Sex differences in discontinuations due to side effects of second-generation integrase strand transfer inhibitors: a systematic review and meta-analysisResearch in context
Summary: Background: Dolutegravir and bictegravir are frequently prescribed second-generation integrase strand transfer inhibitors. Although sex and gender influence drug pharmacokinetics, little is known about the differences in side effects experienced by cisgender men and women on these agents....
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Elsevier
2025-06-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537025001786 |
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| author | Zhou Fang Tetiana Povshedna Rowan Patterson Erin Ready Helene C.F. Cote Melanie C.M. Murray Elizabeth M. King |
| author_facet | Zhou Fang Tetiana Povshedna Rowan Patterson Erin Ready Helene C.F. Cote Melanie C.M. Murray Elizabeth M. King |
| author_sort | Zhou Fang |
| collection | DOAJ |
| description | Summary: Background: Dolutegravir and bictegravir are frequently prescribed second-generation integrase strand transfer inhibitors. Although sex and gender influence drug pharmacokinetics, little is known about the differences in side effects experienced by cisgender men and women on these agents. Therefore, we synthesize data on sex-disaggregated side effects leading to discontinuation in dolutegravir/bictegravir-based regimens. Methods: We conducted a systematic review and meta-analysis (PROSPERO: CRD42023427891) by searching Medline, Embase, Web of Science, and Scopus for studies published from January 2010 to August 2024. We included randomized controlled trials and observational studies reporting sex-disaggregated discontinuations of dolutegravir/bictegravir-based regimens due to general or neuropsychiatric side effects. Studies in pregnancy, post-partum, pediatrics, co-infections (e.g., TB), and monotherapy were excluded. Two reviewers screened and extracted data. Risk of bias was assessed using an adapted version of the Newcastle–Ottawa scale for cohort studies. Meta-analysis was conducted using random effects models on studies reporting raw dolutegravir discontinuations by sex. Findings: We screened 4179 abstracts, conducted 505 full-text reviews, and included 17 observational studies in the review (15 on dolutegravir, two on bictegravir). Notably, 287/505 articles were excluded for lack of sex-disaggregated data. Fifteen dolutegravir studies reported outcomes for 32,352 people with HIV (7506 women, 24,846 men). Meta-analysis showed higher odds of dolutegravir discontinuation due to side effects in women vs men (9.3% vs 7.5%; OR: 1.40 [1.23–1.60], p < 0.001). A second meta-analysis on neuropsychiatric-related discontinuations found no sex differences (3.5% in women vs 3.3% in men; OR: 1.14 [0.84–1.56], p = 0.40). Only two bictegravir studies met inclusion criteria and showed conflicting results. Interpretation: This review reports signals of higher discontinuation rates of dolutegravir due to general side effects in women compared to men which may not be accounted for by neuropsychiatric effects. Further research is needed to determine whether these trends extend to other second-generation integrase strand transfer inhibitors, such as bictegravir and cabotegravir, and to better understand the specific side effects contributing to dolutegravir discontinuation in women. Additionally, the lack of sex-disaggregated reporting during our literature search identifies a need to prioritize sex/gender-based analyses in future research on antiretrovirals. Funding: None. |
| format | Article |
| id | doaj-art-2947e3e479fa4ca58525f5cf2f3d3faf |
| institution | Kabale University |
| issn | 2589-5370 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
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| series | EClinicalMedicine |
| spelling | doaj-art-2947e3e479fa4ca58525f5cf2f3d3faf2025-08-20T03:47:32ZengElsevierEClinicalMedicine2589-53702025-06-018410324610.1016/j.eclinm.2025.103246Sex differences in discontinuations due to side effects of second-generation integrase strand transfer inhibitors: a systematic review and meta-analysisResearch in contextZhou Fang0Tetiana Povshedna1Rowan Patterson2Erin Ready3Helene C.F. Cote4Melanie C.M. Murray5Elizabeth M. King6Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada; Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada; Edwin S.H. Leong Healthy Aging Program, University of British Columbia, Vancouver, British Columbia, CanadaFaculty of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, CanadaPharmacy Department, St. Paul's Hospital, Vancouver, British Columbia, Canada; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada; Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada; Edwin S.H. Leong Healthy Aging Program, University of British Columbia, Vancouver, British Columbia, Canada; Women's Health Research Institute, Vancouver, British Columbia, CanadaDepartment of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Edwin S.H. Leong Healthy Aging Program, University of British