Maraviroc 75mg tablets

The human immunodeficiency virus-1 (HIV-1) enters target cells by binding its envelope glycoprotein gp120 to the CD4 receptor and/or coreceptors such as C-C chemokine receptor type 5 (CCR5; R5) and C-X-C chemokine receptor type 4 (CXCR4; X4), and R5-tropic viruses predominate during the early stages of infection. CCR5 antagonists bind to CCR5 to prevent viral entry. Maraviroc (MVC) is the only CCR5 antagonist currently approved by the United States Food and Drug Administration, the European Commission, Health Canada, and several other countries for the treatment of patients infected with R5-tropic HIV-1. MVC has been shown to be effective at inhibiting HIV-1 entry into cells and is well tolerated. With expanding MVC use by HIV-1-infected humans, different clinical outcomes post-approval have been observed with MVC monotherapy or combination therapy with other antiretroviral drugs, with MVC use in humans infected with dual-R5- and X4-tropic HIV-1, infected with different HIV-1 genotype or infected with HIV-2. This review discuss the role of CCR5 in HIV-1 infection, the development of the CCR5 antagonist MVC, its pharmacokinetics, pharmacodynamics, drug-drug interactions, and the implications of these interactions on treatment outcomes, including viral mutations and drug resistance, and the mechanisms associated with the development of resistance to MVC. This review also discusses available studies investigating the use of MVC in the treatment of other diseases such as cancer, graft-versus-host disease, and inflammatory diseases.

Abstract licence: CC BY-NC 3.0

BACKGROUND Therapeutic options for hospitalized people with COVID-19 remain limited, especially for people with non-severe COVID-19 at risk of progression. The anti-inflammatory role of maraviroc, a CCR5 antagonists, makes it a good candidate for therapeutic strategies for COVID-19. METHODS This was a proof-of-concept, phase II, parallel, open label clinical trial, to evaluate the safety and efficacy of maraviroc (300 mg, bid), CCR5 antagonist, combined with standard of care (SoC) treatment compared to SoC alone during 14 days, in hospitalized people with mild COVID-19 with pneumonia and ambient air oxygen saturation >94 %. Demographical, clinical, and analytical data were assayed at day 0, 7, 14 and 28. RESULTS Thirty-three participants were included, 17 in the control and 16 in the maraviroc group. The proportion of participants who experienced COVID-19 progression was 2.8 times higher in the control group than in the maraviroc group, with three participants admitted in intensive care unit versus none in the maraviroc group. The only variable associated with the time to severe COVID-19 progression was maraviroc treatment. The median time on oxygen therapy was 11 days in the control group, while the two participants in the maraviroc group had oxygen therapy for one and four days. Grade 3-4 events were only present in the control group. Maraviroc treatment was associated with a better neutrophil/lymphocyte ratio and lactate dehydrogenase, IL-6 and TNF-α levels at day 7. CONCLUSIONS We observed a beneficial role of maraviroc in hospitalized participants with mild COVID-19 at risk of progression at admission.

Abstract licence: CC BY-NC-ND