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  • 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

  • 1,
  • 1,
  • 2,
  • 3,
  • 3,
  • 4,
  • 4,
  • 5 and
  • 5
Journal of the International AIDS Society201013 (Suppl 4) :O11

https://doi.org/10.1186/1758-2652-13-S4-O11

  • Published:

Keywords

  • Viral Load
  • Efavirenz
  • Virologic Response
  • Absolute Amount
  • Viral Population

Background

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.

Objective

To determine whether non-R5 viral load contributes to predicting response to a MVC-containing regimen.

Methods

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.

Results

Samples for 343 patients (308 R5, 35 non-R5) were available. Baseline median CD4 and mean viral load (VL) were 247 and 232 cells/µL and 4.9 and 4.6 log10 c/mL in patients with R5 and non-R5 virus. No CXCR4-using viruses were detected in 249/343 (73%) patients. Among the 94 patients with detectable CXCR4-use, median (q25, q75) percent and absolute levels of CXCR4-using viruses were 0.8% (0.4-8.1) and 2.9 (2.3-3.5) log10 c/mL, respectively. Week 48 virologic responses are shown in Table 1.

Table 1

Baseline level of CXCR4-using virus

<50 HIV-1 RNA c/mL at Week 48, n/N (%)

Percentage

 

<2%

207/308 (67.2)

2%—<10%

7/13 (53.8)

≤10%

11/22 (50.0)

Amount (log10 copies/mL)

 

<1.0

171/251 (68.1)

1.0—<2.0

12/15 (80.0)

2.0—<3.0

23/36 (63.9)

3.0—<4.0

13/25 (52.0)

≤4.0

6/16 (37.5)

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).

Conclusion

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.

Authors’ Affiliations

(1)
Pfizer Inc, New York, USA
(2)
Pfizer Inc, Collegeville, USA
(3)
Pfizer Global Research and Development, Sandwich, UK
(4)
Pfizer Global Research and Development, New London, USA
(5)
BC Centre for Excellence in HIV/AIDS, Vancouver, Canada

Copyright

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