In May 2026, the Italian Medicines Agency (AIFA) approved public reimbursement for long-acting PrEP, the long-acting form of pre-exposure prophylaxis that prevents HIV infection in people who don’t have the virus but are at high risk of exposure. Unlike oral PrEP, which requires a daily pill, the long-acting version consists of an intramuscular injection every two months, administered in specialized hospital centres.
Antonella Castagna, professor and Director of the School of Specialization in Infectious and Tropical Diseases at Vita-Salute San Raffaele University explains «this improves adherence to prophylaxis as well as quality of life. Not being forced to take a pill every day to protect against the risk of infection reduces the emotional burden on people and helps break down the stigma that still surrounds HIV». We spoke with her about the latest developments and challenges in HIV research discussed at the 2026 edition of the ICAR congress, the Italian Conference on AIDS and Antiviral Research.
How Long-Acting HIV Drugs Work
HIV infection is now controlled through antiretroviral drugs, which block viral replication and lower the virus’s concentration in the blood. The “classic” HIV drugs are pills taken orally, once a day. Long-acting drugs dominated the 2026 edition of ICAR. Unlike traditional treatments, they can be administered weeks or months apart instead of daily, because they are injected into the muscle and released gradually into the bloodstream, maintaining a durable, effective action over a longer period.
This category of drugs includes:
1. Prophylactic formulations, for people who don’t have HIV but are at high risk of exposure and infection;
2. Therapeutic formulations, for people living with HIV.
For prophylaxis, this means an intramuscular injection of long-acting cabotegravir every two months, the drug that AIFA has just approved for reimbursement in Italy. Long-acting HIV therapy, by contrast, combines cabotegravir and rilpivirine in an intramuscular injection administered every two months. It is used as a maintenance treatment for people with HIV who have already achieved an undetectable viral load through a previous course of “classic” oral antiretroviral therapy.
«The availability of long-acting therapy for HIV treatment is sparking considerable debate», Castagna notes. «When we consider offering this kind of therapy to someone with the infection, we need to weigh both the logistical and administrative capacity of the centre providing it and the needs of the individual patient» she adds. HIV infection carries an internalized stigma that patients with a long history of antiretroviral therapy have often absorbed over time. Eliminating the daily pill is about more than treatment adherence; for many people, it can mark a profound shift in how they experience their condition.
San Raffaele Hospital is among the centres in Italy with the most extensive experience in long-acting therapies, and it currently leads two prospective studies aimed at improving how they are applied. The SCHOOL ART study follows everyone who starts long-acting therapy to assess clinical endpoints, meaning measurable outcomes, and the advantages over traditional oral administration. The second is ALADIN, a randomized study involving 100 patients: 50 receive the drug in hospital, 50 at home. The goal is to explore home-based management of chronic therapies, a model that could reshape how chronic infections are managed well beyond HIV.
HIV and Antimicrobial Resistance: Beyond Viral Suppression
In specialized centres, HIV infection is now largely under control: 95% of people living with the virus maintain a viral concentration so low it is undetectable with standard tests. This would have been unthinkable just a few decades ago, and it raises new clinical questions.
Viral suppression solves the immediate problem, but it doesn’t eliminate the risk. People with HIV have nearly double the incidence of cardiovascular disease compared to the general population: the virus itself is an independent risk factor that persists even under effective therapy. Cancer risk also remains elevated, particularly for tumours linked to HPV (human papillomavirus), HHV-8 (human herpesvirus 8) and EBV (Epstein-Barr virus), which is why screening has become an integral part of clinical management.
Low-Level Viremia: The Multidrug-Resistant Minority
The third area of concern involves that 5% of multidrug-resistant patients who don’t achieve suppression despite antiretroviral therapy. This is closely tied to understanding low-level viremia, the persistence of low concentrations of virus in the blood even while on treatment. «We published a position paper in The Lancet HIV, with first author Tommaso Clemente, a resident in infectious diseases, setting out a series of recommendations for managing low-level viremia» Castagna explains.
This problem can be caused, among other factors, by the virus’s resistance to antiviral drugs.
The Challenges Facing Infectious Disease Specialists
Antimicrobial resistance is one of the most significant global health emergencies. It develops when bacteria, viruses or fungi evolve mechanisms to survive the drugs meant to eliminate them, a process accelerated by the excessive or improper use of antimicrobials in human medicine, veterinary care and agriculture. The result is a growing number of infections that are difficult or impossible to treat with the drugs currently available.
«Managing HIV prevention and treatment, antimicrobial resistance, and shifts in the geographic distribution of infections, closely tied to the ongoing climate crisis: these are just some of the challenges we’re called to face today as infectious disease specialists» Castagna concludes.
