France – Bonjour. Gilles Pialoux, professor of infectious diseases at Tenon Hospital and Sorbonne University and vice-president of the French Society for AIDS, I am delighted to find you for a small update on HIV in the wake of Sidaction and more so of the CROI – conference on retroviruses and opportunistic infections.
You will see that the focus on HIV at CROI has evolved towards that of managing STIs.
This year, the 31st CROI conference took place in Denver, the second largest city in Colorado, with 700,000 inhabitants, 10,000 homeless people, and 180 overdose deaths, more than half of which are related to the opioid crisis.
So much for the peculiar landscape in this American crisis. Paradoxically, the city of Denver is also a reminder of the history of AIDS, as the 40th anniversary of HIV was “celebrated” there. This is the advent of the Denver principle, an associative declaration that has left its mark and has given rise to health democracy with this manifestation of associations in 1983 – “Nothing for us without us” was the motto of the Denver principle.
The spectacular effect of semaglutide
So, the scoop – there have been a few – concerns semaglutide. This drug is making its presence felt in HIV conferences with its effect on hepatic steatosis in a study called SLIM LIVER Study.
But first, data from the CDC regarding the prevalence of steatosis and a case-control study between people with HIV on antiretrovirals and people without HIV, all with NAFLD (MAFLD), that is, non-alcoholic hepatitis, related to this mechanism of steatosis were presented. A very interesting study, as it included about a hundred liver biopsies that show that in HIV patients with MAFLD, there is less steatosis, less portal inflammation but much more fibrosis. A real therapeutic challenge.
Then, the ACTG A5371 Study (SLIM LIVER Study) was presented, with semaglutide at increasing doses – 0.25 mg, 0.5 mg, and 1 mg – and a fairly spectacular efficacy, both on weight, 7.8 kg less on average compared to the control group (abdominal circumference, glucose, and triglycerides decreasing). A new marker used in this study that is quite interesting is MRI imaging with quantification of intrahepatic triglycerides. A relative decrease of -31.3% in hepatic fat was observed in this study presented by a certain Dre Jordan E. Lake.
The media have also added to this, and as you know, semaglutide is gaining indications, authorized in the United States by the FDA since 2011 for the indication of obesity, and now we have a new indication for this product.
SLIM LIVER Study in brief
After 24 weeks of weekly self-injections of the GLP1 agonist semaglutide, in this single-arm phase IIb study, HIV-infected participants with MAFLD, on antiretrovirals, experienced an average reduction of 31% in hepatic fat, with 29% of them experiencing complete resolution of MAFLD. They also lost weight, reduced their fasting glucose and TGs, corresponding to the effects observed in semaglutide studies in non-HIV-infected individuals. Additional data on inflammation and immune response will be necessary.
Bacterial STIs and DoxyPEP
Another piece of information, not a scoop but a confirmation, is the “triumph,” in quotation marks, because there are still questions about PEP, post-exposure prophylaxis with doxycycline for bacterial STIs – syphilis, gonorrhea, and chlamydia.
This is in the context of European figures that came out simultaneously with a significant increase in these three STIs: chlamydia leading the way – increasing from 164,000 to 216,000 European cases – gonorrhea as well as syphilis, and not only among men who have sex with men (MSM). To mention just one figure, MSM account for only 74% of the increase in syphilis.
There was high expectation for the consolidated results of the French trial ANRS DOXYVAC testing two post-exposure preventions for bacterial STIs: one using the meningococcal B vaccine, with its antigenic proximity to gonorrhea, and one using doxycycline, which has already been proven in other studies. A very significant effectiveness of doxycycline was observed with risk rates showing a decrease between 75% and 83% for various infections, except for gonorrhea, where the decrease is much less significant (33%). There was a “failure” of the meningococcal B vaccination (4CMenB) for gonorrhea prevention.
What about resistance?
There was also a very interesting session led by Béatrice Berçot from the Saint-Louis Hospital reference center regarding doxycycline in PEP on comparison and implications, particularly on the microbiome, on resistance, with indeed a number of questions raised in terms of selection pressure and increased resistance to doxycycline of gonorrhea and potentially a shift to third-generation cephalosporin resistance.
Regarding the impact on colonizations or multidrug-resistant bacteria, both the French DOXYVAC trial and the DoxyPEP trial show no increase in prevalence, particularly of ESBLs, of which many MSM, around 35% in these two trials, are colonized.
Obviously, as Dr. Berçot said, “the damage is done on gonorrhea and we really need a vaccine.”
Associations between antiretrovirals to combat infections
In terms of anti-HIV therapy, there were many people with, notably, a new Merck translocation inhibitor, following the development of islatravir, MK-8527, which is probably of interest for extended-action use.
We also saw a festival of extended-action developments ranging from weekly tablets to semi-annual injections for different molecules with this array of new antiretrovirals: GS-1720, a new integrase inhibitor from Gilead, was also extremely promising with viral declines in monotherapy around 2.34 logs, making it a very interesting molecule.
Among other data, the associations between these new antiretrovirals, I think notably of lenacapavir with monoclonal antibodies or broad-spectrum antibodies, with several studies showing very interesting results, although this needs to be confirmed by phase 3 trials.
An intriguing study at the CROI conference was the CARES study on injectable cabotegravir/rilpivirine treatment in Africa, administered monthly or every 2 months.
What was unique about this trial is that many included patients had exclusion criteria for this injectable antiviral bitherapy, including a BMI over 30, a viral genotype of type A1, and even rilpivirine resistance mutations, and yet there was between 96% and 97% viral load control, which is extremely encouraging.
There were also a number of data on the “monkey’s pox” on new antituberculosis treatments, with reduced treatment times – for example, a trial with a combination of antituberculosis drugs including quabodepistat, delamanid, and bedaquiline in drug-sensitive tuberculosis, showing shortened treatments and extremely interesting and innovative elements on the aspect of tuberculosis, while, as I mentioned earlier, we were more focused on HIV at the conference. Thank you!
View all blogs by Prof. Pialoux here
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2024-04-09 13:23:42