美国艾滋病恶性联盟Susan E Krown小组近日取得一项新成果。他们探索了在资源有限的环境中治疗晚期艾滋病相关的卡波西肉瘤的有效方案。该研究成果于2020年3月5日发表于《柳叶刀》杂志上。
Title: Treatment of advanced AIDS-associated Kaposi sarcoma in resource-limited settings: a three-arm, open-label, randomised, non-inferiority trial
Author: Susan E Krown, Carlee B Moser, Patrick MacPhail, Roy M Matining, Catherine Godfrey, Stephanie R Caruso, Mina C Hosseinipour, Wadzanai Samaneka, Mulinda Nyirenda, Naftali W Busakhala, Fred M Okuku, Josphat Kosgei, Brenda Hoagland, Noluthando Mwelase, Vincent O Oliver, Henriette Burger, Rosie Mngqibisa, Mostafa Nokta, Thomas B Campbell, Margaret Z Borok, Agnes Moses, Cecilia Kanyama, Pamela Mukwekwerere, Ivy Gudza, Felluna Chauwa, Godwin Ulaya, Irene Kutto, Priscilla Cheruiyot, Clement Okello, Annet Nakaganda, Geoffrey Koskei, Winnie Keter, Juliana Netto, Tamiris Baio, Iveshni Govender, Jessica OConnell-Maritz, Kevin Cain, John Okanda, Lynne Cornelissen, Marije Van Schalkwyk, Rejoice Sikhosana, Minenhle Ngcobo, Jeannette Y. Lee, Taylor Harrison, William Wachsman, Katherine Shin, Scott Evans, Jennifer Rothenberg, Lara Hosey, Sean McCarthy, Otoniel Martinez-Maza, Charles Rinaldo, Dirk Dittmer, Charles Rinaldo, Courtney Fletcher, Michelle Rudek, Aida Asmelash, Valery Hughes, Jeffrey Schouten, David Shugarts, Tapiwanashe Kujinga, Amanda Zadzilka, Fredrick Kerui, Debora Robertson, James Rooney, Krishna Sewal, Brian Gottshall
Abstract: BackgroundOptimal treatment regimens for AIDS-associated Kaposi sarcoma, a frequent contributor to morbidity and mortality among people with HIV, have not been systematically evaluated in low-income and middle-income countries, where the disease is most common. In this study, we aimed to investigate optimal treatment strategies for advanced stage disease in areas of high prevalence and limited resources.MethodsIn this open-label, non-inferiority trial, we enrolled people with HIV and advanced stage AIDS-associated Kaposi sarcoma attending 11 AIDS Clinical Trials Group sites in Brazil, Kenya, Malawi, South Africa, Uganda, and Zimbabwe. Eligible participants were randomly assigned (1:1:1) with a centralised computer system to receive either intravenous bleomycin and vincristine or oral etoposide (the investigational arms), or intravenous paclitaxel (the control arm), together with antiretroviral therapy (ART; combined efavirenz, tenofovir disoproxil fumarate, and emtricitabine). The primary outcome was progression-free survival (PFS) at week 48, using a 15% non-inferiority margin to compare the investigational groups against the active control group. Safety was assessed in all eligible treated study participants. The study was registered with ClinicalTrials.gov, NCT01435018.Findings334 participants were enrolled between Oct 1, 2013, and March 8, 2018, when the study was closed early due to inferiority of the bleomycin and vincristine plus ART arm, as per the recommendations of the Data and Safety Monitoring Board (DSMB). The etoposide plus ART arm also closed due to inferiority in March, 2016, following a DSMB recommendation. Week-48 PFS rates were higher in the paclitaxel plus ART arm than in both investigational arms. The absolute differences in PFS were 30% (95% CI 52 to 8) for the comparison of paclitaxel plus ART (week 48 PFS 50%, 32 to 67; n=59) and etoposide plus ART (20%, 6 to 33; n=59), and 20% (33% to 7%) for the comparison of paclitaxel plus ART (64%, 55 to 73; n=138) and bleomycin and vincristine plus ART (44%, 35 to 53; n=132). Both CIs overlapped the non-inferiority margin. The most common adverse events, in 329 eligible participants who began treatment, were neutropenia (48 [15%]), low serum albumin (33 [10%]), weight loss (29 [9%]), and anaemia (28 [9%]), occurring at similar frequency across treatment arms.InterpretationNon-inferiority of either investigational intervention was not shown, with paclitaxel plus ART showing superiority to both oral etoposide plus ART and bleomycin and vincristine plus ART, supporting its use in treating advanced AIDS-associated Kaposi sarcoma in resource-limited settings.