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Objectives: Tuberculosis (TB) risk after initiation of antiretroviral treatment (ART) is not well described in a European setting, with an average TB incidence of 25/10 5 in the background population., Methods: We included all adult persons with HIV starting ART in the RESPOND cohort between 2012 and 2020. TB incidence rates (IR) were assessed for consecutive time intervals post-ART initiation. Risk factors for TB within 6 months from ART initiation were evaluated using Poisson regression models., Results: Among 8441 persons with HIV, who started ART, 66 developed TB during 34,239 person-years of follow-up (PYFU), corresponding to 1.87/1000 PYFU (95% confidence interval [CI]: 1.47-2.37). TB IR was highest in the first 3 months after ART initiation (14.41/1000 PY (95%CI 10.08-20.61]) and declined at 3-6, 6-12, and >12 months post-ART initiation (5.89 [95%CI 3.35-10.37], 2.54 [95%CI 1.36-4.73] and 0.51 [95%CI 0.30-0.86]), respectively. Independent risk factors for TB within the first 6 months after ART initiation included follow-up in Northern or Eastern Europe region, African origin, baseline CD4 count <200 cells/mm 3 , HIV RNA >100,000 copies/mL, injecting drug use and heterosexual transmission., Conclusions: TB IR was highest in the first 3 months post-ART initiation and was associated with baseline risk factors, highlighting the importance of thorough TB risk assessment at ART initiation., Competing Interests: Declarations of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JN received honoraria for presentations from Oxford Immunotec and ViiV and working on the advisory board of Gilead Sciences and ViiV. OK received honoraria for presentations at meetings supported by Merck, unconditional research grants from Gilead and travel support from Gilead and Viiv. HG, JR are employees of ViiV Healthcare, Gilead Sciences, respectively. The remaining authors declared no conflicts of interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Transmitted drug resistance (TDR) is still a critical aspect for the management of individuals living with HIV-1. Thus, its evaluation is crucial to optimize HIV care., Methods: Overall, 2386 HIV-1 protease/reverse transcriptase and 1831 integrase sequences from drug-naïve individuals diagnosed in north and central Italy between 2015 and 2021 were analysed. TDR was evaluated over time. Phylogeny was generated by maximum likelihood. Factors associated with TDR were evaluated by logistic regression., Results: Individuals were mainly male (79.1%) and Italian (56.2%), with a median (IQR) age of 38 (30-48). Non-B infected individuals accounted for 44.6% (N = 1065) of the overall population and increased over time (2015-2021, from 42.1% to 51.0%, P = 0.002). TDR prevalence to any class was 8.0% (B subtype 9.5% versus non-B subtypes 6.1%, P = 0.002) and remained almost constant over time. Overall, 300 transmission clusters (TCs) involving 1155 (48.4%) individuals were identified, with a similar proportion in B and non-infected individuals (49.7% versus 46.8%, P = 0.148). A similar prevalence of TDR among individuals in TCs and those out of TCs was found (8.2% versus 7.8%, P = 0.707).By multivariable analysis, subtypes A, F, and CFR02&#95;AG were negatively associated with TDR. No other factors, including being part of TCs, were significantly associated with TDR., Conclusions: Between 2015 and 2021, TDR prevalence in Italy was 8% and remained almost stable over time. Resistant strains were found circulating regardless of being in TCs, but less likely in non-B subtypes. These results highlight the importance of a continuous surveillance of newly diagnosed individuals for evidence of TDR to inform clinical practice., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

With the advancement of artificial intelligence(AI), platforms like ChatGPT have gained traction in different fields, including Medicine. This study aims to evaluate the potential of ChatGPT in addressing questions related to HIV prevention and to assess its accuracy, completeness, and inclusivity. A team consisting of 15 physicians, six members from HIV communities, and three experts in gender and queer studies designed an assessment of ChatGPT. Queries were categorized into five thematic groups: general HIV information, behaviors increasing HIV acquisition risk, HIV and pregnancy, HIV testing, and the prophylaxis use. A team of medical doctors was in charge of developing questions to be submitted to ChatGPT. The other members critically assessed the generated responses regarding level of expertise, accuracy, completeness, and inclusivity. The median accuracy score was 5.5 out of 6, with 88.4% of responses achieving a score ≥ 5. Completeness had a median of 3 out of 3, while the median for inclusivity was 2 out of 3. Some thematic groups, like behaviors associated with HIV transmission and prophylaxis, exhibited higher accuracy, indicating variable performance across different topics. Issues of inclusivity were identified, notably the use of outdated terms and a lack of representation for some communities. ChatGPT demonstrates significant potential in providing accurate information on HIV-related topics. However, while responses were often scientifically accurate, they sometimes lacked the socio-political context and inclusivity essential for effective health communication. This underlines the importance of aligning AI-driven platforms with contemporary health communication strategies and ensuring the balance of accuracy and inclusivity., (© 2024. The Author(s).)

Objective: People with HIV (PWH) have high risk of liver fibrosis. We investigated the effect of weight gain and metabolic dysfunction-associated steatotic liver disease (MASLD) on liver fibrosis dynamics., Design: Multicenter cohort study., Methods: Fibrosis progression was defined as development of significant fibrosis [liver stiffness measurement (LSM) ≥8 kPa], or transition to cirrhosis (LSM ≥13 kPa), for those with significant fibrosis at baseline. Fibrosis regression was defined as transition to LSM less than 8 kPa, or to LSM less than 13 kPa for those with cirrhosis at baseline. MASLD was defined as hepatic steatosis (controlled attenuation parameter >248 dB/m) with at least one metabolic abnormality. A continuous-time multistate Markov model was used to describe transitions across fibrosis states., Results: Among 1183 PWH included from three centers (25.2% with viral hepatitis coinfection), baseline prevalence of significant fibrosis and MASLD was 14.4 and 46.8%, respectively. During a median follow-up of 2.5 years (interquartile range 1.9-3.5), the incidence rate of fibrosis progression and regression was 2.8 [95% confidence interval (CI) 2.3-3.4] and 2.2 (95% CI 1.9-2.6) per 100 person-years, respectively. In Markov model, weight gain increased the odds of fibrosis progression [odds ratio (OR) 3.11, 95% CI 1.59-6.08], whereas weight gain (OR 0.30, 95% CI 0.10-0.84) and male sex (OR 0.32, 95% CI 0.14-0.75) decreased the odds of fibrosis regression. On multivariable Cox regression analysis, predictors of fibrosis progression were weight gain [adjusted hazard ratio (aHR) 3.12, 95% CI 1.41-6.90] and MASLD (aHR 2.72, 95% CI 1.05-7.02)., Conclusion: Fibrosis transitions are driven by metabolic health variables in PWH, independently of viral hepatitis coinfection and antiretroviral class therapy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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/mm 3 without AIDS (non-LD), (ii) pre-ART CD4 count <350/mm 3 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., Competing Interests: Declarations of competing interest A.M. received speaker honoraria from Gilead Sciences and ViiV Healthcare and travel fees and participated in advisory boards sponsored by ViiV Healthcare. A.C. received funding for scientific advisory boards, travel, or speaker honoraria from Gilead Sciences, ViiV Healthcare, Janssen-Cilag, and MSD. A. Giacomelli reports speaker honoraria for ViiV Healthcare and Gilead Sciences and is an adviser for Janssen-Cilag and Mylan. C.P. received personal fees from Gilead Sciences for a case presentation and a travel grant and has served on an advisory board for Janssen-Cilag; A. Gori received speaker honoraria and fees for attending advisory boards from ViiV Healthcare, Gilead Sciences, Janssen-Cilag, MSD, BMS, Pfizer, and Novartis and received research grants from ViiV, BMS, and Gilead Sciences. A.S. received speaker honoraria or participated in advisory boards sponsored by Gilead Sciences, ViiV Healthcare, MSD, and Janssen-Cilag. A.B. received speaker honoraria and fees for attending advisory boards from Astra-Zeneca, BioMerieux, Janssen-Cilag, Nordic Pharma, Pfizer, Qiagen, SOBI, and ViiV and received research grants from Gilead; G.M. participated in the advisory boards of Gilead Sciences, ViiV Healthcare, Angelini, and Janssen-Cilag and received travel grants from ViiV Healthcare, MSD, and Janssen-Cilag; E.G. received grant support from Gilead Sciences and Mylan and speaker honoraria from Gilead Sciences. C.M. received speaker honoraria or participated in advisory boards sponsored by Gilead Sciences, ViiV Healthcare, MSD, and Janssen-Cilag and received research grants from Gilead Sciences; A.d.M. participated in advisory board of Gilead Sciences, ViiV Healthcare, MSD, Pfizer, and GSK and received research grant from Gilead Science, ViiV Healthcare, Merck Sharp and Dohme, GSK, and Janssen-Cilag; A.A. received research grants from Gilead Sciences, AstraZeneca, and ViiV Healthcare and honoraria from Gilead Science, AstraZeneca, GSK, Pfizer, MSD, Moderna, Mylan, Janssen-Cilag, and ViiV Healthcare; A.C-L., A.T., G.D.G., and G.O. have no competing interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Integrase strand-transfer inhibitors (INSTIs) and tenofovir alafenamide have been associated with weight gain in several clinical trials and observational cohorts. However, whether weight gain associated with INSTIs and tenofovir alafenamide confers a higher risk of weight-related clinical events is unclear. We aimed to assess whether changes in BMI differentially increase hypertension or dyslipidaemia risk in people with HIV receiving INSTIs, tenofovir alafenamide, or both versus other contemporary regimens., Methods: This multicentre, prospective observational study analysed prospective data from RESPOND, an international consortium of HIV cohorts for which recruitment began in 2017 and is still ongoing from HIV clinics and hospitals in 37 European countries and Australia. Participants were eligible if they were aged 18 years or older, receiving INSTI-containing antiretroviral therapy (ART) regimens or a contemporary non-INSTI, did not have hypertension or dyslipidaemia at baseline, and had baseline and at least two follow-up BMI, lipid, and blood pressure measurements. We excluded participants without baseline CD4 or HIV RNA results and those receiving non-ART medications associated with weight changes, including antipsychotics and mood stabilisers, corticosteroids, insulin, and insulin secretagogues. They were followed up from baseline until the earliest hypertension or dyslipidaemia event, their last visit, or Dec 31, 2021, whichever was earlier. The