HTB

Importance of using maraviroc in combination with other active drugs in treatment-experienced patients

Simon Collins, HIV i-Base

Two late breaker posters at the meeting presented additional results for maraviroc in treatment-experienced patients.

Elna van der Ryst from Pfizer analysed 24 week efficacy results from the combined Phase III Motivate 1 and 2 studies, by screening genotypic, phenotypic and overall susceptibility scores to OBT, as well as by first-time use of selected background drugs. [1]

Efficacy results, including response by number of active drugs, were presented at CROI this year, and were reported in the March/April issue of HTB. [2]

In these studies, CCR5-tropic patients with triple-class-experience and/or resistance, and HIV-1-RNA >5000 copies/mL were randomised 2:2:1 to OBT (3┬ľ6 ARVs +/- low-dose ritonavir) plus maraviroc QD, BID or placebo.

Viral response by use of active lopinavir/r or T-20 is detailed in Table 1.

Table 1: Viral response by use of active T-20 or lopinavir/r

PBO + OBT: %<50/<400 copies/mL MVC QD + OBT: %<50/<400 copies/mL MVC BID + OBT: %<50/<400 copies/mL
Total population 25%/30% (n=207) 48%/61% (n=408) 48%/65% (n=419)
T-20 first use/no mutations 36%/40% (n=58) 64%/75% (n=91) 53%/75% (n=109)
Lopinavir/r first use/no mutations 50%/60% (n=10) 74%/96% (n=27) 70%/87% (n=23)

In a second poster, Trip Gulick from Weill Medical College of Cornell University, New York, presented efficacy analysis supporting the decision for maraviroc to be dose twice-daily. [3]

Although tolerability was similar between the two dosing groups, twice-daily dosing provided significantly greater viral suppression, especially for patients with lower baseline CD4, higher baseline viral load, and fewer active drugs in the background regimen (see Table 2).

Table 2: Virological efficacy of QD vs BID maraviroc

PBO + OBT: %<50/<400 copies/mL MVC QD + OBT: %<50/<400 copies/mL MVC BID + OBT: %<50/<400 copies/mL
Overall 23%/28% (n=209) 44%/55% (n=414) 45%/61% (n=426)
No active drugs in OBT (based on genotypic/phenotypic test results) 3%/6% (n=35) 18%/26% (n=51) 29%/41% (n=56)
Baseline CD4 count <50 cells/mm3 3%/5% (n=37) 11%/20% (n=85) 20%/31% (n=85)
Screening viral load >100,00 copies/mL 11%/16% (n=84) 28%/45% (n=170) 35%/52% (n=176)

Comment

The underperformance in important patient subgroups (low CD4, high viral load, and fewer active drugs in the regimen) clearly supported the choice to develop maraviroc as a twice-daily drug.

References:

  1. van der Ryst E, Cooper D, Konourina I et al. Efficacy of maraviroc in combination with at least one other potent new antiretroviral drug: 24-week combined analysis of the MOTIVATE 1 and 2 studies. Abstract WEPEB115LB.
    http://www.ias2007.org/pag/Abstracts.aspx?AID=5513
  2. See: Maraviroc Phase2b/3 results in treatment-experienced CCR5-tropic patients. HIV Treatment Bulletin, March/April 2007.
    http://www.i-base.info/htb/v8/htb8-3-4/Maraviroc.html
  3. Gulick RM, van der Ryst E, Lampiris H et al. Efficacy and safety of once-daily (QD) compared with twice-daily (BID) maraviroc plus optimised background therapy (OBT) in treatment-experienced patients infected with CCR5-tropic-HIV-1: 24-week combined analysis of the MOTIVATE 1 and 2 studies. Abstract WEPEB115LB.
    http://www.ias2007.org/pag/Abstracts.aspx?AID=5537

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