Long-term outcomes of bictegravir/emtricitabine/tenofovir alafenamide as first-line therapy and as switch strategy in virologically suppressed persons with HIV: data from the ICONA cohort.

OBJECTIVES: To assess the effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) among people poorly represented in clinical trials and potentially at higher risk of suboptimal response to ART. METHODS: Observational cohort study on persons with HIV (PWH) enrolled in ICONA who started BIC/FTC/TAF as initial therapy or as switching regimen while virologically suppressed. Primary endpoint was time to treatment failure (TF): new AIDS/death or virological failure (VF) or discontinuation for toxicity/failure. Secondary endpoints were time to treatment discontinuation for toxicity (TDT) and to VF. Groups of interest were those aged >50 years, female sex, and advanced HIV disease at first ART start. Probability of the events overall and according to groups and adjusted HR for every endpoint were calculated by Kaplan-Meier curves and Cox regression models. RESULTS: Nine hundred and thirty-three ART-naive and 1655 ART-experienced PWH initiated BIC/FTC/TAF. Over a median follow-up of 69.8 weeks, 89 (9.6%) PWH at their first regimen experienced TF. PWH aged >50 years had 1.83-fold (95% CI: 1.19-2.83) higher risk of TF; PWH with advanced HIV disease had 2.21-fold (95% CI: 1.53-3.82) higher risk; there were no differences in TF according to sex.Over a median follow-up of 146.3 weeks, 109 (6.6%) out of 1655 switching PWH experienced TF; no differences were found in the risk of TF, TDT and VF according to groups of interest. CONCLUSIONS: Overall, BIC/FTC/TAF is well tolerated and virologically effective in the real-world scenario for ART-naive and -experienced PWH. Older ART-naive PWH and those with advanced HIV disease may respond less well as the burden of diseases might compromise treatment efficacy.

Performance evaluation of a self-administered point-of-care test for anal HPV screening in PrEP users: data from a community-based PrEP service.

OBJECTIVES: In this study, we compared the performance of a self-administered point-of-care test (POCT) for anal human papillomavirus (HPV) screening with laboratory gold-standard test in pre-exposure prophylaxis (PrEP) users and evaluated its feasibility. METHODS: We enrolled PrEP users from a local community-based PrEP service. Each participant self-collected an anal swab to test anal HPV with a PCR POCT capable of detecting 14 high-risk HPV genotypes. Anonymous questionnaires on self-sampling feasibility were completed. Participants were then referred to local clinics to undergo standard viral genotyping. Concordance between POCT and gold-standard test was measured with absolute agreement and Cohen's kappa. Receiver operating characteristic (ROC) curves were used to calculate POCT sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: 179 subjects got a valid POCT result, most of them men (98.3%) and men who have sex with men (90.4%). 68.2% tested positive for at least one high-risk HPV genotype on POCT. 150 feasibility questionnaires were collected: 92.7% of compilers found the self-swab easy to perform. For 178 subjects, a gold-standard test valid result was also available: 77% tested positive for at least one high-risk HPV genotype. The median time elapsed between the two tests was 9.8 months, due to COVID-19-related service interruptions. Agreement between POCT and gold-standard test was 79.3% (Cohen's kappa=0.49). POCT showed a sensitivity of 81.0%, a specificity of 73.8%, a PPV of 91.0% and an NPV of 54.4%. CONCLUSIONS: POCT showed a moderate agreement with gold-standard test and a discrete sensitivity and specificity, suggesting that it could be a useful and feasible additional tool for HPV screening, especially in low-resource and community-based settings.

Determinants of worse liver-related outcome according to HDV infection among HBsAg positive persons living with HIV: Data from the ICONA cohort.

