Jennifer Anne Brown, Lara Lewis, Yukteshwar Sookrajh, Lungile Hobe, Thulani Ngwenya, Johan van der Molen, Kwabena Asare, Kwena Tlhaku, Mlungisi Khanyile, Thokozani Khubone, Christian Bottomley, Nigel Garrett, Jienchi Dorward
{"title":"南非HIV感染者多来替韦与洛匹那韦二线抗逆转录病毒治疗的吸收和24个月结局：一项回顾性队列研究和模拟靶标试验","authors":"Jennifer Anne Brown, Lara Lewis, Yukteshwar Sookrajh, Lungile Hobe, Thulani Ngwenya, Johan van der Molen, Kwabena Asare, Kwena Tlhaku, Mlungisi Khanyile, Thokozani Khubone, Christian Bottomley, Nigel Garrett, Jienchi Dorward","doi":"10.1093/ofid/ofaf530","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Aligning with the World Health Organization, South Africa has replaced ritonavir-boosted lopinavir (LPV/r) with dolutegravir (DTG) in second-line antiretroviral therapy (ART) after treatment failure with tenofovir disoproxil fumarate (TDF)/lamivudine or emtricitabine (XTC)/efavirenz (EFV). Initial guidance included special considerations for DTG use among women.</p><p><strong>Methods: </strong>We analyzed routine deidentified data of adults switched from TDF/XTC/EFV to second-line AZT/XTC/LPV/r, AZT/XTC/DTG, or TDF/XTC/DTG between December 2019 and December 2023 at 108 healthcare facilities in KwaZulu-Natal, South Africa. Among people switched before July 2021, we emulated a target trial comparing 24-month death or loss to follow-up (LTFU), and viremia (>50 copies/mL). We conducted intention-to-treat and per-protocol analyses using weighted logistic regression with bootstrapped CIs.</p><p><strong>Results: </strong>Overall, women were less likely than men to switch to DTG (RR: 0.92 [95% CI: .88, .96]; <i>N</i> = 3649). Of 2321 people switched before July 2021, 915 (39%) switched to AZT/XTC/LPV/r, 415 (18%) to zidovudine (AZT)/XTC/DTG, and 991 (43%) to TDF/XTC/DTG. Median age was 36 years (IQR: 30, 43) and 1364 (59%) were women. In intention-to-treat analyses, the standardized 24-month risk of death or LTFU was similar with AZT/XTC/LPV/r (31%), AZT/XTC/DTG (30%), and TDF/XTC/DTG (34%). The standardized risk of 24-month viremia among those retained in care with a viral load result (<i>N</i> = 1270) was higher with AZT/XTC/LPV/r (50%) than with AZT/XTC/DTG (40%; aRD: -10% [95% CI -19%, -2%]) or TDF/XTC/DTG (39%; aRD: -11% [95% CI -18%, -5%]). Per-protocol analyses gave similar results.</p><p><strong>Conclusions: </strong>While retention was similar across regimens, viremia was less common on DTG-based ART, supporting current guidelines.</p>","PeriodicalId":19517,"journal":{"name":"Open Forum Infectious Diseases","volume":"12 9","pages":"ofaf530"},"PeriodicalIF":3.8000,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448401/pdf/","citationCount":"0","resultStr":"{\"title\":\"Uptake and 24-month Outcomes of Dolutegravir- Versus Lopinavir-based Second-line Antiretroviral Therapy for People With HIV in South Africa: A Retrospective Cohort Study and Emulated Target Trial.\",\"authors\":\"Jennifer Anne Brown, Lara Lewis, Yukteshwar Sookrajh, Lungile Hobe, Thulani Ngwenya, Johan van der Molen, Kwabena Asare, Kwena Tlhaku, Mlungisi Khanyile, Thokozani Khubone, Christian Bottomley, Nigel Garrett, Jienchi Dorward\",\"doi\":\"10.1093/ofid/ofaf530\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Aligning with the World Health Organization, South Africa has replaced ritonavir-boosted lopinavir (LPV/r) with dolutegravir (DTG) in second-line antiretroviral therapy (ART) after treatment failure with tenofovir disoproxil fumarate (TDF)/lamivudine or emtricitabine (XTC)/efavirenz (EFV). Initial guidance included special considerations for DTG use among women.</p><p><strong>Methods: </strong>We analyzed routine deidentified data of adults switched from TDF/XTC/EFV to second-line AZT/XTC/LPV/r, AZT/XTC/DTG, or TDF/XTC/DTG between December 2019 and December 2023 at 108 healthcare facilities in KwaZulu-Natal, South Africa. Among people switched before July 2021, we emulated a target trial comparing 24-month death or loss to follow-up (LTFU), and viremia (>50 copies/mL). We conducted intention-to-treat and per-protocol analyses using weighted logistic regression with bootstrapped CIs.