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Ohm. Any thoughts on the likely maraviroc patent expiration coming soon With regards to efficacy and safety, would leronlimab still be preferred by gov regulators, insurance, and physicians if it cost 5x more than a generic maraviroc.

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Ultimately it's physician's choice and physician's are more likely to go for the most effective treatment and they really dislike side effects. The combination of side effects from statins and maraviroc will definitely drive physician's towards leronlimab.

Physician's will write prescriptions for maravaroc/statins for those who don't have any coverage. A lower cost plan initiated by pharmaceutical companies is usually available for those people. Insurance companies will definitely push for the cheaper alternative and some doctors might go for it to keep them happy. Government will cover anything prescribed that's on-label.

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Also if maraviroc patent expires, can it be used instead of leronlimab for conditions where cydy has a patent on the clinical indication.

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Two different drugs so maraviroc could not be used until it was FDA approved specifically for that indication. Biohealth is going to rely on their patent for maraviroc in Long Covid. Any generic manufacturer could only push a generic maraviroc for use in HIV until the Long Covid patent expires. With so few prescriptions in HIV it would be a gamble on their part that it would be used for Long Covid.

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What about someone trying to knockout the ccr5 gene in humans as another circumventing strategy.

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It's possible but with CCR5 being such a controller of the immune system the FDA would probably not approve a trial for it.

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Is leronlimab as a immunomodulator clinically superior and safer than someone with a homozygous ccr5 deletion

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From an evolutionary standpoint with double allele CCR5 deletion you would almost certainly see an increase in the other CCR receptors and increased binding especially with CCL5. Otherwise you would see an increased death rate that would eventually wipe out that genetic variation. The increased expression and binding that occurs with CCR5 deletion would not wholly make up for the loss of CCR5.

The other CCR receptors that bind the same ligands as CCR5 act as a backup to CCR5 in case CCR5 somehow fails and vice versa. CCR5 is the most widely expressed CCR and has the highest binding efficacy for CCL5 which is why blockade of it with an overactive immune system is most effective. The CXCR receptors act as a backup to the entire CCR system with it's own set of ligands that mimic those of CCR receptors. There are some differences on how both systems act on the immune system but they are essentially the same. That massive immune system is why humans even exist today but it's also why you see an overactive response and why viruses, bacteria and tumor cells have learned to hijack it to survive.

With CCR5 deletion you would see a decrease in overactive immune response but with the other CCR receptors taking CCR5's place not as much as you would see with a leronlimab blockade.