Atypical monkeypox presentation in a previously vaccinated MSM HIV-positive adult.

The outbreak of monkeypox virus (MPXV) in non-endemic countries is an international public health emergency, and the diversity in manifestations poses challenges for early diagnosis and isolation. We describe an atypical case of monkeypox (MPX) in a 46-year-old homosexual male living with HIV. He reported 1-day duration fever, a lesion on his chin that, over a period of 18 days, had gradually enlarged and ulcerated. Biopsy examination performed at an external centre revealed pyoderma gangrenosum, unconfirmed at a subsequent biopsy. When he reported to our hospital outpatients' clinic the chin lesion had a diameter of 5 × 5 cm, necrotic margins and ulcerated base and signs of superinfection. He was admitted for further investigations. Three swabs collected from pharynx, skin and chin lesion resulted positive for MPXV. He had a favourable clinical course and was discharged soon after. Pending the achievement of optimal vaccination coverage in at-risk groups, early identification and isolation of infectious patients represent the cornerstones of the containment strategy. Atypical cases of MPX manifestations are not uncommon, particularly in patients with HIV infection. A high level of suspicion should be maintained to identify infectious cases at an early stage and avoid further spread of the infection.

Does the rapid initiation of antiretroviral therapy at HIV diagnosis impact virological response in a real-life setting? A single-centre experience in Northern Italy.

Rapid initiation of antiretroviral therapy (ART) has been proven efficacious and safe, but more investigations are needed to define feasibility of rapid ART approach in real-life settings.We conducted a retrospective, observational study on newly HIVdiagnosed patients referred to our Infectious Diseases Department from September 1st, 2015, to July 31st, 2019. According to the timing of ART initiation, we distinguished 3 groups of patients (rapid, intermediate and late group) and represented the trend of virological response during a 400-days-period. The hazard ratios of each predictor on viral suppression were estimated through the Cox proportional hazard model.The median time from HIV diagnosis to the first medical referral was 15 days and the median time from the first care access to therapy start was 24 days. Among patients, 37.6% started ART within 7 days, 20.6% between 8 and 30 days, and 41.8% after 30 days. Longer time to ART start and higher baseline viral load were associated with a lower probability of viral suppression. After one year, all groups showed a high viral suppression rate (99%). In a high-income setting the rapid ART approach seems useful to accelerate viral suppression which is great over time regardless of ART initiation timing.

Impact of COVID-19 pandemic on HIV viremia: a single-center cohort study in northern Italy.

BACKGROUND: Brescia Province, northern Italy, was one of the worst epicenters of the COVID-19 pandemic. The division of infectious diseases of ASST (Azienda Socio Sanitaria Territoriale) Spedali Civili Hospital of Brescia had to face a great number of inpatients with severe COVID-19 infection and to ensure the continuum of care for almost 4000 outpatients with HIV infection actively followed by us. In a recent manuscript we described the impact of the pandemic on continuum of care in our HIV cohort expressed as number of missed visits, number of new HIV diagnosis, drop in ART (antiretroviral therapy) dispensation and number of hospitalized HIV patients due to SARS-CoV-2 infection. In this short communication, we completed the previous article with data of HIV plasmatic viremia of the same cohort before and during pandemic. METHODS: We considered all HIV-patients in stable ART for at least 6 months and with at least 1 available HIV viremia in the time window March 01-November 30, 2019, and another group of HIV patients with the same two requisites but in different time windows of the COVID-19 period (March 01-May 31, 2020, and June 01-November 30, 2020). For patients with positive viremia (PV) during COVID-19 period, we reported also the values of viral load (VL) just before and after PV. RESULTS: the percentage of patients with PV during COVID-19 period was lower than the previous year (2.8% vs 7%). Only 1% of our outpatients surely suffered from pandemic in term of loss of previous viral suppression. CONCLUSIONS: Our efforts to limit the impact of pandemic on our HIV outpatients were effective to ensure HIV continuum of care.

Effectiveness of kidney transplantation in HIV-infected recipients under combination antiretroviral therapy: a single-cohort experience (Brescia, Northern Italy).