OBJECTIVES: We aimed to study hepatitis D virus (HDV) prevalence and risk of progression to severe liver-related events (SLRE) in HBsAg positive people living with HIV (PLWH) in Italy; role of HDV-RNA copy levels, HCV coinfection and nadir CD4 counts were also investigated. METHODS: People living with HIV (PLWH) from Italian Foundation cohort Naïve antiretrovirals (ICONA) with available HBsAg and HDV Ab were enrolled. HBsAg, HDV Ab, HDV-RNA and HDV genotypes were tested. PRIMARY END-POINT: time from first HDV screening to Severe Liver Related Events (SLRE: decompensated cirrhosis, liver transplantation, HCC). Fine-grey regression models were used to evaluate the association of HDV Ab, HDV-RNA, HDV/HCV coinfection, CD4 nadir and outcome. Secondary end-points: time to SLRE or death; HDV Ab and HDV-RNA prevalence. RESULTS: A total of 152/809 (18.8%) HBsAg positive PLWH showed HDV Ab reactivity; 63/93 (67.7%) were HDV-RNA positive. Being male, persons who inject drugs (PWID), HCV Ab positive, with FIB-4 > 3.25 were independent factors of HDV Ab positivity. In a median follow-up of 5 years, 37 PLWH (4.1% at 5-year) developed SLRE and 97 (12.0%) reached the SLRE or death end-point. HDV-RNA positive (independently from HDV-RNA copy level) PLWH had a 4.6-fold (95%CI 2.0-10.5) higher risk of SLRE than HDV negatives. PLWH positive for both HCV Ab and HDV Ab showed the highest independent risk of SLRE (ASHR: 11.9, 95%CI: 4.6-30.9 vs. HCV neg/HDV neg). Nadir CD4 < 200/mL was associated with SLRE (ASHR: 3.9, 95% 1.0-14.5). CONCLUSIONS: One-fifth of the HBsAg positive PLWH harbour HDV infection, and are at high risk of progression to advanced liver disease. HCV contributes to worse outcomes. This population needs urgently effective treatments.

Do we Still Need Eligibility Criteria to Recommend PrEP? Impact of National Prescribing Requirements on Retention in Care and Sexually Transmitted Infections Acquisition.

Italian guidelines recommend HIV pre-exposure prophylaxis (PrEP) only upon satisfying strict eligibility criteria. The objective of this study is to evaluate if PrEP candidates attending a community-based service comply with these criteria and whether these prescribing conditions affect retention in care and sexually transmitted infections (STIs) acquisition. A retrospective analysis was performed on PrEP candidates evaluated from January 2019 to June 2022. Data were collected from self-administered questionnaires and clinical files. The population was divided in subjects with 0/1 (0/1 C) and ≥ 2 (≥ 2 C) criteria. Descriptive statistics and non-parametric tests were employed to describe study population. Incidence of PrEP discontinuation and of STIs was estimated per 100 persons-year of follow up (PYFU), and incidence rate ratio (IRR) was calculated. Univariate and multivariable Cox regression analyses were used to evaluate the association strength between PrEP drop out and other variables. The analyses enrolled 659 individuals: 422 individuals were included in 0/1 C, 237 in ≥ 2 C group, respectively. Inconsistent condom use was the most reported prescribing criteria (399 individuals, 60.6%), followed by a previous STI (186 individuals, 28.2%). 0/1 C exhibited lower STIs incidence. PrEP discontinuation was 29% in 0/1 C and 38% in ≥ 2 C (p = 0.031). Cox model revealed that inconsistent condom use was the only prescribing criteria associated to PrEP persistence. The majority of PrEP candidate did not comply with prescribing conditions. Eligibility criteria failed to identify individuals with better retention in care. Our results suggest that Italian guidelines should be updated removing barriers to prescription.

Long-term outcome of dolutegravir-containing regimens according to sex: data from the ICONA study.

