Trends in multidrug treatment failure and subsequent mortality among antiretroviral therapy-experienced patients with HIV infection in North America.
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.
Deeks
Steven G
SG
University of California-San Francisco, San Francisco, San Diego, CA 94110, USA. sdeeks@php.ucsf.edu
Gange
Stephen J
SJ
Kitahata
Mari M
MM
Saag
Michael S
MS
Justice
Amy C
AC
Hogg
Robert S
RS
Eron
Joseph J
JJ
Brooks
John T
JT
Rourke
Sean B
SB
Gill
M John
MJ
Bosch
Ronald J
RJ
Benson
Constance A
CA
Collier
Ann C
AC
Martin
Jeffrey N
JN
Klein
Marina B
MB
Jacobson
Lisa P
LP
Rodriguez
Benigno
B
Sterling
Timothy R
TR
Kirk
Gregory D
GD
Napravnik
Sonia
S
Rachlis
Anita R
AR
Calzavara
Liviana M
LM
Horberg
Michael A
MA
Silverberg
Michael J
MJ
Gebo
Kelly A
KA
Kushel
Margot B
MB
Goedert
James J
JJ
McKaig
Rosemary G
RG
Moore
Richard D
RD
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D024921:Drug Resistance, Multiple, Viral; D005260:Female; D006678:HIV / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009656:North America; D016019:Survival Analysis; D017211:Treatment Failure; D019562:Viral Load
D019380:Anti-HIV Agents