primary outcomes were incidence of hypertension and dyslipidaemia, for which we used multivariable Poisson regression adjusted for time-updated BMI to determine unadjusted and adjusted incidence rate ratios (IRRs) of hypertension and dyslipidaemia in people receiving INSTIs, tenofovir alafenamide, or both, and tested for interaction between time-updated ART regimen and BMI., Findings: Of the 35 941 RESPOND participants, 9704 (7327 [75·5 %] male and 2377 [24·5%] female) were included in the hypertension analysis and 5231 (3796 [72·6%] male and 1435 [27·4%] female) were included in the dyslipidaemia analysis. In the univariable model, hypertension was more common in individuals receiving an INSTI with tenofovir alafenamide (IRR 1·70, 95% CI 1·54-1·88) or an INSTI without tenofovir alafenamide (1·41, 1·30-1·53) compared with those receiving neither INSTIs nor tenofovir alafenamide. Adjustment for time-updated BMI and confounders attenuated risk in participants receiving an INSTI with (IRR 1·48, 1·31-1·68) or without (1·25, 1·13-1·39) tenofovir alafenamide. Similarly, dyslipidaemia was more common in participants using tenofovir alafenamide with an INSTI (IRR 1·24, 1·10-1·40) and tenofovir alafenamide alone (1·22, 1·03-1·44) than in participants using neither INSTI nor tenofovir alafenamide. Adjustment for BMI and confounders attenuated the risk in participants receiving tenofovir alafenamide with an INSTI (adjusted IRR 1·21, 1·07-1·37), whereas the risk in those receiving tenofovir alafenamide alone became non-significant (1·15, 0·96-1·38). The associations between increasing BMI and risk of hypertension and dyslipidaemia did not differ between participants receiving different ART regimens (p interaction =0·46 for hypertension; p interaction =0·31 for dyslipidaemia)., Interpretation: Although residual confounding cannot be entirely excluded, the use of INSTIs was associated with incident hypertension, and the use of tenofovir alafenamide was associated with dyslipidaemia, with the latter association partly mediated by weight gain. These results reiterate the need for hypertension and dyslipidaemia screening in people with HIV., Funding: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The Brighton HIV Cohort, The National Croatian HIV Cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort, The University of Cologne HIV Cohort, Merck Life Sciences, ViiV Healthcare, and Gilead Sciences., Competing Interests: Declaration of interests AM has received travel support and lecture and consultancy fees from Gilead Sciences, ViiV Healthcare, Eiland, and Bonnin, all outside the submitted work. VV is an employee of and has stocks in ViiV Healthcare. CC is an employee of and has stocks in Gilead Sciences. EB is an employee of and has stocks in MSD. ML has received sitting fees from Certa Therapeutics data safety monitoring board. KG-P has served on advisory boards and provided lectures for Gilead Sciences and ViiV Healthcare. AR has received support for attending meetings and travel from Gilead Sciences and Pfizer, received an investigator-initiated trial grant from Gilead Sciences, and participated on a data safety monitoring board or advisory board for MSD and Pfizer (all paid to the institution). All other authors declare no competing interests., (© 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active antiretroviral therapy (ART) and increase risk of malignancies. The prognostic role of low CD4:CD8 ratio and elevated CD8 cell counts on the risk of cancer remains unclear., Methods: We investigated the association of CD4:CD8 ratio on the hazard of non-AIDS defining malignancy (NADM), AIDS-defining malignancy (ADM) and most frequent group of cancers in ART-treated people with HIV (PWH) with a CD4 and CD8 cell counts and viral load measurements at baseline. We developed Cox proportional hazard models with adjustment for known confounders of cancer risk and time-dependent cumulative and lagged exposures of CD4:CD8 ratio to account for time-evolving risk factors and avoid reverse causality., Results: CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI }1.10-6.19] and 2.03 [95% CI 1.24-3.33], respectively). CD4 cell counts below 350 cells/μL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies., Conclusions: In ART-treated PWH low CD4:CD8 ratios were associated with ADM and infection-related cancers independently from CD4 and CD8 cell counts and may alert clinicians for cancer screening and prevention of NADM., Competing Interests: Potential conflicts of interest. A. Ma. is full-time employee at Gilead Sciences and owns stock. A. Mo. has received travel support, lecture and consultancy fees from Gilead, ViiV Healthcare, and Eiland and Bonnin, all outside the submitted work. A. E. has received consulting fees and honoraria for lectures and presentations from Roche. C. M. has received honoraria for lectures and presentations from Gilead, ViiV Healthcare, MSD, and travel support from Gilead and a research grant to institution from Gilead. J. J. V. has received honoraria for lectures and presentations from Merck/MSD, Gilead, Pfizer, Astellas Pharma, Basilea, Deutsches Zentrum für Infektionsforschung, Uniklinik Freiburg/Kongress und Kommunikation, Akademie für Infektionsmedizin, University Manchester, Deutsche Gesellschaft für lnfektiologie, Ärztekammer Nordrhein, Uniklinik Aachen, Back Bay Strategies, Deutsche Gesellschaft für Innere Medizin, Shionogi, Molecular Health, Netzwerk Universitätsmedizin, Janssen, NordForsk, Biontech, APOGEPHA, and is part of the data safety monitoring board of APOGEPHA Arznemittel, Biontech, Merck/MSD, Gilead, and Pfizer; and reports research funding from Merck/MSD; Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), German Federal Ministry of Education and Research (BMBF), Deutsches Zetrum für Luft und Raumfahrt (DLR), University of Bristol, Rigshospitalet Kopenhagen. A. C. has received honoraria for lectures and presentation and meetings attendance support from Gilead, ViiV Healthcare, MSD, Janssen-Cilag and is part of the advisory board of Gilead, ViiV Healthcare, MSD and Janssen-Cilag. J. B. has received consulting fees and honoraria for lectures and presentations from ViiV Healthcare, Merck, Gilead, Janssen, Pfizer, and Theratechnology, and honoraria from NovoNordisk and AtraZeneca. S. W. is part of the advisory board of ViiV Healthcare and reports grants or contracts paid to institution from RESPOND. R.M. has received consultancy fees from Tamro Baltics, honoraria honoraria for lectures and presentations from MSD, KRKA, Tamro Baltics, AbbVie and Eurovaistine, payment for expert testimony from Tamor Baltic and meeting attendance support from AbbVie, MSD, Johnson&Johnson, and Swixx BioPharma; and reports unpaid roles as Board member of Lithuanian Infectious Diseases Society and as Scientific committee member of EuroSIDA; and the following grants or contracts unrelated to this work: EuroSIDA/Respond, observational cohort study; WEEPI 1.1, WEEPI 1.2 (Western-Eastern European partnership Initiative on HIV, viral hepatitis and TB). J. T. is a member of the European AIDS Treatment Group, a community organization that receives funding not related to this publication from ViiV Healthcare, Gilead Sciences, MSD, Janssen, Orasure Technologies, European Union (author was paid for project work), Innovative Medicines Initiative, FIND Diagnosis, received consulting fees/honoraria from The Global Fund, UNAIDS, Pan American Health Organization, Frontline AIDS, the Barcelona Institute for Global Health. H. G. is an employee of ViiV healthcare and shareholder of GSK. A.Ma. is an employee and shareholder of Gilead Sciences California. H. C. B. has received in the 36 months prior to the submission of this manuscript one grant from Gilead that was not related to this project. HCB has served as the president of the “association contre le HIV et autres infections transmissibles.” In this role he has received support for the Swiss HIV Cohort Study from ViiV Healthcare, Gilead, BMS, and MSD. M. L. reports paid participation on DSMB with Certa Therapeutics. F.W. reports participation in advisory board for ViiV Healthcare. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: People with HIV and extensive antiretroviral exposure may have limited/exhausted treatment options (LExTO) due to resistance, comorbidities, or antiretroviral-related toxicity. Predictors of LExTO were investigated in the RESPOND cohort., Methods: Participants on ART for at least 5 years were defined as having LExTO when switched to at least two anchor agents and one third antiretroviral (any class), a two-drug regimen of two anchor agents (excluding rilpivirine with dolutegravir/cabotegravir), or at least three nucleoside reverse transcriptase inhibitors. Baseline was the latest of January 1, 2012, cohort enrolment or 5 years after starting antiretrovirals. Poisson regression modeled LExTO rates and clinical events (all-cause mortality, non-AIDS malignancy, cardiovascular disease [CVD], and chronic kidney disease [CKD])., Results: Of 23 827 participants, 2164 progressed to LExTO (9.1%) during 130 061 person-years follow-up (PYFU); incidence 1.66/100 PYFU (95% CI 1.59-1.73). Predictors of LExTO were HIV duration more than 15 years (vs. 7.5-15; adjusted incidence rate ratio [aIRR] 1.32; 95% CI 1.19-1.46), development of CKD (1.84; 1.59-2.13), CVD (1.64; 1.38-1.94), AIDS (1.18; 1.07-1.30), and current CD4 + cell count of 350 cells/μl or less (vs. 351-500 cells/μl, 1.51; 1.32-1.74). Those followed between 2018 and 2021 had lower rates of LExTO (vs. 2015-2017; 0.52; 0.47-0.59), as did those with baseline viral load of 200 cp/ml or less (0.46; 0.40-0.53) and individuals under 40. Development of LExTO was not significantly associated with clinical events after adjustment for age and current CD4, except CKD (1.74; 1.48-2.05)., Conclusion: Despite an aging and increasingly comorbid population, we found declining LExTO rates by 2018-2021, reflecting recent developments in contemporary ART options and clinical management. Reassuringly, LExTO was not associated with a significantly increased incidence of serious clinical events apart from CKD., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Roberta Gagliardini reports payments to her institution from Gilead Sciences, speakers’ honoraria/educational activities for ViiV Healthcare, Merck Sharp and Dohme and Gilead Sciences, advisor for Theratechnologies, Janssen-Cilag and Gilead Sciences. Andrea Giacomelli received consultancy fees from Mylan and Janssen. Speaker honoraria from ViiV, Gilead, and MSD. Educational and grant support from Gilead and ViiV. Antonella D'arminio Monforte is a consultant or participated in advisory boards sponsored by Gilead Sciences, ViiV Healthcare, Janssen-Cilag, GSK, Merck Sharp & Dohme and received research grants from Gilead Sciences and ViiV Healthcare. Enrico Girardi received research grants from Gilead and Mylan and speaker fees from Gilead and ViiV unrelated to the present study. All other authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: GG and CM received research grant and speaker honorariums from Gilead, ViiV, Merck, and Janssen. GG and CM attended advisory boards for Gilead, ViiV, and Merck. We thank Jovana Milic for drawing the table.

