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Objectives: Treatment guidelines recommend single‐tablet regimens for patients with HIV infection starting antiretroviral therapy. These regimens might be as effective and cost less if taken as separate drugs. We assessed whether the one pill once a day combination of efavirenz, emtricitabine and tenofovir reduces the risk of disease progression compared with multiple‐pill formulations of the same regimen. Methods: We selected treatment‐naïve patients starting one‐, two‐ or three‐pill formulations of this regimen in data from the Antiretroviral Therapy Cohort Collaboration. These patients were followed until an AIDS event or death or until they modified their regimen. We analysed these data using Cox regression models, then used our models to predict the potential consequences of exposing a future population to either a one‐pill regimen or a three‐pill regimen. Results: Among 11 739 treatment‐naïve patients starting the regimen, there were 386 AIDS events and 87 deaths. Follow‐up often ended when patients switched to the same regimen with fewer pills. After the first month, two pills rather than one was associated with an increase in the risk of AIDS or death [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.01‐1.91], but three pills rather than two did not appreciably add to that increase (HR 1.19; 95% CI 0.84‐1.68). We estimate that 77 patients would need to be exposed to a one‐pill regimen rather than a three‐pill regimen for 1 year to avoid one additional AIDS event or death. Conclusions: This particular single‐tablet regimen is associated with a modest decrease in the risk of AIDS or death relative to multiple‐pill formulations. [ABSTRACT FROM AUTHOR]