PURPOSE: Kidney transplantation was recently introduced for the treatment of end stage renal disease (ESRD) in HIV-infected patients. We report the results of the first 28 procedures at our centre. METHODS: A retrospective study was conducted on HIV-infected patients evaluated for kidney transplantation between January 2005 and October 2016. Patients were selected and monitored by the kidney transplantation and infectious diseases teams, according to the national protocol. RESULTS: 60 patients were evaluated; 32 entered the list and 28 were transplanted. Median CD4+ count was 337 cell/µL at transplantation and 399 cell/µL 12 months thereafter. HIV RNA was undetectable at transplantation in 27/28 patients and became undetectable within 24 weeks in the only patient starting antiretroviral combination therapy (cART) after surgery. Four patients experienced virological failure, but reached again undetectability after cART regimen change. At last available point of follow-up (median 126.1 weeks), HIV RNA was undetectable in all patients. Three patients experienced AIDS-defining events. We observed a cumulative number of 19 acute rejections in 16 patients (median time from transplantation to first rejection 5.2 weeks). Survival rate was 82.1%. To avoid pharmacokinetics (PK) interactions, cART regimen was changed from a protease inhibitor (PI)/non-nucleoside reverse transcriptase inhibitor (NNRTI)-based to an integrase inhibitor (InSTI)-based regimen in 11/20 alive patients with functioning graft. CONCLUSIONS: Kidney transplantation appears to be safe in HIV-infected patients carefully selected. As previously reported, we observed a high incidence of acute rejection. We expect that the recent implementation of the immunosuppressive protocols will allow a better immunologic control. Moreover, the introduction of InSTI permits a better strategy of cART, with lower incidence of PK interactions with immunosuppressive drugs.

Biochemical and inflammatory modifications after switching to dual antiretroviral therapy in HIV-infected patients in Italy: a multicenter retrospective cohort study from 2007 to 2015.

BACKGROUND: Triple-drug regimens are the gold standard for HIV therapy. Nucleos(t)ide reverse transcriptase inhibitors (NRTIs) reducing regimens are used to decrease drugs toxicity, exposure and costs. Aim of our study was to evaluate trends of biochemical and inflammatory indices in patients switching to dual therapy (DT). METHODS: We included patients that a) switched to a DT from 2007 to 2015 from a tenofovir/abacavir-based triple regimen b) previously maintained a triple and c) subsequently a dual regimen for 12 months with virological suppression. We retrieved data measured at 5 points (at the switch, 6 and 12 months before and after switch). We used platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and CD4/CD8 ratio as inflammatory indices. We assessed temporal trends of viro-immunological, biochemical and inflammatory parameters. RESULTS: Overall, 364 and 65 patients switched from a tenofovir- and an abacavir-triple regimen, respectively. In the tenofovir-reducing group, creatinine clearance and lipids raised after the switch. There was a significant increase in both CD4+ cells and CD4/CD8. CD8+ cells rose after the switch, while opposite trend was found for PLR. In the abacavir-reducing group total lipids showed a decrease during the first 6 months after the switch and then stabilized. An increase of CD4+ and a decrease of CD8+ cells was observed during the study period, although not statistically significant. While CD4/CD8 remained stable after simplification, PLR decreased significantly after 6 months, then returning to baseline. CD8+ cells increased in the tenofovir-reducing group despite a viro-immunological response. Intriguingly, PLR decreased, maintaining this trend for 12 and 6 months after tenofovir and abacavir interruption respectively. CONCLUSIONS: Increased PLR has been linked to hypercholesterolemia and metabolic-syndrome, while high CD8+ cells count to increased risk of non-AIDS-related events regardless of CD4 T-cell recovery and to virological failure. Whether these findings may have clinical implications, and which role DT plays on the immune system and on inflammation should be further investigated.

Lymphoproliferative disease with mixed cryoglobulinemia and hyperviscosity syndrome in an HIV-infected patient: HCV is the only culprit.