OBJECTIVES: To compare the long-term risk of treatment failure of dolutegravir-based ART in men and women in a real-life setting. PATIENTS AND METHODS: Persons living with HIV (PLWH) from the ICONA cohort were included if they had started dolutegravir in a two- or three-drug regimen as ART-naive or as virologically controlled ART-experienced. The primary endpoint was time to treatment failure (virological/clinical failure or dolutegravir discontinuation). Secondary endpoints were: time to dolutegravir discontinuation due to toxicity and to neuropsychiatric adverse events; and time to virological failure. Cox regression analyses focused on differences in outcomes by sex. RESULTS: A total of 2304 PLWH (15% women) initiated dolutegravir-based therapy from ART-naive, and 1916 (19.8% women) while experienced. After a median follow-up of 2.2 (IQR: 0.9-3.9) years in ART-naive and 2.4 (IQR: 1.1-4.3) years in experienced, the 4-year cumulative probability of treatment failure was 33% (95% CI 30.5-35.1) and 20% (95% CI 17.8-22.3), respectively. In the multivariable analyses, in ART-naive the risk of treatment failure was higher for women, but not different after excluding women discontinuing dolutegravir for pregnancy concerns. We also observed a higher risk of discontinuation for toxicity in women (ART-naives: Adjusted Hazard Ratio (AHR): 1.56%; 95% CI: 1.03-2.37; ART-experienced: AHR: 1.53%; 95% CI: 1.01-2.32), although the absolute 4-year probability was low: 7.7% (95% CI 6.5-9.2) in ART-naive and 8.3% (95% CI 6.9-9.9) in experienced. CONCLUSIONS: In our cohort of PLWH treated with dolutegravir-based regimens and followed up for up to 4 years, we observed a low risk of treatment failure and no evidence for a difference by sex, after excluding discontinuation due to pregnancy concerns. However, we observed a higher risk of dolutegravir discontinuation for toxicity in women.

Effect of tecovirimat on healing time and viral clearance by emulation of a target trial in patients hospitalized for mpox.

Tecovirimat is a treatment option for severe mpox, although randomized clinical trials are ongoing. The aim of the study is to assess the effect of tecovirimat on healing time and the extent of viral clearance by target trial emulation using observational data. Clinical and virological data of patients hospitalized for mpox were collected. Samples from the upper respiratory tract (URT) were grouped in two time points: T1 (median 6 days from symptoms onset) and T2 (median 5 days from T1). Patients were followed-up until recovery. Average treatment effect (ATE) in patients untreated versus treated with tecovirimat was estimated on time to healing and variation in viral load in URT, using a weighted and cloning analysis. Among the 41 patients included, 19 completed a course of tecovirimat. The median time from symptoms onset to hospitalization and to drug-starting was 4 days and 10 days, respectively. No improvement in healing time in treated versus untreated was observed. No difference by treatment group in time to viral clearance was detected by ATE fitted in a subset of 13 patients after controlling for confounders. We found no evidence for a large effect of tecovirimat in shortening healing time and viral clearance. While awaiting the results of randomized studies, the use of tecovirimat should be restricted to the clinical trial setting.

Is HCV elimination among persons living with HIV feasible? Data from the NoCo study in the setting of the ICONA cohort.

BACKGROUND AND AIMS: Whether the HCV test-and-treat strategy impacted on the rate of new HCV infections among PLWH in Italy is unknown. METHODS: Prospective study of PLWH in the ICONA network. At baseline, PLWH were tested for HCV-Ab; HCV-RNA (if HCV-Ab positive) and, if positive, treated with DAA. SVR12 indicated eradication. Seroconversions and re-infections were evaluated yearly in HCV-Ab neg and HCV-RNA neg at first screening. We estimated the following: HCV seroconversions, incidence of HCV reinfections, and access to DAA and SVR12 rates tighter with factors associated with each outcome. Data were analysed by Cox regression, Poisson regression and logistic regression models. RESULTS: Sixteen thousand seven hundred and forty-three PLWH were included; 27.3% HCV-Ab positive; of these, 39.3% HCV-RNA positive. HCV seroconversion incidence: .48/100 PYFU (95% CI: .36-.65); re-infections incidence: 1.40/100 PYFU (95% CI: .91-2.04). The risk factor for HCV re-infection was young age: aIRR 1.85, 95% CI: 1.17-2.95) per 10 years younger. 86.4% of HCV viremic in follow-up started DAA. PWID vs. heterosexuals (aHR .75, 95% CI .62-.90), HIV-RNA >50 copies/mL (aHR .70, 95% CI .56-.87), HCV genotype other than G1, G2, G3, G4 or with multiple/missing HCV genotype and post-COVID-19 calendar periods were associated with lower DAA access. 922/965 (95.5%) PLWH achieved SVR12. We estimated 72% reduction of chance to achieve SVR12 in PLWH with a CD4 count <200/mm3 (vs. CD4 ≥200/mm3 aOR .18, 95% CI: .07-.46). 95.5% of DAA-treated individuals eradicated HCV, but they represent only 53.2% of HCV viremic PLWH and 66.4% of those in follow-up. HCV-RNA positivity by year decreased from 41.7% in 2017 to 11.7% in 2022. CONCLUSIONS: The screening-and-treat campaign implemented in Italy, even if only partially effective, resulted in a dramatic drop in HCV circulation in our cohort.