Objective: Interruptions in care of people with HIV (PWH) on antiretroviral therapy (ART) are associated with adverse outcomes, but most studies have relied on composite outcomes. We investigated whether mortality risk following care interruptions differed from mortality risk after first starting ART., Design: Collaboration of 18 European and North American HIV observational cohort studies of adults with HIV starting ART between 2004 and 2019., Methods: Care interruptions were defined as gaps in contact of ≥365 days, with a subsequent return to care (distinct from loss to follow-up), or ≥270 days and ≥545 days in sensitivity analyses. Follow-up time was allocated to no/preinterruption or postinterruption follow-up groups. We used Cox regression to compare hazards of mortality between care interruption groups, adjusting for time-updated demographic and clinical characteristics and biomarkers upon ART initiation or re-initiation of care., Results: Of 89 197 PWH, 83.4% were male and median age at ART start was 39 years [interquartile range (IQR): 31-48)]. 8654 PWH (9.7%) had ≥1 care interruption; 10 913 episodes of follow-up following a care interruption were included. There were 6104 deaths in 536 334 person-years, a crude mortality rate of 11.4 [95% confidence interval (CI): 11.1-11.7] per 1000 person-years. The adjusted mortality hazard ratio (HR) for the postinterruption group was 1.72 (95% CI: 1.57-1.88) compared with the no/preinterruption group. Results were robust to sensitivity analyses assuming ≥270-day (HR 1.49, 95% CI: 1.40-1.60) and ≥545-day (HR 1.67, 95% CI: 1.48-1.88) interruptions., Conclusions: Mortality was higher among PWH reinitiating care following an interruption, compared with when PWH initially start ART, indicating the importance of uninterrupted care., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Mortality rates among people with HIV have fallen since 1996 following the widespread availability of effective antiretroviral therapy (ART). Patterns of cause-specific mortality are evolving as the population with HIV ages. We aimed to investigate longitudinal trends in cause-specific mortality among people with HIV starting ART in Europe and North America., Methods: In this collaborative observational cohort study, we used data from 17 European and North American HIV cohorts contributing data to the Antiretroviral Therapy Cohort Collaboration. We included data for people with HIV who started ART between 1996 and 2020 at the age of 16 years or older. Causes of death were classified into a single cause by both a clinician and an algorithm if International Classification of Diseases, Ninth Revision or Tenth Revision data were available, or independently by two clinicians. Disagreements were resolved through panel discussion. We used Poisson models to compare cause-specific mortality rates during the calendar periods 1996-99, 2000-03, 2004-07, 2008-11, 2012-15, and 2016-20, adjusted for time-updated age, CD4 count, and whether the individual was ART-naive at the start of each period., Findings: Among 189 301 people with HIV included in this study, 16 832 (8·9%) deaths were recorded during 1 519 200 person-years of follow-up. 13 180 (78·3%) deaths were classified by cause: the most common causes were AIDS (4203 deaths; 25·0%), non-AIDS non-hepatitis malignancy (2311; 13·7%), and cardiovascular or heart-related (1403; 8·3%) mortality. The proportion of deaths due to AIDS declined from 49% during 1996-99 to 16% during 2016-20. Rates of all-cause mortality per 1000 person-years decreased from 16·8 deaths (95% CI 15·4-18·4) during 1996-99 to 7·9 deaths (7·6-8·2) during 2016-20. Rates of all-cause mortality declined with time: the average adjusted mortality rate ratio per calendar period was 0·85 (95% CI 0·84-0·86). Rates of cause-specific mortality also declined: the most pronounced reduction was for AIDS-related mortality (0·81; 0·79-0·83). There were also reductions in rates of cardiovascular-related (0·83, 0·79-0·87), liver-related (0·88, 0·84-0·93), non-AIDS infection-related (0·91, 0·86-0·96), non-AIDS-non-hepatocellular carcinoma malignancy-related (0·94, 0·90-0·97), and suicide or accident-related mortality (0·89, 0·82-0·95). Mortality rates among people who acquired HIV through injecting drug use increased in women (1·07, 1·00-1·14) and decreased slightly in men (0·96, 0·93-0·99)., Interpretation: Reductions of most major causes of death, particularly AIDS-related deaths among people with HIV on ART, were not seen for all subgroups. Interventions targeted at high-risk groups, substance use, and comorbidities might further increase life expectancy in people with HIV towards that in the general population., Funding: US National Institute on Alcohol Abuse and Alcoholism., Competing Interests: Declaration of interests AI has received financial compensation for lectures, educational activities, consultancy work, as well as funds for research, from Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme, and ViiV Healthcare. VP has received honoraria from ad-hoc membership of national HIV advisory boards, Merck, Gilead, and ViiV. PR, through his institution, has received scientific grant support for investigator-initiated studies from Gilead Sciences, Janssen Pharmaceuticals, Merck & Co, and ViiV Healthcare, and has served on scientific advisory boards for Gilead Sciences, ViiV Healthcare, and Merck & Co, honoraria for which were all paid to his institution. JB reports honoraria for advice or public speaking from Gilead, GlaxoSmithKline, Janssen, MSD, and ViiV Healthcare; and grants from Gilead, MSD, and ViiV Healthcare. MJG has received honoraria from ad-hoc membership of national HIV advisory boards, Merck, Gilead, and ViiV. HC has received research grant funding from ViiV Healthcare, National Institutes of Health (NIH), and Agency for Healthcare Research and Quality paid to their institution and sits on the NIH Office of AIDS Research Advisory Council. CW reports honoraria for advice or public speaking from Abbott, Gilead, Janssen, MSD, Pfizer, and ViiV Healthcare. KK, TRS, SMI, SG, SA, RT, RZ, MH, MJS, JACS, AT, JLG, KMcG, and Ad'AM declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Mortality rates for people living with HIV (PLHIV) on antiretroviral therapy (ART) in high-income countries continue to decline. We compared mortality rates among PLHIV on ART in Europe for 2016-2020 with Spectrum's estimates., Methods: The AIDS Impact Module in Spectrum is a compartmental HIV epidemic model coupled with a demographic population projection model. We used national Spectrum projections developed for the 2022 HIV estimates round to calculate mortality rates among PLHIV on ART, adjusting to the age/country distribution of PLHIV starting ART from 1996 to 2020 in the Antiretroviral Therapy Cohort Collaboration (ART-CC)'s European cohorts., Results: In the ART-CC, 11,504 of 162,835 PLHIV died. Between 1996-1999 and 2016-2020, AIDS-related mortality in the ART-CC decreased from 8.8 (95% CI: 7.6 to 10.1) to 1.0 (0.9-1.2) and from 5.9 (4.4-8.1) to 1.1 (0.9-1.4) deaths per 1000 person-years among men and women, respectively. Non-AIDS-related mortality decreased from 9.1 (7.9-10.5) to 6.1 (5.8-6.5) and from 7.0 (5.2-9.3) to 4.8 (4.3-5.2) deaths per 1000 person-years among men and women, respectively. Adjusted all-cause mortality rates in Spectrum among men were near ART-CC estimates for 2016-2020 (Spectrum: 7.02-7.47 deaths per 1000 person-years) but approximately 20% lower in women (Spectrum: 4.66-4.70). Adjusted excess mortality rates in Spectrum were 2.5-fold higher in women and 3.1-3.4-fold higher in men in comparison to the ART-CC's AIDS-specific mortality rates., Discussion: Spectrum's all-cause mortality estimates among PLHIV are consistent with age/country-controlled mortality observed in ART-CC, with some underestimation of mortality among women. Comparing results suggest that 60%-70% of excess deaths among PLHIV on ART in Spectrum are from non-AIDS causes., Competing Interests: R.G.'s institution has received grants from UNAIDS and the Bill and Melinda Gates Foundation. N.P. has received grants unrelated to this study and paid to his institution from Gilead Sciences Hellas and ECDC. R.Z. has not received honoraria in the past 3 years. J.V. has personal fees from Merck/MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (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, and German Society for Internal Medicine (DGIM) and grants from Merck/MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), German Federal Ministry of Education and Research (BMBF), (PJ-T: DLR), University of Bristol, and Rigshospitalet Copenhagen. M.C.'s institution received research grants and expert opinion fees from Gilead, MSD, and Viiv. R.T. has received grant funding from Gilead, Janssen, and ViiV unrelated to this work. J.W.E. reports personal fees from Oxford Policy Management. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Among persons with HIV (PWH), higher alcohol use and having hepatitis C virus (HCV) are separately associated with increased morbidity and mortality. We investigated whether the association between alcohol use and mortality among PWH is modified by HCV. Data were combined from European and North American cohorts of adult PWH who started antiretroviral therapy (ART). Self-reported alcohol use data, collected in diverse ways between cohorts, were converted to grams/day. Eligible PWH started ART during 2001-2017 and were followed from ART initiation for mortality. Interactions between the associations of baseline alcohol use (0, 0.1-20.0, >20.0 g/day) and HCV status were assessed using multivariable Cox models. Of 58,769 PWH, 29,711 (51%), 23,974 (41%) and 5084 (9%) self-reported alcohol use of 0 g/day, 0.1-20.0 g/day, and > 20.0 g/day, respectively, and 4799 (8%) had HCV at baseline. There were 844 deaths in 37,729 person-years and 2755 deaths in 443,121 person-years among those with and without HCV, respectively. Among PWH without HCV, adjusted hazard ratios (aHRs) for mortality were 1.18 (95% CI: 1.08-1.29) for 0.0 g/day and 1.84 (1.62-2.09) for >20.0 g/day compared with 0.1-20.0 g/day. This J-shaped pattern was absent among those with HCV: aHRs were 1.00 (0.86-1.17) for 0.0 g/day and 1.64 (1.33-2.02) for >20.0 g/day compared with 0.1-20.0 g/day (interaction p < .001). Among PWH without HCV, mortality was higher in both non-drinkers and heavy drinkers compared with moderate alcohol drinkers. Among those with HCV, mortality was higher in heavy drinkers but not non-drinkers, potentially due to differing reasons for not drinking (e.g. illness) between those with and without HCV., (© 2023 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

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.)

