While
CD4 cell count usually begins to rise as HIV viral load falls when patients start
antiretroviral therapy, immunological
recovery may lag behind HIV RNA reduction, and there is considerable individual
variation. Different drug classes,
too, may be associated with different degrees of CD4 cell recovery, according
to a presentation at the 15th Conference on Retroviruses
and Opportunistic Infections last month in Boston.
Researchers from
Weill Medical College and Harvard School of Public Health performed a meta-analysis
of recent Phase II and III trials that evaluated new therapies in treatment-experienced
patients, including:
All
agents were used in combination with an optimized background regimen. For each
arm of each trial, the investigators collected baseline characteristics, the proportion
of patients achieving plasma HIV RNA below 50 copies/mL, and CD4 cell gains 24
weeks after starting an optimized regimen containing one of the new drugs.
Results
•
The analysis included 37 treatment arms in 16 clinical
trials, including 9 arms from 4 clinical trials testing a CCR5 antagonist.
•
Use of a CCR5 antagonist was associated with an additional
gain of 32 CD4 cells/mm3 at 24 weeks compared to regimens without a CCR5 inhibitor.
•
In a multivariate model, CD4 cell gains were also associated
with:
•
baseline viral load (additional 21 cells/mm3 per 0.5 log10
higher HIV RNA);
•
virological response at week 24 (additional 11 cells/
mm3 per 10% greater proportion of patients with HIV RNA < 50 copies/mL).
•
However, in this model, CD4 cell increases were not associated
with patient age, sex, or baseline CD4 count.
Conclusion
Based
on these findings, the researchers concluded, "Use of a CCR5 inhibitor was
associated with an enhanced CD4 cell count response in treatment-experienced patients
initiating an optimized antiretroviral regimen compared to other regimens."
"This
effect was independent of the degree of virologic suppression," they added.
"The durability and clinical significance of this observation remain to be
determined, but could be explored in subjects with discordant immunologic and
virologic responses to therapy."
Though the investigators were unable
to explain the mechanism underlying the apparent greater immunological recovery
in patients taking CCR5 antagonists, this may be a promising strategy for individuals
with discordant response to HAART, who were shown
in a recent study to have poorer outcomes.
Do
CCR5 Antagonists Boost CD4 Cell Counts More than Other Antiretroviral Drug Classes?
Results
