Short Bio: Aguinaldo R. Pinto is a Full Professor at the Federal University of Santa Catarina (UFSC), Florianópolis, Brazil, and the Retroviruses Section Editor for Virology Journal. He has a PhD in Immunology from the Federal University of São Paulo, Brazil, and was a postdoctoral researcher at the Wistar Institute, Philadelphia, USA. From 2012 to 2016, he worked as Director at the UFSC’s Office of International Affairs. He is currently the Head of the Biotechnology and Biosciences Graduate Program in the same university and scholar from the National Council for Scientific and Technological Development (CNPq), Brazil. His scientific interests involve several aspects related to HIV infection, and he is currently investigating the activation of microglial cells and its relevance to the COVID-19 neuroinflammation, with a particular focus on in vitro models.

• Why did you decide to go into your field of research?

I started research in the area of HIV/AIDS in the early 2000s while I was doing my postdoctoral work on vaccine development at the Wistar Institute. At that time, I was awarded a grant from amfAR, The Foundation for AIDS Research, to study the immune response induced by an experimental HIV vaccine. This vaccine was based on an adenovirus of simian origin, similar to the one used in the COVID-19 vaccine produced by Astra-Zeneca. I was very happy to see that a vaccine that was licensed during the pandemics had used the same platform I had worked with years earlier. After returning to Brazil, I continued my HIV vaccine studies, which were later abandoned due to the limitations imposed by the use of animal models. In the meantime, I dedicated myself to studies of HIV molecular epidemiology in the southern part of Brazil, which has distinct characteristics when compared to the rest of the country. Using several bioinformatics tools, my team was able to characterise the consistent expansion of HIV-1 subtype C in the south of Brazil, as well as the transmission chains that impacted the viral phylodynamics and the emergence of new recombinant forms. We also studied the intestinal microbiota of people exposed to or living with HIV in different clinical conditions. Twenty years later, I continue to study HIV/AIDS, which is a very diverse and dynamic field, making research in this area very exciting.

• How has knowledge of HIV/AIDS developed over the course of your career?

Over the last 20 years, our understanding of HIV/AIDS has advanced significantly, both in terms of scientific knowledge and medical treatment. This progress has dramatically transformed the perspectives for individuals living with HIV and improved global public health efforts in this regard. One of the key developments was the improvement of antiretroviral therapy (ART). In the early 2000s, the treatment options for HIV were often limited and came with significant side effects. Over the past two decades, new classes of drugs have been developed, offering more effective and easier-to-tolerate regimens. Combination therapies now typically involve only one pill a day, thus reducing pill burden. New treatments such as long-acting injectable ART have allowed the use of less frequent dosing, providing more convenience for patients who struggle with daily medication regimens.  On the diagnostic front, we saw the emergence of better screening and early diagnosis. Early detection allows the earlier initiation of ART, which is crucial for maintaining viral suppression and preventing transmission. The prevention strategies, such as Pre-exposure Prophylaxis (PrEP) and Post-exposure Prophylaxis (PEP), became a game-changer in HIV prevention, producing great impact in reducing viral transmission. Finally, there was also a significant shift in the perception of HIV as a chronic, manageable condition, rather than as a fatal illness. With effective ART, people living with HIV had a dramatic improvement in their quality of life and can now have near-normal life expectancies, as the virus can be controlled to the point of being undetectable in the blood (a condition known as "undetectable = untransmittable" or U=U).

• What challenges do those from low- and middle-income countries (LMICs) in particular face?

These challenges are multifaceted and stem from a combination of social, economic, healthcare, and systemic factors that continue to affect our efforts towards prevention, treatment, and care, despite the significant progress that is observed in some areas. The limited access to healthcare and treatment is a very important issue. Insufficient medical supplies and a shortage of healthcare workers make it difficult for people to get timely and effective HIV treatment. Also, access to ART is still limited due to high costs, supply chain issues, or the lack of healthcare facilities capable of administering them. Besides, HIV/AIDS is often stigmatised in many cultures, which can discourage people from seeking testing, treatment, or support. Those living with HIV may face discrimination from family, community members, employers, and healthcare providers. Women, especially those in lower-income settings, face additional stigma related to HIV, often because of gender inequalities. Women may have less power to negotiate safe sex, leading to higher rates of HIV infection. They can also be more vulnerable to violence and abuse if their HIV status is revealed. Cultural and social barriers can also be found, since in some LMICs traditional beliefs and cultural practices can exacerbate the spread of HIV, such as polygamy or gender inequality. Moreover, some countries have conservative attitudes toward sexual health, which can hinder public health campaigns. In these environments, openly discussing HIV prevention and promoting condom use can be taboo. Global cooperation, sustainable funding, and community-led approaches will be essential for continuing the fight against the HIV/AIDS pandemics in LMCIs.

• What are your hopes for progress in the future?

Even though we’ve seen enormous advances in HIV/AIDS research, especially in terms of treatment and prevention, the ultimate goal is to attain a world free of HIV. In order to do so, finding a definitive cure and a successful preventive vaccine must be achieved. Two main strategies have been explored to get to a cure: (i) Sterilising cure, which involves completely eradicating the virus from the body. This is particularly challenging due to the HIV's ability to hide in reservoirs; (ii) Functional cure, which aims to achieve a state where the virus is undetectable in the body without ongoing ART treatment. In the search for a cure, one of the most promising tools is gene editing technologies, like CRISPR. Researchers are exploring ways to use CRISPR to modify the genetic makeup of infected individuals' immune cells or even the virus itself to prevent or even eliminate infection. As far as vaccine development is concerned, this has been one of the most elusive goals of biomedical research. Several promising candidates have undergone trials, but a highly effective HIV vaccine is not on the horizon. Such vaccines can either prevent HIV infection or reduce the viral load in those who are already infected. In my view, this is the major area of HIV research that still needs extensive basic science. Advances in vaccine technology, such as mRNA vaccines, are being explored as potential avenues for future breakthroughs. Such advancements, combined with efforts to improve access and reduce stigma, hold great promises for both a functional cure and an eventual end to the HIV/AIDS epidemics.