As HIV investigators work to control and eradicate the virus worldwide, certain myths or misconceptions about the disease have been embraced, whereas other concepts with merit have been left relatively unexplored, argues American HIV/AIDS researcher Jay Levy, MD, in a commentary publishing April 14 in the journal Trends in Molecular Medicine. He calls on fellow researchers to continue questioning and not to lose sight of alternative strategies that could ultimately lead to a sustainable, long-term solution to HIV infection.

"This paper may be controversial, but people need to know the other side of the story," says Levy, one of the first researchers to isolate the AIDS virus and Director of the Laboratory for Tumor and AIDS Virus Research at the University of California, San Francisco. "The train left the station and no one is stopping to see whether we did the right thing or not. I'm asking anyone who is involved with HIV/AIDS to pause and focus on some research and clinical areas that need more attention."

Levy presents six questions dealing with the science of HIV and with well-designed clinical trials that could offer new explanations and approaches for handling HIV/AIDS:

1. Is HIV infection a universally fatal diagnosis?

A small percentage of people with HIV infection have been observed to possess immune systems that keep the virus at bay for at least 10 years, and some for more than 35 years. Although an HIV diagnosis was once considered a "death sentence," this is evidence that such long-time survivors or non-progressors can live a normal, asymptomatic life without intervention. "Importantly, we can learn a great deal about prevention of disease and infection by studying these exceptional people who have survived without AIDS or have warded off infection," Levy writes.

2. Is the body's innate immune response as important as the adaptive immune response?

Researchers have observed that some people who have been infected for many years do not develop disease. Others have been exposed on many occasions to HIV but do not become infected. In these cases, the innate immune system, the first line of defense against viruses, appears to play an important role. If the innate immune response fails, then adaptive immune activity--reflected by T and B cells--comes into action. Levy calls for increased attention to the innate immune system and its variety of immune cells and secreted factors. By focusing on this early activity against HIV, researchers have a better chance of discovering ways to prevent infection and disease.

3. How do CD8+ T cells combat HIV?

The immune system is a complex collection of cells with multiple mechanisms for taking down a pathogen. Even with 30+ years of HIV research, how immune cells behave when the virus enters the body is not fully understood. One immune cell of long-time interest to HIV/AIDS scientists is the CD8+ T lymphocyte, which is primarily thought to control HIV infection by killing infected cells. Levy discusses how this cell can employ an alternative mechanism for controlling HIV infection: it can secrete factors that suppress the virus without killing the cell, and then the infected cell can continue to function but without virus production and cell death. Because this immune response handles all HIV types, it would be important in approaches aimed at enhancing immune antiviral responses and in the development of a vaccine. Importantly, both activities of the CD8+ T cell need to be appreciated.

4. When should antiretroviral therapy be given?

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Six questions about HIV/AIDS that deserve more attention