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., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

WHO defines ageism as stereotypes, prejudice, and discrimination based on age. Ageism is a multidimensional concept that encompasses multiple components related to the individual, the social group, and the institution in different cultural and environmental settings. In people ageing with HIV these elements include self-stigma, discrimination in society, and experiences in care, many of which are unique to older people. In this Position Paper, we use experience of people with HIV and clinicians taking care of them to explore these issues in high-income countries. The intersectionality of multiple -isms, which affect the lives of older people living with HIV, and ageism enhance several HIV-related issues, including self-inflicted stigma, and loneliness. Research is needed to explore how ageism contributes to worse physical, mental, and social wellbeing outcomes for people with HIV. The model of care for older people living with HIV needs to go beyond virological success by adopting a geriatric mindset, which is attentive to the challenge of ageism and is proactive in promoting a comprehensive approach for the ageing population. All stakeholders and the community should work together to co-create institutional strategies and educational programmes and enable respectful intergenerational dialogue to foster a stigma-free future for older people living with HIV., Competing Interests: Declaration of interests GG received research grants and speaker honorarium from Gilead, ViiV, MERCK, and Jansen and attended advisory boards of Gilead, ViiV, and MERCK. JM received speaker honoraria from Gilead and ViiV. MCa attended advisory boards for ViiV and received speaker honoraria from Gilead. EM received research grants from Merck Sharp & Dohme and ViiV; attended advisory boards for Janssen, Gilead, Merck Sharp & Dohme, and ViiV; and received speaker honoraria from Gilead and ViiV. JF received speaker honorarium from ViiV. CO received research grants from Gilead, GSK, ViiV, Merck Sharp & Dohme, AstraZeneca, and Janssen; speaker honoraria from Gilead, GSK, ViiV, Merck Sharp & Dohme, and Janssen; and support for attending meetings from Gilead and ViiV. JVL reports grants to his institution from AbbVie, Gilead, Roche Diagnostics, and Merck Sharp & Dohme and speaker honoraria from AbbVie, Gilead, Intercept, Janssen, and Novo Nordisk. JL, DC, RM, MCe, and CM declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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/mm 3 (P<0.001) and +233 cell/mm 3 (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., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Introduction: The objective of the study was to develop machine learning (ML) models that predict the percentage weight change in each interval of time in antiretroviral therapy-experienced people living with HIV., Methods: This was an observational study that comprised consecutive people living with HIV attending Modena HIV Metabolic Clinic with at least 2 visits. Data were partitioned in an 80/20 training/test set to generate 10 progressively parsimonious predictive ML models. Weight gain was defined as any weight change >5%, at the next visit. SHapley Additive exPlanations values were used to quantify the positive or negative impact of any single variable included in each model on the predicted weight changes., Results: A total of 3,321 patients generated 18,322 observations. At the last observation, the median age was 50 years and 69% patients were male. Model 1 (the only 1 including body composition assessed with dual-energy x-ray absorptiometry) had an accuracy greater than 90%. This model could predict weight at the next visit with an error of <5%., Conclusions: ML models with the inclusion of body composition and metabolic and endocrinological variables had an excellent performance. The parsimonious models available in standard clinical evaluation are insufficient to obtain reliable prediction, but are good enough to predict who will not experience weight gain., Competing Interests: G.G. and C.M. received research grant and speaker honorarium from Gilead, ViiV, MERCK, and Jansen. G.G. and C.M. attended advisory boards of Gilead, ViiV, and MERCK. Other authors reported no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The objectives of this study were to describe the trajectories of bone mineral density (BMD) and trabecular bone score (TBS) changes throughout pre-menopause (reproductive phase and menopausal transition) and post-menopause (early and late menopause) in women with HIV (WWH) undergoing different antiretroviral therapies (ARTs) and explore the risk factors associated with those changes., Methods: This was an observational longitudinal retrospective study in WWH with a minimum of two DEXA evaluations comprising BMD and TBS measurements, both in the pre-menopausal and post-menopausal periods. Menopause was determined according to the STRAW+10 criteria, comprising four periods: the reproductive period, menopausal transition, and early- and late-menopausal periods. Mixed-effects models were fitted to estimate the trajectories of the two outcomes (BMD and TBS) over time. Annualized lumbar BMD and TBS absolute and percentage changes were calculated in each STRAW+10 time window. A backward elimination procedure was applied to obtain the final model, including the predictors that affected the trajectories of BMD or TBS over time., Results: A total of 202 WWH, all Caucasian, were included. In detail, 1954 BMD and 195 TBS data were analyzed. The median number of DEXA evaluations per woman was 10 (IQR: 7, 12). The median observation periods per patient were 12.0 years (IQR = 8.9-14.4) for BMD and 6.0 years (IQR: 4.3, 7.9) for TBS. The prevalence of osteopenia (63% vs. 76%; p < 0.001) and osteoporosis (16% vs. 36%; p < 0.001) increased significantly between the pre-menopausal and post-menopausal periods. Both BMD (1.03 (±0.14) vs. 0.92 (±0.12) g/cm 2 ; p < 0.001) and TBS (1.41 (IQR: 1.35, 1.45) vs. 1.32 (IQR: 1.28, 1.39); p < 0.001) decreased significantly between the two periods. The trend in BMD decreased across the four STRAW+10 periods, with a slight attenuation only in the late-menopausal period when compared with the other intervals. The TBS slope did not significantly change throughout menopause. The delta mean values of TBS in WWH were lower between the menopausal transition and reproductive period compared with the difference between menopause and menopausal transition., Conclusions: Both BMD and TBS significantly decreased over time. The slope of the change in BMD and TBS significantly decreased in the menopausal transition, suggesting that this period should be considered by clinicians as a key time during which to assess bone health and modifiable risk factors in WWH.

Background: We aimed to describe prevalence, incidence, and risk factors for sarcopenic obesity (SO) phenotypes in people living with HIV (PWH) and their association with subclinical cardiovascular disease (CVD)., Methods: Observational, longitudinal study of PWH. A minimum of 1 criterion was necessary to diagnose sarcopenia: weak hand grip (HG), low appendicular skeletal muscle index (ASMI), short physical performance battery (SPPB < 11). Obesity was defined as body mass index (BMI) ≥ 30 kg/m 2 or visceral adipose tissue (VAT) ≥ 160 cm 2 . These variables combined generated 5 SO phenotypes: severe SO: low HG + low ASMI + low SPPB + high BMI; SO1: weak HG + high VAT; SO2: weak HG + high BMI; SO3: low ASMI + high VAT; SO4: low ASMI + high BMI. Subclinical CVD was defined as carotid intima-media thickness (IMT) ≥ 1 mm, presence of carotid plaque, or coronary artery calcification (CAC) score > 10., Results: Among 2379 male PWH 72%, median age was 52 years, median HIV vintage 21 years, and median BMI 24 kg/m 2 . Two PWH had severe SO. The prevalence of SO1-SO4 was 19.7%, 3.6%, 20.8% and 0.8%, respectively. Incidence of SO1-SO4 was 6.90, 1.2, 5.6, and 0.29 × 100 person-years, respectively. SO1 was associated with risk of IMT ≥ 1, and SO3 with risk of CAC score > 10., Conclusions: There was a large variability in incidence and prevalence of SO phenotypes. The presence of SO may have important implications for cardiovascular prevention and cardiac rehabilitation of PWH who suffered events., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this randomized clinical trial (RCT) was to compare immunological changes in virally suppressed people living with HIV (PLWH) switching from a three-drug regimen (3DR) to a two-drug regimen (2DR)., Methods: An open-label, prospective RCT enrolling PLWH receiving a 3DR who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir/lamivudine (DTG/3TC) was performed. Blood was taken at baseline and months 6 and 12. The primary outcome was the change in CD4+ or CD8+ T-cell counts and CD4/CD8 ratio over time points. The secondary outcomes were the changes in immunological and inflammatory parameters. Parametric mixed-linear models with random intercepts and slopes were fitted separately for each marker after controlling for potential confounders., Results: Between the two arms (33 PLWH each), there was no difference in CD4+ or CD8+ T cells, CD4/CD8 ratio, and IL-6 trajectories. PLWH switching to DTG/3TC had increased levels of both transitional memory and terminally differentiated CD4+ T cells (arm-time interaction p-value = 0.02) and to a lesser extent for the corresponding CD8+ T-cell subsets (p = 0.09). Significantly lower levels of non-classical monocytes were detected in the B/F/TAF arm at T6 (diff = -6.7 cells/mm 3 ; 95% CI; -16, +2.6; p-value for interaction between arm and time = 0.03). All differences were attenuated at T12., Conclusion: No evidence for a difference in absolute CD4+ and CD8+ T-cell counts, CD4/CD8 ratio, and IL-6 trajectories by study arm over 12 months was found. PLWH on DTG/3TC showed higher levels of terminally differentiated and exhausted CD4+ and CD8+ T lymphocytes and non-classical monocytes at T6. Further studies are warranted to better understand the clinical impact of our results., Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT04054089., Competing Interests: GG and CM received a research grant and a speaker honorarium from Gilead, ViiV, MERCK, and Jansen. GG and CM are on the advisory boards of Gilead, ViiV, and MERCK. JM received a speaker honorarium from Gilead and ViiV. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cossarizza, Cozzi-Lepri, Mattioli, Paolini, Neroni, De Biasi, Tartaro, Borella, Fidanza, Gibellini, Beghetto, Roncaglia, Nardini, Milic, Menozzi, Cuomo, Digaetano, Orlando, Borghi, Guaraldi and Mussini.)

Real-life comparisons of dolutegravir/rilpivirine (DTG/RPV) and DTG/lamivudine (3TC) regimens in people living with human immunodeficiency virus (PLWHIV) who switched from a standard three-drug regimen based on nonnucleoside reverse transcriptase inhibitors (NNRTIs) are missing. This study aimed to compare DTG/3TC and DTG/RPV in virologically suppressed patients (HIV-RNA < 50 copies/mL) coming from any NNRTI-based regimen in terms of discontinuation due to virologic failure (VF) discontinuation rates due to all causes, and adverse events. As a secondary outcome, we evaluated the difference in creatinine, total cholesterol, CD4, and triglycerides from baseline to weeks 48 after the switch. Of the 415 PLWHs included in the study, 278 (66.9%) switched to DTG/3TC, and 137 (33.1%) switched to DTG/RPV. Overall, 48 PLWHs (11.6%) discontinued the treatment:38 with DTG/3TC and 10 with DTG/RPV with similar discontinuation rates: 5.01 × 100 py (95% confidence interval [CI] 3.64-6.94) and 4.66 × 100 py (95% CI 2.51-8.67), respectively. The most common reason for discontinuation was toxicity (26 patients, 22/278 [7.9%] in the DTG/3TC group and 4/137 [2.9%] in the DTG/RPV group), mainly neurologic toxicity (never above grade 2). We found no differences in discontinuation rates due to treatment adverse events. Two study participants experienced virological failure in the DTG/3TC arm. We observed no significant difference in CD4 cell counts, lipid parameters, or renal function between the two groups at 48 weeks. This study demonstrated that, in clinical practice, a two-drug regimen with DTG/3TC or DTG/RPV is characterized by a low discontinuation rate and VF in virologically suppressed PLWHs switched from an NNRTI-based three antiretroviral drugs regimen., (© 2023 Wiley Periodicals LLC.)