Background: The life expectancy of people with HIV taking antiretroviral therapy (ART) has increased substantially over the past 25 years. Most previous studies of life expectancy were based on data from the first few years after starting ART, when mortality is highest. However, many people with HIV have been successfully treated with ART for many years, and up-to-date prognosis data are needed. We aimed to estimate life expectancy in adults with HIV on ART for at least 1 year in Europe and North America from 2015 onwards., Methods: We used data for people with HIV taking ART from the Antiretroviral Therapy Cohort Collaboration and the UK Collaborative HIV Cohort Study. Included participants started ART between 1996 and 2014 and had been on ART for at least 1 year by 2015, or started ART between 2015 and 2019 and survived for at least 1 year; all participants were aged at least 16 years at ART initiation. We used Poisson models to estimate the associations between mortality and demographic and clinical characteristics, including CD4 cell count at the start of follow-up. We also estimated the remaining years of life left for people with HIV aged 40 years who were taking ART, and stratified these estimates by variables associated with mortality. These estimates were compared with estimates for years of life remaining in a corresponding multi-country general population., Findings: Among 206 891 people with HIV included, 5780 deaths were recorded since 2015. We estimated that women with HIV at age 40 years had 35·8 years (95% CI 35·2-36·4) of life left if they started ART before 2015, and 39·0 years (38·5-39·5) left if they started ART after 2015. For men with HIV, the corresponding estimates were 34·5 years (33·8-35·2) and 37·0 (36·5-37·6). Women with CD4 counts of fewer than 49 cells per μL at the start of follow-up had an estimated 19·4 years (18·2-20·5) of life left at age 40 years if they started ART before 2015 and 24·9 years (23·9-25·9) left if they started ART after 2015. The corresponding estimates for men were 18·2 years (17·1-19·4) and 23·7 years (22·7-24·8). Women with CD4 counts of at least 500 cells per μL at the start of follow-up had an estimated 40·2 years (39·7-40·6) of life left at age 40 years if they started ART before 2015 and 42·0 years (41·7-42·3) left if they started ART after 2015. The corresponding estimates for men were 38·0 years (37·5-38·5) and 39·2 years (38·7-39·7)., Interpretation: For people with HIV on ART and with high CD4 cell counts who survived to 2015 or started ART after 2015, life expectancy was only a few years lower than that in the general population, irrespective of when ART was started. However, for people with low CD4 counts at the start of follow-up, life-expectancy estimates were substantially lower, emphasising the continuing importance of early diagnosis and sustained treatment of HIV., Funding: US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council., Competing Interests: Declaration of interests CAS has received honoraria from Gilead, ViiV Healthcare, and Janssen-Cilag for participation on data safety and monitoring boards and advisory boards and for preparation of educational materials, and is the Vice Chair of the British HIV Association. GB has received consulting fees from MedIQ and payments and honoraria from the University of Kentucky and StateServ. GB's institution has received funding from Merck, Eli Lilly, Kaiser Permanente, and Amgen. HC has received research funding from ViiV, the US National Institutes of Health (NIH), and the US Agency for Healthcare Research and Quality, all paid to their institution, and sits on the NIH Office of AIDS Research Advisory Council. ME chairs the National Research Council of the Swiss National Science Foundation, which supports the Swiss HIV Cohort Study that contributed data to this analysis. MJG has received honoraria for membership of national HIV advisory boards and from Merck, Gilead, and ViiV. IJ has received teaching fees from ViiV, fees for evaluating scientific projects and participating in expert panels from Gilead, and fees for statistical analyses from Grupo de Estudio del SIDA. NO's institution has received funding from the Preben og Anne Simonsens Fond. CS has received honoraria from Gilead, ViiV Healthcare, and Janssen-Cilag for participation on scientific advisory boards and for delivering educational lectures. RT has received research funding from Gilead. GT has received research funding from Gilead, the EU, University College London, Novo Nordisk, and the Greek Government, all paid to her institution. FW has received consulting fees from ViiV Healthcare. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Standard therapy for HIV treatment has consisted of two nucleoside analogue reverse transcriptase inhibitors (NRTI) paired with a third agent. Use of two-drug regimens (2DR) has been considered for selected patients in part to avoid toxicities associated with the use of NRTIs. This study aimed to compare the real-world outcomes of integrase inhibitor (INSTI)-based three-drug regimens (3DR) versus 2DR of dolutegravir (DTG) + rilpivirine (RPV) or DTG + lamivudine (3TC)., Methods: All patients in the Spanish VACH cohort switching to INSTI-based 3DR or a 2DR consisting of DTG + RPV or DTG + 3TC between May 2, 2016 and May 15, 2019 were included. Kaplan-Meier curves and Cox proportional hazard models were used to assess time to/risk of discontinuation due to treatment failure (TF) (defined as virologic failure [VF], immunologic failure, or disease progression) and adverse events (AEs). Three secondary analyses were performed: (1) in restricting the analysis to patients who were virologically suppressed (HIV RNA < 50 copies/mL) at switch; (2) matched analysis (2:1, matched by age, sex, number of previous VFs, and line of regimen), and (3) using VF as the primary endpoint in all patients., Results: Overall, 5047 3DR and 617 2DR patients were analyzed. Baseline characteristics differed between groups; 2DR patients were older, more treatment experienced, and more likely to be virologically suppressed at switch. Time to discontinuation due to TF was significantly shorter for 2DR (P = 0.002). The hazard ratio (HR) for discontinuation due to TF on 2DR vs 3DR was 2.33 (P = 0.003). No difference was observed for time to discontinuation (P = 0.908) or risk of discontinuation due to AEs (HR = 0.80; P = 0.488). Results were qualitatively similar in virologically suppressed patients, matched analysis, and for VF., Conclusion: In the real world, the risks of discontinuation due to TF and VF were more than two times higher in patients switching to DTG-based 2DR than INSTI-based 3DR, with no difference in discontinuation due to AEs., (© 2022. The Author(s).)

