People with HIV in the United States are likely to get a further option for use in first-line drug combinations within the next few weeks, following yesterday’s decision by the US Food and Drug Administration’s Antiviral Drugs Advisory Committee to recommend marketing approval for maraviroc (Selzentry in the USA, Celsentri elsewhere), the CCR5 inhibitor manufactured by Pfizer.
Maraviroc has already been approved for use in combination with other antiretroviral drugs in treatment-experienced patients with HIV that is CCR5-tropic (virus which uses the CCR5 receptor to gain entry to CD4 cells). Maraviroc is the first of a new class of antiretroviral drugs which block the CCR5 receptor.
All patients being considered for maraviroc treatment must undergo tropism testing to ensure that they have CCR5-tropic virus. Anyone with a virus population that is not CCR5-tropic will not experience a viral load reduction when treated with maraviroc.
Maraviroc has now been recommended for first-line approval on the basis of re-analysis of results from the MERIT study, which compared maraviroc to efavirenz in treatment-naive patients, all of whom received AZT/3TC (Combivir). The initial analysis of the study failed to prove that maraviroc was non-inferior to efavirenz when the proportions of patients who achieved a viral load below 50 copies/ml at week 48 were compared.
However, subsequent analysis of study participants using a more sensitive version of the Trofile tropism test determined that in patients who were CCR5-tropic at baseline, there was no significant difference in rates of viral suppression. The previous analysis had included a number of patients who turned out to have non-CCR5-tropic virus undetectable by the first generation Trofile assay.
The MERIT study also showed that maraviroc was better tolerated in some respects that efavirenz. Significantly fewer patients experienced central nervous system side-effects in the maraviroc treatment group.
The requirement for tropism testing has hindered the uptake of maraviroc due to the high cost of tropism testing, but recent research suggest that the technology used for resistance testing – genotyping – can also be used, with the same degree of accuracy as tropism testing, to determine whether patients have CCR5-tropic virus.
Maraviroc will still face a significant disadvantage in the first-line drug market; it is dosed twice daily, whereas efavirenz (Sustiva) and the leading protease inhibitor in the market, atazanavir (Reyataz) are dosed once-daily.
The twice-daily dosing will also prevent coformulation with Glaxo SmithKline’s once-daily nucleoside analogue tablet which contains abacavir and 3TC (Epzicom in the US, Kivexa elsewhere). Pfizer and Glaxo SmithKline announced in April that they planned to merge their HIV businesses to create a new specialised company.