ROME (ITALPRESS) – HIV treatment and prevention is undergoing a major transformation thanks to injectable drugs with long-term effects, which are able to maintain effectiveness and tolerability with just one administration every two months. This is what emerged from the 20th European AIDS Clinical Society (EACS) Congress held in recent weeks in Paris, which presented dozens of studies dedicated to new therapies and prevention strategies.
For treatment, studies confirm that long-term therapy based on cabotegravir and rilpivirine, administered every two months, guarantees infection control equal to or greater than 90%, with very few cases of virological failure (less than 1%) and excellent tolerability. The Long-ICONA study, conducted as part of the Italian ICONA cohort, involved about a hundred people with HIV who switched from daily oral therapy to a bimonthly injectable combination of cabotegravir and rilpivirine.
“This is a prospective study that evaluates not only the virological response, but also specific biological parameters such as plasma drug concentrations and inflammatory markers – comments Andrea Giacomelli, infectious disease specialist, University of Milan, Department of Biomedical and Clinical Sciences; ASST Fatebenefratelli Sacco; SIMIT Board Member – The results show that there are no significant variations in systemic inflammation and drug levels are always above the efficacy threshold, which ensures the safety of the treatment over time. In addition, no participant had suboptimal drug concentrations.”
Among the works presented at EACS 2025 were a meta-analysis of observational studies of real-life use of cabotegravir/rilpivirine in more than 2 thousand people with HIV and the prominent VOLITION study, which explored the perception and feasibility of injectable therapy among healthcare workers. ‘Meta-analysis confirmed efficacy of more than 90% at 12 months, with a virological failure rate of approximately 1% and treatment discontinuation primarily associated with pain at the injection site. However, VOLITION has gathered the opinions of doctors, who consider this strategy simple and manageable, even in the early stages of treatment – explains Andrea Giacomelli – This is an important new option opportunity for people with HIV: the ability to switch from daily oral therapy to bimonthly centrally controlled administration is a paradigm shift”.
Data on the actual application of treatment with cabotegravir and rilpivirine also emerged from the SCohoLART study conducted by IRCCS San Raffaele in Milan, which looked at 549 people with HIV who experienced virological suppression for an average of 24 months after switching to long-term injectable therapy.
“We observed that 99% of patients maintained viral suppression after two years, with only six cases of virological failure, all of which returned to undetectable viremia after a change in therapy – explains Camilla Muccini, infectious disease specialist, San Raffaele Hospital -. Compliance is very high: more than 98% of injections were carried out within the expected time period, thanks to direct monitoring by the center. CD4/CD8 is associated with a decrease in CD8 lymphocytes, and its benefits at the metabolic and renal level: reduction in LDL cholesterol and improvement in kidney function, without changes in weight body. These results tell us that long-term therapy is not only effective and tolerable, but also able to maintain metabolic and immunological balance in the long term.”
Regarding the option of long-term Pre-Exposure Prophylaxis (PrEP), in particular, it was found that long-acting cabotegravir stood out for its better tolerability compared with other formulations: the CLARITY study showed that 90% of participants, after trying one dose of both treatments, and 86% of healthcare workers, expressed a preference for cabotegravir. The CLARITY study enrolled 63 adults without HIV infection in an alternating sequence (each participant received both formulations at different times): one intramuscular injection of cabotegravir and two subcutaneous injections of lenacapavir. Interesting data emerged from these results: 69% of participants rated cabotegravir as “very or completely acceptable,” compared with 48% of participants who rated lenacapavir; 90% of participants and 86% of physicians chose cabotegravir; injection site reactions (lumps, redness, swelling) were 4.4 times more common with lenacapavir compared with cabotegravir; overall, no serious side effects were noted.
“In the CLARITY study we have the first direct comparison between two injection options for PrEP – explains Davide Moschese, infectious disease specialist at L. Sacco Hospital, Milan –. Both are highly effective in preventing HIV infection, but the preference for cabotegravir shows how tolerability and acceptability depend on the user’s perception. Although these are preliminary results, these data represent a first step towards an increasingly personalized prevention approach that can be achieved exclusively with the availability of different strategies that adapt to the needs and perceptions of the individual”.
“The results of the CLARITY study are the first randomized data regarding the comparison of tolerability and acceptability between the two injectable PrEP options – comments Valentina Mazzotta, head of the clinic for counselling, testing and prophylaxis of HIV infection and sexually transmitted infections at INMI Spallanzani in Rome – The data obtained in favor of cabotegravir are preliminary, but very important because they show how the experience of administering the drug can influence the acceptance of new long-acting drug formulations. in terms of perception and acceptability helps the public and their doctors to choose what best suits their lifestyle, establishing effective prevention. and sustainable.
“The CLARITY study highlights once again how the person must be at the center of prevention options – added Silvia Nozza, infectious disease specialist, San Raffaele Hospital, Milan –. The feeling of normality and well-being, also compared to the pain felt at the point of injection and the small side effects, the importance of limiting stigma, are important elements: prevention works if society accepts it”.
Simultaneously with the CLARITY study, the first European data in real-world clinical practice regarding the long-term use of cabotegravir for PrEP were also presented. The study, conducted by Sacco hospital in Milan and INMI Spallanzani in Rome, involved more than 300 people who chose injectable PrEP as part of an expanded access program. The results showed excellent tolerance, with most local reactions being mild and transient; no new HIV infections were recorded after a median of 28 weeks; treatment continuity rate 92%; furthermore, only one-third of reasons for drug discontinuation were related to drug tolerability, while more often they were related to changes in personal circumstances due to exposure to HIV risks (such as entering a stable monogamous relationship).
“We favor access to injectable PrEP for people who cannot or do not want to use oral PrEP, such as those who have intolerance or difficulties with adherence – explains Davide Moschese – These data are very encouraging: high acceptance rates, no infections, and adherence above 90%.
– Diessecom Photo –
(ITALPRES).