Background: Legionella is a well known but infrequent cause of bacterial endocarditis., Methods: We report a case of endocarditis caused by Legionella spp. We reviewed previously reported cases in PubMed, Google Scholar and in references included in previous reports, and summarized relevant clinical data., Results: A 63-year-old man with a history of aortic valve replacement developed persistent fever and monoarthritis. Transesophageal echocardiography showed perivalvular abscess. He died during surgery. Blood and valve cultures were negative. Legionella spp. was demonstrated with 16S-rRNA PCR from the resected material. Twenty cases of Legionella endocarditis have been reported. Harboring a prosthetic valve was the main risk factor. Prognosis was favorable, both for patients treated with or without surgical valve replacement. Overall mortality was <10%., Conclusions: Legionella is an infrequent cause of endocarditis. It frequently requires surgical treatment. Prognosis is good. Molecular techniques are likely to become the gold standard for diagnosis., (Copyright © 2020 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

People living with HIV (PLWH) have an increased risk of cardiovascular (CV) disease, likely due to a higher prevalence of CV risk factors. We compared the age-standardized prevalence and management of CV risk factors in PLWH to that of the general population in Spain. Blood pressure, lipid, glucose, and anthropometric profiles were cross-sectionally compared along with the treatment of hypertension, dyslipidemia, and diabetes in a general population cohort and a PLWH cohort. Prevalence rates were standardized by the direct method by 10-year age groups in European standard populations and stratified by gender. We included 47,593 individuals aged 35 to 74 years, 28,360 from the general population cohort and 19,233 from the PLWH cohort. Compared to the general population, PLWH had a higher concentration of triglycerides (>35 mg/dL in women and >26 mg/dL in men) and a higher prevalence of smoking (>23% and >17%) and diabetes (>9.9% and >8.5%). The prevalence of treated diabetes, hypertension, and dyslipidemia were up to three-fold lower in both women and men living with HIV. There was a significant difference in PLWH compared to the general population in the lipid, glucose, and anthropometric profile. In addition, PLWH were less often treated for diagnosed diabetes, hypertension, and dyslipidemia.

Background: Evidence from clinical practice on the effects of switching from emtricitabine/tenofovir disoproxil fumarate (F/TDF) to emtricitabine/tenofovir alafenamide (F/TAF)-based triple-therapy (TT) regimens on renal parameters is limited. Objective: This retrospective analysis evaluated the effects on renal function of switching from F/TDF to F/TAF-based TT regimens with no change in third agent among people living with HIV (PLWH). Methods: Data were from a multicenter Spanish PLWH cohort. Patients with a baseline estimated glomerular filtration rate (eGFR-EPI) measurement, ≥1 follow-up measurement, ≥30 days treatment with F/TAF, and who switched from F/TDF to F/TAF with no change in third agent were included. Multivariate mixed linear models were used to evaluate change from baseline over time in eGFR-EPI. eGFR-EPI changes before and after switch were analyzed in a matched patient subgroup. Results: Overall, 340 patients were included. Mean (95% CI) eGFR-EPI in patients with baseline eGFR-EPI <90 ml/min/1.73m 2 ( n  = 125) was 79.6 (78.0; 81.2) ml/min/1.73m 2 at baseline and 81.3 (79.9; 82.7) ml/min/1.73m 2 at 12 months after switch. In the patient-matched subgroup ( n  = 175), median annual eGFR-EPI declined -4.24 ml/min/1.73m 2 while on F/TDF and increased +0.93 ml/min/1.73m 2 after switch to F/TAF ( P  < 0.0001). In patients with baseline eGFR-EPI <90 ml/min/1.73m 2 , median annual eGFR-EPI increased +4.19 mL/min/1.73m 2 after switch ( P  < 0.0001). Conclusion: Switching from F/TDF to F/TAF-based TT regimens while maintaining the same third agent numerically improved eGFR-EPI in PLWH with baseline eGFR-EPI <90 mL/min/1.73m 2 . eGFR-EPI improved significantly when comparing progression while on F/TDF vs progression after switch, confirming beneficial renal effects of switching to F/TAF in a clinical practice setting.

