Melanie Stecher1,2, Annika Claßen1,2, Florian Klein2,3,4, Clara Lehmann1,2, Henning Gruell1,2,3, Martin Platten5, Christoph Wyen1,6, Georg Behrens7,8, Gerd Fätkenheuer1,2, Jörg Janne Vehreschild1,2,9. 1. Department I for Internal Medicine, University Hospital of Cologne. 2. German Center for Infection Research, Partner Site Bonn-Cologne. 3. Laboratory of Experimental Immunology, Institute of Virology. 4. Center for Molecular Medicine Cologne, University of Cologne. 5. Labor Dr. Wisplinghoff, Cologne. 6. Praxis am Ebertplatz, Cologne. 7. Department for Clinical Immunology and Rheumatology Hannover Medical School. 8. German Center for Infection Research, Partner Site Hannover. 9. Medical Department II, University Hospital of Frankfurt, Germany.
Abstract
BACKGROUND: Safety and tolerability of analytical treatment interruptions (ATIs) as a vital part of human immunodeficiency virus type 1 (HIV-1) cure studies are discussed. We analyzed current evidence for the occurrence of adverse events (AEs) during TIs. METHODS: Our analysis included studies that reported on AEs in HIV-1-infected patients undergoing TIs. All interventional and observational studies were reviewed, and results were extracted based on predefined criteria. The proportion of AEs was pooled using random-effects models. Metaregression was used to explore the influence of baseline CD4+ T-cell count, viral load, study type, previous time on combined antiretroviral therapy, and follow-up interval during TIs. RESULTS: We identified 1048 studies, of which 22 studies including 7104 individuals fulfilled the defined selection criteria. Included studies had sample sizes between 6 and 5472 participants, with durations of TI cycles ranging from 7 days to 27 months. The intervals of HIV-1-RNA testing varied from 2 days to 3 months during TIs. The overall proportion of AEs during TIs >4 weeks was 3% (95% confidence interval [CI], 0%-7%) and was lower in studies with follow-up intervals ≤14 days (0%; 95% CI, 0%-1%) than in studies with wider follow-up intervals (6%; 95% CI, 2%-13%; P value for interaction = .01). CONCLUSIONS: We found moderate-quality evidence indicating that studies with narrow follow-up intervals did not show a substantial increase in AEs during TIs. Our findings indicate that ATI may be a safe strategy as part of HIV-1 cure trials by closely monitoring for HIV-1 rebound.
BACKGROUND: Safety and tolerability of analytical treatment interruptions (ATIs) as a vital part of human immunodeficiency virus type 1 (HIV-1) cure studies are discussed. We analyzed current evidence for the occurrence of adverse events (AEs) during TIs. METHODS: Our analysis included studies that reported on AEs in HIV-1-infected patients undergoing TIs. All interventional and observational studies were reviewed, and results were extracted based on predefined criteria. The proportion of AEs was pooled using random-effects models. Metaregression was used to explore the influence of baseline CD4+ T-cell count, viral load, study type, previous time on combined antiretroviral therapy, and follow-up interval during TIs. RESULTS: We identified 1048 studies, of which 22 studies including 7104 individuals fulfilled the defined selection criteria. Included studies had sample sizes between 6 and 5472 participants, with durations of TI cycles ranging from 7 days to 27 months. The intervals of HIV-1-RNA testing varied from 2 days to 3 months during TIs. The overall proportion of AEs during TIs >4 weeks was 3% (95% confidence interval [CI], 0%-7%) and was lower in studies with follow-up intervals ≤14 days (0%; 95% CI, 0%-1%) than in studies with wider follow-up intervals (6%; 95% CI, 2%-13%; P value for interaction = .01). CONCLUSIONS: We found moderate-quality evidence indicating that studies with narrow follow-up intervals did not show a substantial increase in AEs during TIs. Our findings indicate that ATI may be a safe strategy as part of HIV-1 cure trials by closely monitoring for HIV-1 rebound.
Authors: Karen L Diepstra; Liz Barr; David Palm; Evelyn Hogg; Katie R Mollan; Laney Henley; Angela M Stover; Jane M Simoni; Jeremy Sugarman; Brandon Brown; John A Sauceda; Steven Deeks; Lawrence Fox; Rajesh T Gandhi; Davey Smith; Jonathan Z Li; Karine Dubé Journal: AIDS Res Hum Retroviruses Date: 2021-02-16 Impact factor: 1.723
Authors: Karine Dubé; John Kanazawa; Jeff Taylor; Lynda Dee; Nora Jones; Christopher Roebuck; Laurie Sylla; Michael Louella; Jan Kosmyna; David Kelly; Orbit Clanton; David Palm; Danielle M Campbell; Morénike Giwa Onaiwu; Hursch Patel; Samuel Ndukwe; Laney Henley; Mallory O Johnson; Parya Saberi; Brandon Brown; John A Sauceda; Jeremy Sugarman Journal: BMC Med Ethics Date: 2021-06-30 Impact factor: 2.834