@article{df446560af2f4aa9a93b52fa2a678e14,
title = "Trends in multidrug treatment failure and subsequent mortality among antiretroviral therapy-experienced patients with HIV infection in North America",
abstract = "Background: Although combination antiretroviral therapy continues to evolve, with potentially more effective options emerging each year, the ability of therapy to prevent multiple regimen failure and mortality in clinical practice remains poorly defined. Methods: Sixteen cohorts representing over 60 sites contributed data on all individuals who initiated combination antiretroviral therapy. We identified those individuals who experienced virologic failure (defined as a human immunodeficiency virus [HIV] RNA level >1000 copies/mL), received modified therapy, and subsequently had a second episode of virologic failure. Multivariate Cox regression was used to assess factors associated with time to second regimen failure and the time to death after the onset of second regimen failure. Results: Of the 42,790 individuals who received therapy, 7159 experienced a second virologic failure. The risk of second virologic failure decreased from 1996 (56 cases per 100 person-years) through 2005 (16 cases per 100 person-years; P < .001). The cumulative mortality after onset of second virologic failure was 26% at 5 years and decreased over time. A history of AIDS, a lower CD4+ T cell count, and a higher plasma HIV RNA level were each independently associated with mortality. Similar trends were observed when analysis was limited to the subset of previously treatment-naive patients Conclusions: Although the rates of multiple regimen failure have decreased dramatically over the past decade, mortality rates for those who have experienced failure of at least 2 regimens have remained high. Plasma HIV RNA levels, CD4+ T cell counts at time of treatment failure, and a history of AIDS remain independent risk factors for death, which emphasizes that these factors remain important targets for those in need of more-aggressive therapeutic interventions.",
author = "Deeks, {Steven G.} and Gange, {Stephen J.} and Kitahata, {Mari M.} and Saag, {Michael S.} and Justice, {Amy C.} and Hogg, {Robert S.} and Eron, {Joseph J.} and Brooks, {John T.} and Rourke, {Sean B.} and Gill, {M. John} and Bosch, {Ronald J.} and Benson, {Constance A.} and Collier, {Ann C.} and Martin, {Jeffrey N.} and Klein, {Marina B.} and Jacobson, {Lisa P.} and Benigno Rodriguez and Sterling., {Timothy R.} and Kirk, {Gregory D.} and Sonia Napravnik and Rachlis, {Anita R.} and Calzavara, {Liviana M.} and Horberg, {Michael A.} and Silverberg, {Michael J.} and Gebo, {Kelly A.} and Kushel, {Margot B.} and Goedert, {James J.} and McKaig, {Rosemary G.} and Moore, {Richard D.}",
note = "Funding Information: Potential conflicts of interest. S.G.D. has received consulting fees from GlaxoSmithKline, Roche, Gilead, and Boehringer-Ingelheim and grant support from Merck, Gilead, Bristol-Myers Squibb, and Pfizer. M.S.S. has received consulting fees from Ardea Biosciences, Avexa, Boehringer-Ingel-heim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck, Monogram Biosciences, Pain Therapeutics, Panacos, Pfizer, Progenics, Roche Laboratories, Tibotec, Tobira Therapeutics, and Vicro and research support from Achillion Pharmaceuticals, Boehringer-Ingelheim, Merck, Pfizer, Progenics, and Tibotec. J.J.E. has received consulting fees from Ti-botec, Bristol-Myers Squibb, Merck, GlaxoSmithKline, and Pfizer; lecture fees from Roche, Bristol-Myers Squibb, Tibotec, and Merck; and grant support from GlaxoSmithKline, Merck, and Boehringer-Ingelheim. J.G. has received consulting fees from Gilead, Abbott, Merck, Boehringer-Ingelheim, Tibotec, and Pfizer and grant support from GlaxoSmithKline, Abbott, Canadian Institutes of Health Research, Tibotec, and Pfizer. R.S.H. has received payment from a commercial entity that sponsored his study and grant support from Merck. M. B. Klein has received consulting fees from GlaxoSmithKline, Abbott, Pfizer, and Boehringer-Ingelheim; lecture fees from Abbott, Gilead, Tibotec, Bristol-Myers Squibb, and GlaxoSmithKline; and research support from Canadian Institutes of Health Research/Fonds de la recherche en sant{\'e} du Qu{\'e}bec, Canadian HIV Trials Network, Ontario HIV Treatment Network, and Schering Plough Canada. A.R.R. has received consulting fees and lecture fees from GlaxoSmithKline, Abbott, Merck, Pfizer, and Tibotec and grant support from GlaxoSmithKline, Tibotec, Boehringer-Ingelheim, Abbott, Merck, Pfizer, and Roche. M.A.H. has received grant support from Gilead, Abbott, and Bristol-Myers Squibb. M.J.S. has received grant support from Pfizer, Merck, Gilead, Universitywide AIDS Research Program, and Community Benefit/Kaiser Permanente; K.A.G. has received consulting fees from Tibotec and grant support from Johns Hopkins University Richard Ross Award and Agency for Healthcare Research and Quality. R.D.M. has received consulting fees from Bristol-Myers Squibb and Glaxo-SmithKline; lecture fees from Gilead; and grant support from Pfizer, Merck, Gilead, and Agency for Healthcare Research and Quality. A.C.C. has received consulting fees from Merck, Pfizer, and GlaxoSmithKline; has equity ownership/stock options in Bristol-Myers Squibb and Abbott; and has received grant support from Schering-Plough, Tibotec-Virco, Gilead, Koronis, and Merck. C.A.B. has received consulting fees from GlaxoSmithKline, Pfizer, Merck, and Achillion and grant support from Gilead. B.R. has received consulting fees from Gilead and Bristol-Myers Squibb, lecture fees from Bristol-Myers Squibb, and grant support from STERIS. All other authors: no conflicts.",
year = "2009",
month = nov,
doi = "10.1086/644768",
language = "English (US)",
volume = "49",
pages = "1582--1590",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "10",
}