Current
HIV treatment guidelines recommend
prompt modification of combination
antiretroviral therapy in patients who do not achieve full viral load suppression,
but this recommendation has not been directly tested in observational studies
or randomized clinical trials.
In a study presented as a poster at the
15th Conference on Retroviruses and Opportunistic Infections
last month in Boston, researchers analyzed prospective data from 2 U.S. clinical
cohorts (Johns Hopkins in Baltimore and University of North Carolina in Chapel
Hill) followed prospectively between 1990 and 2006 to estimate the effect of delaying
regimen modification following a first virological failure while on HAART.
They also compared the effect of early versus delayed treatment modification among
patients failing on a protease
inhibitor (PI)-based versus a non-PI-based (usually
NNRTI-based) regimen.
Virological failure was defined as 2 consecutive
viral load measurements above 1000 copies/mL 12-24 weeks after starting therapy,
or above 500 copies/mL after week 24. Treatment modification was defined as switching
to a new antiretroviral drug class or to 2 or more new agents not in the failing
regimen.
Results
•
A total of 982 subjects contributed a total of 3414 person-years
of follow-up after a first regimen failure.
•
Most first HAART failures (76%) occurred among patients
treated with at least 1 PI, including 32% using a ritonavir-boosted PI.
•
After controlling for time-dependent confounding by HIV
RNA level, CD4 cell count, treatment experience, HIV risk group, and other factors,
delaying treatment modification was associated with an elevated risk of all-cause
mortality among patients on a failing non-PI-based regimen (HR 1.23).
•
However, delayed treatment modification appeared to have
a small protective effect among subjects on a failing PI-based regimen (HR 0.93
per additional 3-month delay).
•
The effect of delaying modification after a second regimen
failure was similar to that observed after a first failure (HR 1.12 for non-PI-based
and 0.88 for PI-based regimens).
Conclusion
"Delay
in modification after failure of NNRTI-based
regimens is associated with increased risk in disease progression," the
investigators concluded, but "PI-based
regimens are less dependent on early vs delayed switching strategies."
They
recommended that, "Efforts should be made to minimize delay until treatment
modification in resource-poor regions, where the vast majority of patients are
starting a NNRTI-based regimen and plasma HIV RNA level monitoring may not be
available."
Univ of California at San Francisco, CA; Univ of California
at Berkeley, CA; Univ of North Carolina at Chapel Hill, NC; Johns Hopkins Univ,
Baltimore, MD.
Antiretroviral
Regimen Should Be Modified Promptly after Virological Failure
Results
