Uncertainties, good and bad news

Transcription

Bonjour Gilles PialouxI am delighted to find you on Medscape France. I am a professor of infectious and tropical diseases at Tenon Hospital in Paris and at Sorbonne University. I was asked to do a best-of of the year, which is always very complicated, focusing more on what is sexually transmitted.

The spectrum of sexually transmitted infections has expanded significantly in 2024

It’s all the more complicated since sexually transmitted diseases are constantly growing since, as you will hear now, everything is sexually transmitted: arboviruses, Zika, Ebola… And finally year, we have had a resurgence of Oropouche, an arboviral disease which until then was considered minor, mainly in South Africa. A few days ago, in December 2024, an article was published by Emerging Infectious Diseases which showed the presence of this Oropouche virus in the semen of an Italian tourist returning from Cuba. This is the spectrum of sexually transmitted infections, which will widen considerably in 2024.

The emergence of the Mpox 1B variant and its implications

We will start instead with the bad news in this spectrum of sexually transmitted infections, in particular with the arrival of a new variant of Mpox, the 1B variant. Mpox, which dates back to the end of the 1950s, was until then ignored. It was only in 2022, with the epidemic which affected Europe and the United States, that it was publicized. The emergence of the 1B variant, reported by our colleagues from the Democratic Republic of Congo (DRC) in Eurosurveillance, constitutes bad news for three reasons. First, this variant is leading to a significant increase in Mpox cases worldwide. Second, new countries, such as Uganda, Kenya, Rwanda and Burundi, which were previously unaffected, are now affected. Third, the variant has a deletion of the POP Go 32 (OPG032) gene, an unexpected mutation in a DNA virus. This epidemic continues to progress quietly, with very rare imported cases of the 1B variant in Sweden, Thailand, Great Britain and Germany, but not yet in France.

The current challenges of PrEP and PEP in France

Another bad news, although it is not a publication, but a report from the group EPI-PHARE of theHealth Insurance and of Public Health France. This EPI-PHARE group gave the figures for November 2024 for PrEP initiation with Truvada or its generics. Since 2016, we have been following the progression, and for the first time, a drop in PrEP initiations in France has been confirmed, which is obviously not considered good news.

Finally, another piece of news that we consider negative is the data on condom use in the major survey on French sexualities that we were expecting, since the last one dated from 2016.CSF investigation (Context of Sexualities in France) of 2023, which covered 31,000 people, shows that the condom is only used in the younger age group by 51% of women aged 18-29, which is obviously quite different. insufficient fact.

We also have, in a subgroup of this survey on French sexuality, a prevalence survey with a kit returned by people, showing prevalences of chlamydia and Mycoplasma. Thus, the prevalence is 2.22% among women for chlamydia and 1.2% among men. For Mycoplasma, the rates vary between 2.8% and 0.3%, with worrying figures in the 18-29 age group, the most sexually active.

PrEP: a new dimension

But there is also good news in 2024. One of the major good news is a 100% effect in PrEP, with a new molecule, lenacapavir, the first capsid inhibitor which was developed by Gilead. A series of trials will affect all populations potentially eligible for this PrEP with subcutaneous injections every 6 months. A first try, PURPOSE-1was published this year in the New England Journal of Medicine conducted among more than 5,000 women and adolescent girls aged 16 to 25 across 25 sites in South Africa and Uganda. The 100% effect is absolutely spectacular, with zero HIV infections among cisgender women who received lenacapavir, compared to the expected incidence.

We are moving towards four PrEP tools

Participants were assigned 2:2:1 to receive subcutaneous lenacapavir every 26 weeks, daily oral emtricitabine-tenofovir alafenamide (F/TAF), or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF; active control); all participants also received the other subcutaneous or oral placebo.

The results of the PURPOSE 2 trial were also published. PURPOSE 2 was conducted among men who have sex with men and trans people. The effectiveness of lenacapavir is 99%, which truly marks a new dimension of PrEP.

We are moving towards four PrEP tools: continuous oral PrEP, on-demand oral PrEP, as demonstrated in the trial Hypergae against placebo, afterwards with cabotegravir, an intramuscular injection every two months, and PrEP with lenacapavir by subcutaneous injection. All this will obviously depend on emerging countries’ access to these extremely effective PrEP tools, with 100% effect for lenacapavir.

PEP and STI

We also published, in a complete conflict of interest, the results of the trial ANRS 174 DOXYVAC this year, which was a trial, no longer in PrEP, but in PEP (post-exposure) of sexually transmitted infections, post-exposure prophylaxis with doxycycline. There was also an arm which studied by antigenic relationship the possible effectiveness of the vaccine against meningococcus B on gonococcus, for the prevention of gonococcus, with very good results in terms of reduction in the incidence of chlamydia and syphilis. .

For chlamydia, we have a hazard ratio adjusted to 0.14 and for syphilis, a hazard ratio adjusted to 0.21, representing a reduction in the risk of chlamydia of 86% and of 79% for syphilis.

For gonococci, we thought we would have negative results given the prevalence of resistance to doxycycline, but we still have a hazard ratio adjusted to 0.67, with disappointing results for the meningococcal B vaccine.

These results were presented to the CROI, particularly in San Francisco, in terms of prevalence and incidence of chlamydia and syphilis, with the implementation of PEP using doxycycline which reduced the occurrence of syphilis by more than 50% and of chlamydia in the gay population in one year.

Waiting for new French recommendations on STIs

Finally, one last thing, we are waiting for the French recommendations on STIs. The Pr. Charles Cazanave (CHU Bordeaux), during the congress of the French Society for the Fight against AIDS in November in Biarritz, attempted to lift a veil. It is likely that these recommendations will include maintenance of monitoring of DoxyPEP, as in the United States, on a case-by-case basis, more prolonged treatments for trachomatis chlamydia with doxycycline, therefore no Belgium statement.

The positioning of ceftriaxone as first-line treatment for neurosyphilis will be interesting to follow. Treatment of gonococcal pharyngeal carriage returning from Asia could include ceftriaxone, plus azithromycin in mixed treatment.

Finally, a certain number of new developments are expected with a focus on the emergence of resistance to macrolides in different STI agents.

A final curiosity is the transplantation of HIV-positive people to HIV-positive people, with an HIV-positive donor who is controlled. According to a study published in NEJM this year, HIV-positive kidney transplant recipients who receive organs from HIV-positive donors do not have worse safety outcomes than those who receive organs from non-HIV-positive donors. This research takes place in the context of the opioid crisis, where more and more organs are being harvested from people who have died of overdose and are affected by HIV.

Thank you and happy holidays.

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