Sergio Serrano-Villar1, Yan Zhou2, Anthony J Rodgers2, Santiago Moreno3. 1. Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Facultad de Medicina, Universidad de Alcalá (IRYCIS), Madrid, Spain sergio.serrano@salud.madrid.org. 2. Merck, North Wales, PA 19454, USA. 3. Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Facultad de Medicina, Universidad de Alcalá (IRYCIS), Madrid, Spain.
Abstract
OBJECTIVES: A low CD4/CD8 ratio during treated HIV identifies individuals with heightened immunoactivation and excess mortality. Whether ART regimens elicit distinct CD4/CD8 ratio recovery remains unknown. We aimed to compare the efficacy of an integrase inhibitor versus a non-nucleoside to normalize the CD4/CD8 ratio. METHODS: We conducted a post hoc analysis of the STARTMRK study, a randomized, blinded, double-dummy Phase III trial of raltegravir versus efavirenz, and each in combination with tenofovir/emtricitabine, in treatment-naive HIV-infected adults. Blinding was maintained for the entire 5 year duration of the study. Kaplan-Meier methods for time-dependent variables were used to calculate the rates of CD4/CD8 normalization at different cut-offs and cumulative probabilities. Cox proportional hazard models were used to compare probabilities of CD4/CD8 normalization by treatment arm. RESULTS:A total of 563 patients were analysed; 81% were males and the mean age (SD) was 37 (10) years. Raltegravir was associated with higher rates of CD4/CD8 ratio normalization at the >0.4 cut-off (median time to normalization = 56 versus 84 days; P = 0.048 by log-rank test). A Cox proportional hazard model stratified based on baseline CD4 counts showed an association between raltegravir and higher rates of CD4/CD8 ratio normalization (HR = 1.23; P = 0.02). CONCLUSIONS: We herein show that normalization of the CD4/CD8 ratio above a clinically meaningful threshold may be dependent on the drug class used. Raltegravir showed faster CD4/CD8 ratio normalization compared with efavirenz, a finding with potential clinical implications. Whether other integrase inhibitors have a similar impact for this outcome remains to be explored.
RCT Entities:
OBJECTIVES: A low CD4/CD8 ratio during treated HIV identifies individuals with heightened immunoactivation and excess mortality. Whether ART regimens elicit distinct CD4/CD8 ratio recovery remains unknown. We aimed to compare the efficacy of an integrase inhibitor versus a non-nucleoside to normalize the CD4/CD8 ratio. METHODS: We conducted a post hoc analysis of the STARTMRK study, a randomized, blinded, double-dummy Phase III trial of raltegravir versus efavirenz, and each in combination with tenofovir/emtricitabine, in treatment-naive HIV-infected adults. Blinding was maintained for the entire 5 year duration of the study. Kaplan-Meier methods for time-dependent variables were used to calculate the rates of CD4/CD8 normalization at different cut-offs and cumulative probabilities. Cox proportional hazard models were used to compare probabilities of CD4/CD8 normalization by treatment arm. RESULTS: A total of 563 patients were analysed; 81% were males and the mean age (SD) was 37 (10) years. Raltegravir was associated with higher rates of CD4/CD8 ratio normalization at the >0.4 cut-off (median time to normalization = 56 versus 84 days; P = 0.048 by log-rank test). A Cox proportional hazard model stratified based on baseline CD4 counts showed an association between raltegravir and higher rates of CD4/CD8 ratio normalization (HR = 1.23; P = 0.02). CONCLUSIONS: We herein show that normalization of the CD4/CD8 ratio above a clinically meaningful threshold may be dependent on the drug class used. Raltegravir showed faster CD4/CD8 ratio normalization compared with efavirenz, a finding with potential clinical implications. Whether other integrase inhibitors have a similar impact for this outcome remains to be explored.
Authors: Sabina Herrera; Borja M Fernandez-Felix; Peter W Hunt; Steven G Deeks; Talía Sainz; Sonya L Heath; Chad J Achenbach; Benigno Rodríguez; Christopher Mathews; Katerina Christopoulos; Kenneth Mayer; Sonia Napravnik; Santiago Moreno; Sergio Serrano-Villar Journal: J Antimicrob Chemother Date: 2020-06-01 Impact factor: 5.790
Authors: Cissy Kityo; Alexander J Szubert; Abraham Siika; Robert Heyderman; Mutsa Bwakura-Dangarembizi; Abbas Lugemwa; Shalton Mwaringa; Anna Griffiths; Immaculate Nkanya; Sheila Kabahenda; Simon Wachira; Godfrey Musoro; Chatu Rajapakse; Timothy Etyang; James Abach; Moira J Spyer; Priscilla Wavamunno; Linda Nyondo-Mipando; Ennie Chidziva; Kusum Nathoo; Nigel Klein; James Hakim; Diana M Gibb; A Sarah Walker; Sarah L Pett Journal: PLoS Med Date: 2018-12-04 Impact factor: 11.069