Along
with the CD4 receptor, HIV must also attach to one of 2 co-receptors to enter
host cells: CCR5 or CXCR4. Patients can have HIV that is CCR5-tropic (uses the
CCR5 co-receptor), CXCR4-tropic, dual-tropic (able to use both co-receptors),
or a mix of CCR5-tropic and CCR4-tropic (collectively known as dual/mixed, or
D/M-tropic).
Prior research has indicated that CXCR4-tropic HIV strains
tend to predominate later in the course of disease and appear to be associated
with more rapid disease progression.
Now,
new research published in the May 15, 2008 issue of Clinical Infectious Diseases
shows that individuals with CXCR4-tropic or dual/mixed-tropic HIV experience more
rapid CD4 cell loss and are at greater risk of clinical illness than those with
exclusively CCR5-tropic strains.
British investigators looked at the relationship
between co-receptor tropism and decreases in CD4 cell count before starting antiretroviral
therapy, the frequency of clinical events, and response to treatment in a cohort
of more than 400 treatment-naive participants.
Results
•
Of the 402
total patients, 326 harbored CCR5-tropic virus and 76 had CXCR4-tropic or dual/mixed-tropic
HIV.
•
Those with
CXCR4-tropic or dual/mixed-tropic virus had a lower CD4 cell count at baseline
than those with CCR5-tropic virus (median 203 vs 325 cells/mm3).
•
After adjusting
for baseline characteristics, individuals with CXCR4-tropic or dual/mixed-tropic
virus had a significantly greater rate of CD4 cell decline at 12 months (P = 0.026).
•
229 cohort
participants with CCR5-tropic virus and 60 with CXCR4-tropic or dual/mixed-tropic
virus started antiretroviral therapy between the time of initial tropism testing
and the time of data analysis.
•
The time to
viral suppression and the proportion of patients achieving viral suppression were
similar in the 2 groups at 6, 12, and 24 months.
•
CD4 cell count
increases after starting treatment were also similar (182 vs 185 cells/mm3).
•
Clinical events
were significantly more common in the patients with CXCR4-tropic or dual/mixed-tropic
HIV compared to those with CCR5-tropic virus (22% vs 7%, respectively).
•
In a multivariate
analysis, patients with CXCR4-tropic or dual/mixed-tropic virus were more than
twice as likely to experience a clinical event (relative risk 2.56; P = 0.003).
Conclusion
"The
presence of [dual/mixed or CXCR4-tropic] virus has a deleterious effect on CD4
cell count decrease and risk of clinical disease," the study authors wrote
in conclusion.
However, they noted that, "Response to standard antiretroviral
therapy is not affected by viral tropism."
Since individuals with
CXCR4-tropic or dual/mixed-tropic HIV experienced faster CD4 cell decline and
more clinical events, but responded equally well to therapy, these findings suggest
that such patients may benefit from earlier antiretroviral therapy.
St.
Stephens AIDS Trust, Department of Genitourinary/HIV Medicine, Chelsea and Westminster
Hospital, London, UK.
5/06/08
Reference L
Waters, S Mandalia, P Randell, and others. The impact of HIV tropism on decreases
in CD4 cell count, clinical progression, and subsequent response to first antiretroviral
therapy regimen. Clinical Infectious Diseases 46(10): 1617-1623. May 15,
2008.
Along
with the CD4 receptor, HIV must also attach to one of 2 co-receptors to enter
host cells: CCR5 or CXCR4. Patients can have HIV that is CCR5-tropic (uses the
CCR5 co-receptor), CXCR4-tropic, dual-tropic (able to use both co-receptors),
or a mix of CCR5-tropic and CCR4-tropic (collectively known as dual/mixed, or
D/M-tropic).
Results
