Now that I have been thinking about HIV and LL tod

Now that I have been thinking about HIV and LL today, I will be very interested to see if or how many of the HIV patients in each arm of the Inflammation trial develop mutations.

The HIV virus replicates very rapidly and as we noted with patients on monotherapy with AZT when it was the first, and therefore only HIV antiviral used to treat HIV, the virus mutated and formed virions that were not affected by AZT. It became apparent that another drug that worked differently than AZT needed to be added to slow the disease progression of HIV as well as slow the process of Resistance; mutations occurring in the HIV RNA that cause the virions to become resistant to antiviral treatments.

So NRTI’s were developed then protease inhibitors, then NNRTI’s etc and it soon became apparent that, to keep viral load (amount of virus in a given quantity of blood) “undetectable” (used to be less than 50 copies per ml), at least three different medicines that blocked HIV in different ways were needed. This became known as HAART - Highly Active Anti-Retroviral Therapy; The proverbial “HIV Cocktail Therapy. Combo pills were formed by different companies like Combivir and Truvada and the first three pill in one (HAART in one pill) was approved in the US in 2006 (Atripla).

The problem of resistance still existed as over time, HIV was able to find its way around one or more of the three regimens while the patient was taking it. Sometimes this was due to patients not taking the medicine as prescribed i.e. every day, but sometimes HIV was just sneaky enough to learn to survive With a mutation against a given drug.

So as HIV medicines were developed, it became important to look at the resistance profile of a drug and see which mutations were popping up with that drug and how often. The efficacy of the drug, meaning its ability to suppress viral load to undetectable levels, as well as the side effect profiles of the drug were also very important.

As I said in a previous post, the FDA wants drugs that are being developed for any disease state to be not just “me too” drugs, but a meaningful differentiation from current standard of care (SOC). We have been fortunate to see many drugs over the past decade that have very very low resistance profiles, but resistance still occurs, unfortunately.

So this brings me back to my point, LL is an entry inhibitor. It stops HIV on the outside of a T cell and prevents it from entering the cell and starting its replication process. I don’t know what the inclusion and exclusion criteria for this inflammation trial will be, but I am going to assume that patients will be allowed to be on a regimen of their doctors’ choosing. It is also possible that CYDY chooses patient populations that don’t have high levels of resistance.

So it will be very interesting to see if adding LL to standard of care decreases the number of mutations in the LL arm versus the compared arm (SOC alone). I think that the numbers of patients in this trial will be too small to be able to show LL‘s impact on resistance, but it will be interesting to see what mutations pop up and in which arm. I am alluding to the idea that LL Could potentially provide improved protection against further mutations developing vs SOC. I think a bigger trial will be needed to show this but it’s something interesting to look for.

Happy Sunday to All