The availability of direct antiviral agents (DAAs) offers the possibility to treat HCV-infected patients with a high rate of efficacy and a good safety profile. Little is known about the benefit of DAAs on HCV-related hematological diseases and their complications. We describe the case of an HIV/HCV-infected patient with HCV-related chronic lymphoproliferative disease, mixed cryoglobulinemia and hyperviscosity syndrome. Treatment with direct antiviral agents (DAAs) cured HCV infection and its complications, while HCV re-infection caused recrudescence of the associated diseases.

Colitis during new direct-acting antiviral agents (DAAs) therapy with sofosbuvir, simeprevir and ribavirin for genotype 1b hepatitis C.

Since 2014 several direct-acting antivirals (DAAs) have been made available, allowing interferon-free antiviral treatments with high sustained virological response rates. Side effects are, however, a real challenge during treatment. Sarkar et al. recently published a case of colitis following initiation of sofosbuvir and simeprevir for genotype 1 hepatitis C. We report the case of a patient with no prior history of inflammatory bowel disease, who developed significant bloody diarrhea within 3 weeks of sofosbuvir/simeprevir/ribavirin initiation. Colonoscopy and biopsy suggested a drug-induced colitis.

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.

Increase in standard cholesterol and large HDL particle subclasses in antiretroviral-naïve patients prescribed efavirenz compared to atazanavir/ritonavir.

BACKGROUND: Cardiovascular risk in HIV-infected patients is related, at least in part, to serum lipid alterations before and after HAART. Lipoprotein-particle subclasses may also have an effect, but comparative data after standard HAART regimens are limited. METHODS: This was a substudy of a trial in 91 antiretroviral-naïve patients randomized to tenofovir + emtricitabine + atazanavir/ritonavir (ATV/r) or efavirenz (EFV). Over-time trends from baseline to week 48 in total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), HDL particles (HDLp), and TC:HDL-C and TG:HDL-C ratios were analyzed by analysis of covariance (ANCOVA). Furthermore, confidence intervals for differences between the 2 groups at week 48 were calculated. Indications for lipid-lowering interventions and low HDL-C were also studied. RESULTS: ANCOVA showed that, with respect to patients receiving ATV/r, those prescribed efavirenz (EFV) had greater increases reported as mean differences in lipid values at week 48: 14 mg/dL (95% CI, 0.2 to 27) for TC, 14 mg/dL (95% CI, 4 to 25) for LDL-C, 5 mg/dL (95% CI, 2 to 9) for HDL-C, and 2.2 mg/dL (95% CI, 0.4 to 4) for large HDLp. Proportions of subjects with indications for lipid-lowering interventions and with HDL-C <40 mg/dL did not differ significantly. CONCLUSIONS: Patients prescribed EFV had greater increases in TC, LDL-C, and HDL-C. Although no significant differences were detected between the 2 groups for the TC:HDL ratio and for indications to start lipid-lowering interventions, large HDLp increased more in the EFV group compared to the ATV/r group, suggesting a protective effect associated with EFV use.

Prospective evaluation of bone markers, parathormone and 1,25-(OH)2 vitamin D in HIV-positive patients after the initiation of tenofovir/emtricitabine with atazanavir/ritonavir or efavirenz.