</p><p><strong>Results: </strong>Overall, women were less likely than men to switch to DTG (RR: 0.92 [95% CI: .88, .96]; <i>N</i> = 3649). Of 2321 people switched before July 2021, 915 (39%) switched to AZT/XTC/LPV/r, 415 (18%) to zidovudine (AZT)/XTC/DTG, and 991 (43%) to TDF/XTC/DTG. Median age was 36 years (IQR: 30, 43) and 1364 (59%) were women. In intention-to-treat analyses, the standardized 24-month risk of death or LTFU was similar with AZT/XTC/LPV/r (31%), AZT/XTC/DTG (30%), and TDF/XTC/DTG (34%). The standardized risk of 24-month viremia among those retained in care with a viral load result (<i>N</i> = 1270) was higher with AZT/XTC/LPV/r (50%) than with AZT/XTC/DTG (40%; aRD: -10% [95% CI -19%, -2%]) or TDF/XTC/DTG (39%; aRD: -11% [95% CI -18%, -5%]). Per-protocol analyses gave similar results.</p><p><strong>Conclusions: </strong>While retention was similar across regimens, viremia was less common on DTG-based ART, supporting current guidelines.</p>\",\"PeriodicalId\":19517,\"journal\":{\"name\":\"Open Forum Infectious Diseases\",\"volume\":\"12 9\",\"pages\":\"ofaf530\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2025-08-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448401/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Open Forum Infectious Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/ofid/ofaf530\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/9/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Open Forum Infectious Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ofid/ofaf530","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Uptake and 24-month Outcomes of Dolutegravir- Versus Lopinavir-based Second-line Antiretroviral Therapy for People With HIV in South Africa: A Retrospective Cohort Study and Emulated Target Trial.
Background: Aligning with the World Health Organization, South Africa has replaced ritonavir-boosted lopinavir (LPV/r) with dolutegravir (DTG) in second-line antiretroviral therapy (ART) after treatment failure with tenofovir disoproxil fumarate (TDF)/lamivudine or emtricitabine (XTC)/efavirenz (EFV). Initial guidance included special considerations for DTG use among women.
Methods: We analyzed routine deidentified data of adults switched from TDF/XTC/EFV to second-line AZT/XTC/LPV/r, AZT/XTC/DTG, or TDF/XTC/DTG between December 2019 and December 2023 at 108 healthcare facilities in KwaZulu-Natal, South Africa. Among people switched before July 2021, we emulated a target trial comparing 24-month death or loss to follow-up (LTFU), and viremia (>50 copies/mL). We conducted intention-to-treat and per-protocol analyses using weighted logistic regression with bootstrapped CIs.
Results: Overall, women were less likely than men to switch to DTG (RR: 0.92 [95% CI: .88, .96]; N = 3649). Of 2321 people switched before July 2021, 915 (39%) switched to AZT/XTC/LPV/r, 415 (18%) to zidovudine (AZT)/XTC/DTG, and 991 (43%) to TDF/XTC/DTG. Median age was 36 years (IQR: 30, 43) and 1364 (59%) were women. In intention-to-treat analyses, the standardized 24-month risk of death or LTFU was similar with AZT/XTC/LPV/r (31%), AZT/XTC/DTG (30%), and TDF/XTC/DTG (34%). The standardized risk of 24-month viremia among those retained in care with a viral load result (N = 1270) was higher with AZT/XTC/LPV/r (50%) than with AZT/XTC/DTG (40%; aRD: -10% [95% CI -19%, -2%]) or TDF/XTC/DTG (39%; aRD: -11% [95% CI -18%, -5%]). Per-protocol analyses gave similar results.
Conclusions: While retention was similar across regimens, viremia was less common on DTG-based ART, supporting current guidelines.
期刊介绍：
Open Forum Infectious Diseases provides a global forum for the publication of clinical, translational, and basic research findings in a fully open access, online journal environment. The journal reflects the broad diversity of the field of infectious diseases, and focuses on the intersection of biomedical science and clinical practice, with a particular emphasis on knowledge that holds the potential to improve patient care in populations around the world. Fully peer-reviewed, OFID supports the international community of infectious diseases experts by providing a venue for articles that further the understanding of all aspects of infectious diseases.
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