- Oral presentation
- Open Access
O125. Influence of amount and percentage of CXCR4-using virus in predicting week 48 responses to maraviroc in treatment-naïve patients
© Valdez et al; licensee BioMed Central Ltd. 2010
Published: 8 November 2010
Both population and ultra-deep sequencing (UDS) of the HIV-1 V3 loop are useful in selecting candidates for maraviroc (MVC) therapy. We used mathematical modeling to determine that patients whose non-R5 HIV comprises <2% of the viral population by UDS are likely to respond to a MVC-containing regimen. However, the predictive value of absolute amount of non-R5 HIV is unknown.
To determine whether non-R5 viral load contributes to predicting response to a MVC-containing regimen.
Patients enrolled in the MERIT study (MVC or efavirenz plus zidovudine/lamivudine in treatment-naïve patients) with R5 virus at screening (by original Trofile assay) and randomized to the twice-daily MVC arm were included. UDS was performed with a 454/Roche GS-FLX instrument. Tropism was predicted using the "geno2pheno" co-receptor algorithm (g2p). A sample was considered R5 if <2% of variants had a score below 3.5 FPR. MVC responses at Week 48 were predicted by descriptive statistics and mathematical modeling.
Baseline level of CXCR4-using virus
<50 HIV-1 RNA c/mL at Week 48, n/N (%)
Amount (log10 copies/mL)
In univariate models, baseline CD4 and percent of CXCR4-using virus were not significant predictors of week 48 response (p=0.12; p=0.26); VL and absolute amount of CXCR4-using virus were significant (p=0.02; p=0.03) and were included in the multivariate model (p=0.02 for both in final model).
In MVC-treated patients in the MERIT study, baseline VL and absolute amount of CXCR4-using virus were predictive of Week 48 response. It is possible that total burden of CXCR4-using virus in drug-naive individuals may play a greater role than the percentage of such virus in predicting response to regimens containing a CCR5 antagonist.
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