groups.

Autochthonous dengue outbreak in Rome, Italy, in 2023.

Dengue, traditionally confined to endemic regions, is now emerging in non-endemic areas, including Italy. This manuscript describes the 2023 Italian autochthonous dengue outbreak, reporting the clinical and demographic characteristics of 19 patients followed by the Fondazione Policlinico Universitario Gemelli IRCCS in Rome, Italy.

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.

Comparing the efficacy and safety of a first-line regimen with emtricitabine/tenofovir alafenamide fumarate plus either bictegravir or dolutegravir: Results from clinical practice.

BACKGROUND: First-line integrase strand transfer inhibitor-based regimens have become commonly used in clinical practice over the last decade. This study aimed to analyse and compare the efficacy and safety of bictegravir (BIC) and dolutegravir (DTG) when prescribed in association with emtricitabine/tenofovir alafenamide (FTC/TAF) as part of a first-line regimen for the treatment of human immunodeficiency-1 (HIV-1) infection. METHODS: Treatment-naïve people living with HIV (PLWHIV) starting a first-line regimen with either BIC/FTC/TAF (BIC group) or FTC/TAF+DTG (DTG group) were analysed. Snapshot analyses were performed after 24 and 48 weeks to evaluate virological efficacy. In addition, differences in the rate of treatment discontinuation (TD) between the two groups were evaluated using the Kaplan-Meier method and the log rank test. RESULTS: Data from 327 PLWHIV were analysed: 140 in the DTG group and 187 in the BIC group. At 48 weeks, 90.0% of individuals in the DTG group and 86.7% of those in the BIC group achieved HIV-RNA <50 copies/mL. In total, 88 and 38 cases of TD were observed in the DTG group and BIC group, respectively. The estimated probability of maintaining the study regimen at week 48 was 59.5% in the DTG group and 84.2% in the BIC group. Analysing changes in immunological parameters after 48 weeks, median improvements of +169 cell/mm3 (P<0.001) and +233 cell/mm3 (P<0.001) were observed in the DTG group and the BIC group, respectively. CONCLUSIONS: Both BIC and DTG, in combination with FTC/TAF, show promising efficacy and safety as first-line strategies in clinical practice, with favourable immunological recovery even in the short term.

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).

Efficacy and Durability of Dolutegravir- or Darunavir-Based Regimens in ART-Naïve AIDS- or Late-Presenting HIV-Infected Patients.

BACKGROUND: Since limited data are available, we aimed to compare the efficacy and durability of dolutegravir and darunavir in advanced naïve patients. METHODS: Retrospective multicenter study including AIDS- or late-presenting (def. CD4 ≤ 200/µL) HIV-infected patients starting dolutegravir or ritonavir/cobicistat-boosted darunavir+2NRTIs. Patients were followed from the date of first-line therapy initiation (baseline, BL) to the discontinuation of darunavir or dolutegravir, or for a maximum of 36 months of follow-up. RESULTS: Overall 308 patients (79.2% males, median age 43 years, 40.3% AIDS-presenters, median CD4 66 cells/µL) were enrolled; 181 (58.8%) and 127 (41.2%) were treated with dolutegravir and darunavir, respectively. Incidence of treatment discontinuation (TD), virological failure (VF, defined as a single HIV-RNA > 1000 cp/mL or two consecutive HIV-RNA > 50 cp/mL after 6 months of therapy or after virological suppression had been achieved), treatment failure (the first of TD or VF), and optimal immunological recovery (defined as CD4 ≥ 500/µL + CD4 ≥ 30% + CD4/CD8 ≥ 1) were 21.9, 5.2, 25.6 and 1.4 per 100 person-years of follow-up, respectively, without significant differences between dolutegravir and darunavir (p > 0.05 for all outcomes). However, a higher estimated probability of TD for central nervous system (CNS) toxicity (at 36 months: 11.7% vs. 0%, p = 0.002) was observed for dolutegravir, whereas darunavir showed a higher probability of TD for simplification (at 36 months: 21.3% vs. 5.7%, p = 0.046). CONCLUSIONS: Dolutegravir and darunavir showed similar efficacy in AIDS- and late-presenting patients. A higher risk of TD due to CNS toxicity was observed with dolutegravir, and a higher probability of treatment simplification with darunavir.

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.

Cardiovascular Disease Risk in a Cohort of Virologically Suppressed People Living with HIV Switching to Doravirine: Preliminary Data from the Real Life.