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/mm 3 (vs. CD4 ≥200/mm 3 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., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: There are conflicting data regarding baseline determinants of virological nonsuppression outcomes in persons with human immunodeficiency virus (HIV) starting antiretroviral treatment (ART). We evaluated the impact of different baseline variables in the RESPOND cohort., Methods: We included treatment-naive participants aged ≥18 who initiated 3-drug ART, in 2014-2020. We assessed the odds of virological suppression (VS) at weeks 48 and 96 using logistic regression. Viral blips, low-level viremia (LLV), residual viremia (RV), and virological failure (VF) rates were assessed using Cox regression., Results: Of 4310 eligible participants, 72% started integrase strand transfer inhibitor (INSTI)-based regimens. At 48 and 96 weeks, 91.0% and 93.3% achieved VS, respectively. At 48 weeks, Kaplan-Meier estimates of rates were 9.6% for viral blips, 2.1% for LLV, 22.2% for RV, and 2.1% for VF. Baseline HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤200/µL were negatively associated with VS at weeks 48 (adjusted odds ratio, 0.51 [95% confidence interval, .39-.68] and .40 [.27-.58], respectively) and 96 and with significantly higher rates of blips, LLV, and RV. CD4+ T-cell counts ≤200/µL were associated with higher risk of VF (adjusted hazard ratio, 3.12 [95% confidence interval, 2.02-4.83]). Results were consistent in those starting INSTIs versus other regimens and those starting dolutegravir versus other INSTIs., Conclusions: Initial high HIV-1 RNA and low CD4+ T-cell counts are associated with lower rates of VS at 48 and 96 weeks and higher rates of viral blips, LLV, and RV. Low baseline CD4+ T-cell counts are associated with higher VF rates. These associations remain with INSTI-based and specifically with dolutegravir-based regimens. These findings suggest that the impact of these baseline determinants is independent of the ART regimen initiated., Competing Interests: Potential conflicts of interest. H. A. has received support for attending meetings from Janssen-Cilag, Gilead Sciences and ViiV Healthcare and honoraria for presentations from Gilead Sciences and ViiV Healthcare, outside the present work. A. M. has received payments or honoraria for lectures, presentations and travel support from ViiV Healthcare and Gilead Sciences and consultancy fees as an expert witness for Eiland and Bonnin, outside the submitted work. H. F. G. has received unrestricted research grants and a travel grant from Gilead Sciences; fees for data and safety monitoring board membership from Merck; consulting/advisory board membership fees from Gilead Sciences, Merck, Johnson & Johnson, Janssen, Novartis, GSK and ViiV Healthcare; and grants from the Swiss National Science Foundation, Yvonne Jacob Foundation, and the National Institutes of Health, outside the present work. C.S. reports payment or honoraria for speaking engagements from Gilead Sciences. F. W. reports membership on the advisory board for ViiV. C. L. reports grants or contracts (paid to the institution) from the German federal ministry of education and research, the Federal Joint Committee (Gemeinsamer Bundesausschuss Innovationsausschuss), the Ministerium für Kultur und Wissenschaft in Nordrhein-Westfalen, and the German Center for Infection Research; payment for speaking engagements from Pfizer, ViiV, Gilead, Novartis, MSD, and Biontech; travel support for the 2023 Conference on Retroviruses and Opportunistic Infections (CROI 2023) from Pfizer; and participation on a data safety monitoring or advisory board for ViiV, Pfizer, and Biontech. C. M. reports a research grant from Gilead (paid to the institution), consulting fees (paid to the author) from ViiV, MSD, Gilead, and Janssen, and participation on a data safety monitoring or advisory board for Corimuno. J. C. W. has received payments or honoraria for lectures from Merck Sharp & Dohme. A. S. reports grants or contracts from Gilead Sciences, participation on data safety monitoring or advisory board for GlaxoSmithKline and Gilead Sciences, and a role on the Swedish Reference Group of Antiviral Therapy. C. Smith Stephan has received grants or contracts from the Robert Koch Institute (ClinSurv Steering committee and grant) abd Gesellschaft für Internationale Zusammenarbeit (Hospital Partnership Developing Project [Esther]); consulting fees from Gilead Sciences (speaker fees and advisory board membership) and from Janssen Cilag, Merck Sharp & Dohme, ViiV Healthcare (advisory board membership); payment for expert testimony for Verwaltungsgericht Berlin; and support for attending meetings form Gilead Sciences (Conference on Retrovirus and Opportunistic Infection [American Retrovirus Conference]), Janssen-Cilag (European AIDS Conference travel grant), and AbbVie (Dagnä-Workshop travel grant), outside the present work. K. P. has received grants or contracts from ViiV Healthcare Australia and Gilead Sciences Australia, outside the present work. V. V. is an employee and shareholder of ViiV Healthcare. J. G. is an employee and shareholder of Gilead Sciences. R. M. I. has received payments for presentations in meetings and symposia as a speaker in HIV Clinical Topics (22–23 September 2022; lecture about late human immunodeficiency virus [HIV] presentation) and from the HIV Nordic Symposium (September 2022; role as chairman in a session about long-acting cabotegravir/rilpivirine [GSK]) and reports participation on an advisory board for GSK (November–December 2022) (personal consulting fee in relation to an advisory board regarding new data on dolutegravir-lamivudine and long-acting treatment with cabotegravir-rilpivirine), outside the present work. L. Y. reports other financial or nonfinancial interests with Merck Sharp & Dohme. J. M. L. has received payments or honoraria for lectures, presentations, or speakers bureau participation from Janssen-Cilag, Gilead Sciences, Thera Technologies, and ViiV Healthcare; consulting fees from and participation on a data safety monitoring or advisory board for Janssen-Cilag, Gilead Sciences, and ViiV Healthcare; and support for attending meetings from Gilead Sciences, outside the present work. A.C. reports grants or contracts (paid to institution) from ViiV Healthcare, consulting fees, payment for speaking engagements, and participation on data safety monitoring or advisory boards for Janssen Cilag, Gilead, MSD, and ViiV Healthcare (alls support paid to author). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Randomized controlled trials (RCTs) from low- and middle-income settings suggested that early initiation of antiretroviral therapy (ART) leads to higher mortality rates among people with HIV (PWH) who present with cryptococcal meningitis (CM). There is limited information about the impact of ART timing on mortality rates in similar people in high-income settings., Methods: Data on ART-naive PWH with CM diagnosed from 1994 to 2012 from Europe/North America were pooled from the COHERE, NA-ACCORD, and CNICS HIV cohort collaborations. Follow-up was considered to span from the date of CM diagnosis to earliest of the following: death, last follow-up, or 6 months. We used marginal structural models to mimic an RCT comparing the effects of early (within 14 days of CM) and late (14-56 days after CM) ART on all-cause mortality, adjusting for potential confounders., Results: Of 190 participants identified, 33 (17%) died within 6 months. At CM diagnosis, their median age (interquartile range) was 38 (33-44) years; the median CD4+ T-cell count, 19/μL (10-56/μL); and median HIV viral load, 5.3 (4.9-5.6) log10 copies/mL. Most participants (n = 157 [83%]) were male, and 145 (76%) started ART. Mimicking an RCT, with 190 people in each group, there were 13 deaths among participants with an early ART regimen and 20 deaths among those with a late ART regimen. The crude and adjusted hazard ratios comparing late with early ART were 1.28 (95% confidence interval, .64-2.56) and 1.40 (.66-2.95), respectively., Conclusions: We found little evidence that early ART was associated with higher mortality rates among PWH presenting with CM in high-income settings, although confidence intervals were wide., Competing Interests: Potential conflicts of interest. J. M. M. has received consulting honoraria and/or research grants from AbbVie, Angelini, Contrafect, Cubist, Genentech, Gilead Sciences, Jansen, Medtronic, MSD, Novartis, Pfizer, and ViiV Healthcare, outside the submitted work, as well as consulting fees from Lysovant. L. E. C. has stock or stock options and is an employee of AbbVie. C. Sabin reports payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events from Gilead Sciences and ViiV Healthcare (payments to the author for preparation of educational materials); participation on a data and safety monitoring board (DSMB) or advisory board for Gilead Sciences and ViiV Healthcare (paid to the author); and service as vice chair of the British HIV Association. H. S. reports consulting fees from ViiV and MSD and payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events from MSD, ViiV, and Gilead. P. R., through his institution, has received independent scientific grant support from Gilead Sciences, Janssen Pharmaceuticals, Merck, and ViiV Healthcare and has served on scientific advisory boards for Gilead Sciences, ViiV Healthcare, and Merck, honoraria for which were all paid to his institution (all support outside the submitted work). V. B. reports support for attending meetings and/or travel from Gilead and Janssen and has stock or stock options in DWS Biotech LC Fond (private self-investment; no payments to author or institution received from any third party). F. V. received research or teaching grants from Gilead Sciences, ViiV Healthcare, and MSD, unrelated to the submitted work. N. O. reports grants or contracts from Simonsens Fond (paid to the institution). A. M. reports travel support, lecture fees, honorarium and consultancy fees from ViiV, Gilead, Eiland, and Bonnin, all outside the submitted work. L. W. reports grants or contracts from ANRS MIE. R. T. reports a research grant from Gilead Science; payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events from Gilead Science (payment for lectures), Janssen (payment for lectures), and ViiV Healthcare (payment for lectures); support for travel from Gilead Science and Janssen; and participation on an advisory board for Gilead Science. A. D. M. reports consulting fees from ViiV, Gilead, and Janssen (paid to the author); payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events from Gilead and ViiV (paid to the author); and participation on a DSMB or advisory board for Janssen, Gilead, and ViiV (payment to the author). C. M. reports research grant from Gilead; payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events from ViiV and Gilead; and participation on a DSMB or advisory board for Corimuno, Gilead, ViiV, Janssen, and MSD. H. F.’s institution received educational grants from AbbVie, ViiV, Gilead, MSD, Sandoz, and Pfizer, all outside the submitted work. M. S. S. reports research grants from Gilead Sciences and ViiV Healthcare (paid to the institution); payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing; or educational events from IAS-USA (not-for-profit organization); serving on the DSMB for the I-Spy COVID trial; and serving as board chair for IAS-USA. H. M. C. reports grants or contracts from the National Institutes of Health (NIH), the Agency for Healthcare Research and Quality, and ViiV (paid to institution); consulting fees from ViiV (pending); and participation on the Office of AIDS Research Scientific Advisory Board. J. J. E. reports grants or contracts from ViiV Healthcare, Gilead Sciences, and Janssen; consulting fees from Merck, ViiV Healthcare, Gilead Science, and Janssen; and leadership or fiduciary roles in other boards, societies, committees, or advocacy groups for the IAS-USA antiretroviral therapy guidelines committee. K. N. A. reports grants or contracts from the NIH (paid to institution), royalties or licenses from Coursera, consulting fees from the NIH (for the All of US Study), and payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events for DC HIV Cohort (author served on the DC HIV Cohort’s external advisory board). M. J. G. reports consulting fees from Merck, Gilead, and ViiV (with occasional honoraria for ad hoc membership on human immunodeficiency virus advisory boards). H. C. B., in the 36 months before the submission of the current manuscript, has received grants, support for traveling, consultancy fees, and honoraria from Gilead, BMS, ViiV Healthcare, Roche, and Pfizer, unrelated to the current work. He served as the president of the Association Contre le HIV et Autres Infections Transmissibles until June 2022; in this function he received support for the Swiss HIV Cohort Study from ViiV Healthcare, Gilead, BMS, and MSD. