A switch to an HIV population that utilises the CXCR4 receptor does not presage a poorer response to first-line treatment, even though it is linked to faster disease progression in untreated people, researchers from London’s Chelsea and Westminster Hospital reported last week at the Forty-Sixth Interscience Conference on Antimicrobial Agents and Chemotherapy in San Francisco.
The switch from a virus population that uses the CCR5 receptor to gain entry to CD4 cells to a population that predominantly uses the CXCR4 receptor is associated with faster disease progression, and it has been suggested that tropism testing may help identify patients at high risk of rapid disease progression, and possibly poorer response to treatment.
A previous study reporting on the Swiss HIV Cohort had found that individuals with CXCR4 or mixed-tropic virus had significantly smaller CD4 cell increases after six months on antiretroviral therapy, and had a fourfold greater risk of clinical disease progression during the same period (Philpott 2006).
In order to examine the effects of CXCR4-tropic and mixed or dual-tropic virus populations on response to antiretroviral therapy, the Chelsea and Westminister group analysed data from patients who had already undergone phenotyping for viral tropism as part of an epidemiological study of the prevalence of CCR5 and CXCR4-tropic virus by CD4 cell strata.
Highly active antiretroviral therapy (HAART) was defined as any combination of at least three drugs apart from triple nucleoside analogue combinations. Participants were excluded from the analysis if they had received less than six months of treatment, and data were censored either after 96 weeks of treatment, or after a treatment switch due to virologic failure, or if treatment was discontinued altogether.
Four hundred and two patients underwent tropism testing at the clinic, of whom 289 had at least six months of treatment outcome data available by August 2006. Two hundred and twenty-nine had CCR5-tropic virus, and 60 had CXCR4-tropic, dual-tropic or mixed-tropic virus (the assay is not able to distinguish which of these categories a patient falls into).
The only significant baseline pre-treatment differences between the CCR5-tropic and CXCR4-tropic groups lay in CD4 cell count and viral load: patients in whom the shift towards CXCR4-tropic virus had begun had lower CD4 cell counts (203 vs 325 cells/mm3) and higher viral load (142,000 copies/ml vs 39,000 copies/ml) (both p<0.001). They had also experienced a faster CD4 cell decline in the twelve months following tropism testing (p=0.029) (although this difference had disappeared by month 24, the numbers available for analysis in the CXCR4 group make it difficult to determine the long-term predictive value of tropism testing in predicting disease progression).
However, when treatment outcomes were compared between the two groups, no significant differences were apparent. CD4 cell counts rose to the same extent in the two groups over two years of follow-up (approximately 250-300 cells/mm3), and there was no difference in the eraly rate of immune restoration.
Rates of virological suppression below 50 copies/ml were similar at six months, 12 months and 24 months, at around 70-75%, and time to viral suppression was almost identical.
The findings suggest that, unless a CCR5 inhibitor such as maraviroc is being considered as part of the first regimen, tropism testing will not supply any information that might affect the choice of treatment or the monitoring of treatment for patients.
Waters L et al. HIV co-receptor tropism in treatment-naïve patients: impact on CD4 decline and subsequent response to HAART. Forty-Sixth Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, abstract H-1667, 2006.