Background: Since 1996, the standard of care (SOC) therapy for HIV treatment has consisted of a backbone of two nucleoside analogue reverse transcriptase inhibitors (NRTI) paired with a third agent. Use of two-drug combinations (2DC) has been considered for selected patients to avoid toxicities associated with the use of NRTIs. This study aimed to compare the real-world outcomes of integrase strand transfer inhibitor (INSTI)-containing triple therapy (TT) to dolutegravir- (DTG) and/or boosted protease inhibitor (bPI)-based 2DC in a large Spanish cohort of HIV patients., Methods: A retrospective analysis was performed using data from the VACH cohort, a prospective multicentre Spanish cohort of adult HIV patients. All treatment experienced patients initiating a TT of an INSTI combined with two NRTIs or a 2DC-containing DTG and/or a bPI between 01/01/2012 and 01/06/2017 were included. The unit of analysis was patient-regimens. The overall sample analysis was complemented with two sub-analyses. The first sub-analysis focused on patients treated with a backbone plus DTG compared to those treated with DTG+ one other antiretroviral. The second sub-analysis focused on patients with HIV RNA<50 copies/mL at baseline, irrespective of the regimen used. The following endpoints were assessed: time to discontinuation for any reason, time to switch due to virologic failure, and time to switch due to toxicity (reasons for discontinuation according to clinician report in the database). Time-to-event analyses were conducted using Kaplan-Meier survival curves and Cox regression models., Results: Overall 7,481 patients were included in the analysis, contributing to 9,243 patient-regimens. Patient characteristics at baseline differed among groups, with the 2DC group being significantly older and having a higher proportion of women, a longer time on ART and a higher number of previous virologic failures. Median (95% Confidence Interval [C.I.]) time to switch was 2.5 years (2.3, 2.7) in 2DC group versus 2.9 years (2.7, 3.0) in TT. Adjusted hazard ratios (95% C.I.) for discontinuation due to any reason, virologic failure and toxicity in the 2DC vs TT group were 1.29 (1.15; 1.44), 2.06 (1.54; 2.77) and 1.18 (0.94; 1.48), respectively. Results were consistent in the two sub-analyses., Conclusion: In this analysis, time to discontinuation and probability of remaining free of virologic failure were significantly higher in patients on INSTI-based TT compared to DTG- and/or bPI-containing 2DC, with no differences in toxicity., Competing Interests: We have read the journal’s policy and the authors of this manuscript listed below have the following competing interests: Helena Diaz-Cuervo is a Gilead Sciences employee Filipa Aragão and Sophie Marguet are employees of consulting companies contracted by Gilead Sciences to work on this project. Ramón Teira, Nuria Espinosa, Pere Domingo, Marta Montero, Elisa Martínez, M.ª Dolores Merino, Fernando Lozano, Mª José Galindo, Joaquim Peraire, Elisabeth Deig, Pepa Muñoz- Sánchez, Esteban Ribera, Nadia Abdulghani, Belén de la Fuente, Bernardino Roca, Alberto Romero, Paloma Geijo, Vicente Estrada, Josefina García, M.ª Antonia Sepúlveda and Juan Berenguer declare at least one of the following: having performed consultancy, or having received research grants, or having received financial compensation for scientific talks, or having collaborated in the preparation of educational material, or having received travel grants for attending scientific congresses, from at least one of the following: Bristol-Myers Squibb, Gilead Sciences, Janssen-Cilag, MSD, ViiV Healthcare or AbbVie. Partial funding was provided by Gilead Sciences. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Legionella is a well known but infrequent cause of bacterial endocarditis., Methods: We report a case of endocarditis caused by Legionella spp. We reviewed previously reported cases in PubMed, Google Scholar and in references included in previous reports, and summarized relevant clinical data., Results: A 63-year-old man with a history of aortic valve replacement developed persistent fever and monoarthritis. Transesophageal echocardiography showed perivalvular abscess. He died during surgery. Blood and valve cultures were negative. Legionella spp. was demonstrated with 16S-rRNA PCR from the resected material. Twenty cases of Legionella endocarditis have been reported. Harboring a prosthetic valve was the main risk factor. Prognosis was favorable, both for patients treated with or without surgical valve replacement. Overall mortality was <10%., Conclusions: Legionella is an infrequent cause of endocarditis. It frequently requires surgical treatment. Prognosis is good. Molecular techniques are likely to become the gold standard for diagnosis., (Copyright © 2020 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Publicado por Elsevier España, S.L.U. All rights reserved.)

People living with HIV (PLHIV) are more likely than the general population to develop AIDS-defining malignancies (ADMs) and several non-ADMs (NADMs). Information is lacking on survival outcomes and cause-specific mortality after cancer diagnosis among PLHIV. We investigated causes of death within 5 years of cancer diagnosis in PLHIV enrolled in European and North American HIV cohorts starting antiretroviral therapy (ART) 1996-2015, aged ≥16 years, and subsequently diagnosed with cancer. Cancers were grouped: ADMs, viral NADMs and nonviral NADMs. We calculated cause-specific mortality rates (MR) after diagnosis of specific cancers and compared 5-year survival with the UK and France general populations. Among 83,856 PLHIV there were 4,436 cancer diagnoses. Of 603 deaths after ADM diagnosis, 292 (48%) were due to an ADM. There were 467/847 (55%) and 74/189 (39%) deaths that were due to an NADM after nonviral and viral NADM diagnoses, respectively. MR were higher for diagnoses between 1996 and 2005 versus 2006-2015: ADMs 102 (95% CI 92-113) per 1,000 years versus 88 (78-100), viral NADMs 134 (106-169) versus 111 (93-133) and nonviral NADMs 264 (232-300) versus 226 (206-248). Estimated 5-year survival for PLHIV diagnosed with liver (29% [19-39%]), lung (18% [13-23%]) and cervical (75% [63-84%]) cancer was similar to general populations. Survival after Hodgkin's lymphoma diagnosis was lower in PLHIV (75% [67-81%]). Among ART-treated PLHIV diagnosed with cancer, MR and causes of death varied by cancer type, with mortality highest for liver and lung cancers. Deaths within 5 years of NADM diagnoses were more likely to be from cancer than AIDS., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

This study evaluated whether the interval from the first clinic visit until the start of antiretroviral treatment (ART) was correlated with common parameters of immunological recovery among patients with early HIV infection (EHI).We reviewed the medical records of patients with EHI who started ART using integrase strand-transfer inhibitors (ISTIs) within the first 6 months after diagnosis. Simple linear regression analyses were performed to determine whether the interval from the first visit to the start of ART was correlated with 1-year changes in CD4+ cell count, CD8+ cell count, CD4+ percentage, and CD4+/CD8+ ratio.Fifty-three patients with probable or definite EHI started ART using ISTIs between April 2014 and August 2016. Forty-nine patients completed 1 year of follow-up, including 48 men. The routes of HIV transmission were 1 case of needle sharing, 5 cases of heterosexual activity, and 43 cases of men who had sex with men. None of the immunological recovery parameters were correlated with time to the start of ART (CD4+ cell count: R = .12, P = .42; CD8+ cell count: R = .107, P = .5; CD4+ percentage: R = .14, P = .34; CD4+/CD8+ ratio: R = .23, P = .14). Furthermore, subgroup sensitivity analyses failed to detect significant correlations based on definite or probable diagnoses, treatment using elvitegravir or dolutegravir, or the time from HIV diagnosis to ART initiation.This series of EHI cases indicate that using ART with ISTI-based regimens is efficacious and well-tolerated. However, earlier initiation of treatment was not significantly correlated with common parameters of immunological recovery.