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Despite the availability of pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART), 21 793 people were newly diagnosed with HIV in Europe in 2019. The Concerted action on seroconversion to AIDS and death in Europe study aims to understand current drivers of the HIV epidemic; factors associated with access to, and uptake of prevention methods and ART initiation; and the experiences, needs and outcomes of people with recently acquired HIV., Methods and Analysis: This longitudinal observational study is recruiting participants aged ≥16 years with documented laboratory evidence of HIV seroconversion from clinics in Canada and six European countries. We will analyse data from medical records, self-administered questionnaires, semistructured interviews and participatory photography. We will assess temporal trends in transmitted drug resistance and viral subtype and examine outcomes following early ART initiation. We will investigate patient-reported outcomes, well-being, and experiences of, knowledge of, and attitudes to HIV preventions, including PrEP. We will analyse qualitative data thematically and triangulate quantitative and qualitative findings. As patient public involvement is central to this work, we have convened a community advisory board (CAB) comprising people living with HIV., Ethics and Dissemination: All respective research ethics committees have approval for data to contribute to international collaborations. Written informed consent is required to take part. A dissemination strategy will be developed in collaboration with CAB and the scientific committee. It will include peer-reviewed publications, conference presentations and accessible summaries of findings on the study's website, social media and via community organisations., Competing Interests: Competing interests: The funders did not participate in the study design and will not intervene in its process, analysis or publication of the findings. ST has received speaker honoraria and consultancy fees from Gilead Sciences. CC has received speaker/moderator honoraria and advisory board fees from Gilead Sciences, GSK/ViiV and MSD as well as an unrestricted Gilead Sciences Nordic Fellowship Research Grant. CS has received funding from Gilead Sciences, ViiV Healthcare and Janssen-Cilag for participation in Advisory Boards, speaker panels and for preparation of educational materials. MVdV has received consultancies fees for participation in advisory boards and research grants from Gilead, MSD and ViiV all paid to his institution. FMB has received funding from Gilead Sciences Ltd for preparation and delivery of educational materials. IJ has received teaching fees from ViiV Healthcare and advisory fees from Gilead Sciences. GT has received research grants and advisory board fees from Gilead, all paid to her institution, and MJG has received honoraria for ad hoc participation in national Advisory boards of Gilead Merck and ViiV., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Background: Dolutegravir (DTG) +lamivudine (3TC) combination has been found to be as effective as triple therapies, and has been extensively prescribed in clinical practice as a maintenance therapy. We aimed to investigate the effect of previous virological failures (VFs) on virological efficacy., Methods: The analysis included data of people living with HIV (PLWH) with HIV-RNA ≤50 copies/mL enrolled in an Italian retrospective multicohort study who were switching to DTG+3TC. Primary endpoint was viral rebound (VR; confirmed HIV-RNA ≥50 copies/mL or single HIV-RNA ≥50 copies/mL followed by change of antiretroviral therapies [ART]). Kaplan-Meier curves were used to estimate probabilities of VR based upon histories of previous VFs (single HIV-RNA ≥1000 copies/mL or confirmed HIV-RNA ≥50 copies/mL). A weighted Cox regression model was fitted to estimate the causal hazard ratio (HR) of history of failure on the risk of VR., Results: A total of 966 PLWH were included; 20.1% had a history of previous VF. VR was detected in 23 PLWH. The one-year probability was 1.2% (95% confidence interval [CI], 0.2%-2.2%) in PLWH without previous VF and 3.3% (95% CI, 0.4%-6.2%) in those with ≥1 VF (log-rank P = 0.042). By multivariate analysis adjusted for CD4+ cell count at nadir, duration of virological suppression, and mode of HIV transmission, PLWH with ≥1 previous VF had a higher risk of virological rebound than those without previous VF (adjusted hazard ratio 3.06 [95% CI, 1.00-9.44], P = 0.051)., Conclusion: Despite the low absolute one-year risk in both groups, real-world data confirmed that PLWH with a previous failure have an increased risk of viral rebound., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Assessing whether the previously reported association between abacavir (ABC) and cardiovascular disease (CVD) remained amongst contemporarily treated people with HIV., Design: Multinational cohort collaboration., Methods: RESPOND participants were followed from the latest of 1 January 2012 or cohort enrolment until the first of a CVD event (myocardial infarction, stroke, invasive cardiovascular procedure), last follow-up or 31 December 2019. Logistic regression examined the odds of starting ABC by 5-year CVD or chronic kidney disease (CKD) D:A:D risk score. We assessed associations between recent ABC use (use within the past 6 months) and risk of CVD with negative binomial regression models, adjusted for potential confounders., Results: Of 29 340 individuals, 34% recently used ABC. Compared with those at low estimated CVD and CKD risks, the odds of starting ABC were significantly higher among individuals at high CKD risk [odds ratio 1.12 (95% confidence interval = 1.04-1.21)] and significantly lower for individuals at moderate, high or very high CVD risk [0.80 (0.72-0.88), 0.75 (0.64-0.87), 0.71 (0.56-0.90), respectively]. During 6.2 years of median follow-up (interquartile range; 3.87-7.52), there were 748 CVD events (incidence rate 4.7 of 1000 persons-years of follow up (4.3-5.0)]. The adjusted CVD incidence rate ratio was higher for individuals with recent ABC use [1.40 (1.20-1.64)] compared with individuals without, consistent across sensitivity analyses. The association did not differ according to estimated CVD (interaction P  = 0.56) or CKD ( P  = 0.98) risk strata., Conclusion: Within RESPOND's contemporarily treated population, a significant association between CVD incidence and recent ABC use was confirmed and not explained by preferential ABC use in individuals at increased CVD or CKD risk., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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/mm 3 , 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/mm 3 , 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., (© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Objectives and Design: Using pol sequences obtained for routine resistance testing, we characterised the molecular patterns of HIV-1 transmission and factors associated with being part of a transmission cluster among individuals who in 2008-2014 presented with primary HIV-1 infection (PHI) at 11 urban centres across Italy., Methods: Pol sequences were obtained by Sanger sequencing. Transmission clusters were identified by phylogenetic analysis (maximum likelihood method, confirmed by Bayesian analysis). Multivariable logistic regression explored factors associated with a participant being part of a transmission cluster., Results: The PHI cohort comprised 186 participants (159/186, 85.5% males) with median age 44 years, median CD4 count 464 cells/mm 3 and median plasma HIV-1 RNA 5.6 log 10 copies/mL. Drug resistance associated mutations were found in 16/186 (8.6%). A diversity of non-B subtypes accounted for 60/186 (32.3%) of all infections. A total of 17 transmission clusters were identified, including 44/186 (23.7%) participants. Each cluster comprised 2-6 sequences. Non-B subtypes accounted for seven clusters and 22/44 (50%) of clustered sequences. In multivariable logistic regression analysis, factors associated with being part of a transmission cluster comprised harbouring a non-B subtype (adjusted OR (adjOR) 2.28; 95% CI 1.03 to 5.05; p=0.04) and showing a lower plasma HIV-1 RNA (adjOR 0.80, 95% CI 0.64 to 0.99; p=0.04)., Conclusions: There was a large contribution of diverse non-B subtypes to transmission clusters among people presenting with acute or recent HIV-1 infection in this cohort, illustrating the evolving dynamics of the HIV-1 epidemic in Italy, where subtype B previously dominated., Competing Interests: Competing interests: LT reports past (within 36 months) financial relationships (advisory board membership or consultancy fees, speakers’ honoraria or travel support) with Gilead Sciences, Janssen, Viiv Healthcare and no other conflict of interest. MF reports past (within 36 months) financial relationships (advisory board membership or consultancy fees, speakers’ honoraria or travel support) with Gilead Sciences, Janssen, Viiv Healthcare, BMS, MSD and no other conflict of interest. SR reports past (within 36 months) financial relationships (advisory board membership or consultancy fees, speakers’ honoraria or travel support) with Gilead Sciences, Janssen, Viiv Healthcare and no other conflict of interest. AG reports past (within 36 months) financial relationships (educational support) with Mylan and no other conflict of interest. EF reports past (within 36 months) financial relationships (advisory board membership or consultancy fees, speakers’ honoraria or travel support) with Gilead Sciences, Janssen, Viiv Healthcare, MSD and no other conflict of interest. CP reports past (within 36 months) financial relationships (advisory board membership or consultancy fees, speakers’ honoraria or travel support) with Janssen. GM reports past (within 36 months) financial relationships (advisory board membership or consultancy fees, speakers’ honoraria or travel support) with Gilead Sciences, Janssen, Viiv Healthcare, MSD and no other conflict of interest. AG reports past (within 36 months) grant/research supports, honoraria or consultation fees, speaker’s bureau compensation and/or travel support from Abbvie, Astellas, BMS, Boeringher, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, ViiV and no other conflict of interest., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: We aimed to investigate and compare the efficacy and safety of two dolutegravir-based two-drug regimens: dolutegravir + lamivudine versus dolutegravir + rilpivirine., Methods: We analysed a cohort of people living with HIV (PLWHIV) switching to dolutegravir + lamivudine or dolutegravir + rilpivirine. We excluded from the analysis PLWHIV with no available pre-switch genotypic test or with a known resistance mutation to one of the study drugs. We evaluated incidence of virological failure (VF) and treatment discontinuation (TD), as well as changes in immunological and metabolic parameters., Results: We enrolled 592 PLWHIV: 306 in the lamivudine group and 286 in the rilpivirine group. We observed nine VFs in the lamivudine group [1.4 VF per 100 patient-years of follow-up (PYFU)] and four VFs in the rilpivirine group (0.6 VF per 100 PYFU). Subsequent genotypic analysis showed no acquired resistance-associated mutations in those experiencing VF. Estimated probability of maintaining virological suppression at 144 and 240 weeks were 96.6% and 92.7%, respectively, in the lamivudine group and 98.7% and 98.7%, respectively, in the rilpivirine group (log-rank P = 0.172). The estimated probability of maintaining study regimen at Week 240 was 82.3% in the lamivudine group and 85.9% in the rilpivirine group (log-rank P = 0.018). We observed a significant improvement in CD4+ cell count at Week 240 in the lamivudine group (P = 0.012); in the rilpivirine group we registered a significant increase in CD4/CD8 ratio (P = 0.014)., Conclusions: Both analysed strategies are effective and safe as switch strategies in clinical practice, with a low incidence of VF and a favourable immunological recovery, even in the long term., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study aimed to develop a new approach to manage people living with HIV (PLWH), investigating preferences of clinicians and PLWH in order to improve linkage to care of PLWH. A survey was performed with the Discrete Choice Experiment (DCE) method to investigate the preferences of two categories, clinicians and PLWH, for attributes of HIV care pathways, therapy and quality of life. Our results suggest that the most important feature of a care pathway was the site of testing for both categories, followed by modality of counselling for clinicians and by pre-exposure prophylaxis for PLWH. Regarding therapy, choices were mostly oriented by modality of administration for both categories, and by CD4 cells increase for clinicians and side effects for PLWH. People living with HIV reported that, out of 13 candidates, the two most important factors related to good long-term quality of life would be reduction of viral transmissibility and good emotional life. A tailored approach could be the key to long-term treatment success, but this approach must necessarily be based on evaluation of the specific complexities of the patient.

Background: Integrase inhibitor (INSTI) use has been associated with greater weight gain (WG) among people living with HIV (PLWH), but it is unclear how this effect compares in magnitude to traditional risk factors for WG. We assessed the population attributable fractions (PAFs) of modifiable lifestyle factors and INSTI regimens in PLWH who experienced a ≥5% WG over follow-up., Methods: In an observational cohort study from 2007 to 2019 at Modena HIV Metabolic Clinic, Italy, ART-experienced but INSTI-naive PLWH were grouped as INSTI-switchers vs non-INSTI. Groups were matched for sex, age, baseline BMI and follow-up duration. Significant WG was defined as an increase of ≥5% from 1st visit weight over follow-up. PAFs and 95% CIs were estimated to quantify the proportion of the outcome that could be avoided if the risk factors were not present., Results: 118 PLWH switched to INSTI and 163 remained on current ART. Of 281 PLWH (74.3% males), mean follow-up was 4.2 years, age 50.3 years, median time since HIV diagnosis 17.8 years, CD4 cell count 630 cells/µL at baseline. PAF for weight gain was the greatest for high BMI (45%, 95% CI: 27-59, p  < 0.001), followed by high CD4/CD8 ratio (41%, 21-57, p  < 0.001) and lower physical activity (32%, 95% CI 5-52, p  = 0.03). PAF was not significant for daily caloric intake (-1%, -9-13, p  = 0.45), smoking cessation during follow-up (5%, 0-12, p  = 0.10), INSTI switch (11%, -19-36; p  = 0.34)., Conclusions: WG in PLWH on ART is mostly influenced by pre-existing weight and low physical activity, rather than switch to INSTI.

