Associations of modern initial antiretroviral drug regimens with all-cause mortality in adults with HIV in Europe and North America: a cohort study.

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.

Informations de copyright

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.

Déclaration de conflit d'intérêts

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.