HIV and AIDS still represent one of the most complex challenges for world medicine today. After four decades of research, the human immunodeficiency virus continues to infect over a million people each year, while scientists work tirelessly to find new strategies for prevention, treatment and, one day, definitive cure. Let's take a general point for research on HIV and AIDS, starting as always with the general "field".
What is meant by HIV and AIDS research?
Le HIV and AIDS research include all scientific studies dedicated to understanding the human immunodeficiency virus, developing new therapies, improving prevention and finding a definitive cure. This research ranges from basic virology to drug development, from clinical medicine to epidemiological studies.
The field of research has evolved dramatically in recent years. If in the 80s HIV was an almost certain death sentence, today a HIV-positive person who correctly follows antiretroviral therapy can have a nearly normal life expectancy. This transformation is the fruit of decades of intense HIV research which he brought to more than 30 drugs approved for the treatment of HIV.
The current landscape sees several particularly promising research directions. The data that emerged from the research They focus on long-acting drugs, which allow injections every six months instead of daily pills. In parallel, research into a definitive cure (the so-called “sterilizing cure”) continues through innovative approaches such as gene editing and neutralizing monoclonal antibodies.
How does new long-term HIV research work?
the 2024 marked a turning point with the emergence of drugs long acting, which are revolutionizing the therapeutic landscape. Lenacapavir, the drug that won the magazine's “Breakthrough of the Year” award Science, represents the spearhead of this revolution: with a single injection every six months, it guarantees control of the virus with an efficacy close to 100%.
How does it work? Lenacapavir has an innovative mechanism of action that prevents the virus from entering cells, blocking viral replication more effectively than traditional drugs. It is the first HIV capsid inhibitor, a protein essential for virus assembly.
But he is not the only protagonist of this revolution. Also other long-acting drugs they can do their part.
The combination Cabotegravir and Rilpivirine, already available in Italy, allows injections every eight weeks. The ALADDIN studio, coordinated by the doctor Silvia Nozza of the IRCCS Ospedale San Raffaele, is comparing the hospital and home administration of the treatment Cabotegravir Long Acting associated with Rilpivirine Long Acting for HIV-positive patients.
These drugs are not only more convenient for patients: they are a true social revolution. Long-Acting Treatment Helps to overcome the stigma and self-stigma associated with both the disease and the therapy and reduces the likelihood of discontinuing treatment.
Think about the psychological impact: Instead of being reminded of their condition every day by taking a pill, the patient can almost “forget” that they are HIV positive for months at a time.
Why is HIV research changing prevention?
La Pre-exposure prophylaxis (PrEP) represents one of the greatest successes in HIV prevention in recent decades. In Italy, the use of prophylaxis pre-exposure PrEP to prevent HIV infection is growing rapidly: in 2024 there were 16.220 users, with a jump of 43,2% compared to the previous year.
But what makes PrEP so effective? This is a prophylaxis recommended for people who are HIV-negative and who have sexual behaviors that are high risk for HIV infection. If PrEP is followed precisely, almost all HIV infections can be prevented.
The real leap in quality comes with the Long-acting PrEP. Long-Acting Pre-Exposure Prophylaxis (PrEP), administered intramuscularly every two or three months, ensures a prolonged and constant release of the active ingredient into the blood, maintaining optimal therapeutic levels to combat the infection.
However, not everything is perfect. Using PrEP protects against HIV, but not from other sexually transmitted infections (STIs), which are on the rise among prophylaxis users. According to two scientific studies, about a quarter of people on PrEP have contracted at least one STI.
There is also a worrying emerging phenomenon: chemsex related data (the use of substances to prolong or intensify sexual intercourse) emerged from a study conducted in Milan between 2024 and 2025. The percentage of PrEP users who declared they practiced it rose from 14% to 22%.
What are the challenges in HIV research for a definitive cure?
The search for one sterilizing treatment for HIV remains one of the most ambitious goals of modern medicine. Currently, only a handful of people in the world have been cured of HIV through stem cell transplants, while others are considered “potentially” cured through the same process.
The most famous case is that of the “Berlin patient”, Timothy Ray Brown, the first man cured of HIV. Paul Edmonds, a Californian patient, has managed to simultaneously win two of the toughest battles: HIV and cancer. Five years ago, Edmonds received an allogeneic hematopoietic stem cell transplant that had a genetic mutation associated with resistance to HIV-1.
How does this “cure” work? Stem cells received by Edmonds had two copies of a rare genetic mutation called CCR5 delta-32. Only about 1-2% of the population has this mutation, but it makes people resistant to HIV. HIV uses the CCR5 receptor to enter and attack the immune system, but the CCR5 mutation prevents the virus from entering.
However, stem cell transplants carry substantial risks, so not all people living with HIV will be eligible for this treatment. It is still only available to those with life-threatening blood cancer.
Research is exploring alternative avenues. At the San Raffaele Hospital the study is underway CORE 007, aimed at exploring the potential application of a therapeutic vaccine in people with HIV infection, in virological suppression. There have been disappointments related to the possibility of applying the gene editing strategy in HIV infection, but also hopes fueled by the use of the monoclonal antibody that blocks the PD-1 receptor, in delaying the resumption of viral replication.
How is HIV drug research evolving?
Pharmacological research is experiencing a moment of extraordinary innovation. Two presentations of CROI 2024 seem to indicate that two long-acting antiretrovirals (the aforementioned lenacapavir and Cabotegravir) could be successfully combined with neutralizing monoclonal antibodies (bnAbs) for the treatment of HIV.