EuCARE-POSTCOVID Study: a multicentre cohort study on long-term post-COVID-19 manifestations.

BACKGROUND: Post-COVID-19 condition refers to persistent or new onset symptoms occurring three months after acute COVID-19, which are unrelated to alternative diagnoses. Symptoms include fatigue, breathlessness, palpitations, pain, concentration difficulties ("brain fog"), sleep disorders, and anxiety/depression. The prevalence of post-COVID-19 condition ranges widely across studies, affecting 10-20% of patients and reaching 50-60% in certain cohorts, while the associated risk factors remain poorly understood. METHODS: This multicentre cohort study, both retrospective and prospective, aims to assess the incidence and risk factors of post-COVID-19 condition in a cohort of recovered patients. Secondary objectives include evaluating the association between circulating SARS-CoV-2 variants and the risk of post-COVID-19 condition, as well as assessing long-term residual organ damage (lung, heart, central nervous system, peripheral nervous system) in relation to patient characteristics and virology (variant and viral load during the acute phase). Participants will include hospitalised and outpatient COVID-19 patients diagnosed between 01/03/2020 and 01/02/2025 from 8 participating centres. A control group will consist of hospitalised patients with respiratory infections other than COVID-19 during the same period. Patients will be followed up at the post-COVID-19 clinic of each centre at 2-3, 6-9, and 12-15 months after clinical recovery. Routine blood exams will be conducted, and patients will complete questionnaires to assess persisting symptoms, fatigue, dyspnoea, quality of life, disability, anxiety and depression, and post-traumatic stress disorders. DISCUSSION: This study aims to understand post-COVID-19 syndrome's incidence and predictors by comparing pandemic waves, utilising retrospective and prospective data. Gender association, especially the potential higher prevalence in females, will be investigated. Symptom tracking via questionnaires and scales will monitor duration and evolution. Questionnaires will also collect data on vaccination, reinfections, and new health issues. Biological samples will enable future studies on post-COVID-19 sequelae mechanisms, including inflammation, immune dysregulation, and viral reservoirs. TRIAL REGISTRATION: This study has been registered with ClinicalTrials.gov under the identifier NCT05531773.

Anxiety and depression symptoms after virological clearance of COVID-19: A cross-sectional study in Milan, Italy.

Prevalence of anxiety or depression was investigated in 105 coronavirus disease 2019 (COVID-19) patients at 1 to 3 months from virological clearance by hospital anxiety and depression scale (HADS-A/D). 30% of patients displayed pathological HADS-A/D, 52.4% showed persistent symptoms. Pathological patients with HADS-A/D more commonly reported symptom persistence, even after adjustment for age, gender, and disease severity. Psychological assessments should be encouraged in COVID-19 patients' follow-up.

Virological response and retention in care according to time of starting ART in Italy: data from the Icona Foundation Study cohort.

OBJECTIVES: To describe: (i) factors associated with rapid and delayed ART initiation; (ii) rates of 12 week virological response; and (iii) virologically controlled retention in care by 1 year from ART initiation according to timing of start in a real-life setting. METHODS: All individuals in the Icona cohort diagnosed with HIV in 2016-17 who initiated ART were grouped according to the time between HIV diagnosis and ART initiation: Group 1, ≤7 days; Group 2, 8-14 days; Group 3, 15-30 days; Group 4, 31-120 days; and Group 5, >120 days. Multivariable logistic regression models were used to identify factors associated with: (i) the probability of rapid (Group 1) and very delayed (Group 5) ART initiation; (ii) the 12 week virological response (by a modified snapshot algorithm); and (iii) the probability of retention in care at 1 year (on ART with HIV-RNA <50 copies/mL). RESULTS: A total of 1247 individuals were included [82 (6.6%) in Group 1, 115 (9.2%) in Group 2, 267 (21.4%) in Group 3, 641 (51.4%) in Group 4 and 142 (11.4%) in Group 5]. Main predictors of rapid ART start (Group 1) were low CD4 cell count and high HIV-RNA at first contact with the infectious diseases centre. There was no association between probability of virological response and timing of ART initiation. Overall, 90% of individuals remained on ART after 1 year, 91% with undetectable HIV-RNA. Participants of Italian nationality, those with higher CD4 cell count and lower HIV-RNA at ART initiation were more likely to be retained in care after 1 year. CONCLUSIONS: In our high-income observational setting, we did not observe differences in the 1 year rate of virological response and retention in care according to timing of ART initiation.