Columbia, Vancouver, British Columbia, Canada; Women's Health Research Institute, Vancouver, British Columbia, Canada; Oak Tree Clinic, BC Women's Hospital, Vancouver, British Columbia, CanadaDepartment of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Women's Health Research Institute, Vancouver, British Columbia, Canada; Oak Tree Clinic, BC Women's Hospital, Vancouver, British Columbia, Canada; Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada; Corresponding author. E600B – 4500 Oak Street, Vancouver, V6H 3N1, Canada.Summary: Background: Dolutegravir and bictegravir are frequently prescribed second-generation integrase strand transfer inhibitors. Although sex and gender influence drug pharmacokinetics, little is known about the differences in side effects experienced by cisgender men and women on these agents. Therefore, we synthesize data on sex-disaggregated side effects leading to discontinuation in dolutegravir/bictegravir-based regimens. Methods: We conducted a systematic review and meta-analysis (PROSPERO: CRD42023427891) by searching Medline, Embase, Web of Science, and Scopus for studies published from January 2010 to August 2024. We included randomized controlled trials and observational studies reporting sex-disaggregated discontinuations of dolutegravir/bictegravir-based regimens due to general or neuropsychiatric side effects. Studies in pregnancy, post-partum, pediatrics, co-infections (e.g., TB), and monotherapy were excluded. Two reviewers screened and extracted data. Risk of bias was assessed using an adapted version of the Newcastle–Ottawa scale for cohort studies. Meta-analysis was conducted using random effects models on studies reporting raw dolutegravir discontinuations by sex. Findings: We screened 4179 abstracts, conducted 505 full-text reviews, and included 17 observational studies in the review (15 on dolutegravir, two on bictegravir). Notably, 287/505 articles were excluded for lack of sex-disaggregated data. Fifteen dolutegravir studies reported outcomes for 32,352 people with HIV (7506 women, 24,846 men). Meta-analysis showed higher odds of dolutegravir discontinuation due to side effects in women vs men (9.3% vs 7.5%; OR: 1.40 [1.23–1.60], p < 0.001). A second meta-analysis on neuropsychiatric-related discontinuations found no sex differences (3.5% in women vs 3.3% in men; OR: 1.14 [0.84–1.56], p = 0.40). Only two bictegravir studies met inclusion criteria and showed conflicting results. Interpretation: This review reports signals of higher discontinuation rates of dolutegravir due to general side effects in women compared to men which may not be accounted for by neuropsychiatric effects. Further research is needed to determine whether these trends extend to other second-generation integrase strand transfer inhibitors, such as bictegravir and cabotegravir, and to better understand the specific side effects contributing to dolutegravir discontinuation in women. Additionally, the lack of sex-disaggregated reporting during our literature search identifies a need to prioritize sex/gender-based analyses in future research on antiretrovirals. Funding: None.http://www.sciencedirect.com/science/article/pii/S2589537025001786AntiretroviralsSide effectsAdverse drug reactionsDolutegravirBictegravirWomen living with HIV |
| spellingShingle | Zhou Fang Tetiana Povshedna Rowan Patterson Erin Ready Helene C.F. Cote Melanie C.M. Murray Elizabeth M. King Sex differences in discontinuations due to side effects of second-generation integrase strand transfer inhibitors: a systematic review and meta-analysisResearch in context EClinicalMedicine Antiretrovirals Side effects Adverse drug reactions Dolutegravir Bictegravir Women living with HIV |
| title | Sex differences in discontinuations due to side effects of second-generation integrase strand transfer inhibitors: a systematic review and meta-analysisResearch in context |
| title_full | Sex differences in discontinuations due to side effects of second-generation integrase strand transfer inhibitors: a systematic review and meta-analysisResearch in context |
| title_fullStr | Sex differences in discontinuations due to side effects of second-generation integrase strand transfer inhibitors: a systematic review and meta-analysisResearch in context |
| title_full_unstemmed | Sex differences in discontinuations due to side effects of second-generation integrase strand transfer inhibitors: a systematic review and meta-analysisResearch in context |
| title_short | Sex differences in discontinuations due to side effects of second-generation integrase strand transfer inhibitors: a systematic review and meta-analysisResearch in context |
| title_sort | sex differences in discontinuations due to side effects of second generation integrase strand transfer inhibitors a systematic review and meta analysisresearch in context |
| topic | Antiretrovirals Side effects Adverse drug reactions Dolutegravir Bictegravir Women living with HIV |
| url | http://www.sciencedirect.com/science/article/pii/S2589537025001786 |
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