Improvements
in antiretroviral therapy over
the past decade have dramatically reduced the risk of disease progression and
death in people with HIV. Yet while state-of-the-art
HAART allows many HIV positive
individuals to keep their viral load under control, virological failure remains
a concern for some patients.
As
reported at the 15th Conference on Retroviruses and Opportunistic
Infections this month in Boston, researchers with the North American AIDS
Cohort Collaboration on Research and Design -- part of the larger International
Epidemiologic Databases to Evaluate AIDS collaboration - conducted an analysis
of rates of, risk factors for, and outcomes following virological failure of a
second HAART regimen.
The analysis included more than 33,000 HIV positive
participants who initiated HAART in 16 cohorts in the U.S. and Canada. The investigators
identified patients who demonstrated virological failure (defined as either failure
to suppress HIV RNA < 400 copies/mL or rebound to > 1000 copies/mL), modified
therapy, and subsequently experienced a second failure. They looked at treatment
switches involving the non-NRTI
component of a regimen, i.e., switching from a NNRTI to a protease
inhibitor or vice versa.
Results
•
Of the individuals who started HAART, 15,457 experienced a first virological failure.
•
Of
these, 9337 switched therapy and 5057 experienced a second failure after modifying
their regimen.
•
Follow-up data were available for 4242 patients, accounting for 14,485 total person-years
(PY) of follow-up.
•
The subgroup who experienced second virological failure was 85% men with a median
age of 44 years, a median CD4 cell count of 222 cells/mm3, and a median viral
load of 15, 723 copies/mL.
•
31% were antiretroviral-naive when they started their first HAART regimen, while
the rest had some treatment experience (including NRTI
monotherapy or dual therapy).
•
The rate of virological failure declined over time:
•
114 cases per 100 PY during the early HAART years (1996-1997); •
71 per 100 PY in 1998-1999; •
42 per 100 PY in 2000-2001; •
18 per 100 PY in 2002-2003; •
15 per 100 PY in 2004-2005.
•
1126 patients died during follow-up, a median of 7.1 years after experiencing
the second virological failure.
•
Higher HIV RNA, lower CD4 cell count, and clinical AIDS at the time of second
failure were associated with an increased risk of death.
•
However, antiretroviral experience prior to the first combination HAART regimen,
total number of HAART regimens, time since the first HAART regimen, and pre-HAART
HIV RNA and CD4 count were not associated with greater mortality risk.
Conclusion
"The
risk of progressing to a second episode of virologic failure on HAART has declined
dramatically over the past decade," the researchers concluded.
However,
they added, "Mortality after second HAART failure has not improved over time."
Finally,
they recommended that patients at greatest risk of death based on the identified
factors should be managed as quickly as possible when virological failure occurs,
and emphasized the importance of access to new drugs for patients who experience
multiple treatment failures in resource-poor settings.
2/29/08
Reference S
Deeks, R Moore, and others (North American AIDS Cohort Collaboration on Research
and Design of the IeDEA). Trends in Second Virologic Failure and Predictors of
Subsequent Mortality among ART-experienced Patients: North American Experience.
15th Conference on Retroviruses and Opportunistic Infections (CROI 2008). Boston,
MA. February 3-6, 2008. Abstract 41.
Second
Virological Failure on Antiretroviral Therapy Is Now Less Common, but Still Hazardous
Results