Objectives: To describe the timing of tuberculosis (TB) presentation in relation to diagnosis of HIV infection and antiretroviral therapy (ART) initiation and to evaluate whether the established impact from late presentation to care and late initiation of ART on the risk of TB is retained beyond the observation period of clinical trials., Design: We used marginal structural models to emulate a clinical trial with up to 5 years of follow-up to evaluate the impact of late initiation on TB risk., Methods: People with HIV (PWH) were enrolled from 2007 to 2016 in observational cohorts from Uganda, Peru, Mexico and Italy. The risk of TB was compared in LP (accessing care with CD4 + cell count ≤350 cells/μl) vs. nonlate presentation using survival curves and a weighted Cox regression. We emulated two strategies: initiating ART with CD4 + cell count less than 350 cells/μl vs. CD4 + cell count at least 350 cells/μl (late initiation). We estimated TB attributable risk and population attributable fraction up to 5 years from the emulated date of randomization., Results: Twenty thousand one hundred and twelve patients and 1936 TB cases were recorded. Over 50% of TB cases were diagnosed at presentation for HIV care. More than 50% of the incident cases of TB after ART initiation were attributable to late presentation; nearly 70% of TB cases during the first year of follow-up could be attributed to late presentation and more than 50%, 5 years after first attending HIV care., Conclusion: Late presentation accounted for a large share of TB cases. Delaying ART initiation was detrimental for incident TB rates, and the impact of late presentation persisted up to 5 years from HIV care entry., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: CM reports grants and travel support from Gilead, personal fees from ViiV Healthcare, and participation on advisory boards from CORIMUNO, ViiV Healthcare, ROCHE, Janssen, Gilead Sciences, and Merck Sharp & Dohme. GG reports grants, personal fees, travel support, and participation on advisory boards from Gilead Sciences, ViiV Healthcare, and Merck Sharp & Dohme, and personal fees from Janssen. CO reports grants, personal fees, and travel sponsorship from ViiV Healthcare, and grants and personal fees from GlaxoSmithKline, Gilead Sciences, Merck Sharp & Dohme, Janssen, and AstraZeneca.

Background: The use of DTG-containing two-drug regimens is one of the most promising solutions to the need to ease the management of HIV treatment without harming its efficacy and safety. We report long- term results in patients switched, while virologically suppressed, to the combination of dolutegravir (DTG) plus lamivudine (3TC)., Methods: This is a prospective, clinical, uncontrolled cohort enrolling ART-experienced people living with HIV (PLWH) with HIV-RNA < 50 copies/ml for 6 months or longer, negative hepatitis B virus surface antigen, and without known M184V/I mutations. Kaplan-Meiers curves are used to describe persistency of virological suppression on therapy and a Cox regression model to evaluate baseline characteristics and the risk of stopping therapy., Results: 218 individuals switched their regimen since 2015. The mean estimated follow-up was of 64.3 months (95% CI 61.3-67.3) for approximately 1000 patient/years. After 5 years of follow-up, 77.1% were still on the DTG-3TC combination. No virologic failure was detected throughout the whole study period, and only 15 subjects presented single isolated viral blips above 50 copies/ml. Most patients stopped therapy because of reasons unrelated to study drugs (lost to follow-up; patients' decision; moved to other Centers), but due to the unselected nature of the casuistry; 11 subjects died in the 5 years of follow-up mostly because of pre-existing co-morbidities (6 neoplastic diseases and 2 end-stage liver disease). The median baseline CD4 count was 669 cells/mcl (IQR 483-927). After 5 years it raised to 899 cells/mcl (IQR 646-1160) (P < 0.001) without a significant change of CD8 counts that lowered from 767 cells/mcl (IQR 532-1034) to 683 cells/mcl (IQR 538-988). Consequently, the CD4/CD8 ratio varied from 0.93 (IQR 0.60-1.30) to 1.15 (IQR 0.77-1.45) (P < 0.0001). A non-significant (P = 0.320) increment of mean creatinine, 0.06 mg/dl in magnitude, was observed over the whole follow-up., Conclusion: These long-term results over 5 years reinforce the durability and good tolerability of DTG-3TC. Our results continue to support the recommended switch use of this 2DR as a well-accepted treatment option for ART-experienced PLWH., (© 2022. The Author(s).)

Objective: The primary objective was to explore weight and BMI changes in people with HIV (PWH) undergoing integrase strand transfer inhibitors (INSTI)-based regimens (vs. non-INSTI) in a large cohort and in the subsets of individuals without diabetes and insulin resistance (IR) at the time of switch to INSTI. The secondary objective was to identify risk factors for IR and cut-off of weight or BMI increase associated with IR in PWH switching to INSTI., Design: A longitudinal matched-cohort study including PWH attending Modena HIV Metabolic Clinic, Italy., Methods: PWH were divided into two groups: non-INSTI and INSTI-switch. The effect of switching to INSTI on weight and BMI change was tested through a linear mixed model. A mediation analysis explored the mediation effect of weight and BMI change in the association between the switch to INSTI and IR., Results: We analyzed 2437 PWH (1025 INSTI-switch, 1412 non-INSTI), in 54 826 weight assessments. Trends for weight increase were significantly higher in early-INSTI-switch (vs. early-non-INSTI), but no difference was observed in the late period after the switch. In the subset of 634 PWH without IR, switching to INSTI (vs. non-INSTI) was associated with a lower risk of IR (hazard ratio = 0.70, 95% confidence interval: 0.51, 0.98). A weight increase by 1% reduced the total protective effect of INSTI by 21.1% over 1 year of follow-up, which identifies a 5% weight increase as a clinically meaningful weight gain definition., Conclusion: A cut-off of 5% weight gain from the time of INSTI-switch is associated with IR, which may be a clinically meaningful endpoint that could be used in clinical and research settings., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: We evaluated virological response and resistance profiles in individuals who were virologically suppressed who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in real life., Methods: Survival analysis was used to assess probability of virological rebound (VR). Cumulative major resistance mutations (MRM) and cumulative genotypic susceptibility score (cGSS) were evaluated before the switch., Results: Overall, 283 individuals virologically suppressed for a median (interquartile [IQR]) time of 7 (3-9) y were analyzed. Of these, 20.8% were in first-line treatment, 13.1% were highly treatment-experienced (HTE), and 8.5% had experienced previous integrase inhibitor (INI)-failures. Before the switch, nucleotide reverse transcriptase inhibitor NRTI MRM prevalence was 29% (M184V:13.8%; any thymidine analogue mutation: 14.1%; K65R: 0.7%; K70E 0.4%); only three (2.1%) individuals showed INI major resistance mutations (Y143C/H/R [n = 1]; Y143C [n = 1]; N155H [n = 1]), and 82.0% of individuals received fully active B/F/TAF. Ninety-six wk after switch, the probability of VR was 5%, with only 12 events of VR at a median (IQR) viremia level of 284 (187-980) copies/mL, mainly transient. No significant associations between virological outcomes and genotypic susceptibility to B/F/TAF were observed. People who experienced previous INI failures showed a significantly higher adjusted hazard ratio (AHR [95% CI]) to experience VR under B/F/TAF (3.9 [1.1-13.4], P = 0.031). This AHR increased in people who experienced INI failures and received partially active B/F/TAF (5.5 [1.4-21.1], P = 0.013)., Conclusion: Within 96 wk, a switch to B/F/TAF in individuals who were virologically suppressed ensured a very high rate of virological control in a clinical setting. Previous resistance alone did not affect B/F/TAF response. However, people who had previous INI failures were more prone to losing virological control under B/F/TAF., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Several studies have identified main changes in T- and B-lymphocyte subsets during chronic HIV infection, but few data exist on how these subsets behave during the initial phase of HIV infection. We enrolled 22 HIV-infected patients during the acute stage of infection before the initiation of antiretroviral therapy (ART). Patients had blood samples drawn previous to ART initiation (T0), and at 2 (T1) and 12 (T2) months after ART initiation. We quantified cellular HIV-DNA content in sorted naïve and effector memory CD4 T cells and identified the main subsets of T- and B-lymphocytes using an 18-parameter flow cytometry panel. We identified correlations between the patients' clinical and immunological data using PCA. Effective HIV treatment reduces integrated HIV DNA in effector memory T cells after 12 months (T2) of ART. The main changes in CD4+ T cells occurred at T2, with a reduction of activated memory, cytolytic and activated/exhausted stem cell memory T (T SCM ) cells. Changes were present among CD8+ T cells since T1, with a reduction of several activated subsets, including activated/exhausted T SCM . At T2 a reduction of plasmablasts and exhausted B cells was also observed. A negative correlation was found between the total CD4+ T-cell count and IgM-negative plasmablasts. In patients initiating ART immediately following acute/early HIV infection, the fine analysis of T- and B-cell subsets has allowed us to identify and follow main modifications due to effective treatment, and to identify significant changes in CD4+ and CD8+ T memory stem cells.

