BACKGROUND: Raltegravir became the first integrase inhibitor to gain FDA approval; but with limited evidence documenting long-term risks in real world care, especially for major health outcomes of interest. OBJECTIVE: Assess raltegravir safety in clinical practice within an integrated health system. METHODS: We conducted a cohort study of HIV-infected adults within Kaiser Permanente California from 2005 to 2013. We compared patients initiating raltegravir during the study period with two groups; a historical cohort (started new antiretroviral regimen [ART] 2005-2007) and a concurrent cohort that did not initiate raltegravir (2007-2013). We used multivariate Cox proportional hazard regression to obtain hazard ratios (HR) for pre-specified incident health outcomes, employing propensity scores to adjust for potential confounding. RESULTS: The population included 8,219 HIV-infected adults (raltegravir cohort N = 1,757; 4,798 patient-years), with greater years known HIV-infected among raltegravir patients. The raltegravir cohort had increased HR for AIDS-defining (HR 2.69 [1.53-4.71]; HR 1.85 [1.21-2.82]) and non-AIDS-defining malignancies (HR 2.26 [1.29-3.94]; HR 1.88 [1.26-2.78]) relative to both comparison cohorts. Compared to the historical cohort we found no significant difference in all-cause mortality; the raltegravir cohort experienced increased HR for all-cause mortality compared to concurrent (HR 1.53 [1.02-2.31]). Raltegravir appeared protective of lipodystrophy when compared to the historical cohort but associated with increased incidence compared to concurrent. There were no significant differences in the incidence of hepatic, skin, or cardiovascular events. CONCLUSIONS: The potentially elevated risk for malignancy and mortality with raltegravir and residual confounding merits further investigation. We demonstrate the value of observational cohorts for monitoring post-licensure medication safety.
BACKGROUND:Raltegravir became the first integrase inhibitor to gain FDA approval; but with limited evidence documenting long-term risks in real world care, especially for major health outcomes of interest. OBJECTIVE: Assess raltegravir safety in clinical practice within an integrated health system. METHODS: We conducted a cohort study of HIV-infected adults within Kaiser Permanente California from 2005 to 2013. We compared patients initiating raltegravir during the study period with two groups; a historical cohort (started new antiretroviral regimen [ART] 2005-2007) and a concurrent cohort that did not initiate raltegravir (2007-2013). We used multivariate Cox proportional hazard regression to obtain hazard ratios (HR) for pre-specified incident health outcomes, employing propensity scores to adjust for potential confounding. RESULTS: The population included 8,219 HIV-infected adults (raltegravir cohort N = 1,757; 4,798 patient-years), with greater years known HIV-infected among raltegravirpatients. The raltegravir cohort had increased HR for AIDS-defining (HR 2.69 [1.53-4.71]; HR 1.85 [1.21-2.82]) and non-AIDS-defining malignancies (HR 2.26 [1.29-3.94]; HR 1.88 [1.26-2.78]) relative to both comparison cohorts. Compared to the historical cohort we found no significant difference in all-cause mortality; the raltegravir cohort experienced increased HR for all-cause mortality compared to concurrent (HR 1.53 [1.02-2.31]). Raltegravir appeared protective of lipodystrophy when compared to the historical cohort but associated with increased incidence compared to concurrent. There were no significant differences in the incidence of hepatic, skin, or cardiovascular events. CONCLUSIONS: The potentially elevated risk for malignancy and mortality with raltegravir and residual confounding merits further investigation. We demonstrate the value of observational cohorts for monitoring post-licensure medication safety.
Entities:
Keywords:
Raltegravir; drug safety; observational treatment comparison; propensity scores
Authors: Jim Young; Vincent Lo Re; H Nina Kim; Timothy R Sterling; Keri N Althoff; Kelly A Gebo; M John Gill; Michael A Horberg; Angel M Mayor; Richard D Moore; Michael J Silverberg; Marina B Klein Journal: Pharmacoepidemiol Drug Saf Date: 2021-11-23 Impact factor: 2.732
Authors: Anne K Monroe; Matthew E Levy; Alan E Greenberg; Jeanne C Keruly; Richard D Moore; Michael A Horberg; Paige Kulie; Bernadine S Mohanraj; Princy N Kumar; Amanda D Castel Journal: Open Forum Infect Dis Date: 2021-07-27 Impact factor: 3.835
Authors: Lauren Greenberg; Lene Ryom; Bastian Neesgaard; Jose M Miró; Line Dahlerup Rasmussen; Robert Zangerle; Katharina Grabmeier-Pfistershammer; Huldrych F Günthard; Katharina Kusejko; Colette Smith; Cristina Mussini; Marianna Menozzi; Ferdinand Wit; Marc Van Der Valk; Antonella d'Arminio Monforte; Stéphane De Wit; Coca Necsoi; Annegret Pelchen-Matthews; Jens Lundgren; Lars Peters; Antonella Castagna; Camilla Muccini; Jörg Janne Vehreschild; Christian Pradier; Andreu Bruguera Riera; Anders Sönnerborg; Kathy Petoumenos; Harmony Garges; Felipe Rogatto; Nikos Dedes; Loveleen Bansi-Matharu; Amanda Mocroft Journal: Open Forum Infect Dis Date: 2022-01-19 Impact factor: 3.835
Authors: Haidong Lu; Stephen R Cole; Daniel Westreich; Michael G Hudgens; Adaora A Adimora; Keri N Althoff; Michael J Silverberg; Kate Buchacz; Jun Li; Jessie K Edwards; Peter F Rebeiro; Viviane D Lima; Vincent C Marconi; Timothy R Sterling; Michael A Horberg; M John Gill; Mari M Kitahata; Joseph J Eron; Richard D Moore Journal: Clin Infect Dis Date: 2021-10-05 Impact factor: 9.079