Tixagevimab/Cilgavimab as SARS-CoV-2 Pre-Exposure Prophylaxis in Lung Transplant Recipients during the Omicron Wave: A Real-World Monocentric Experience.

Lung transplant recipients (LTRs) respond poorly to vaccination. SARS-CoV-2 pre-exposure prophylaxis (PrEP) with tixagevimab/cilgavimab (TIX/CIL) reduces the incidence of infection and the evolution to severe COVID-19. In vitro data show decreased activity against Omicron variants. We evaluated the clinical efficacy and safety of TIX/CIL in LTRs during the Omicron wave. A prospective observational cohort study was conducted at ISMETT in Palermo (Italy). In June 2022, SARS-CoV-2 PrEP with TIX/CIL 150/150 mg was offered to LTRs. LTRs who received TIX/CIL were compared to LTRs who did not. Logistic regression analysis (adjusted for prior COVID-19, SARS-CoV-2 vaccination, age, years from transplant, and rejection) was performed. The objective of this study was to compare the following among the two populations: prevalence of SARS-CoV-2, length of SARS-CoV-2 positivity, and COVID-19 disease severity. Among 110 eligible LTRs, 79 (72%) received TIX/CIL and 31 (28%) did not. SARS-CoV-2 infections occurred in 6% (n = 5) of patients who received TIX/CIL and 29% (n = 9) of patients who did not (p < 0.001). In both groups, infections were mild/asymptomatic, and no one was hospitalized or died. At multivariate analysis, TIX/CIL was associated with a lower risk of infection (aOR 0.22; 95%CI 0.06-0.78; p = 0.02). TIX/CIL was safe and effective in reducing the risk of SARS-CoV-2 in LTRs during the Omicron wave.

Impact of COVID-19 pandemic on retention in care of native and migrant people with HIV in the ICONA cohort.

BACKGROUND: COVID-19 pandemic challenged the UNAIDS 90-90-90 targets. How the COVID-19 pandemic affected HIV retention in care and whether it has disproportionally affected migrant people with HIV (PWH) remained to be investigated. METHODS: PWH in ICONA Cohort in follow-up in each of the study periods were included: 01/09/2019-29/02/2020 (pandemic period) and 01/03/2018-31/08/2018 (historical period, as a control). Risk of temporary loss to follow-up (LTFU, defined as no data recorded for a person for one year) was analyzed by logistic regression, with migrant status as the main exposure variable. Difference in difference (DID) analysis was applied to evaluate the effect of COVID-19 pandemic in the different risk of LTFU between natives and migrants. RESULTS: 8864 (17.1% migrants) and 8071 (16.8% migrants) PWH constituted the pandemic and the historical period population, respectively. Proportion of PWH defined as LTFU in the pandemic period was 10.5% in native and 19.6% in migrant PWH. After controlling for age, sex and geographical location of enrolling site, risk of temporary LTFU was higher for migrants than native PWH [adjusted odds ratio 1.85 (95%CI 1.54-2.22)] in pandemic period. In PWH contributing to both periods, LTFU was 9.0% (95% CI 8.3-9.8) in natives vs 17.0% (95% CI 14.7-19.4) in migrants during the pandemic. Instead, LTFU was 1.2% (95%CI 0.9, 1.5) in natives vs 2.2% (95% CI 1.3-3.1) in migrants during the historical period, with a resulting DID of 7.0% (95% CI 4.4-9.6). CONCLUSIONS: A greater proportion of LTFU in migrant PWH was observed in both periods, which remained unaltered over time. Interventions to reduce LTFU of migrants are necessary.

