HIV tropism has a significant impact on the virological
success of first-line antiretroviral therapy, a Spanish study published in the
July 1st edition of the
Journal of Infectious Diseases suggests.
Individuals whose HIV used the CXCR4 co-receptor were significantly
less likely to achieve an undetectable viral load than patients whose virus
used the CCR5 co-receptor. The association between the CXCR4 co-receptor and
poorer outcomes was especially strong in patients infected with HIV subtype B.
In this study patients were receiving treatment with tenofovir/FTC (Truvada) and either nevirapine or atazanavir/ritonavir. No patients received a drug from the CCR5 inhibitor class.
“It may be worthwhile to perform baseline viral tropism
testing before beginning any antiretroviral regimen,” comment the
HIV uses a co-receptor to latch onto CD4 cells.
In the earlier stages of infection, virus using the CCR5
co-receptor predominate, whereas virus utilising CXCR4 tends to be associated
with the later stages of HIV infection.The preference for a receptor type is called tropism, and can be determined by tropism testing.
In patients who are not taking antiretroviral treatment, the
presence of CXCR4 virus has been associated with faster disease progression. Tropism testing is recommended before starting treatment with the CCR5 inhibitor maraviroc (Celsentri), the only licensed drug in this class of antiretroviral.
the impact of co-receptor tropism on the outcomes of first-line HIV treatment that does not contain a CCR5 inhibitor is
Investigators from the Hospital Carlos III in Madrid
therefore performed a retrospective study involving treatment-naïve patients
who were enrolled into a randomised study. This was designed to compare the
efficacy of therapy based on atazanavir (Reyataz)
boosted by ritonavir (Norvir) with
treatment including nevirapine (Viramune).
The patients also took Truvada
(FTC/tenofovir), and results showed that the combinations were equally
Blood samples obtained at the start of therapy were tested
to determine which co-receptor was used by patients’ virus.
Changes in viral load and CD4 cell count after six and
twelve months of treatment were compared according to co-receptor.
A total of 569 patients were randomised and 428 completed 48
weeks of treatment.
Virus using the CXCR4 co-receptor was found in 14%, and 22%
of individuals were infected with a non-subtype B strain of HIV.
At baseline, patients with CXCR4 virus had significantly
higher viral load (5.4 vs. 5.2 log10 copies/ml; p =0.044) and lower
CD4 cell counts (145 vs. 188 cells/mm3; p < 0.001) than
individuals with virus using the CCR5 co-receptor.
After a year of therapy, patients with CXCR4 virus were
significantly less likely than individuals with CCR5 virus to have an
undetectable viral load (77% vs. 92%; p = 0.009).
This association between the CXCR4 co-receptor and poorer
virological control at week 24 (p = 0.012) was confirmed in multivariate
analysis. There was also a trend
towards poorer treatment response at week 48.
It is harder to isolate HIV tropism in patients with non-B
subtypes. Therefore the investigators performed further analysis, which was
this time restricted to individuals with HIV subtype B.
This showed a strong association between the CXCR4
co-receptor and poorer virological control at both week 24 (p = 0.001) and week
48 (p < 0.001).
“When we limited our analyses to participants infected with
clade B viruses, the strength of the impact of viral tropism on virological
response was more robust than in the whole study population,” observe the
Unlike some other research, there was no evidence that the
CXCR4 co-receptor had a negative impact on CD4 cell recovery.
“In antiretroviral-naïve patients beginning antiretroviral
therapy, baseline HIV-1 tropism seems to be an independent predictor of
virologic response,” conclude the investigators, adding “this observation may
have important clinical implications for the monitoring of antiretroviral
therapy and interpretation of comparative trials.”