Importance of using maraviroc in combination with other active drugs in treatment-experienced patients
3 September 2007. Related: Conference reports, Antiretrovirals, IAS 4th Sydney 2007.
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 (36 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:
- 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 - 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 - 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