Persistent poor clinical outcomes of people living with HIV presenting with AIDS and late HIV diagnosis - results from the ICONA cohort in Italy, 2009-2022.

OBJECTIVES: Limited data are available on the long-term outcomes in recent years for late HIV diagnosis (LD). METHODS: All subjects with HIV enrolled in the ICONA cohort in 2009-2022 who started antiretroviral treatment (ART) within 4 months from diagnosis were included and divided into: (i) pre-ART CD4 count ≥350/mm3 without AIDS (non-LD), (ii) pre-ART CD4 count <350/mm3 without AIDS (LD asymptomatic), and (iii) with AIDS events pre-ART (LD-AIDS). The estimated probability and independent risk for mortality (all-cause and cause-specific) and treatment failure were evaluated. RESULTS: Of 6813 participants (2448 non-LD, 3198 LD asymptomatic, and 1167 LD-AIDS), 161 (2.4%) died after ART initiation. At survival analysis, a higher probability of all-cause mortality has been identified for LD than non-LD (P <0.001) and within the former, for LD-AIDS over LD asymptomatic (P <0.001). After adjusting for confounders, LD showed a higher risk of all-cause mortality (vs non-LD adjusted hazard ratio (aHR) 5.51, P <0.001) and, in particular, being an AIDS presenter predicted a greater risk of all-cause (aHR = 4.42, P <0.001), AIDS-related (adjusted subhazard ratio [aSHR] = 16.86, P <0.001), and non-AIDS-related mortality (aSHR = 1.74, P = 0.022) than the rest of the late presenters. Among the short-term survivors in the LD-AIDS group, the long-term mortality was mediated by the lack of immune recovery at 2 years. Finally, LD compared with non-LD and, particularly, among the former, LD-AIDS over LD asymptomatic showed a greater risk of treatment failure. CONCLUSIONS: In recent years, LD subjects, particularly, AIDS presenters, remained at a higher risk of poorer outcomes. Public health strategies for early HIV diagnosis are urgently needed to constrain the mortality gap.

Heavily treatment-experienced persons living with HIV currently in care in Italy: characteristics, risk factors, and therapeutic options-the ICONA Foundation cohort study.

OBJECTIVES: Heavily treatment-experienced (HTE) people living with HIV (PLWH) pose unique challenges due to limited antiretroviral treatment (ART) options. Our study aimed to investigate the prevalence and features of HTE individuals followed up in the Italian Cohort Naïve Antiretrovirals (ICONA) cohort as of December 31, 2021. METHODS: HTE were defined based on meeting specific conditions concerning their current ART and their ART history up to December 31, 2021. Descriptive statistics were performed by HTE status. Regression analyses explored factors associated with becoming HTE based on pre-ART patients' characteristics. Cluster dendrogram analysis provided insights into subgroups with inadequate responses based on clusters of differentiation (CD4) counts and viral load (VL) trajectories. RESULTS: Among the 8758 PLWH actively followed in our cohort, 163 individuals (1.9%), mainly female, younger, Italian, and infected through heterosexual contact, met the HTE criteria. A lower CD4 count at ART initiation (odds ratio [OR] 1.60 per 100 cells/mmc lower CD4, 95% confidence interval [CI] 1.06-2.41, P = 0.03) and hepatitis C virus antibody positivity (OR 1.90, 95% CI 1.16-3.11, P = 0.01) were associated with higher HTE risk. Thirty PLWH exhibited ongoing immune-virological failure (18% of the HTE subgroup and 0.003% of the total population). Thirty PLWH exhibited ongoing immune-virological failure (i.e., with a current CD4 count <200 cells/mmc or VL>200 copies/mL). A cluster analysis identified 13 (43%) with a current CD4 count <200 cells/mmc. Also, notably, 19/30 (63%) had major acquired resistance-associated mutations to at least one antiretroviral drug class. CONCLUSIONS: HTE is rare in our cohort and tends to co-exist with major resistance mutations. A focused investigation into treatment history and immuno-virological response is warranted, particularly given the availability of new antiretroviral drugs.

SARS-CoV-2 mRNA vaccination and short-term changes in viral load and CD4/CD8 T-cell counts in people living with HIV.

