Maraviroc results similar to efavirenz when analysed using more sensitive tropism test
5 October 2009. Related: Conference reports, Antiretrovirals, IAS 5th Cape Town 2009.
Simon Collins, HIV i-Base
Several studies provided results that might increase the confidence in using the CCR5 inhibitor maraviroc. Although approved over two years ago, the potential use was has been limited because Phase III studies, using background AZT/3TC, did not shown non-inferiority compared to efavirenz, and it was not approved in Europe as a first-line option.
However, the efficacy of CCR5 inhibitors are dependent on accurately screening and enroling patients who are CCR5-tropic, which in turn is dependent of the accuracy of the available tropism test.
A post hoc analysis of the 48-week results from the MERIT study (called MERIT-ES), using the recently developed more sensitive Trofile ES tropism test, provided an indication of current results that could be expected based on this change in standard of care diagnostics. [18]
The initial analysis from MERIT also showed poorer responses in patients from the Southern compared to Northern hemispheres and in patients with higher baseline viral load (> vs <100.000 copies/mL.
Virologic results, summarised in Table 1, showed that using Trofile ES, maraviroc produced comparable results to the efavirenz group at any baseline viral load, and for patients in the Northern hemisphere. A difference remains for Southern hemisphere patients that has yet to be explained.
Table 1: MERIT ES: 48-week response rates <50 copies/mL
| MERIT | MERIT ES | |||
| EFV | MVC | EFV | MVC | |
| Baseline >100,000 c/mL | 66.0% | 59.6% | 62.5% | 64.2% |
| Baseline <100,000 c/mL | 71.6% | 69.6% | 72.1% | 71.8% |
| N. hemisphere | 67.8% | 68.0% | 65.4% | 72.0% |
| S. hemisphere | 71.0% | 62.1% | 71.6% | 64.6% |
Significantly more patients changed treatment due to side effects in the efavirenz arm (13.6% [49/361] vs 4.2% [15/360]), with changes occurring earlier (78.0% vs 60.0% by week 16) and at higher viral load (69.0% vs 60.0% = 50 copies/mL) before discontinuation.
The sustainability of these results out to week 96, together with a modelled analysis for the impact on the non-inferiority criteria (defined lower limit -12%) were presented by Saag and colleagues, and are summarised in Table 2 (though neither MERIT nor MERIT ES studies were powered to assess results at this time point). [19]
Table 2: MERIT ES: non-inferiority analysis at week 96: difference* (lower bound of 1 sided 97.5% CI)
| HIV-1 RNA | MERIT: original Trofile Diff. (lower limit) | MERIT ES: new Trofile ES analysis Diff. (lower limit) |
| <400 copies/mL, % | -3.2 (-10.2) | -0.4 (-7.9) |
| <400 copies/mL, % (TLOVR) | -2.7 (-9.7) | 0.2 (-7.3) |
| <50 copies/mL, % | -5.8 (-12.8) | -3.9 (-11.5) |
| <50 copies/mL, % (TLOVR) | -3.2 (-10.3) | -0.3 (-7.9) |
* Adjusted for randomisation strata; For descriptive purposes only; TLOVR = time to loss of virologic response.
References:
- Nelson M et al. Virologic suppression on maraviroc in treatment-naive patients with R5 HIV-1 is similar to efavirenz at high baseline viral load, and maraviroc discontinuations for adverse events are less likely to show drug resistance: 48-week results from the MERIT Study. Poster abstract MOPEB040.
http://www.ias2009.org/pag/Abstracts.aspx?AID=2657 - Saag M et al. The MERIT study of maraviroc in antiretroviral-naive patients with R5 HIV-1: 96-week results. Oral abstract TUAB103
http://www.ias2009.org/pag/Abstracts.aspx?AID=2556