Purpose: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality., Methods: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk., Results: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32-3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39-1.88),and non-performed surgery (HR:1.64;95% CI:11.16-1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality., Conclusion: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group., (Copyright © 2019. Published by Elsevier B.V.)

The analysis of the available databases related to HIV/AIDS confirms a paradigm shift in the patient's life expectancy: now HIV has become a chronic disease, so patients are aging. However, this advance is accompanied by a negative counterpart: due to the increase in the number of years of life gained, there is a prevalence of comorbidities greater than the general population and at an earlier age. Reducing the risk associated with all the comorbidities that the ageing patient with HIV/AIDS may develop, must now be a health objective; it must be added to the traditional objectives that until now were part of the strategy to reduce the impact of the HIV infection. In the specific case of women, it is also necessary to train peri and postmenopausal women to increase their skills and motivation to care for their health; It is also very important to examine the role that hormone replacement therapy can play in reducing their symptoms.

Background: We assessed the prevalence of antibodies against hepatitis C virus (HCV-Abs) and active HCV infection in patients infected with human immunodeficiency virus (HIV) in Spain in 2016 and compared the results with those of similar studies performed in 2002, 2009, and 2015., Methods: The study was performed in 43 centers during October-November 2016. The sample was estimated for an accuracy of 2% and selected by proportional allocation and simple random sampling. During 2016, criteria for therapy based on direct-acting antiviral agents (DAA) were at least significant liver fibrosis, severe extrahepatic manifestations of HCV, and high risk of HCV transmissibility., Results: The reference population and the sample size were 38904 and 1588 patients, respectively. The prevalence of HCV-Abs in 2002, 2009, 2015, and 2016 was 60.8%, 50.2%, 37.7%, and 34.6%, respectively ( P trend <.001, from 2002 to 2015). The prevalence of active HCV in 2002, 2009, 2015, and 2016 was 54.0%, 34.0%, 22.1%, and 11.7%, respectively ( P trend <.001). The anti-HCV treatment uptake in 2002, 2009, 2015, and 2016 was 23.0%, 48.0%, 59.3%, and 74.7%, respectively ( P trend <.001). In 2016, HCV-related cirrhosis was present in 7.6% of all HIV-infected individuals, 15.0% of patients with active HCV, and 31.5% of patients who cleared HCV after anti-HCV therapy., Conclusions: Our findings suggest that with universal access to DAA-based therapy and continued efforts in prevention and screening, it will be possible to eliminate active HCV among HIV-infected individuals in Spain in the short term. However, the burden of HCV-related cirrhosis will continue to be significant among HIV-infected individuals.

Introduction: HIV-1 infection leads to chronic inflammation and to an increased risk of non-AIDS mortality. Our objective was to determine whether AIDS-defining events (ADEs) were associated with increased overall and cause-specific non-AIDS related mortality after antiretroviral therapy (ART) initiation., Methods: We included HIV treatment-naïve adults from the Antiretroviral Therapy Cohort Collaboration (ART-CC) who initiated ART from 1996 to 2014. Causes of death were assigned using the Coding Causes of Death in HIV (CoDe) protocol. The adjusted hazard ratio (aHR) for overall and cause-specific non-AIDS mortality among those with an ADE (all ADEs, tuberculosis (TB), Pneumocystis jiroveci pneumonia (PJP), and non-Hodgkin's lymphoma (NHL)) compared to those without an ADE was estimated using a marginal structural model., Results: The adjusted hazard of overall non-AIDS mortality was higher among those with any ADE compared to those without any ADE (aHR 2.21, 95% confidence interval (CI) 2.00 to 2.43). The adjusted hazard of each of the cause-specific non-AIDS related deaths were higher among those with any ADE compared to those without, except metabolic deaths (malignancy aHR 2.59 (95% CI 2.13 to 3.14), accident/suicide/overdose aHR 1.37 (95% CI 1.05 to 1.79), cardiovascular aHR 1.95 (95% CI 1.54 to 2.48), infection aHR (95% CI 1.68 to 2.81), hepatic aHR 2.09 (95% CI 1.61 to 2.72), respiratory aHR 4.28 (95% CI 2.67 to 6.88), renal aHR 5.81 (95% CI 2.69 to 12.56) and central nervous aHR 1.53 (95% CI 1.18 to 5.44)). The risk of overall and cause-specific non-AIDS mortality differed depending on the specific ADE of interest (TB, PJP, NHL)., Conclusions: In this large multi-centre cohort collaboration with standardized assignment of causes of death, non-AIDS mortality was twice as high among patients with an ADE compared to without an ADE. However, non-AIDS related mortality after an ADE depended on the ADE of interest. Although there may be unmeasured confounders, these findings suggest that a common pathway may be independently driving both ADEs and NADE mortality. While prevention of ADEs may reduce subsequent death due to NADEs following ART initiation, modification of risk factors for NADE mortality remains important after ADE survival., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)

