Maraviroc a new class of antiretroviral which targets chemokine receptor CCR5, a host protein, is claimed to be the 'promising new antiretroviral'.
The following are reasons to believe:
-Inhibits viral entry, the most vital mechanism of viral inhibition, unlike any of its predecessors
-It was found to have antiviral activity in vitro against various clades of different origins of HIV-1
-No dose adjustments are required for renal or hepatic impairment because it is mainly excreted in faeces; nevertheless cautious use is recommended in this group of patients
-Up to 1.60 log reductions in viral load were noted along with the apparent rise in CD4 counts of up to 120 cells per micro lit.
-Concentration in cervicovaginal secretions was found to be higher than in plasma suggesting the possibility of its use in prevention
-No cross-resistance was noted with fusion inhibitor enfuvirtide and the percentage of toxicity related treatment discontinuations was no greater than the control group
-Occupancy of CCR5 receptors by Maraviroc remained 60% on day 5 following discontinuation of the drug, the antiviral equivalent of the 'post-antibiotic effect' that may account for the observed delay in viral load rebound following discontinuation
And now the cons...
-Potential side effects include increased risk of development of malignancies subsequent to decreased immune surveillance and increased risk of symptomatic West Nile virus infection as observed in populations with a genetic absence of surface expressed CCR5 co receptors (although none have yet been demonstrated in clinical trials)
-Resistance to Maraviroc can occur either by mutations in the virus that allow the virus to continue using the CCR5 receptors 'blocked' by Maraviroc, OR use an alternate coreceptor CXCR4
-It is necessary to determine the tropism of the virus as the drug is active specifically against CCR5 tropic HIV-1 and has been proven to be ineffective in patients with dual and/or mixed-tropic HIV infections
-Requires adjustment in the presence of drugs that alter the activity of the enzyme CYP3A4 for which Maraviroc is a substrate. Dosing is thus complicated with concurrent use of inducers such as efavirenz or inhibitors such as ritonavir.
-Little is known about the safety of maraviroc in populations co-infected with Hep B/Hep C
FJ
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