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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: 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: 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.)

Background: Over the past decade, antiretroviral therapy (ART) regimens that include integrase strand inhibitors (INSTIs) have become the most commonly used for people with HIV starting ART. Although trials and observational studies have compared virological failure on INSTI-based with other regimens, few data are available on mortality in people with HIV treated with INSTIs in routine care. Therefore, we compared all-cause mortality between different INSTI-based and non-INSTI-based regimens in adults with HIV starting ART from 2013 to 2018., Methods: This cohort study used data on people with HIV in Europe and North America from the Antiretroviral Therapy Cohort Collaboration (ART-CC) and UK Collaborative HIV Cohort (UK CHIC). We studied the most common third antiretroviral drugs (additional to nucleoside reverse transcriptase inhibitor) used from 2013 to 2018: rilpivirine, darunavir, raltegravir, elvitegravir, dolutegravir, efavirenz, and others. Adjusted hazard ratios (aHRs; adjusted for clinical and demographic characteristics, comorbid conditions, and other drugs in the regimen) for mortality were estimated using Cox models stratified by ART start year and cohort, with multiple imputation of missing data., Findings: 62 500 ART-naive people with HIV starting ART (12 422 [19·9%] women; median age 38 [IQR 30-48]) were included in the study. 1243 (2·0%) died during 188 952 person-years of follow-up (median 3·0 years [IQR 1·6-4·4]). There was little evidence that mortality rates differed between regimens with dolutegravir, elvitegravir, rilpivirine, darunavir, or efavirenz as the third drug. However, mortality was higher for raltegravir compared with dolutegravir (aHR 1·49, 95% CI 1·15-1·94), elvitegravir (1·86, 1·43-2·42), rilpivirine (1·99, 1·49-2·66), darunavir (1·62, 1·33-1·98), and efavirenz (2·12, 1·60-2·81) regimens. Results were similar for analyses making different assumptions about missing data and consistent across the time periods 2013-15 and 2016-18. Rates of virological suppression were higher for dolutegravir than other third drugs., Interpretation: This large study of patients starting ART since the introduction of INSTIs found little evidence that mortality rates differed between most first-line ART regimens; however, raltegravir-based regimens were associated with higher mortality. Although unmeasured confounding cannot be excluded as an explanation for our findings, virological benefits of first-line INSTIs-based ART might not translate to differences in mortality., Funding: US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council., Competing Interests: Declaration of interests MC reports grants and payments for expert testimony from Gilead, Merck, and ViiV Healthcare, paid to their institution; and payment support for attending meetings from Gilead. PC reports advisory board and expert fees from ViiV Healthcare, Gilead, and Merck; lecture fees from ViiV Healthcare and Gilead; and travel grants paid to their institution from ViiV Healthcare and Gilead. CS reports fees from Gilead for an educational presentation. MJG reports honoraria in the last 3 years from ad hoc membership of national HIV advisory boards, and from Merck, Gilead, and ViiV Healthcare. MP reports honoraria for presentations from Gilead and Merck; consulting fees from Gilead, Merck, and AbbVie; and a research grant from Gilead. FB reports travel grants and honoraria from ViiV Healthcare, Gilead, Janssen, and Merck; consulting fees and payment for expert testimony from Gilead; and support for attending meetings from Gilead, Janssen, Merck, and ViiV Healthcare. PR reports independent scientific grant support from Gilead Sciences, Merck, and ViiV Healthcare, paid to their institution; and has served on scientific advisory boards for Gilead Sciences, ViiV Healthcare, and Merck, for which honoraria were all paid to their institution, none related to the content of this Article. MRi reports funds from Gilead for attending meetings; and payment for lectures from ViiV Healthcare. MRa reports grants from Gilead. GB reports consulting fee from MedIQ; payments and honoraria from the University of Kentucky, Lexington, Kentucky, and StateServ; and funding from Merck, Eli Lily, Kaiser Permanente, and Amgen paid to their institution. HC reports research grant funding from ViiV Healthcare, National Institute of Health, and Agency for Healthcare Research and Quality, paid to their institution; and sits on the National Institute of Health Office of AIDS Research Advisory Council. NO reports funding from the Preben og Anne Simonsens Fond. CAS reports honoraria from Gilead Sciences, ViiV Healthcare, and Janssen–Cilag for membership of Data Safety and Monitoring Boards, Advisory Boards, and for preparation of educational materials; and is the vice-chair of the British HIV Association. PD reports consulting fees from Gilead, Merck, Janssen and Cilag, ViiV Healthcare, Roche, and Theratechnologies; and payment or honoraria for lectures from Gilead, Merck, Janssen, ViiV Healthcare, and Roche. All other authors declare no competing interests., (Copyright © 2022 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.)

We compared invasive cervical cancer (ICC) incidence rates in Europe, South Africa, Latin and North America among women living with HIV who initiated antiretroviral therapy (ART) between 1996 and 2014. We analyzed cohort data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord. We used flexible parametric survival models to determine regional ICC rates and risk factors for incident ICC. We included 64,231 women from 45 countries. During 320,141 person-years (pys), 356 incident ICC cases were diagnosed (Europe 164, South Africa 156, North America 19 and Latin America 17). Raw ICC incidence rates per 100,000 pys were 447 in South Africa (95% confidence interval [CI]: 382-523), 136 in Latin America (95% CI: 85-219), 76 in North America (95% CI: 48-119) and 66 in Europe (95% CI: 57-77). Compared to European women ICC rates at 5 years after ART initiation were more than double in Latin America (adjusted hazard ratio [aHR]: 2.43, 95% CI: 1.27-4.68) and 11 times higher in South Africa (aHR: 10.66, 95% CI: 6.73-16.88), but similar in North America (aHR: 0.79, 95% CI: 0.37-1.71). Overall, ICC rates increased with age (>50 years vs. 16-30 years, aHR: 1.57, 95% CI: 1.03-2.40) and lower CD4 cell counts at ART initiation (per 100 cell/μl decrease, aHR: 1.25, 95% CI: 1.15-1.36). Improving access to early ART initiation and effective cervical cancer screening in women living with HIV should be key parts of global efforts to reduce cancer-related health inequities., (© 2019 UICC.)