Background: CD4 cell recovery following first-line combination ART (cART) is poorer in HIV-2+ than in HIV-1+ patients. Only large comparisons may allow adjustments for demographic and pretreatment plasma viral load (pVL)., Methods: ART-naive HIV+ adults from two European multicohort collaborations, COHERE (HIV-1 alone) and ACHIeV2e (HIV-2 alone), were included, if they started first-line cART (without NNRTIs or fusion inhibitors) between 1997 and 2011. Patients without at least one CD4 cell count before start of cART, without a pretreatment pVL and with missing a priori-defined covariables were excluded. Evolution of CD4 cell count was studied using adjusted linear mixed models., Results: We included 185 HIV-2+ and 30321 HIV-1+ patients with median age of 46 years (IQR 36-52) and 37 years (IQR 31-44), respectively. Median observed pretreatment CD4 cell counts/mm3 were 203 (95% CI 100-290) in HIV-2+ patients and 223 (95% CI 100-353) in HIV-1+ patients. Mean observed CD4 cell count changes from start of cART to 12 months were +105 (95% CI 77-134) in HIV-2+ patients and +202 (95% CI 199-205) in HIV-1+ patients, an observed difference of 97 cells/mm3 in 1 year. In adjusted analysis, the mean CD4 cell increase was overall 25 CD4 cells/mm3/year lower (95% CI 5-44; P = 0.0127) in HIV-2+ patients compared with HIV-1+ patients., Conclusions: A poorer CD4 cell increase during first-line cART was observed in HIV-2+ patients, even after adjusting for pretreatment pVL and other potential confounders. Our results underline the need to identify more potent therapeutic regimens or strategies against HIV-2., (© The Author 2017. 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: When a clinical treatment fails or shows suboptimal results, the question of when to switch to another treatment arises. Treatment switching strategies are often dynamic because the time of switching depends on the evolution of an individual's time-varying covariates. Dynamic strategies can be directly compared in randomized trials. For example, HIV-infected individuals receiving antiretroviral therapy could be randomized to switching therapy within 90 days of HIV-1 RNA crossing above a threshold of either 400 copies/ml (tight-control strategy) or 1000 copies/ml (loose-control strategy)., Methods: We review an approach to emulate a randomized trial of dynamic switching strategies using observational data from the Antiretroviral Therapy Cohort Collaboration, the Centers for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration. We estimated the comparative effect of tight-control vs. loose-control strategies on death and AIDS or death via inverse-probability weighting., Results: Of 43 803 individuals who initiated an eligible antiretroviral therapy regimen in 2002 or later, 2001 met the baseline inclusion criteria for the mortality analysis and 1641 for the AIDS or death analysis. There were 21 deaths and 33 AIDS or death events in the tight-control group, and 28 deaths and 41 AIDS or death events in the loose-control group. Compared with tight control, the adjusted hazard ratios (95% confidence interval) for loose control were 1.10 (0.73, 1.66) for death, and 1.04 (0.86, 1.27) for AIDS or death., Conclusions: Although our effective sample sizes were small and our estimates imprecise, the described methodological approach can serve as an example for future analyses., (© The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association)

Background: Few studies have evaluated the impact of pre-treatment drug resistance (PDR) on response to combination antiretroviral treatment (cART) in children. The objective of this joint EuroCoord-CHAIN-EPPICC/PENTA project was to assess the prevalence of PDR mutations and their association with virological outcome in the first year of cART in children., Methods: HIV-infected children <18 years initiating cART between 1998 and 2008 were included if having at least one genotypic resistance test prior to cART initiation. We used the World Health Organization 2009 resistance mutation list and Stanford algorithm to infer resistance to prescribed drugs. Time to virological failure (VF) was defined as the first of two consecutive HIV-RNA > 500 copies/mL after 6 months cART and was assessed by Cox proportional hazards models. All models were adjusted for baseline demographic, clinical, immunology and virology characteristics and calendar period of cART start and initial cART regimen., Results: Of 476 children, 88 % were vertically infected. At cART initiation, median (interquartile range) age was 6.6 years (2.1-10.1), CD4 cell count 297 cells/mm 3 (98-639), and HIV-RNA 5.2 log 10 copies/mL (4.7-5.7). Of 37 children (7.8 %, 95 % confidence interval (CI), 5.5-10.6) harboring a virus with ≥1 PDR mutations, 30 children had a virus resistant to ≥1 of the prescribed drugs. Overall, the cumulative Kaplan-Meier estimate for virological failure was 19.8 % (95 %CI, 16.4-23.9). Cumulative risk for VF tended to be higher among children harboring a virus with PDR and resistant to ≥1 drug prescribed than among those receiving fully active cART: 32.1 % (17.2-54.8) versus 19.4 % (15.9-23.6) (P = 0.095). In multivariable analysis, age was associated with a higher risk of VF with a 12 % reduced risk per additional year (HR 0.88; 95 %CI, 0.82-0.95; P < 0.001)., Conclusions: PDR was not significantly associated with a higher risk of VF in children in the first year of cART. The risk of VF decreased by 12 % per additional year at treatment initiation which may be due to fading of PDR mutations over time. Lack of appropriate formulations, in particular for the younger age group, may be an important determinant of virological failure.