OBJECTIVES: To investigate whether SARS-CoV-2 messenger RNA (mRNA) vaccination has an impact on HIV-related viro-immunological parameters. METHODS: People with HIV (PWH) in the VAXICONA-ORCHESTRA cohort who received one or more doses of SARS-CoV-2 mRNA vaccine and for whom paired measures of immuno-virological markers (viral load, clusters of differentiation [CD]4, and CD8 count 1 month before and after a vaccine dose [VD]) were available were included. Paired t-test and generalized estimating equation linear regression analyses were used to study changes over ± 1 month around the VD. Subgroup analyses were performed. RESULTS: A total of 510 PWH were enrolled: the median age was 55 years (interquartile range 46-60 years), the CD4 and CD8 count were 489 (287-719) and 790 (59-1104) cells/mm3, respectively, and 81% received three VDs. After a median of 28 (3-53) days from VD, CD4 count increased by +15 cells/mm3 (SD ± 129.7, P = 0.001) and CD8 by +12 (±250.5, P = 0.199) and the viral load decreased by -0.11 log10 (±0.88, P = 0.001). Similar results were observed after restricting the analysis to viro-suppressed PWH, with CD4 ≤200/mm3, more than 6 months of antiretroviral therapy before VD and after excluding previous COVID-19. CONCLUSIONS: A small significant increase in CD4 count and a negligible drop in HIV RNA were observed. Our findings are consistent with the hypothesis that SARS-CoV-2 mRNA vaccine can prime CD4 T spike-specific cells, even in the more immuno-compromised PWH.

Characterization and outcomes of difficult-to-treat patients starting modern first-line ART regimens: Data from the ICONA cohort.

OBJECTIVES: Treatment failures to modern antiretroviral therapy (ART) raise concerns, as they could reduce future options. Evaluations of occurrence of multiple failures to modern ART are missing and their significance in the long run is unclear. METHODS: People with HIV (PWH) in the ICONA cohort who started a modern first-line ART were defined as 'difficult to treat' (DTT) if they experienced ≥1 among: i) ≥2 VF (2 viral loads, VL>200 copies/mL or 1 VL>1000 copies/mL) with or without ART change; ii) ≥2 treatment discontinuations (TD) due to toxicity/intolerance/failure; iii) ≥1 VF followed by ART change plus ≥1 TD due to toxicity/intolerance/failure. A subgroup of the DTT participants were matched to PWH that, after the same time, were non-DTT. Treatment response, analysing VF, TD, treatment failure, AIDS/death, and SNAE (Serious non-AIDS event)/death, were compared. Survival analysis by KM curves and Cox regression models were employed. RESULTS: Among 8061 PWH, 320 (4%) became DTT. Estimates of becoming DTT was 6.5% (95% CI: 5.8-7.4%) by 6 years. DTT PWH were significantly older, with a higher prevalence of AIDS and lower CD4+ at nadir than the non-DTT. In the prospective analysis, DTT demonstrated a higher unadjusted risk for all the outcomes. Once controlled for confounders, significant associations were confirmed for VF (aHR 2.23, 1.33-3.73), treatment failure (aHR 1.70, 1.03-2.78), and SNAE/death (aHR 2.79, 1.18-6.61). CONCLUSION: A total of 6.5% of PWH satisfied our definition of DTT by 6 years from ART starting. This appears to be a more fragile group who may have higher risk of failure.

Clinical and laboratory predictors of mpox severity and duration: an Italian multicentre cohort study (mpox-Icona).

