Researchers from the Centers for Disease Control and Prevention (CDC) have identified what may be an important factor in understanding disease progression among people infected with HIV. Today at the 12th World AIDS Conference, CDC Biologist Renu B. Lal, Ph.D., will present research indicating how certain variations of HIV may lead to rapid AIDS development in some HIV-infected patients.
After initial HIV infection, the time it takes for infected individuals to experience HIV-related symptoms varies among those infected. While some people have no symptoms even 10 years after infection, others develop AIDS within months. Lal and other CDC researchers found that the virus" ability to enter a cell through multiple entry points is an important factor in understanding why some people develop AIDS more rapidly than others.
Basically, instead of having only one door to enter the cell, the virus can adapt and learn how to enter through multiple doors," explains Lal. These "doors" are called coreceptors. In this study, researchers found that the development of viral variants capable of using multiple coreceptors to enter cells correlated with disease progression among study participants.
Researchers examined virus samples from HIV-positive men throughout different stages of disease progression. Participants were categorized as rapid progressors, individuals with AIDS-defining symptoms and CD4+ T cell counts below 200 cells per microliter within five years of entry into the study; late progressors, individuals whose CD4+ T cell counts declined gradually or after five years; and long-term nonprogressors, individuals who showed no symptoms for more than 12-14 years.
Early in infection, the virus typically enters a cell through a single coreceptor called CCR5. In this study, however, researchers discovered the emergence of viral variants that were able to enter cells through additional coreceptors. These viral variants were found in all of the study's rapid progressors and in half of the late progressors prior to the onset of AIDS. In long-term nonprogressors, the virus continued to use only the CCR5 coreceptor for cell entry.
The virus" ability to adapt to multiple routes of entry has many important implications. Most interesting, though, is what we have seen in long-term nonprogressors, some who have had the virus for 12-14 years and have continued to maintain exclusive CCR5 usage," Lal commented. "An understanding of why the virus in these patients is not evolving may provide insight about how to delay disease progression in people infected with HIV."