Background: CD4 count at start of combination antiretroviral therapy (ART) is strongly associated with short-term survival, but its association with longer-term survival is less well characterized., Methods: We estimated mortality rates (MRs) by time since start of ART (<0.5, 0.5-0.9, 1-2.9, 3-4.9, 5-9.9, and ≥10 years) among patients from 18 European and North American cohorts who started ART during 1996-2001. Piecewise exponential models stratified by cohort were used to estimate crude and adjusted (for sex, age, transmission risk, period of starting ART [1996-1997, 1998-1999, 2000-2001], and AIDS and human immunodeficiency virus type 1 RNA at baseline) mortality rate ratios (MRRs) by CD4 count at start of ART (0-49, 50-99, 100-199, 200-349, 350-499, ≥500 cells/µL) overall and separately according to time since start of ART., Results: A total of 6344 of 37 496 patients died during 359 219 years of follow-up. The MR per 1000 person-years was 32.8 (95% confidence interval [CI], 30.2-35.5) during the first 6 months, declining to 16.0 (95% CI, 15.4-16.8) during 5-9.9 years and 14.2 (95% CI, 13.3-15.1) after 10 years' duration of ART. During the first year of ART, there was a strong inverse association of CD4 count at start of ART with mortality. This diminished over the next 4 years. The adjusted MRR per CD4 group was 0.97 (95% CI, .94-1.00; P = .054) and 1.02 (95% CI, .98-1.07; P = .32) among patients followed for 5-9.9 and ≥10 years, respectively., Conclusions: After surviving 5 years of ART, the mortality of patients who started ART with low baseline CD4 count converged with mortality of patients with intermediate and high baseline CD4 counts., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objectives: In Europe and elsewhere, health inequalities among HIV-positive individuals are of concern. We investigated late HIV diagnosis and late initiation of combination antiretroviral therapy (cART) by educational level, a proxy of socioeconomic position., Design and Methods: We used data from nine HIV cohorts within COHERE in Austria, France, Greece, Italy, Spain and Switzerland, collecting data on level of education in categories of the UNESCO/International Standard Classification of Education standard classification: non-completed basic, basic, secondary and tertiary education. We included individuals diagnosed with HIV between 1996 and 2011, aged at least 16 years, with known educational level and at least one CD4 cell count within 6 months of HIV diagnosis. We examined trends by education level in presentation with advanced HIV disease (AHD) (CD4 <200 cells/μl or AIDS within 6 months) using logistic regression, and distribution of CD4 cell count at cART initiation overall and among presenters without AHD using median regression., Results: Among 15 414 individuals, 52, 45,37, and 31% with uncompleted basic, basic, secondary and tertiary education, respectively, presented with AHD (P trend <0.001). Compared to patients with tertiary education, adjusted odds ratios of AHD were 1.72 (95% confidence interval 1.48-2.00) for uncompleted basic, 1.39 (1.24-1.56) for basic and 1.20 (1.08-1.34) for secondary education (P < 0.001). In unadjusted and adjusted analyses, median CD4 cell count at cART initiation was lower with poorer educational level., Conclusions: Socioeconomic inequalities in delayed HIV diagnosis and initiation of cART are present in European countries with universal healthcare systems and individuals with lower educational level do not equally benefit from timely cART initiation.

Background: Patterns of cause-specific mortality in individuals infected with human immunodeficiency virus type 1 (HIV-1) are changing dramatically in the era of antiretroviral therapy (ART)., Methods: Sixteen cohorts from Europe and North America contributed data on adult patients followed from the start of ART. Procedures for coding causes of death were standardized. Estimated hazard ratios (HRs) were adjusted for transmission risk group, sex, age, year of ART initiation, baseline CD4 count, viral load, and AIDS status, before and after the first year of ART., Results: A total of 4237 of 65 121 (6.5%) patients died (median, 4.5 years follow-up). Rates of AIDS death decreased substantially with time since starting ART, but mortality from non-AIDS malignancy increased (rate ratio, 1.04 per year; 95% confidence interval [CI], 1.0-1.1). Higher mortality in men than women during the first year of ART was mostly due to non-AIDS malignancy and liver-related deaths. Associations with age were strongest for cardiovascular disease, heart/vascular, and malignancy deaths. Patients with presumed transmission through injection drug use had higher rates of all causes of death, particularly for liver-related causes (HRs compared with men who have sex with men: 18.1 [95% CI, 6.2-52.7] during the first year of ART and 9.1 [95% CI, 5.8-14.2] thereafter). There was a persistent role of CD4 count at baseline and at 12 months in predicting AIDS, non-AIDS infection, and non-AIDS malignancy deaths. Lack of viral suppression on ART was associated with AIDS, non-AIDS infection, and other causes of death., Conclusions: Better understanding of patterns of and risk factors for cause-specific mortality in the ART era can aid in development of appropriate care for HIV-infected individuals and inform guidelines for risk factor management., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Background: Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years of sustained viral suppression and (2) the association of the achieved CD4 count with subsequent mortality., Methods: We included treated HIV-infected adults from 2 large international HIV cohorts, who had viral suppression (≤500 HIV type 1 RNA copies/mL) for >3 years with CD4 count ≤200 cells/µL at start of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/µL) and Cox regression to identify associations with mortality., Results: Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/µL after 3 years of suppression. Increasing age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/µL. Individuals with CD4 ≤200 cells/µL after 3 years of viral suppression had substantially increased mortality (adjusted hazard ratio, 2.60; 95% confidence interval, 1.86-3.61) compared with those who achieved CD4 count >200 cells/µL. The increased mortality was seen across different patient groups and for all causes of death., Conclusions: Virally suppressed HIV-positive individuals on cART who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality.

Objective: To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC), and high-income (HIC) countries., Methods: Patients aged 16 years or older starting cART in a clinic participating in a multicohort collaboration spanning 6 continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multilevel linear regression models were adjusted for age, gender, and calendar year; missing CD4 counts were imputed., Results: In total, 379,865 patients from 9 LIC, 4 LMIC, 4 UMIC, and 6 HIC were included. In LIC, the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/μL between 2002 and 2009. Corresponding increases in LMIC, UMIC, and HIC were from 87 to 155 cells/μL (76% increase), 88 to 135 cells/μL (53%), and 209 to 274 cells/μL (31%). In 2009, compared with LIC, median counts were 13 cells/μL [95% confidence interval (CI): -56 to +30] lower in LMIC, 22 cells/μL (-62 to +18) lower in UMIC, and 112 cells/μL (+75 to +149) higher in HIC. They were 23 cells/μL (95% CI: +18 to +28 cells/μL) higher in women than men. Median counts were 88 cells/μL (95% CI: +35 to +141 cells/μL) higher in countries with an estimated national cART coverage >80%, compared with countries with <40% coverage., Conclusions: Median CD4 cell counts at the start of cART increased 2000-2009 but remained below 200 cells/μL in LIC and MIC and below 300 cells/μL in HIC. Earlier start of cART will require substantial efforts and resources globally.