Aim of this study is to assess the impact of doravirine (DOR)-based regimens on cardiovascular risk in treatment-experienced people living with HIV (PLWHIV). We retrospectively analyzed a cohort of 40 treatment-experienced PLWHIV switching to a DOR-based three-drug regimen, evaluating 10-year risk of manifesting clinical cardiovascular diseases (CD) through the Framingham Risk Score at baseline, 12, and 24 weeks of follow-up. At baseline, median predicted 10-year risk of cardiovascular disease (10Y-CD) was 8.0% (interquartile range 4.0-13.0). After 12 weeks, we observed a significant reduction in 10Y-CD (mean decrease -2.21, p = .012); similarly, we observed a nonsignificant reduction at week 24 (p = .336). Regarding metabolic parameters, after 24 weeks we observed a significant reduction in total cholesterol (median change -8.8 mg/dL, p = .018), low-density lipoprotein cholesterol (median -9.5 mg/dL, p = .007), and triglycerides (median -19.8 mg/dL, p < .001). Our results show a favorable metabolic impact of DOR-based regimens along with a promising reduction in 10-year risk of cardiovascular disease.

Real-Life Impact of Drug Toxicity on Dolutegravir Tolerability: Clinical Practice Data from a Multicenter Italian Cohort.

Dolutegravir (DTG) is currently one of the most used Integrase inhibitors (INI) in antiretroviral therapies (ARV) in both naïve and experienced people living with HIV (PLWHIV). We analyzed a multicenter cohort of PLWHIV, both naïve and experienced, starting an ARV including DTG. We enrolled 3775 PLWHIV: 2763 (73.2%) were males, with a median age of 50 years. During 9890.7 PYFU, we observed 930 discontinuations (9.4 per 100 PYFU). Estimated probabilities of maintaining DTG at three and five years were 75.1% and 67.2%, respectively. Treatment-naïve pts showed a lower probability of maintaining DTG at three and five years compared to treatment-experienced PLWHIV (log-rank p < 0.001). At a multivariate analysis, a longer time of virological suppression (aHR 0.994, p < 0.001) and having experienced a previous virological failure (aHR 0.788, p = 0.016) resulted protective against DTG discontinuation. Most discontinuations (84.0%) happened within the first 12 months of DTG initiation, in particular, 92.2% of discontinuations due to neuropsychiatric toxicity were observed in the first year. Our data confirm the overall good tolerability of DTG in clinical practice, with a low rate of discontinuations. CNS toxicity resulted the main reason for DTG discontinuation, with most related interruptions happening in the first year from DTG introduction.

Has COVID-19 changed the approach to HIV diagnosis?: A multicentric Italian experience.

ABSTRACT: The occurrence of COVID-19 pandemic had a significant negative effect on health care systems over the last year. Health care providers were forced to focus mainly on COVID-19 patients, neglecting in many cases equally important diseases, both acute and chronic. Therefore, also screening and diagnostic strategies for HIV could have been significantly impaired.This retrospective, multicenter, observational study aimed at assessing the number and characteristics of new HIV/AIDS diagnoses during COVID-19 pandemic in Italy and compared characteristics of people living with HIV at diagnosis between pre- and post-COVID-19 era (2019 vs 2020).Our results showed a significant reduction of HIV diagnoses during pandemic. By contrast, people living with HIV during pandemic were older and were diagnosed in earlier stage of disease (considering CD4+ T cell count) compared to those who were diagnosed the year before. Moreover, there was a significant decrease of new HIV diagnoses among men who have sex with men, probably for the impact of social distancing and restriction applied by the Italian Government. Late presentation incidence, if numbers in 2020 were lower than those in 2019, is still an issue.Routinely performing HIV testing in patients with suspected SARS-CoV-2 infection is identifying and linking to care underdiagnosed people living with HIV earlier. Thus, combined tests (HIV and SARS-CoV-2) should be implemented in patients with SARS-CoV-2 symptoms overlapping HIV's ones. Lastly, our results lastly showed how urgent implementation of a national policy for HIV screening is necessary.

Five Years With Dolutegravir Plus Lamivudine as a Switch Strategy: Much More Than a Positive Finding.

BACKGROUND: Results from clinical trials and observational studies suggest that dolutegravir plus lamivudine could be an effective and well-tolerated option for simplification in HIV-1-positive patients. We aimed to assess long-time efficacy and safety in our multicenter cohort. METHODS: This was a retrospective study enrolling HIV-1-infected, virologically suppressed patients switching to dolutegravir + lamivudine. We performed survival analysis to evaluate time to virological failure (VF, defined by a single HIV-RNA ≥1000 copies/mL or by 2 consecutive HIV-RNA ≥ 50 copies/mL) and treatment discontinuation (defined as the interruption of either 3TC or dolutegravir), assessing predictors via Cox regression analyses. RESULTS: Seven-hundred eighty-five patients were considered for the analysis: 554 were men (70.6%), with a median age of 52 years (interquartile range 45-58 years). Estimated probabilities of maintaining virological suppression at weeks 96, 144, and 240 were 97.7% (SD ±0.6), 96.9% (SD ±0.8), and 96.4% (SD ±0.9), respectively. A non-B HIV subtype (P = 0.014) and a previous VF (P = 0.037) resulted predictors of VF. We did not observe differences in probability of VF in people living with HIV with an M184V resistance mutation (P = 0.689); however, in a deeper analysis, M184V mutation was a predictor of VF (P = 0.038) in patients with time of virological suppression <88 months. Estimated probabilities of remaining on study regimen at 96, 144, and 240 weeks were 82.9% (SD ±1.4), 79.7% (SD ±1.6) and 74.3% (SD ±2.2), respectively. CONCLUSIONS: Our findings show the long-term efficacy and tolerability of dolutegravir plus lamivudine in virologically suppressed patients.