BACKGROUND: Severe and prolonged mpox courses have been described during the 2022-2023 outbreak. Identifying predictors of severe evolution is crucial for improving management and therapeutic strategies. We explored the predictors of mpox severity and tested the association between mpox severity and viral load in biological fluids. We also analysed the predictors of disease duration and kinetics of inflammatory markers and described the viral presence and duration of shedding in biological fluids. METHODS: This multicentre historical cohort study included adults diagnosed with laboratory-confirmed mpox diagnosis between May 2022 and September 2023 at 15 Italian centres. Patients were followed up from the day of diagnosis until clinical recovery. Biological fluids (blood, urine, saliva, and oropharyngeal and rectal swabs) were collected from each subgroup during the course of the disease and after healing. The primary outcomes were disease severity (presence of mucosal involvement, extended rash, or need for hospitalisation) and its association with the cycle threshold value (Ct-value, surrogate of viral load) in biological fluids, using standard linear and linear mixed-effect logistic regression models. Among the secondary outcomes, predictors of disease duration were assessed using a linear regression model. FINDINGS: A total of 541 patients were enrolled, including four (0.74%) women, with a median age of 38 years (IQR 33-44). Among the 235 people living with HIV (PLWH) (43.44%), 22 (4.07%) had a CD4 count lower than 350 cells/µL. Severe mpox was reported in 215 patients (39.74%). No patient died. Multivariable analysis showed that, severe mpox was more likely among Caucasians (OR 1.82; 95% CI 1.14-2.90, p = 0.012) and patients who had an onset of fever (1.95; 1.27-2.99, p = 0.002), lymphadenopathy (2.30; 1.52-3.48, p < 0.001), sore throat (2.14; 1.27-3.59, p = 0.004), and peri-anal lesions (2.91; 1.93-4.37, p < 0.001). There was a significant difference (p = 0.003) between the median Ct-value in the upper respiratory tract for patients presenting with either mild (35.15; IQR 28.77-42.01) or severe infection (31.00; 25.00-42.01). The risk of developing severe disease decreased by approximately 5% per Ct increase (0.95; 0.91-0.98; p = 0.005). The disease lasted longer in the case of proctitis (+4.78 days; 1.95-7.61, p = 0.001), sore throat (+3.12; 0.05-6.20, p = 0.046), extended rash (+3.42; 0.55-6.28, p = 0.020), as well as in PLWH with a low CD4 count (+12.51; 6.79-18.22, p < 0.001). INTERPRETATION: The identification of predictors of severe or prolonged disease and the direct association MPXV Ct-value in the upper respiratory tract and disease severity could be useful in establishing proper management and early treatment of new mpox cases. FUNDING: ICONA Foundation; Italian Ministry of Health "Ricerca Corrente Linea 2", INMI Lazzaro Spallanzani IRCCS.

HIV-Indicator Condition Guided Testing in a Hospital Setting.

Late diagnosis is still a major issue in HIV infection management, leading to important consequences for both patients and community. In this perspective, HIV screening targeted on some clinical conditions (HIV indicator conditions-HIVICs) emerged as a useful strategy, also involving patients not considered at high behavioral risk. We organized an in-hospital HIVICs guided screening campaign named ICEBERG in Milan, Italy, between 2019 and 2021. Among the 520 subjects enrolled, mainly presenting with viral hepatitis or mononucleosis-like syndrome, 20 resulted HIV positive (3.8% prevalence). A significant proportion of them had multiple conditions and advanced immunosuppression, with 40% being AIDS-presenters. As adherence to the screening campaign was modest for non-ID specialists, educational interventions to raise clinicians' sensitivity are urgently needed. HIV-ICs guided testing was confirmed as a useful tool, but a combined approach with other screening strategies seems to be essential for early HIV diagnosis.

Detection of Asymptomatic Mpox Carriers among High-Ri Men Who Have Sex with Men: A Prospective Analysis.

Mpox is traditionally considered a zoonotic disease with endemic circulation in Africa, but the 2022-2023 outbreak reached an unprecedented high number of cases in non-endemic countries, so that it was declared a public health emergency of international concern. The reasons for this extensive global spread, characterized by sexual transmission amongst men who have sex with men (MSM), have not been fully clarified. The existence of asymptomatic carriers with viable viral shedding might be an explanation and is under-debated after retrospective studies suggested that infection without symptoms might have a prevalence of 6.5%. We aimed to prospectively assess the presence of mpox infection in asymptomatic high-risk MSM using HIV pre-exposure prophylaxis and living with HIV. We selected individuals with no signs of active infection nor suggestive symptoms in the previous 21 days. Eligible individuals collected oral and anal swabs to undergo point-of-care testing for mpox and completed a 21-days follow-up. Seventy-two individuals were enrolled, and none tested positive for mpox infection nor developed symptoms during follow-up. We selected a high-risk population with a significant history of sexual exposure, but we failed to detect any asymptomatic infection. This observation might have important consequences in terms of contact management and epidemic control.