Introduction: HIV cohort data from high-income European countries were compared with the UNAIDS Spectrum modelling parameters for these same countries to validate mortality rates and excess mortality estimates for people living with HIV (PLHIV) on antiretroviral therapy (ART)., Methods: Data from 2000 to 2015 were analysed from the Antiretroviral Therapy Cohort Collaboration (ART-CC) for Austria, Denmark, France, Italy, the Netherlands, Spain, and Switzerland. Flexible parametric models were used to compare all-cause mortality rates in the ART-CC and Spectrum. The percentage of AIDS-related deaths and excess mortality (both are the same within Spectrum) were compared, with excess mortality defined as that in excess of the general population mortality., Results: Analyses included 94 026 PLHIV with 585 784 person-years of follow-up, from which there were 5515 deaths. All-cause annual mortality rates in Spectrum for 2000-2003 were 0.0121, reducing to 0.0078 in 2012-2015, whilst the ART-CC's corresponding annual mortality rates were 0.0151 [95% confidence interval (95% CI): 0.0130-0.0171] reducing to 0.0049 (95% CI: 0.0039-0.0060). The percentage of AIDS-related deaths in Spectrum was 74.7% in 2000-2003, dropping to 43.6% in 2012-2015. In the ART-CC, AIDS-related mortality constitutes 45.3% (95% CI: 38.4-52.9%) of mortality in 2000-2003 and 26.7% (95% CI: 19-46%) between 2012 and 2015. Excess mortality in the ART-CC was broadly similar to the Spectrum estimates, dropping from 75.3% (95% CI: 60.3-95.2%) in 2000-2003 to 30.7% (95% CI: 25.5-63.7%) in 2012-2015., Conclusion: All-cause mortality assumptions for PLHIV on ART in high-income European settings should be adjusted in Spectrum to be higher in 2000-2003 and decline more quickly to levels currently captured for recent years.

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: We obtained estimates of the incidence of tuberculosis (TB) among patients receiving HAART and identified determinants of the incidence., Methods: We analyzed the incidence of TB during the first 3 years after initiation of HAART among 17,142 treatment-naive, AIDS-free persons starting HAART who were enrolled in 12 cohorts from Europe and North America. We used univariable and multivariable Poisson regression models to identify factors associated with the incidence., Results: During the first 3 years (36,906 person-years), 173 patients developed TB (incidence, 4.69 cases per 1000 person-years). In multivariable analysis, the incidence rate was lower for men who have sex with men, compared with injection drug users (relative rate, 2.46; 95% confidence interval [CI], 1.51-4.01), heterosexuals (relative rate, 2.42; 95% CI, 1.64-3.59), those with other suspected modes of transmission (relative rate, 1.66; 95% CI, 0.91-3.06), and those with a higher CD4+ count at the time of HAART initiation (relative rate per log2 cells/microL, 0.87; 95% CI, 0.84-0.91). During 28,846 person-years of follow-up after the first 6 months of HAART, 88 patients developed TB (incidence, 3.1 cases per 1000 person-years of follow-up). In multivariable analyses, a low baseline CD4+ count (relative rate per log2 cells/microL, 0.89; 95% CI, 0.83-0.96), 6-month CD4+ count (relative rate per log2 cells/microL, 0.90; 95% CI, 0.81-0.99), and a 6-month HIV RNA level >400 copies/mL (relative rate, 2.21; 95% CI, 1.33-3.67) were significantly associated with the risk of acquiring TB after 6 months of HAART., Conclusion: The level of immunodeficiency at which HAART is initiated and the response to HAART are important determinants of the risk of TB. However, this risk remains appreciable even among those with a good response to HAART, suggesting that other interventions may be needed to control the TB epidemic in the HIV-infected population.

Background: Although the incidence of most AIDS events declines after initiation of highly active antiretroviral therapy (HAART), this decline is more rapid for some conditions than others. We herein describe the decline in incidence of AIDS-defining events among 12,574 antiretroviral-naive individuals who started HAART in the Antiretorviral Therapy Cohort Collaboration and determined whether the rate of decline is similar for events with different etiologies., Methods: Rates of AIDS were calculated for the periods 0 to 3, 4 to 6, 7 to 12, 13 to 24, and 25 to 36 months after starting HAART. Changes in incidence over time were investigated using Poisson regression., Results: During 22 958 person-years of follow-up, 928 AIDS events developed (25.3% viral, 24.6% bacterial, 20.7% fungal, 8.1% protozoal, and 21.2% other). The incidence of any AIDS event declined from 129.3 (95% confidence interval [CI], 116.7-141.8) per 1000 person-years in the first 3 months to 13.2 (95% CI, 9.4-17.0) in the third year after starting HAART (P<.001). The rate of decline in incidence was greatest for events with a viral etiology (87.0% per year) and lowest for those with a fungal etiology (54.0% per year). In the third year, fungal events represented 37.0% of AIDS events that occurred. After adjustment for the CD4 count and human immunodeficiency virus 1 RNA level, changes in the incidence of bacterial and viral events from months 0 to 6 and 7 to 12 remained significant, suggesting that changes in these markers did not fully explain the changes in incidence seen., Conclusion: Although the incidence of all AIDS-defining events decreased substantially after starting HAART, the pattern of decline was most pronounced for events with a viral etiology.