Seroprevalence of SARS-CoV-2 Antibodies in HIV-Infected Patients in Rome, Italy during the COVID-19 Outbreak.

BACKGROUND: this study aimed to determine the proportion of people living with HIV (PLWH) with anti-SARS-CoV-2 IgG antibodies in a large sample from a single HIV referral center in Rome, Italy; the time-frame included both the first and the second wave of the Italian COVID-19 pandemic; Methods: we conducted a cross-sectional study on stored cryopreserved samples from 1 March 2020 to 30 November 2020. Total antibodies against SARS-CoV-2 were preliminarily tested using a chemiluminescent immunoassay. Positive results were re-tested with an ELISA assay as an IgG confirmatory test; Results: overall, 1389 samples were analyzed from 1106 PLWH: 69% males, median age 53 years, 94% on antiretroviral treatment, 93% with HIV-RNA < 50 copies/mL, median CD4 cell count 610 cell/µL. Our analysis revealed a total of n = 8 patients who tested IgG positive during the study period. Seroprevalence was equal to 0% in the first months (March-June); this started to increase in July and reached a maximum rate of 1.59% in October 2020. The overall seroprevalence was 0.72% (8/1106, 95% CI 0.37-1.42). CONCLUSION: our findings from this setting show a low IgG SARS-CoV-2 prevalence among PLWH as compared to data available from the general population.

Comparative safety review of recommended, first-line single-tablet regimens in patients with HIV.

Introduction Different single-tablet regimens (STRs), containing one or two nucleoside reverse transcriptase inhibitors (NRTIs) plus an anchor drug, are available for the use in naïve, HIV-infected patients. Despite some restrictions in the use of particular regimens in certain situations (e.g., HBV coinfection), International guidelines do not provide indications to prefer any regimen over others concerning the tolerability profile. We aimed to assess advantages and disadvantages of the most prescribed STRs.Areas covered An extensive review of articles published in English language was conducted on PubMed, looking for evidence about STRs in naïve, HIV-infected population. Safety outcomes of registrational trials were assessed, giving priority to studies directly comparing STRs included in our research (abacavir/lamivudine/dolutegravir, tenofovir alafenamide/emtricitabine/bictegravir, lamivudine/dolutegravir, tenofovir alafenamide/emtricitabine/darunavir/cobicistat, tenovofir disoproxil fumarate/lamivudine/doravirine). Data from cohort studies and meta-analyses were also assessed, extrapolating the main evidence about the combinations of interest.Expert opinion Integrase inhibitors (InsTIs)-based regimens have few interruptions for adverse events and few drug-related adverse events, with tenofovir alafenamide/emtricitabine/dolutegravir and lamivudine/dolutegravir being the most tolerable ones. However, neuropsychiatric adverse events and metabolic issues could prompt the alternative use of darunavir or doravirine-based combinations, even if a superior safety profile of these combinations over InSTIs has yet to be demonstrated.

Short Communication: Efficacy and Safety of Dolutegravir Plus Lamivudine as a First-Line Regimen in Clinical Practice.

The GEMINI trials have showed that the two drugs regimen of dolutegravir+lamivudine (DTG +3TC) was noninferior to a three-drug regimen as a first line regimen for treatment-naive people living with HIV. The aim of our study was to confirm, in a real-life setting, the efficacy of this regimen. We conducted a retrospective, observational study enrolling treatment-naive patients starting a first-line regimen with lamivudine plus dolutegravir. We evaluated the virological efficacy and the immunological and metabolic profiles. Changes from baseline were evaluated through linear-mixed models for repeated measures. Linear regression analyses were performed to explore variables associated to significant changes in laboratory parameters. We analyzed a total of 20 patients: 15 (75%) were men with a median age of 34.5 years. During a cumulative time of 15.4 patients years of follow up (PYFU), we did not observe any adverse event or treatment discontinuation and all patients achieved virological suppression in the first 6 months from treatment initiation. Increase in CD4+ cells was significant at both week 24 (p = .003) and week 48 (p = .007) of follow-up. Moreover, CD4/CD8 ratio also significantly improved [median increase of +0.22 (p = .028) after 48 weeks of follow-up]. As to metabolic parameters, we observed no significant changes in total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. In a subgroup of 11 patients, we further investigate HIV-1 DNA variations. Our results are in line with the findings of the GEMINI trials, confirming the efficacy and safety of DTG +3TC in treatment-naive patients.