BACKGROUND: Increased risk of fractures and osteoporosis have been associated with the use of antiretroviral drugs. There is a paucity of prospective evaluations of bone markers after the initiation of drugs currently recommended to treat HIV infection and results on the evolution of these markers are conflicting. Lastly, the effect of tenofovir on 1,25-(OH)2 vitamin D is uncertain. METHODS: We performed a prospective study on the evolution of bone markers, parathormone and 1,25-(OH)2 vitamin D before and after standard antiretroviral regimens. This was a sub-study of a trial conducted in antiretroviral-naïve patients randomized to tenofovir + emtricitabine in combination with either atazanavir/ritonavir (ATV/r) or efavirenz (EFV). Follow-up lasted 48 weeks. The following bone markers were analyzed: C-terminal cross-laps (CTx), osteocalcin (OC), osteoprotegerin (OPG), and receptor activator of nuclear factor κB ligand (RANKL). Mixed-factorial analysis of variance with random-coefficient general linear model was used to compare their trends over time and linear multivariable regression was performed with a backward selection method to assess predictors of their variations from baseline to week 48. Trends of parathormone and 1,25-(OH)2 vitamin D were also evaluated. RESULTS: Seventy-five patients were studied: 33 received EFV and 42 ATV/r. Significant increases were found for all markers except for RANKL. There was a significant direct association between CTx and OC increases. Multivariable analysis showed that higher glomerular filtration rate (estimated through cystatin C clearance) predicted greater OPG increase, while older age, higher HIV RNA at baseline and use of ATV/r predicted greater CTx increase. A significant increase of parathormone accompanied the evolution of the study markers. 1,25-(OH)2 vitamin D remained stable, though a seasonality variation was demonstrated. CONCLUSIONS: These data demonstrate CTx increase (bone resorption marker) corresponding to OC increase (bone formation marker) early upon HAART initiation. Moreover, predictors of bone marker increases have been suggested, possibly indicating that a stricter monitoring of bone health and pro-active interventions are needed in older patients, those with higher HIV RNA, prescribed ATV/r rather than EFV, and with decreased renal function at baseline. Further studies are needed to clarify the mechanisms responsible for up-regulation of bone turnover markers, as well as to understand if and what markers are best correlated or predictive of pathological fractures.

Emergence of exhausted B cells in asymptomatic HIV-1-infected patients naïve for HAART is related to reduced immune surveillance.

Alterations of B cell subpopulations have been described up to date as characterizing advanced stage of HIV-1 infection. However, whether such defects are relevant in subjects with a preserved number of CD4⁺ T cells (>350 cells/µL) is unclear. In a cross-sectional study, we investigated if signs of B cells exhaustion and impaired viral immune surveillance are present in a cohort of 43 asymptomatic HIV-1-infected patients with preserved CD4⁺ T cell counts (>350 cells/µL) and highly active antiretroviral therapy (HAART) untreated. A dramatic expansion of exhausted tissue-like memory B cells (CD10⁻CD21(low)CD27⁻) was observed. B cells alteration was related to an increase in Torque teno virus (TTV) load, used as surrogate marker of immune function. Successfully HAART-treated patients showed normalization of B cell subpopulations frequency and TTV load. These results provide new insights on B cell in HIV-1 infection and show that development of B cell abnormalities precedes CD4⁺ T cell decline.

SARS-CoV-2 Infection and Vaccination Coverage among Fragile Populations in a Local Health Area of Northern Italy.

Italy was dramatically hit by the COVID-19 pandemic, and the province of Brescia was one of the epicenters of the outbreak. Furthermore, Brescia has one of the highest incidences of people living with HIV (PLWH) and a substantial presence of migrants. We conducted a retrospective cohort study involving all citizens connected to the Brescia Health Protection Agency, assessing the SARS-CoV-2 burden, COVID-19 prevalence, and vaccination coverage. A total of 1,004,210 persons were included, 3817 PLWH and 134,492 foreigners. SARS-CoV-2 infection, hospitalizations and death were more frequent among Italians than foreigners. SARS-CoV-2 infections and deaths were more frequent in HIV-uninfected people than in PLWH. PLWH and foreigners were less likely to have a SARS-CoV-2 diagnosis compared to HIV-negative patients. Migrants were more likely to be hospitalized but had a lower risk of death compared to HIV-negative patients. Regarding vaccination, 89.1% of the population received at least one dose of vaccine, while 70.4% of the Italian citizens and 36.3% of the foreigner subjects received three doses of vaccine. Foreigners showed a lower risk of being diagnosed with SARS-CoV-2 but a higher risk of complications. HIV infection was not associated with a higher risk of SARS-CoV-2 severe manifestations compared to the general population. COVID-19 vaccine hesitancy was not different between PLWH and HIV uninfected people, but foreigners were more hesitant.

Immunological Evolution of a Cohort of HIV-2 Infected Patients: Peculiarities of an Underestimated Infection.