One of the most interesting novelties concerns the weekly regimens. An oral regimen of lenacapavir and islatravir which can be taken just once a week has been shown to keep HIV replication at bay as effectively as a regimen that requires daily drug intake.
These advances are not accidental. With the new drugs, available for about two years, we have been able to extend the frequency of administration to 8 weeks for intramuscular injection therapy and to six months for the subcutaneous route.
However, there is a problem of access: with the long-acting drugs currently available, it is estimated that only 50% of people with HIV can access these treatments. With the new drugs, whose studies are in phase 2 and 3, the vast majority of patients will be able to benefit from prolonged-release treatments.
What is the global epidemiological situation of HIV?
Global data paint a complex picture, one of significant progress but also worrying slowdowns. Among the nearly 40 million people living with HIV in the world (39,9 million), three out of four are currently receiving treatment; This is an extraordinary figure if we consider that up until 2010 treatment coverage was only 47%.
However, it is truly unacceptable that nearly a quarter of the world's population living with HIV (9,3 million people) still do not receive life-saving treatment. The consequence is that Every minute, someone in the world dies from AIDS-related diseases.
New infections also tell an ambivalent story. New annual infections have dropped 39% since 2010, with an even more marked decline in Eastern and Southern Africa. However, according to the commitments made by the member states, new HIV infections were expected to drop below 370 per year by 2025, but at the end of 2023 they were still 1,3 million.
A particularly worrying aspect is that in three regions of the world, infections are actually increasing: Middle East/North Africa, Eastern Europe/Central Asia, Latin America.
For the first time in the history of the HIV pandemic, new infections are occurring to a greater extent outside sub-Saharan Africa.
What role does Italian HIV research play in the global panorama?
Italy occupies a prominent position in global HIV research, with significant contributions both clinically and scientifically. The National Center for HIV/AIDS Research of the Istituto Superiore di Sanità shares with WHO and UNAIDS the goal of stopping the epidemic and ensuring that people living with HIV have a good quality of life.
The most advanced products of the HIV research Italian developments include a therapeutic HIV vaccine based on the viral protein Tat, and a new therapy for Kaposi's sarcoma, both ready for phase III efficacy clinical trials.
La ICONA Foundation represents one of the most important patient cohorts in the world. In the NoCo studio In the period 2017-2022, 16.700 people with HIV were included; 27,3% were HCV positive. 86,4% of HCV viremic people started direct-acting antiviral drugs.
An interesting aspect of the HIV research Italian concerns the territorial disparities. If regions like Friuli-Venezia Giulia (+65,4%) and Emilia-Romagna (+54,7%) record significant increases in PrEP, in the South the numbers remain low: +10% in Campania, zero growth in Puglia.
What does the U=U principle mean for patients?
One of the most important achievements of recent years is the scientific recognition of the principle U=U (Undetectable = Untransmittable). Scientific evidence shows that a person with HIV, who regularly follows therapy and has an undetectable viral load, does not transmit the virus to sexual partners.
This discovery has a huge psychological and social impact. In 2019, the Italian Consensus Conference on U=U was held in Rome, at the Ministry of Health, an event that marked a historic step. The main Italian scientific communities, gathered with associations and communities, officially recognized the validity of this principle.
The scientific evidence is overwhelming. The study ended in 2018 and in eight years of observation and about 77.000 unprotected sexual encounters, not a single case of transmission within couples. The probability that a person with HIV and an undetectable viral load transmits the virus sexually is scientifically equivalent to zero.
What are the future prospects for the fight against HIV?
The future of the fight against HIV presents both opportunities and challenges. World leaders have committed to End the AIDS pandemic as a public health threat by 2030 and they can deliver on their promise but only if they ensure that the HIV response has the resources it needs.
However, all global funding for HIV is decreasing. The decrease in available resources, 19,8 billion dollars in 2023, was 5% compared to 2022. Compared to the need indicated for 2025, that is 29,3 billion dollars, the gap is still XNUMX billion.
On the therapeutic front, the prospects are more encouraging. In 2025, HIV treatment continues to evolve, with new antiretroviral therapies improving efficacy and reducing side effects. New forms of PrEP are becoming more widely available.
Research is also exploring entirely new approaches. An Israeli team has used gene editing to engineer B-type white blood cells that activate the immune system against the virus. When the engineered white blood cells encounter the virus, it encourages them to divide—and if the virus mutates, the B-type white blood cells will, too.
The hope of a future without AIDS
Forty years after HIV was first identified, science has transformed what was a death sentence into a manageable chronic condition. Today, antiretroviral therapy allows HIV-positive patients to survive increasingly close to that of the general population; if the therapy is taken regularly, viremia can be reduced to zero to the point of making the virus non-transmissible.
Today we have prevention tools such as PrEP, while antiretroviral therapy allows people with HIV to have a quality of life similar to the general population; however, the infection is still present and threatening.
The goal remains ambitious but achievable: the end of AIDS could be within reach, progress is indeed significant but too slow and, compared to the 2030 SDGs, the world is globally off track.
As always in medical research, each step forward opens up new possibilities but also reveals new complexities. HIV has taught humanity the importance of scientific research, global solidarity, and the fight against stigma. Perhaps, in the end, this virus will have made us not only healthier, but also more human.