Background: Although associations between older antiretroviral drug classes and cardiovascular disease in people living with HIV are well described, there is a paucity of data regarding a possible association with integrase strand-transfer inhibitors (INSTIs). We investigated whether exposure to INSTIs was associated with an increased incidence of cardiovascular disease., Methods: RESPOND is a prospective, multicentre, collaboration study between 17 pre-existing European and Australian cohorts and includes more than 32 000 adults living with HIV in clinical care after Jan 1, 2012. Individuals were eligible for inclusion in these analyses if they were older than 18 years, had CD4 cell counts and HIV viral load measurements in the 12 months before or within 3 months after baseline (latest of cohort enrolment or Jan 1, 2012), and had no exposure to INSTIs before baseline. These individuals were subsequently followed up to the earliest of the first cardiovascular disease event (ie, myocardial infarction, stroke, or invasive cardiovascular procedure), last follow-up, or Dec 31, 2019. We used multivariable negative binomial regression to assess associations between cardiovascular disease and INSTI exposure (0 months [no exposure] vs >0 to 6 months, >6 to 12 months, >12 to 24 months, >24 to 36 months, and >36 months), adjusted for cardiovascular risk factors. RESPOND is registered with ClinicalTrials.gov, NCT04090151, and is ongoing., Findings: 29 340 people living with HIV were included in these analyses, of whom 7478 (25·5%) were female, 21 818 (74·4%) were male, and 44 (<1%) were transgender, with a median age of 44·3 years (IQR 36·2-51·3) at baseline. As of Dec 31, 2019, 14 000 (47·7%) of 29 340 participants had been exposed to an INSTI. During a median follow-up of 6·16 years (IQR 3·87-7·52; 160 252 person-years), 748 (2·5%) individuals had a cardiovascular disease event (incidence rate of 4·67 events [95% CI 4·34-5·01] per 1000 person-years of follow-up). The crude cardiovascular disease incidence rate was 4·19 events (3·83-4·57) per 1000 person-years in those with no INSTI exposure, which increased to 8·46 events (6·58-10·71) per 1000 person-years in those with more than 0 months to 6 months of exposure, and gradually decreased with increasing length of exposure, until it decreased to similar levels of no exposure at more than 24 months of exposure (4·25 events [2·89-6·04] per 1000 person-years among those with >24 to 36 months of exposure). Compared with those with no INSTI exposure, the risk of cardiovascular disease was increased in the first 24 months of INSTI exposure and thereafter decreased to levels similar to those never exposed (>0 to 6 months of exposure: adjusted incidence rate ratio of 1·85 [1·44-2·39]; >6 to 12 months of exposure: 1·19 [0·84-1·68]; >12 to 24 months of exposure: 1·46 [1·13-1·88]; >24 to 36 months of exposure: 0·89 [0·62-1·29]; and >36 months of exposure: 0·96 [0·69-1·33]; p<0·0001)., Interpretation: Although the potential for unmeasured confounding and channelling bias cannot fully be excluded, INSTIs initiation was associated with an early onset, excess incidence of cardiovascular disease in the first 2 years of exposure, after accounting for known cardiovascular disease risk factors. These early findings call for analyses in other large studies, and the potential underlying mechanisms explored further., Funding: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands National Observational HIV cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort and The University of Cologne HIV Cohorts, ViiV Healthcare, and Gilead Sciences., Competing Interests: Declaration of interests JMM reports a personal 80:20 research grant from Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017–22, and consulting honoraria or research grants from AbbVie, Angelini, Contrafect, Genentech, Gilead Sciences, Jansen, Medtronic, MSD, Novartis, Pfizer, and ViiV Healthcare. CS reports payment or honoraria from Gilead for educational presentations. FW reports consulting fees from ViiV Healthcare. JJV reports grants or contracts from Merck, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), German Federal Ministry of Education and Research, Deutsches Zetrum für Luft- und Raumfahrt, University of Bristol, and Rigshospitalet Copenhagen; consulting fees from Pfizer, Gilead, and Shionogi; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or education events from Merck, Gilead, Pfizer, Astellas Pharma, Basilea, DZIF, University Hospital Freiburg/Congress and Communication, Academy for Infectious Medicine, University Manchester, German Society for Infectious Diseases (DGI), Ärztekammer Nordrhein, University Hospital Aachen, Back Bay Strategies, German Society for Internal Medicine (DGIM), Shionogi, Molecular Health, Netzwerk Universitätsmedizin, Janssen, and NordForsk. AS reports grants from Gilead Sciences (payment to institution) and GSK (payment to institution); and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or education events from Merck. ACar reports grants from ViiV Healthcare and MSD; consulting fees from Gilead Sciences, ViiV healthcare, and MSD; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or education events Gilead Sciences; and support for attending meetings or travel from Gilead Sciences, MSD. HG owns stock in GSK and is an employee of ViiV Healthcare. FR is an employee of and has stock options in Gilead Sciences. HG reports grants or contracts from Swiss National Science Foundation (payment made to institution), Yvonne Jacob Foundation (payment made to institution), Gilead Sciences (COVID-19 program; payment made to institution); and participation a Data Safety Monitoring Board or Advisory Board for Merck, Gilead Sciences, Janssen, ViiV Healthcare, and Novartis. LDR reports payment for conference fee, transport, and accommodation, and participation at meetings held by, Takeda, MSD, Gilead Sciences, and GSK. MvdV reports grants or contracts with ViiV Healthcare (payment made to institution) and Gilead Sciences (payment made to institution); consulting fees from Merck (payment made to institution), ViiV Healthcare (payment made to institution), and Gilead Sciences (payment made to institution); and being a board member for Amsterdam Dinner foundation (unpaid). AM reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or education events from ViiV Healthcare and Gilead Sciences; payment for expert testimonial from Eiland and Bonnin; and support for attending meetings and travel from ViiV Healthcare. AP-M reports honoraria for lectures, presentations, speakers bureaus, manuscript writing, or education events from Gilead Sciences. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Syphilis represents a major public health concern disproportionately affecting HIV positive patients and, in many cases, both infections are newly diagnosed at the same time. To date, limited studies are available on syphilis incidence in patients with a new HIV diagnosis., Methods: Patients newly diagnosed with HIV in 2010-2018 were included in the study and screening tests for syphilis were performed at baseline and at least once a year. Primary aims were to analyze the incidence rate of HIV-syphilis coinfection and syphilis reinfection. Secondary objective was to identify characteristics independently associated with coinfection and reinfection., Results: Of 500 newly diagnosed HIV patients, 20% presented a concomitant positive syphilis serology. Among them, 54 patients had a serology indicative for an active syphilis requiring therapy, while 46 had a history of prior treatments. The independent factors for syphilis acquisition were: MSM contact (OR=2.64; 95% CI: 1.48-4.72; P<0.001), male gender (OR=2.43; 95% CI: 1.08-5.48; P=0.032), and age (OR=1.03; 95% CI: 1.01-1.05; P=0.005 per year increasing). Presence of syphilis at the time of HIV diagnosis remained fairly stable during the study period (P for trend, P=0.689). We observed 52 syphilis reinfections related to 37 people. Patients with at least one reinfection were all males and 86.5% MSM., Conclusions: Males and MSM with HIV presented high rates of syphilis coinfection and reinfection suggesting persistent high-risk sexual behaviors and the need for appropriate intervention strategies in order to early detect and treat syphilis avoiding life-threatening complications and the spread of the infection in the community.

Background: Resilience is defined as an individual's positive adaptation to stressors. The COVID-19 pandemic represents a generalized stressor which may affect differently people living with HIV (PLWH). The objective of this study was to characterize resilience in PLWH with particular regarding the identification of frailty-resilience phenotypes, which may differently affect health-related quality of life (HR-QoL)., Methods: This was an observational study of PLWH attending Modena HIV Metabolic Clinic. Frailty was assessed in 2019, before the onset of the COVID-19 pandemic by using 37-Item frailty index ranging from 0 to 1. The frailty index score was categorized as fit (<0.25) or frail (>0.25). In January 2021, PLWH were offered to complete a set of electronic questionnaires including the CD-RISC-25 for resilience and EQ-5D5L and SF-36 for HR-QoL. Resilience was defined as CD-RISC-25 score >75.7 (ranging from 0 to 100)., Results: Of 800 PLWH reached by mail, 575 (72%) completed the questionnaires. The median age and HIV duration were 54.5 and 24.3 years, respectively. Impaired resilience was associated with loneliness [odds ratio (OR = 2.39; 1.20 to 4.76, P < 0.001)]. Predictors for EQ-5D5L <89.7% were the phenotypes "frail/nonresilient" [OR = 5.21, 95% confidence interval (CI): 2.62 to 10.33] and "fit/nonresilient" (OR = 5.48, 95% CI: 2.8 to 10.74). Predictors for SF-36 <64.40 were the phenotypes "frail/nonresilient" (OR = 7.43, 95% CI: 2.57 to 21.22) and "fit/nonresilient" (OR = 6.27, 95% CI: 2.17 to 18.16). Both models were corrected for age, sex, HIV duration, and nadir CD4., Conclusions: Resilience characterizes the well-being of PLWH during the COVID-19 crisis. This construct is complementary to frailty in the identification of clinical phenotypes with different impacts on HR-QoL., Competing Interests: G.G. and C.M. received research grant and speaker honorarium from Gilead, ViiV, MERCK, and Jansen. G.G. and C.M. attended advisory boards of Gilead, ViiV, and MERCK. The other authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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.

Background: The impact of drug resistance mutational load and APOBEC editing in heavily treatment-experienced (HTE) people living with multidrug-resistant HIV has not been investigated., Material and Methods: This study explored the HIV-DNA and HIV-RNA mutational load of drug resistance and APOBEC-related mutations through next-generation sequencing (NGS, Illumina MiSeq) in 20 failing HTE participants enrolled in the PRESTIGIO registry., Results: The patients showed high levels of both HIV-DNA (4.5 [4.0-5.2] log 10 copies/10 6 T-CD4+ cell) and HIV-RNA (4.5 [4.1-5.0] log 10 copies/mL) with complex resistance patterns in both compartments. Among the 255 drug-resistant mutations found, 66.3% were concordantly detected in both HIV-DNA and HIV-RNA; 71.3% of mutations were already present in historical Sanger genotypes. At an intra-patient frequency > 5%, a considerable proportion of mutations detected through DNA-NGS were found in historical genotypes but not through RNA-NGS, and few patients had APOBEC-related mutations. Of 14 patients who switched therapy, the five who failed treatment had DNA resistance with higher intra-patient frequency and higher DNA/RNA mutational load in a context of tendentially less pronounced APOBEC editing compared with those who responded., Conclusions: Using NGS in HIV-DNA and HIV-RNA together with APOBEC editing evaluation might help to identify HTE individuals with MDR who are more prone to experience virological failure., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Objectives: To evaluate HIV-1 tropism in 1382 combined antiretroviral therapy (cART)-experienced patients failing therapy to characterize those with exhausted therapeutic options., Methods: HIV-1 genotypic tropism was inferred through Geno2Pheno by estimating the false-positive-rate (FPR) values. Cumulative resistance and drug activity were evaluated by Stanford algorithm., Results: Overall, median (IQR) CD4 count (cells/mm3) nadir and at last genotypic resistance test (GRT) available were 98 (33-211) and 312 (155-517), respectively. Considering HIV-1 tropism, 30.5% had X4/dual-mixed strains (FPR ≤5%: 22.2%; FPR 5%-10%: 8.3%). By stratifying according to tropism, by decreasing FPR, a significant decrease of CD4 nadir and at last GRT was observed. The proportion of individuals with CD4 count <200 cells/mm3, who were perinatally infected and with a long treatment history significantly increased as FPR levels decreased. Regarding resistance, 933 (67.5%) individuals accumulated at least one class resistance, with 52.7%, 48.2%, 23.5% and 13.2% of individuals showing resistance to NRTIs, NNRTIs, PIs and INIs; while 23.2%, 27.2%, 14.3% and 2.8% harboured resistance to 1, 2, 3 and 4 classes, respectively. Individuals with FPR ≤5% showed a significantly higher level of resistance to PIs, NRTIs and INIs compared with others. The proportion of individuals harbouring strains susceptible to ≤2 active drugs was only about 2%; nonetheless, this proportion doubled (4.6%) in patients infected with FPR ≤5%., Conclusions: Our findings showed that a small proportion of cART failing individuals have limited therapeutic options. However, tropism determination might help to identify people who have accumulated a high level of resistance and have a greater risk of advanced disease., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Weight gain effects of individual antiretroviral drugs are not fully understood. We investigated associations between a prespecified clinically significant increase (>7%) in body-mass index (BMI) and contemporary antiretroviral use., Methods: The International Cohort Consortium of Infectious Diseases (RESPOND) is a prospective, multicohort collaboration, including data from 