Background: Human Immunodeficiency Virus type 2 (HIV-2) affects a minority of patients in Italy; nevertheless, the increasing migratory flow from higher prevalence areas led to the spread of this virus into our Country. We evaluate clinical, viro-immunological, and therapeutic characteristics of patients with HIV-2 infection and HIV-1/HIV-2 dual-infection and the early treatment impact on overall survival and incidence of AIDS events. Methods: We retrospectively analyzed all HIV-2, and HIV-1/HIV-2 positive patients followed in a large Italian clinic from January 1987 to December 2020. We recorded demographic, viro-immunological, clinical, and therapeutic data. We performed a descriptive analysis followed by a longitudinal analysis to explore the factors associated with the CD4+ lymphocyte trend; lastly, we studied the possible predictors of death and AIDS in our cohort in a multivariable model. Results: 32 subjects were enrolled, 17 (53%) HIV-2 infected and 15 (46.8%) HIV-1/HIV-2 dual-infected; 12 patients were lost to follow up, while 3 died. We found a lack of HIV-2 viremia in 12/32 subjects (37.5%). Most of the patients at baseline had a good viro-immunological profile with HIV-2 RNA <200 copies/ml and CD4+ lymphocyte >200 cell/mcl. We found a CD4+ lymphocyte improvement over time, both in the absolute number (ß 472.61, 95%CI 383.05-562.18, p<0.001) and in percentage (ß 25.28, 95%CI 21.91 - 28.66, p<0.001). Nevertheless, subjects taking cART had CD4+ lymphocyte percentage increase over time, and this trend appeared significantly better than those who did not receive therapy. Lastly, in the multivariable model CD4+, T-cell count increase was negatively associated with AIDS (HR 0.34 95%CI 0.13-0.91, p=0.032). Conclusion: We found a higher prevalence of HIV-1/2 dual infection than in previous observations. Subjects with HIV-2 infection showed a favorable immunological condition at diagnosis, and the benefits of cART in those who received treatment are undiscussed. Moreover, our data suggest a different disease course based on age at diagnosis, as in HIV-1 infections. We encourage starting cART at diagnosis in HIV-2 patients, regardless of CD4+ lymphocyte, because even in the new cART era, CD4+ lymphocyte decrease remains the strongest predictor of death and AIDS also in this population.

Maternal characteristics during pregnancy and risk factors for positive HIV RNA at delivery: a single-cohort observational study (Brescia, Northern Italy).

BACKGROUND: Detectable HIV RNA in mothers at delivery is an important risk factor for HIV transmission to newborns. Our hypothesis was that, in migrant women, the risk of detectable HIV RNA at delivery is greater owing to late HIV diagnosis. Therefore, we examined pregnant women by regional provenance and measured variables that could be associated with detectable HIV RNA at delivery. METHODS: A observational retrospective study was conducted from January 1999 to May 2008. Univariate and multivariable regression analyses (generalized linear models) were used, with detectable HIV RNA at delivery as dependent variable. RESULTS: The overall population comprised 154 women (46.8% migrants). Presentation was later in migrant women than Italians, as assessed by CD4-T-cell count at first contact (mean 417/mm³ versus 545/mm³, respectively; p = 0.003). Likewise, HIV diagnosis was made before pregnancy and HAART was already prescribed at the time of pregnancy in more Italians (91% and 75%, respectively) than migrants (61% and 42.8%, respectively). A subgroup of women with available HIV RNA close to term (i.e., ≤30 days before labour) was studied for risk factors of detectable HIV RNA (≥50 copies/ml) at delivery. Among 93 women, 25 (26.9%) had detectable HIV RNA. A trend toward an association between non-Italian nationality and detectable HIV RNA at delivery was demonstrated by univariate analysis (relative risk, RR = 1.86; p = 0.099). However, by multivariable regression analysis, the following factors appeared to be more important: lack of stable (i.e., ≥14 days) antiretroviral therapy at the time of HIV RNA testing (RR = 4.3; p < 0.0001), and higher CD4+ T-cell count at pregnancy (per 50/mm³, RR = 0.94; p = 0.038). CONCLUSIONS: These results reinforce the importance of extensive screening for HIV infection, earlier initiation of antiretroviral therapy and stricter monitoring of pregnant women to reduce the risk of detectable HIV RNA at delivery. Public health interventions should be particularly targeted to migrant women who are frequently unaware of their HIV status at the time of pregnancy.

