Comparing the long-term effectiveness and safety of dolutegravir/lamivudine versus bictegravir/emtricitabine/tenofovir alafenamide fumarate as first-line regimens: a real life multicentre cohort.

OBJECTIVES: We compared the effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) and dolutegravir plus lamivudine (DTG + 3TC) in our cohort of treatment-naive people with HIV (PWH). METHODS: In a multicentre cohort of treatment-naive PWH starting a first-line regimen with either dolutegravir plus lamivudine or BIC/FTC/TAF, Kaplan-Meier survival analysis was used to estimate time to virological failure (VF) and time to treatment discontinuation (TD), whereas Cox regression was used to evaluate predictors of VF and TD. Changes in CD4+ cell count were assessed via non-parametric tests, and linear regression analyses were performed to explore predictors of CD4+ cell count changes. RESULTS: One hundred and seventy individuals were included: 66 started dolutegravir plus lamivudine (DTG group) and 104 started BIC/FTC/TAF (BIC group). During follow-up, we observed two VFs in the DTG group [1.7 per 100 person-years of follow-up (PYFU)] and two in the BIC group (1.7 per 100 PYFU). Estimated probability of remaining free from VF at Week 144 was 95.9% in the DTG group and 95.2% in the BIC group (log-rank P = 0.955). Four TDs were observed in the DTG group (3.4 per 100 PYFU) and 21 in the BIC group (17.6 per 100 PYFU). Estimated probability of maintaining the study regimen at Week 144 was 90.3% in the DTG group and 70.0% in the BIC group; individuals in the BIC group had a higher probability of TD (log-rank P = 0.003). In both groups, the CD4+ count improved significantly during follow-up. CONCLUSIONS: Our study shows that both strategies are effective and safe, with few VFs and TDs due to tolerability issues.

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.

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 and tolerability of lamivudine plus dolutegravir compared with lamivudine plus boosted PIs in HIV-1 positive individuals with virologic suppression: a retrospective study from the clinical practice.

BACKGROUND: Direct comparisons between lamivudine plus bPIs and lamivudine plus dolutegravir as maintenance strategies in virologically-suppressed HIV positive patients are lacking. METHODS: Time to treatment discontinuation (TD) and virological failure (VF) were compared in a cohort of HIV+ patients on a virologically-effective ART starting lamivudine with either darunavir/r, atazanavir/r or dolutegravir. Changes in laboratory parameters were also evaluated. RESULTS: Four-hundred-ninety-four patients were analyzed (170 switching to darunavir/r, 141 to atazanavir/r, 183 to dolutegravir): median age was 49 years, with 8 years since ART start. Groups differed for age, HIV-risk factor, time since HIV-diagnosis and on ART, previous therapy and reasons for switching. Estimated proportions free from TD at week 48 and 96 were 79.8 and 48.3% of patients with darunavir/r, 87.0 and 70.9% with atazanavir/r, and 88.2 and 82.6% with dolutegravir, respectively (p < 0.001). Calendar years, HIV-risk factor, higher baseline cholesterol and an InSTI-based previous regimen predicted TD, whereas lamivudine+dolutegravir therapy and previous tenofovir use were protective. VF was the cause of TD in 6/123 cases with darunavir/r, 4/97 with atazanavir/r and 3/21 with dolutegravir. Other main reasons for TD were: toxicity (43.1% with darunavir/r, 39.2% with atazanavir/r, 52.4% with dolutegravir), further simplification (36.6% with darunavir/r, 30.9% with atazanavir/r, 14.3% with dolutegravir). Incidence of VF did not differ among study groups (p = 0.747). No factor could predict VF. Lipid profile improved in the dolutegravir group, whereas renal function improved in the bPIs groups. CONCLUSIONS: In real practice, a switch to lamivudine+dolutegravir showed similar efficacy but longer durability than a switch to lamivudine+bPIs.

Systemic inflammation markers after simplification to atazanavir/ritonavir plus lamivudine in virologically suppressed HIV-1-infected patients: ATLAS-M substudy.