17 well established cohorts and over 29 000 people living with HIV. People with HIV under prospective follow-up from Jan 1, 2012, and older than 18 years were eligible for inclusion. Each cohort contributed a predefined minimum number of participants related to the size of the specific cohort (with a minimum of 1000 participants). Participants were required to have CD4 cell counts and HIV viral load measurement in the 12 months before or within 3 months after baseline. For all antiretroviral drugs received at or after RESPOND entry, changes from pre-antiretroviral BMI levels (baseline) were considered at each BMI measurement during antiretroviral treatment. We used logistic regression to identify individual antiretrovirals that were associated with first occurrence of a more than 7% increase in BMI from pre-antiretroviral BMI. We adjusted analyses for time on antiretrovirals, pre-antiretroviral BMI, demographics, geographical region, CD4 cell count, viral load, smoking status, and AIDS at baseline., Results: 14 703 people were included in this study, of whom 7863 (53·5%) had a more than 7% increase in BMI. Compared with lamivudine, use of dolutegravir (odds ratio [OR] 1·27, 95% CI 1·17-1·38), raltegravir (1·37, 1·20-1·56), and tenofovir alafenamide (1·38, 1·22-1·35) was significantly associated with a more than 7% BMI increase, as was low pre-antiretroviral BMI (2·10, 1·91-2·31 for underweight vs healthy weight) and Black ethnicity (1·61, 1·47-1·76 vs White ethnicity). Higher CD4 count was associated with a reduced risk of BMI increase (0·97, 0·96-0·98 per 100 cells per μL increase). Relative to lamivudine, dolutegravir without tenofovir alafenamide (OR 1·21, 95% CI 1·19-1·32) and tenofovir alafenamide without dolutegravir (1·33, 1·15-1·53) remained independently associated with a more than 7% increase in BMI; the associations were higher when dolutegravir and tenofovir alafenamide were used concomitantly (1·79, 1·52-2·11, and 1·70, 1·44-2·01, respectively)., Interpretation: Clinicians and people with HIV should be aware of associations between weight gain and use of dolutegravir, tenofovir alafenamide, and raltegravir, particularly given the potential consequences of weight gain, such as insulin resistance, dyslipidaemia, and hypertension., Funding: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort and The University of Cologne HIV Cohorts, ViiV Healthcare, and Gilead Sciences., Competing Interests: Declaration of interests JMM received a personal 80:20 research grant from Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017–21. JMM also reports grants and personal fees from AbbVie, Angelini, Contrafect, Cubist, Genentech, Gilead Sciences, Jansen, Lysovant, Medtronic, MSD, Novartis, Pfizer, and ViiV Healthcare, outside the submitted work. DLB reports honoraria from ViiV Healthcare, Gilead Sciences, and Merck, outside the submitted work. OK reports personal fees from Gilead Sciences, ViiV Healthcare, and Merck, outside the submitted work. ML reports grants from Gilead Sciences, Janssen-Cilag, and ViiV Healthcare, outside the submitted work. JH reports reimbursement to their institute from Gilead Sciences, ViiV Healthcare, and MSD, outside the submitted work. HFG reports grants from the Swiss National Science Foundation, National Institutes of Health (NIH), and the Swiss HIV Cohort Study, unrestricted research grants from Gilead Sciences, Roche, and Yvonne Jacob Foundation, personal fees from consulting or advisory boards or data safety monitoring boards for Merck, Gilead Sciences, ViiV Healthcare, Mepha, and Sandoz. HFG's institution received money for participation in the following clinical COVID-19 studies: 540-7773/5774 (Gilead), TICO (ACTIV-3, INSIGHT/NIH), and the Morningsky study (Roche). CSt reports personal fees and non-financial support from Gilead Sciences, ViiV Healthcare, and Janssen, outside the submitted work. VV is a salaried employee of ViiV Healthcare and receives GlaxoSmithKline stock. CD reports grants and personal fees from MSD, Gilead Sciences, and ViiV Healthcare, outside the submitted work. SDW reports grants from Gilead Sciences, MSD, Janssen, and ViiV Healthcare, outside the submitted work. FW reports membership of advisory boards for ViiV Healthcare and Gilead Sciences. JL reports personal fees from ViiV Healthcare, Gilead Sciences, and Janssen Cilag, outside the submitted work. CSm reports personal fees from Gilead Sciences, outside the submitted work. AdM reports grants from Gilead Sciences and ViiV Healthcare, during the conduct of the study, and personal fees from ViiV Healthcare, Gilead Sciences, Eiland, and Bonnin, outside the submitted work. NC reports personal fees from Virology Education, outside the submitted work. CO reports personal fees from ViiV Healthcare, Neola, and MSD, outside the submitted work. CO is also an elected member of the European AIDS Society governing body and of the EuroSIDA Steering Committee. JJV reports personal fees from MSD, Gilead Sciences, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research, University Hospital Freiburg, Congress and Communication, Academy for Infectious Medicine, University of Manchester, German Society for Infectious Diseases, Arztekammer Nordrhein, University Hospital Aachen, Back Bay Strategies, German Society for Internal Medicine, Shionogi, Molecular Health, Netzwerk Universitätsmedizin, Janssen, and NordForsk, and grants from MSD, Gilead Sciences, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research, German Federal Ministry of Education and Research, University of Bristol, and Rigshospitalet Copenhagen. JG is a paid employee of Gilead Sciences. ND reports he is a board member of non-governmental associations and initiatives (not for profit) that receive financial support from pharmaceutical companies and foundations for various projects. Those that have contributed are: GlaxoSmithKline, ViiV Healthcare, AbbVie, BMS, Gilead, Janssen-Cilag, MSD, AIDS Healthcare Foundation, Positive Action, Novartis, Roche, Mylam ELPEN, Cepheid, IPSEN, AstraZeneca, Amgen, Bayer, Pamaserve-Lilly, Roche Diagnostics, Sanofi, Pfizer, Theratechnologies, Vianex, Boehringer-Ingelheim, Chiesi, Takeda, and Leo Pharma. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Results from clinical trials and observational studies suggest that dolutegravir plus lamivudine could be an effective and well-tolerated option for simplification in HIV-1-positive patients. We aimed to assess long-time efficacy and safety in our multicenter cohort., Methods: This was a retrospective study enrolling HIV-1-infected, virologically suppressed patients switching to dolutegravir + lamivudine. We performed survival analysis to evaluate time to virological failure (VF, defined by a single HIV-RNA ≥1000 copies/mL or by 2 consecutive HIV-RNA ≥ 50 copies/mL) and treatment discontinuation (defined as the interruption of either 3TC or dolutegravir), assessing predictors via Cox regression analyses., Results: Seven-hundred eighty-five patients were considered for the analysis: 554 were men (70.6%), with a median age of 52 years (interquartile range 45-58 years). Estimated probabilities of maintaining virological suppression at weeks 96, 144, and 240 were 97.7% (SD ±0.6), 96.9% (SD ±0.8), and 96.4% (SD ±0.9), respectively. A non-B HIV subtype (P = 0.014) and a previous VF (P = 0.037) resulted predictors of VF. We did not observe differences in probability of VF in people living with HIV with an M184V resistance mutation (P = 0.689); however, in a deeper analysis, M184V mutation was a predictor of VF (P = 0.038) in patients with time of virological suppression <88 months. Estimated probabilities of remaining on study regimen at 96, 144, and 240 weeks were 82.9% (SD ±1.4), 79.7% (SD ±1.6) and 74.3% (SD ±2.2), respectively., Conclusions: Our findings show the long-term efficacy and tolerability of dolutegravir plus lamivudine in virologically suppressed patients., Competing Interests: A. Ciccullo received travel grants from ViiV Healthcare. A.G. reports grants and/or personal fees from BMS, Gliead, Janssen, MSD and ViiV Healthcare. A. Capetti has received a personal grant from AB, Gilead, and ViiV. G.S. has received funds for speaking by Gilead, Merck, Janssen, AbbVie, and ViiV. C.M. has participated in advisory boards and received study grants and/or speaker honoraria from AbbVie, Gilead, ViiV, Janssen, Angelini, BMS, and MSD. S.R. received research grants to his institution from ViiV Heathcare, Gilead Sciences, and Janssen, outside the submitted work; he was also a paid consultant for ViiV Heathcare, Gilead Sciences, Merck Sharp & Dohme, Bristol-Myers Squibb, and Janssen. S.D.G. was a paid consultant or member of advisory boards for Gilead, ViiV Healthcare, Janssen-Cilag, Merck Sharp & Dohme, and Bristol-Myers Squibb. The remainig authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: The occurrence of COVID-19 pandemic had a significant negative effect on health care systems over the last year. Health care providers were forced to focus mainly on COVID-19 patients, neglecting in many cases equally important diseases, both acute and chronic. Therefore, also screening and diagnostic strategies for HIV could have been significantly impaired.This retrospective, multicenter, observational study aimed at assessing the number and characteristics of new HIV/AIDS diagnoses during COVID-19 pandemic in Italy and compared characteristics of people living with HIV at diagnosis between pre- and post-COVID-19 era (2019 vs 2020).Our results showed a significant reduction of HIV diagnoses during pandemic. By contrast, people living with HIV during pandemic were older and were diagnosed in earlier stage of disease (considering CD4+ T cell count) compared to those who were diagnosed the year before. Moreover, there was a significant decrease of new HIV diagnoses among men who have sex with men, probably for the impact of social distancing and restriction applied by the Italian Government. Late presentation incidence, if numbers in 2020 were lower than those in 2019, is still an issue.Routinely performing HIV testing in patients with suspected SARS-CoV-2 infection is identifying and linking to care underdiagnosed people living with HIV earlier. Thus, combined tests (HIV and SARS-CoV-2) should be implemented in patients with SARS-CoV-2 symptoms overlapping HIV's ones. Lastly, our results lastly showed how urgent implementation of a national policy for HIV screening is necessary., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Limited data exist that compare clinical outcomes of 2-drug regimens (2DRs) and 3-drug regimens (3DRs) in people living with human immunodeficiency virus., Methods: Antiretroviral treatment-experienced individuals in the International Cohort Consortium of Infectious Diseases (RESPOND) who switched to a new 2DR or 3DR from 1 January 2012-1 October 2018 were included. The incidence of clinical events (AIDS, non-AIDS cancer, cardiovascular disease, end-stage liver and renal disease, death) was compared between regimens using Poisson regression., Results: Of 9791 individuals included, 1088 (11.1%) started 2DRs and 8703 (88.9%) started 3DRs. The most common 2DRs were dolutegravir plus lamivudine (22.8%) and raltegravir plus boosted darunavir (19.8%); the most common 3DR was dolutegravir plus 2 nucleoside reverse transcriptase inhibitors (46.9%). Individuals on 2DRs were older (median, 52.6 years [interquartile range, 46.7-59.0] vs 47.7 [39.7-54.3]), and a higher proportion had ≥1 comorbidity (81.6% vs 73.9%). There were 619 events during 27 159 person-years of follow-up (PYFU): 540 (incidence rate [IR] 22.5/1000 PYFU; 95% confidence interval [CI]: 20.7-24.5) on 3DRs and 79 (30.9/1000 PYFU; 95% CI: 24.8-38.5) on 2DRs. The most common events were death (7.5/1000 PYFU; 95% CI: 6.5-8.6) and non-AIDS cancer (5.8/1000 PYFU; 95% CI: 4.9-6.8). After adjustment for baseline demographic and clinical characteristics, there was a similar incidence of events on both regimen types (2DRs vs 3DRs IR ratio, 0.92; 95% CI: .72-1.19; P = .53)., Conclusions: This is the first large, international cohort to assess clinical outcomes on 2DRs. After accounting for baseline characteristics, there was a similar incidence of events on 2DRs and 3DRs. 2DRs appear to be a viable treatment option with regard to clinical outcomes. Further research on resistance barriers and long-term durability of 2DRs is needed., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: Comparisons between rilpivirine (RPV) and integrase strand transfer inhibitors (INSTIs) in antiretroviral therapy (ART)-naïve HIV-infected individuals are currently lacking. This study aimed to compare, in an observational cohort setting, the durability of treatment with RPV-based and INSTI-based first-line regimens., Methods: Patients who started first-line ARTs based on RPV or INSTIs, with HIV-RNA < 100 000 copies/mL and CD4 cell count > 200 cells/μL were included. The primary endpoint was the cumulative probability of treatment failure (TF = virological failure [confirmed HIV-RNA > 50 copies/mL] or discontinuation of the anchor drug in the regimen), as assessed by the Kaplan-Meier method. A multivariable Cox regression was used to control for potential confounding., Results: Of the 1991 included patients, 986 started ART with an RPV-based regimen and 1005 with an INSTIs-based regimen. The median (IQR) follow-up was 20 (10, 35) months. The cumulative 2-year probability of TF with RPV (9.1% [95% 7.2, 11.1]) was lower than that observed in the INSTIs group (16.6% [13.8, 19.4], P = 0.0002) but not when compared with dolutegravir (DTG) alone. Starting ART with an INSTIs-based regimen vs. RPV was associated with a higher risk of TF after controlling for potential confounding factors (adjusted hazard ratio, AHR [95% CI]: 1.64 [1.28, 2.10]; P < 0.001). The results were similar when restricting the analysis to single-tablet regimens, although the probability of virological success was higher for INSTIs and DTG., Conclusions: In ART-naïve patients with low viral loads and high CD4 counts, the risk of treatment failure was lower in those who started RPV-based vs. INSTIs-based regimens other than DTG-based ones., (Copyright © 2021 Elsevier Ltd. All rights reserved.)