Expert says sustainable HIV control without antiretroviral therapy is achievable

July 26, 2018

Enduring control of HIV infection without antiretroviral therapy (ART) is a workable goal that deserves a vigorous pursuit, will say Anthony S. Fauci, MD, at the time of writing. a conference on Wednesday 25 July at the 22nd International AIDS Conference (AIDS 2018) in Amsterdam. Dr. Fauci is head of the National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health. His talk is titled "Sustainable Control of HIV Infection in the Absence of Antiretroviral Therapy: Opportunities and Challenges."

A cure in the clbadic sense of the term requires the elimination of all cells carrying the virus. These cells, which have a DNA encoding the HIV proteins, have entered a state of rest such that they do not produce any part of the virus. HIV reservoir cells can survive for years, even for life, while remaining invisible to the immune system. Although the search for a clbadic healing is underway, Dr. Fauci notes that additional scientific breakthroughs will be needed to achieve this goal.

Another goal of a clbadic cure is a remission without antiretrovirals, according to Dr. Fauci. This goal would not imply the eradication of the HIV reservoir. On the contrary, it would allow a person living with HIV to keep the latent virus suppressed without daily medications. Today, people living with HIV usually need antiretroviral treatment – usually a daily treatment of three or more antiretroviral drugs – to stay healthy and avoid spreading the virus to others.

Dr. Fauci will explain. One approach is intermittent or continuous non-ART interventions, while the other is to stimulate the immune system to exert lasting control over HIV.

Promising intermittent or continual interventions for long-term remission without ART usually include neutralizing anti-HIV antibodies (bNAbs), according to Dr. Fauci. These strong antibodies can stop almost all HIV strains from the infecting cells in the laboratory. Studies are underway in animals and people to determine whether periodic infusions or injections of bNAbs can prevent HIV acquisition and suppress the virus in people living with HIV. Dr. Fauci will describe how scientists develop bNAbs with improved attributes, including greater potency and longer duration in the body, and test treatment with combinations of two or three bNAbs in a manner similar to combined antiretroviral therapy. He will be cautiously optimistic about the success of bNAb therapy.

Scientists are also evaluating whether the administration of bNAbs against the virus or antibodies directed against certain parts of the immune system can lead to remission without ART by inducing long-lasting immune control. of the virus without further intervention, Dr. Fauci will explain. A study conducted by scientists at NIAID and Rockefeller University showed that administering two different bNAbs to monkeys infected with a simian form of HIV allowed the immune systems of some of the animals to control the virus. long after the disappearance of antibodies

. Another study conducted by scientists at Emory University in collaboration with Dr. Fauci's lab involved antibodies that bind to an immunocellular host receptor called alpha-4 beta-7. Dr. Fauci will describe how short-term administration of antiretroviral and anti-alpha-4 beta-7 antibody infusions to monkeys infected with simian form of HIV resulted in prolonged control of virus and reconstitution of immune cells after complete cessation of treatment. He will note that a NIH study that tried to replicate this result did not achieve consistent results.

Finally, Dr. Fauci will present the preliminary results of a small early clinical trial in which people living with HIV were well controlled. ART received infusions of vedolizumab, an FDA-approved anti-alpha-4-beta-7 antibody for ulcerative colitis and Crohn's disease. These volunteers received both ART and vedolizumab at the beginning of the study, discontinued ART while still receiving the antibody, and eventually stopped any treatment. It will describe how the diet was safe and well tolerated but did not produce a lasting control of the virus. He will also pose potential explanations for the differences between studies on alpha-4 beta-7 in monkeys and humans.

Fauci's lecture will be broadcast live on the AIDS 2018 website.

Dr. Fauci also lectured on several other important topics at AIDS 2018 and related pre-conference meetings. On July 22, he gave a lecture titled "U = U: Science and Policy", in which he traced the science behind the "Undetectable = Untransmittable" message from early observational studies to more recent large-scale clinical trials.

On July 22, he also presented a conference entitled "Ending the HIV / AIDS Pandemic: Individual and Global Considerations", in which he argued that the end of the pandemic involves a dual path. HIV treatment and prevention need to be optimized for people living with HIV or at risk. At the same time, these advances must be implemented globally and complemented by the development of an HIV preventive vaccine that is at least 50% effective.

Finally, on July 23, Dr. Fauci gave a lecture entitled Progress in the Field of HIV / AIDS: Science and Policy "which summarizes the history of scientific advances in the understanding, treatment and prevention of HIV infection since the first AIDS cases were reported in 1981.