ARTIST IMPRESSION OF HIV. About 37 million people worldwide live with HIV, the human immunodeficiency virus. While treatments are available to prevent or treat HIV infections, there is no vaccine for it. Many approaches are currently being developed: some are preventative to be used by people at risk of getting the disease and some are aimed at ridding the virus hiding in cells. The goal of a vaccine is to give our immune system the right weapons to defeat the virus. Unfortunately, HIV is extremely adaptable – it can change components and become unrecognizable. Due to this, many efforts to produce a vaccine have encountered limitations. The most famous example of this was the "RV HIV trial", which showed a reduced rate of HIV infection by 31.2 percent compared to a placebo. The vaccine was safe and well-tolerated, but it was, unfortunately, only moderately effective. “RV144 was not a public health success, but was highly important for the scientific endeavour. Immune analyses after the trial revealed signals that correlated with protection or lack of protection, which laid the foundation to develop improved approaches,” Dr Jill Gilmour, executive director for Human Immunology at the International AIDS Vaccine Initiative (IAVI), told IFLScience. “Coupled with new scientific discoveries, the pipeline today is more diverse and robust, increasing the chances for success to achieve effective vaccines and related immune-based interventions to stop HIV infection and AIDS.” While the search for an effective treatment has been an uphill struggle, several approaches are now coming to fruition. Earlier this year, it was announced that the phase I human testing of one of these vaccines would take place in 2019. This particular vaccine targets a fusion peptide on the surface of the virus. Peptides are short chains of amino acids (the components of proteins), and HIV uses them to enter cells. The vaccine aims to stop this action and prevent the virus from infecting cells. So far, it has been effective across a promising 31 percent of HIV strains out of 208 tested. Tests conducted in animals have shown that the vaccine is effective across multiple species and it is believed it will be effective in humans as well. The 2019 trial will assess side-effects and safety limitations for the vaccine. A different approach was recently reported in Science Advances. In the study, researchers injected animal models with antigens that are designed to stimulate the production of precursor antibodies. These will eventually develop in bNAbs, or "broadly neutralizing antibodies", which will bind to the virus and envelope it in order to stop it from infecting other cells. It has been recently announced by IAVI that the first vaccine candidate aimed at eliciting bNABs is going into clinical trial. This is the first of its kind. There is currently a vaccine in a phase II efficacy trial that will run until 2022 and a phase III study (comparison between treatments) of RV144 that started in 2016 and will run until mid-2021. “The development of an effective HIV vaccine has been challenging in light of the nature of the virus and its interaction with the human immune system; no person has ever naturally recovered from an HIV infection, and there are no correlates that signal what immune responses are needed to block or clear HIV,” Dr Gilmour explained. “An HIV vaccine remains an essential tool to halt the spread of HIV and end AIDS. The number of new HIV infections has hardly decreased over the last 5 years, and could increase if prevention efforts are not scaled up substantially.” HIV is, unfortunately, a terribly clever virus. By attacking and hijacking T-cells, one of the important components of the immune system, it disables a crucial line of defense in the human body. It uses the proteins found in the T-cells to reproduce, destroying the cell itself and spreading through the host. The vaccine and future treatments hope to give new weapons to our cellular soldiers. Treatments have become extremely successful at making the virus inactive. By following the correct approach, it is possible to have an undetectable viral load, which makes it virtually impossible to transmit the virus to somebody else. Still, the virus remains inside cells. There is a lot that we don’t know about HIV and the work done to understand it is crucial. “One of the things that surprises people is when I tell them that we still don’t really know how the virus is working in cells,” Dr Kate Bishop, group leader at the Retroviral Replication Laboratory at the Francis Crick Institute, told IFLScience. “We look at particular viral proteins and how they interact with the cell. What other proteins they bind to, where, and how. Because it's such a large area to cover, we focus on the early stages of replication after the virus has entered the cell.” Dr Bishop’s group also looks at the opposite approach. The virus needs to overcome certain “antiviral proteins” or restriction factors. These are natural barriers evolved to stop viruses, and scientists want to know exactly how HIV gets around them. The first restriction factor was discovered in 2002 and has since been of particular focus for HIV researchers. “Understanding this sort of back and forth fight between the virus and, in this case, humans, could potentially lead to the development of drugs against HIV,” Dr Paula Ordonez, principal laboratory research scientist at the Retrovirus-Host Interactions Laboratory, told IFLScience. Her lab studies this "arms race" between retroviruses, including HIV, and their hosts. The goal is to find new therapeutic strategies to treat or prevent retroviruses. Dr Ordonez hopes that her work in this area might lead to the development of treatments with extremely low toxicity. This could be used to treat infants that acquire the condition in the womb as well as to reduce the potential long-term effects of anti-retroviral drugs for people that live with HIV for many decades. There is certainly optimism for the production of an effective vaccine against HIV in the very near future. Supporting research is important, but there is a lot more we can all do, such as fighting stigma and stopping the spread of disinformation. Thanks to the latest treatments, people living with HIV can expect the same quality of life as people who don’t have the virus. The “undetectable = untransmittable” message has been taken on board by charities, healthcare organizations, and by the Centers for Disease Control and Prevention in the US. The increase in use of PrEP (pre-exposure prophylaxis) and other approaches have helped significantly in reducing the spreading of the virus. "New prevention technologies – like PrEP and HIV self-testing – have the potential to help reduce HIV transmissions outside of the groups we already see this happening in," Charles Witzel, research fellow at the London School of Hygiene and Tropical Medicine, told IFLScience. "Barriers like stigma and lack of risk perception have to be addressed for this to be successful, however. This is especially true for priority groups like black MSM and trans people. How we package interventions is totally key as different groups have distinct needs which we need to consider in order to reduce health inequalities." Lack of public and government-sponsored campaigns and the “stigmatization” of the disease by politicians and religious leaders have certainly contributed to the spread of ignorance and misunderstanding about both HIV and AIDS. The same goes for conspiracy theorists claiming the existence of fictitious cures, or even that the disease doesn’t exist at all. HIV affects many minority groups due to societal barriers. Stigma, poverty, education, access to healthcare, racism, and homophobia are the main reasons why individuals can’t get the help they need. Not all of us can find a cure to the disease, but fighting ignorance is something all of us can and should do. Source