Background: Biomarkers of systemic inflammation predict non-AIDS events and overall mortality in virologically suppressed HIV-1-infected patients. Objectives: To determine whether switching to a dual antiretroviral maintenance therapy was associated with modification of biomarkers of systemic inflammation as compared with continuation of successful standard triple therapy. Methods: In this substudy of the randomized ATLAS-M trial, we compared in virologically suppressed patients the impact at 1 year of simplification to a dual therapy with atazanavir/ritonavir plus lamivudine versus maintaining atazanavir/ritonavir plus two NRTI triple therapy on markers of systemic inflammation. Plasma levels of interleukin-6, C-reactive protein (CRP), soluble CD14 (sCD14) and D-dimer were quantified by ELISA at baseline and at 48 weeks. Results: A subset of 139 of 266 randomized patients with available samples was analysed: 69 in the triple therapy arm and 70 in the dual therapy arm. The baseline biomarker levels were comparable between randomization arms. No significant differences in changes from baseline to week 48 were observed between arms (dual therapy versus triple therapy): IL-6, -0.030 versus -0.016 log10 pg/L; CRP, +0.022 versus +0.027 log10 pg/mL; sCD14, -0.016 versus +0.019 log10 pg/mL; and D-dimer, -0.031 versus +0.004 log10 pg/mL. A history of cancer was associated with higher baseline levels of IL-6 (P = 0.002) and CRP (P = 0.049). No relationship was observed between baseline biomarker level and persistent residual viraemia, HIV-1 DNA load, plasma lipids and other potential explanatory variables. Conclusions: Simplification with atazanavir/ritonavir plus lamivudine does not affect plasma markers of systemic inflammation in virologically suppressed patients. The association between these findings and clinical outcomes requires further evaluation.

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.

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.

Association among therapeutic adherence, health literacy, and engagement in care: How to increase health-conscious management of HIV disease.

BACKGROUND: In the context of People Living with HIV (PLWH), poor health literacy (HL) seems to be linked to poorer health outcomes and reduced engagement in care. Additionally, the level of HL can affect HIV knowledge and may impact adherence to antiretroviral therapy (ART). This research explored the connection between ART adherence, HL, and engagement in care in a cohort of 250 PLWH receiving ART in Italy. METHODS: A questionnaire was given to PLWH at Policlinico Gemelli in Rome to assess their health literacy and adherence to therapy. The Brief Health Literacy Screening (BHLS) and the Newest Vital Sign (NVS) were used to evaluate subjective and objective HL. Adherence levels were self-reported as poor, good, or excellent, and the assessment included the Patient Health Engagement Scale (PHE-S). RESULTS: Notably, the majority of the sample comprised male individuals (67.9%), with 69.2% reporting a 10-years or longer duration between their HIV diagnosis and their initiation of ART. It was found that PLWH with poor adherence had low schooling, had been living with HIV for 1-5 years, were HCV co-infected, had a viremia >50 copies/mL, poor health status, poor engagement in care, and poor HL (p = <0.001). They exhibited lower mean scores on the subjective HL scale and lower CD4 T-cell counts and nadir CD4 T-cell counts (p < .001). CONCLUSION: Our study demonstrated a positive correlation between higher HL levels and improved disease management, treatment adherence, and overall physical and mental well-being. Enhanced HL capabilities are paramount in bolstering health management and treatment adherence.

Cardiovascular Safety of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate in Virologically Suppressed PLWHIV: A Comparative Analysis of CVD Scores.

The Aim of this study is to assess the cardiovascular safety of doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF). We analyzed data from 37 virologically suppressed people living with HIV starting DOR/3TC/TDF, collecting viro-immunological and metabolic parameters as well as the 10-year risk of cardiovascular disease (10Y-CD) using both the Framingham risk score and D:A:D score.After 48 weeks, we observed a significant reduction in 10Y-CD both via the Framingham score (-0.7, p = .021) and the D:A:D score (-0.41, p = .012). After 96 weeks, we registered a significant reduction in 10Y-CD calculated via the D:A:D score (-0.98, p = .009). Regarding serum lipid markers, after 48 weeks we observed a significant reduction in total cholesterol (-17 mg/dL, p < .001), triglycerides (-21 mg/dL, p = .015), and LDL cholesterol (-8 mg/dL, p = .022). After 96 weeks, we registered a significant reduction in total cholesterol (-19 mg/dL, p < .001). DOR/3TC/TDF has shown a favorable metabolic profile, with a significant reduction in 10Y-CD, independently from the use of lipid-lowering drugs.

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.

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.

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.

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.