{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:53:48Z","timestamp":1790952828193,"version":"4.1.0"},"reference-count":67,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HIV Medicine"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Antiretroviral therapy (ART) for people living with HIV has led to dramatically reduced mortality and improved life expectancy. This achievement is accompanied by a higher risk for metabolic and other non\u2010communicable diseases. The role and contribution of various ART regimens to adverse metabolic outcomes are not fully understood. We aimed to systematically evaluate the risk of metabolic outcomes associated with ART and to describe temporal trends in these risks across the modern ART era.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Following our prespecified, registered protocol, we conducted a systematic review and meta\u2010analysis of non\u2010randomized observational studies, comparing ART\u2010treated and ART\u2010na\u00efve adult people living with HIV and report the metabolic outcomes of interest. We extracted ART regimen combinations and metabolic outcomes and calculated pooled odds ratios (ORs) with 95% confidence intervals (95% CI) using a random\u2010effects model. Temporal patterns were summarized by publication year and year of ART rollout.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified 6827 studies, in which 39 studies were eligible for analysis with information from 24\u2009632 people living with HIV. Nucleoside reverse transcriptase inhibitors (NRTIs) were present throughout the review period. Non\u2010nucleoside reverse transcriptase inhibitors (NNRTIs) predominated from the early 2000s to 2014, while protease inhibitors (PIs) dominated 1998\u20132014. Integrase strand transfer inhibitors (INSTIs) appeared from 2016 onwards. ART\u2010treated adult people living with HIV had higher odds for metabolic syndrome (OR\u2009=\u20092.16, 95% CI\u2009=\u20091.33\u20133.52), while no statistically significant association was observed for type 2 diabetes mellitus (T2DM) (OR\u2009=\u20091.37, 95% CI\u2009=\u20090.65\u20132.90).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Metabolic burden associated with modern HIV treatment shifted from lipid abnormalities to weight\u2010 and glucose\u2010related outcomes. Meta\u2010analysis results showed that ART\u2010treated adults had nearly twice the odds of metabolic syndrome compared with ART\u2010na\u00efve adults. In contrast, our meta\u2010analytic evidence did not demonstrate a statistically significant association between ART use and the odds of developing T2DM. Findings should be interpreted with caution given potential confounding by disease stage, access to healthcare and survivorship bias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ART regimens and their metabolic outcomes have shifted over time. ART\u2010treated adult people living with HIV had higher odds of metabolic syndrome than their ART\u2010na\u00efve peers. Given heterogeneity and residual confounding, robust, long\u2010term studies would be needed to refine regimen\u2010specific risks.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hiv.70260","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T09:53:46Z","timestamp":1779357226000},"page":"1399-1420","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Temporal shifts in antiretroviral therapy regimens and metabolic outcomes in people living with\n                    <scp>HIV<\/scp>\n                    : A systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3391-934X","authenticated-orcid":false,"given":"Melani Ratih","family":"Mahanani","sequence":"first","affiliation":[{"name":"Heidelberg Institute of Global Health, Heidelberg University Hospital  Heidelberg Germany"},{"name":"Division of Prevention of Cardiovascular and Metabolic Diseases, Medical Faculty Mannheim, Centre for Preventive Medicine and Digital Health Heidelberg University  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8711-8008","authenticated-orcid":false,"given":"Myo","family":"Chit","sequence":"additional","affiliation":[{"name":"Heidelberg Institute of Global Health, Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9775-6504","authenticated-orcid":false,"given":"Sophie","family":"Mohr","sequence":"additional","affiliation":[{"name":"Heidelberg Institute of Global Health, Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisenda","family":"Cama i Gibernau","sequence":"additional","affiliation":[{"name":"Heidelberg Institute of Global Health, Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Hetjens","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics and Biomathematics, Medical Faculty Mannheim Heidelberg University  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9974-1145","authenticated-orcid":false,"given":"Volker","family":"Winkler","sequence":"additional","affiliation":[{"name":"Heidelberg Institute of Global Health, Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans\u2010Michael","family":"Steffen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Faculty of Medicine and University Hospital Cologne, University of Cologne  Cologne Germany"},{"name":"Faculty of Medicine and University Hospital Cologne, Hypertension Centre, University of Cologne  Cologne Germany"},{"name":"Department of Postgraduate Studies and Research Chreso University  Lusaka Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5944-1597","authenticated-orcid":false,"given":"Florian","family":"Neuhann","sequence":"additional","affiliation":[{"name":"Heidelberg Institute of Global Health, Heidelberg University Hospital  Heidelberg Germany"},{"name":"School of Medicine and Clinical Sciences Levy Mwanawasa Medical University  Lusaka Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199803263381301"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61113-7"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e3181f9c09e"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2020.0216"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-137-5_Part_2-200209031-00001"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.qai.0000233310.90484.16"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000257"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2015.0147"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2004.12.007"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12113644"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0956462417732226"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2025.1498165"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(16)30091-1"},{"key":"e_1_2_10_15_1","unstructured":"Covidence systematic review software.2025. 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