Trends in multidrug treatment failure and subsequent mortality among antiretroviral therapy-experienced patients with HIV infection in North America.

TitleTrends in multidrug treatment failure and subsequent mortality among antiretroviral therapy-experienced patients with HIV infection in North America.
Publication TypeJournal Article
Year of Publication2009
AuthorsDeeks SG, Gange SJ, Kitahata MM, Saag MS, Justice AC, Hogg RS, Eron JJ, Brooks JT, Rourke SB, M Gill J, Bosch RJ, Benson CA, Collier AC, Martin JN, Klein MB, Jacobson LP, Rodriguez B, Sterling TR, Kirk GD, Napravnik S, Rachlis AR, Calzavara LM, Horberg MA, Silverberg MJ, Gebo KA, Kushel MB, Goedert JJ, McKaig RG, Moore RD
JournalClin Infect Dis
Volume49
Issue10
Pagination1582-90
Date Published2009 Nov 15
ISSN1537-6591
KeywordsAdult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Cohort Studies, Drug Resistance, Multiple, Viral, Female, HIV, HIV Infections, Humans, Male, Middle Aged, Models, Statistical, North America, Survival Analysis, Treatment Failure, Viral Load
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.

DOI10.1086/644768
Alternate JournalClin. Infect. Dis.
PubMed ID19845473
PubMed Central IDPMC2871149
Grant ListAHQ290-01-0012 / / PHS HHS / United States
AI-69432 / AI / NIAID NIH HHS / United States
K01-AI071754 / AI / NIAID NIH HHS / United States
K23-AI-61-0320 / AI / NIAID NIH HHS / United States
K24-00432 / / PHS HHS / United States
M01-RR00071 / RR / NCRR NIH HHS / United States
M01-RR00079 / RR / NCRR NIH HHS / United States
M01-RR00083 / RR / NCRR NIH HHS / United States
M01-RR00722 / RR / NCRR NIH HHS / United States
N02-CP55504 / CP / NCI NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
P30-AI27757 / AI / NIAID NIH HHS / United States
P30-AI27767 / AI / NIAID NIH HHS / United States
P30-AI50410 / AI / NIAID NIH HHS / United States
P30-AI54999 / AI / NIAID NIH HHS / United States
R01 AA016893 / AA / NIAAA NIH HHS / United States
R01 DA004334 / DA / NIDA NIH HHS / United States
R01-AA16893 / AA / NIAAA NIH HHS / United States
R01-DA04334 / DA / NIDA NIH HHS / United States
R01-DA11602 / DA / NIDA NIH HHS / United States
R01-DA12568 / DA / NIDA NIH HHS / United States
R01-MH54907 / MH / NIMH NIH HHS / United States
R24-AI067039 / AI / NIAID NIH HHS / United States
R56 DA004334 / DA / NIDA NIH HHS / United States
U01 AI069918 / AI / NIAID NIH HHS / United States
U01 AI069918-01 / AI / NIAID NIH HHS / United States
U01-AA013566 / AA / NIAAA NIH HHS / United States
U01-AI069918 / AI / NIAID NIH HHS / United States
U01-AI31834 / AI / NIAID NIH HHS / United States
U01-AI34989 / AI / NIAID NIH HHS / United States
U01-AI34993 / AI / NIAID NIH HHS / United States
U01-AI34994 / AI / NIAID NIH HHS / United States
U01-AI35004 / AI / NIAID NIH HHS / United States
U01-AI35039 / AI / NIAID NIH HHS / United States
U01-AI35040 / AI / NIAID NIH HHS / United States
U01-AI35041 / AI / NIAID NIH HHS / United States
U01-AI35042 / AI / NIAID NIH HHS / United States
U01-AI35043 / AI / NIAID NIH HHS / United States
U01-AI37613 / AI / NIAID NIH HHS / United States
U01-AI37984 / AI / NIAID NIH HHS / United States
U01-AI38855 / AI / NIAID NIH HHS / United States
U01-AI38858 / AI / NIAID NIH HHS / United States
U01-AI42590 / AI / NIAID NIH HHS / United States
U01-AI68634 / AI / NIAID NIH HHS / United States
U01-AI68636 / AI / NIAID NIH HHS / United States
U01-HD32632 / HD / NICHD NIH HHS / United States
Z01-CP010176 / CP / NCI NIH HHS / United States