2024-04-02 14:32:43
High mass for specialists in sexually transmitted infections (STIs), the 31st Conference on Retroviruses and Opportunistic Infections (CROI), which took place from March 3 to 6, 2024 in Denver (Colorado), provided new data concerning the epidemiology of HIV, as well as the management of different STIs, whether this concerns prevention or curative treatment.
First of all, a French study presented in Denver highlighted that too many people living with HIV are not screened in time, and discover their HIV status at a late stage of infection. And this has a strong impact on mortality.
This large study analyzed the impact on 5-year mortality of advanced-stage treatment of a person living with HIV (PLHIV), between 2002 and 2016. It covered 64,400 newly diagnosed people. supported from the ANRS CO4 FHDH cohort. It appears that 29% of them were at an advanced stage of the disease (CD4 <200 or AIDS stage), 20% at an intermediate stage (200‐350 CD4). The other 51% were diagnosed at an early stage (primary infection or CD4≥350/mm3). Additionally, the authors found very little improvement over the study period. Thus, the share of people taken into care at an early stage was 27% after 2014, compared to 29% before.
The study also showed that late access to care remains associated with an increased risk of death even after 4 years of follow-up. Thus, the death rate for people who were at the AIDS stage was 6% at 5 years, compared to 0.9% for people treated early. In addition, the introduction of integrase inhibitors (in 2014) did not lead to a significant improvement in the risk of death, regardless of the stage of treatment. The authors conclude that early diagnosis among PLHIV “remains a major objective to reduce the burden of HIV infection and improve the vital prognosis of newly diagnosed people.”
HIV prevention: where are we?
Overall, for STIs“prevention is taking up more and more space”, noted Professor Jean-Michel Molina (Saint-Louis and Lariboisière Hospital, University of Paris Cité). And for HIV, in particular, extensive data presented in Denver showed the impact of pre-exposure prophylaxis (Prep) on the HIV epidemic. Thus, new data from the Centers for disease control and prevention (CDC) showed a correlation between the increase in the prescription of Prep and the decline in the incidence of new cases of HIV, in certain American states. “In France, we have data which also goes perfectly in this direction”, added Professor Molina.
Prep on demand also confirms its effectiveness. The data we currently have appears “very solid”et “This scheme could also work in women.”
The new modalities of this Prep were also highlighted, and in particular of injectable cabotegravir, which is not yet available in France, but in the United States, in the form of an injection every 2 months. “We hope to have it in France in 2025”, Professor Molina said. And, in the future, this molecule could be available in an ultra-long-acting manner.
Data concerning lenacapavir in Prep, every 6 months were also presented. Phase 3 results are expected by the end of 2024.
Regarding the vaccine, “studies are continuing to try to propose prophylactic vaccines which would promote the production of neutralizing antibodies in individuals, with recombinant vaccines. […] But we are still far from being able to have it.” added the expert.
STI: effectiveness of doxycycline post-exposure
Furthermore, there was at this CROI, “a lot of enthusiasm for the use of doxycycline post-exposure”, said Professor Molina.
This strategy was the subject of a large French trial, called ANRS Doxyvac, the results of which provide new elements for STI prevention.
This trial – promoted and financed by the ANRS Emerging Infectious Diseases in partnership with the Roche laboratory – was carried out by research teams from Inserm, AP-HP, Paris Cité University and Sorbonne University. . Its objective was twofold: to evaluate the effectiveness of doxycycline as post-exposure prevention of bacterial STIs; and evaluate the effectiveness of Bexsero, (GSK’s meningococcal B vaccine) on reducing the risk of gonococcal infection.
The trial involved 556 men who have sex with men (MSM), who were recruited between January 2021 and September 2022, in the Paris region. Participants were randomly divided into 4 groups: post-exposure prophylaxis with doxycycline (to be taken within 72 hours after unprotected sexual intercourse); pre-exposure vaccination with Bexsero; combination of the two interventions; neither intervention.
The final results, which were presented at the 31st Conference on Retroviruses and Opportunistic Infections (Croi, Denver from March 3 to 6), firstly confirm the interim data – presented 1 year ago – concerning the antibiotic . Thus, the latter made it possible to reduce the risk of chlamydia or syphilis infection by 83%, and that of gonococcal infection by 33%.
On the other hand, the final analysis revealed discordant results compared to those of the interim analysis concerning Bexsero. Thus, this vaccine has not shown any conclusive effect in preventing gonococcal infections. Studies with vaccines targeting gonococci more specifically are underway.
Furthermore, this post-exposure strategy with doxycycline was supported in a real-life study. This post-exposure treatment was thus implemented in San Francisco among Prep users who had unprotected sex. The results then showed a 50% reduction in cases of syphilis and chlamydia infections in the year that followed.
Better understand viral reservoirs to cure HIV
In terms of curative care, “curing HIV requires a good knowledge of the viral reservoirs, and the mechanisms of virus persistence, to consider strategies for absolute cure or remission – defined by a very weak reservoir, and without treatment”, also affirmed Professor Pierre Delobel (Toulouse University Hospital, Inserm UMR1291).
In this context, the reservoir of the digestive tract is important because it contains a large number of lymphocytes and is very affected in the disease.
Several works on this digestive reservoir were presented in Denver. In particular, the ANRS EP61 Galt trial was carried out in 42 patients living with HIV, well controlled by antiretroviral treatment, who underwent upper and lower digestive endoscopies.
The results provided a better understanding of where the virus persists under treatment. Thus, in patients, this organ is rich in intact viruses, that is to say capable of reinfecting the patient if treatment is stopped. These are mainly CD4 lymphocytes, but also macrophages and other lymphocytes of the intestinal mucosa.
More generally on the curative level, various immunotherapy strategies were presented at the CROI, in particular with broad-spectrum neutralizing antibodies. “We can administer them by infusion, but we cannot yet get them produced in people by vaccines,” Professor Delobel clarified. Studies are underway, but still quite fundamental, with modified adenoviruses in particular.
HBV: alternatives to liver biopsy to assess viral reservoirs
Much progress has been made in the treatment of hepatitis B. However, “current treatments are capable of containing the replication of the virus but not of eliminating it from its hepatic reservoir. When the treatment is stopped, the resumption of replication can be violent”, declared Dr. Barbara Testoni, (Lyon Cancer Research Center, Inserm U1052, Lyon Hepatology Institute). This is due to the existence of an intrahepatic reservoir of ccc DNA (for covalently closed circular) which is not reached by treatments.
To try to cure the patient, it is therefore necessary to know how much ccc DNA is present in the hepatocytes and whether it is active. Until now, only liver biopsy provided this information. But it is an invasive, painful procedure, and not without risk. It would therefore be necessary to benefit from markers that are easier to obtain. This is why a French team led by Dr. Testoni presented work to the CROI evaluating two new methods: fine needle aspiration; and quantification of circulating HBV RNA.
Fine needle biopsy is, as its name suggests, a procedure similar to standard biopsy, but with a much less traumatic needle. Study results demonstrated proof of concept that this technique can be used to assess intrahepatic cccDNA. “We manage to detect and evaluate whether the viral genome is active or not,” said Barbara Testoni. And regarding serum markers, “we show the performance and relevance of the quantification of circulating RNA as an indicator of the transcriptional activity of cccDNA”, specify the authors. These results support the use of both approaches in clinical trials to develop and evaluate novel antivirals and immunomodulatory agents.
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