The most important event in the near future is the

The most important event in the near future is the start Leronlimab's clinical trial for the modulating of chronic inflammation.

This is a blessing and a course.

It is a blessing because successful modulation of inflammation has so many applications that could launch Leronlimab into the category of "platform drug” and the SP in the “three fingers” category.

It is a course because the characterization biomarkers of the mechanisms of chronic inflammation and immune exhaustion are not well understood (because the illness itself is not well understood).

The question here is: what are we going to measure ??, what are the primary, secondary points of our trial ?? How far up the chain of inflammation are we going ??? (the higher the more impactful but the more difficult to characterize).

People living with HIV and AIDS (PLWHA) now have much better mortality outcomes thanks to cART, however, the toll paid is still very high with several disorders of, typical of old people, appearing in relatively young PLWHA subjects, such as neurocognitive disorders, cardiovascular diseases, metabolic dysfunctions, bone abnormalities, cancers and so on.

Any way … back to the point: what are we going to measure ??? What are we going for ???

One of the causes of Chronic Immune Activation is, of course, the HIV-1 replication mechanism. Leronlimab will tackle that one up and I guess we will be measuring the viral load (copies/ML) and will be a good start.

Now, what about the indirect stimuli ?. Are we going to try and measure the levels of Type I and II interferons? (persistently elevated in chronic immune activation). If so, which ones ??

HIV preferentially infects and kills activated CD4+ T-helper cells destroying T-cell homeostasis opening the gates for damaging pathogens to multiply. So, I would think we will be measuring CD4+ cells??

Also, a low CD4/CD8 ratio is a predictor of mortality in HIV-1-infected individuals (and in general), so I guess we will be measuring this predictor. As a matter of fact, this ratio and the number of CD8+ T cells are currently used as markers to be evaluated at baseline and during follow-up of patients under ART.

What about the pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, and TNF-α), what about the anti-inflammatory cytokines, such as IL-4, IL-10, and IL-13?

I can’t wait for the trial to be made public to see what we are aiming at … I really hope we start our trial with very practical primary/secondary end-points and have some modesty as far as the complexity of chronic immune activation understanding and treatment.

A properly designed this trial will “put the foot on the door” for multiple indications but we need to know where we are going, otherwise we will never get there. This truer now that we are in a not so strong economical position.

With several decades of practical experience in his clinic Dr. Lalezari is the perfect skipper. Hopefully we will be soon in calmer waters ... Let's "trial" and let's succeed!!!