Decrease in new diagnosis of HIV/AIDS in the two years period 2019-2020: impact of COVID-19 pandemic.

The emergence SARS-CoV-2 in late 2019 and early 2020 has caused a pandemic of unprecedented proportions. Management of COVID-19 became emergent public health priorities, and the impact on other public health initiatives, such as expanded HIV screening and linkage to care, remain largely unknown. In this Single-Center retrospective observational study, we describe the characteristics and circumstance of the new HIV cases during 2020 compared to 2019. We observed a decrease of HIV diagnosis during this period. Interestingly, median age at HIV diagnosis decreased of one decade and percentage of female patients was higher. In addition, more patients received diagnosis during hospitalization and more AIDS-defining conditions, such as Pneumocystis pneumonia, were detected. We express our concern that HIV new diagnoses will increase as a result of people's inability to get tested or treated in this period. More efforts are needed to improve local screening programs both during and after COVID-19 pandemic.

Discharge ward during the SARS-CoV-2 pandemic: an effective way to increase patient turnover when human resources are scarce.

During the SARS-CoV-2 pandemic, the province of Brescia (Italy) had a significant number of COVID-19 cases, which led to a subversion of the ordinary structure of the university hospital ASST Spedali Civili, driven by the need to hospitalize as many patients as possible in a narrow period of time. At the peak of the epidemic, a rapid hospitalization discharge area, the Discharge Ward (DW), was set up with the aim of facilitating the rapid turnover of patients in the wards where the most severe patients had to be hospitalized. The organization and activities carried out are described in the results of this reproducible experience during epidemic events.

Presence of V72I, G123S and R127K Integrase Inhibitor polymorphisms could reduce ART effectiveness: a retrospective longitudinal study.

Objectives: Structural aspects of HIV-1 integrase complex and role of integrase minor mutations and polymorphisms in ART effectiveness is still unknown. The objective of this study was to assess the 24 and 48 weeks (W) effectiveness of ART regimens in patients with Integrase Inhibitors (InSTI) minor mutations and polymorphisms receiving InSTI-based regimens.Methods: We enrolled all ART-naïve or InSTI-naïve HIV-infected patients, with a baseline InSTI genotypic resistances test between 2011 and 2016. We analyzed integrase resistance mutations using the Stanford University HIV Drug Resistance Database (HIVdb Program, version 6.3.0). The outcome was virological response at 24 and 48 W of follow up (FU) according to snapshot analysis. We defined virological failure as two consecutive HIV-RNA > 50 copies/ml, or one >1000 copies/ml. Patients were divided in those presenting InSTI minor mutations (Group 1), and those with only polymorphisms or wild type (Group 2).Results: We enrolled 83 patients. 81 patients reached 24 W of FU: 2/20 (10%) and 4/61 (6.5%) showed virological failure in Group 1 and 2 respectively. 66 patients reached 48 W of FU: 0/17 (0%) and 2/49 (4%) showed virological failure in Group 1 and 2 respectively. Interestingly, patients with polymorphisms G123S and R127K had higher risk of failure at 24 W (respectively, relative risk - RR - 36, IQR 2.1-613, p = 0.01; RR 36, IQR 2.1-613, p = 0.01) and patients with V72I had an higher risk of failure both at 24 W (RR 6.52, IQR 1.29-32.9, p = 0.02) and 48 W (RR 21.1, IQR 1.07-414, p = 0.04).Conclusions: Our study showed that the presence of V72I, G123S and R127K polymorphisms could play a role in reducing InSTI effectiveness.

Disengagement and reengagement of HIV continuum of care in a single center cohort in northern Italy.

Background: Despite the progress in HIV care, adherence to follow up remains critical. Disengagement impairs the benefit of HIV care and the increasing number of data that associates failed retention with worse outcomes has led public health institutions to consider retention in care as a new tool to fight against HIV pandemic. Objective: The aim of this retrospective, observational study was to estimate the burden of disengagement and reengagement in care in our HIV cohort and to identify the characteristics of our LTFU and reengaged patients. Moreover, we build our cascade of care to explore how closely our center aligned with the "90-90-90" targets. Methods: From the local electronic database we extracted all HIV-infected patients with at least one contact with HIV Clinic between 2012 and 2018 excluding deceased and transferred patients. Our definition of LTFU was based on the lack of any visit during at least 1 year after the last visit. Patients re-engaged were defined as those firstly considered as LTFU patients who subsequently were newly linked to HIV care. Results: About 8% of patients were lost to follow up during the period of study, with a rate of less than 2% per year and 14.1% of them were re-engaged in care. The cascade of care shows, among HIV cases diagnosed between 2011 and 2018, 86.7% patients retained in care, 94.1% of whom were on cART and 95.6% of whom were virologically suppressed. A higher attrition was found among infections diagnosed since 2011 than before 2011, such as women, patients coming from foreign countries and those with poor virological control. Conclusions: The retention rate found in our cohort is high and is in accordance with the 90-90-90 strategy. Nevertheless, understanding disengagement and re-engagement determinants is important to strengthen retention in care in the most fragile population.

Prevalence of Non-B HIV-1 Subtypes in North Italy and Analysis of Transmission Clusters Based on Sequence Data Analysis.

HIV-1 diversity is increasing in European countries due to immigration flows, as well as travels and human mobility, leading to the circulation of both new viral subtypes and new recombinant forms, with important implications for public health. We analyzed 710 HIV-1 sequences comprising protease and reverse-transcriptase (PR/RT) coding regions, sampled from 2011 to 2017, from naive patients in Spedali Civili Hospital, Brescia, Italy. Subtyping was performed by using a combination of different tools; the phylogenetic analysis with a structured coalescence model and Makarov Chain Monte Carlo was used on the datasets, to determine clusters and evolution. We detected 304 (43%) patients infected with HIV-1 non-B variants, of which only 293 sequences were available, with four pure subtypes and five recombinant forms; subtype F1 (17%) and CRF02_AG (51.1%) were most common. Twenty-five transmission clusters were identified, three of which included >10 patients, belonging to subtype CRF02_AG and subtype F. Most cases of alleged transmission were between heterosexual couples. Probably due to strong migratory flows, we have identified different subtypes with particular patterns of recombination or, as in the case of the subtype G (18/293, 6.1%), to a complete lack of relationship between the sequenced strains, revealing that they are all singletons. Continued HIV molecular surveillance is most important to analyze the dynamics of the boost of transmission clusters in order to implement public health interventions aimed at controlling the HIV epidemic.

Hepatitis A outbreak in men who have sex with men (MSM) in Brescia (Northern Italy), July 2016-July 2017.

Since June 2016, an outbreak of hepatitis A has been reported in Europe. Here we report the HAV outbreak in Brescia (Northern Italy) from July 2016 to July 2017. We actively recorded all HAV cases defined by detection of HAV IgM antibodies in serum. Data on sexual behaviour, travel attitudes, concomitant sexually transmitted diseases (STDs), clinical presentation and laboratory results were collected. Forty-two confirmed cases were recorded: 25 (60%) were MSM and reported sexual contact at risk of STDs. Compared to 2015 and the first half of 2016, when only three hepatitis A cases were recorded, in the 12 months in question the number of cases rose 14-fold. Among 25 MSM, 14 were HIV-infected. Hepatitis A is usually a self-limiting disease, but it could be more serious in the case of HIV co-infection, immunosuppression and chronic hepatitis. HAV infection has a high outbreak potential in MSM because of more common oro-anal practices compared to HS, a high interconnectedness global network, chemsex practices and a new tendency to travel abroad to attend group sex events. In our experience, most cases occurred in MSM and 56% of them were HIV-infected, suggesting the need to promote active screening, immunization and education in this population.