In recent years, highly active antiretroviral therapy, or HAART, has dramatically changed the prognosis for people diagnosed with HIV. Instead of certain death in a few years, most can enjoy decades of relatively good health. The combination of drugs, if taken consistently, works by reducing the levels of virus in a patient's blood to undetectable and so less damaging levels. But if the treatment is stopped or interrupted, the virus typically bounds back almost immediately. Scientists have long suspected that virus particles under attack from HAART hide out in CD4+ T cells, which are invaded and killed early on during an infection. But researchers from the National Institute of Allergy and Infectious Diseases (NIAID) describe another possible hiding place--cells called macrophages--in today's issue of the Proceedings of the National Academy of Sciences.
"Our research suggests that macrophages are an underappreciated reservoir of virus in HIV infection," says study author Malcolm A. Martin, chief of NIAID's Laboratory of Molecular Microbiology. "These cells become infected immediately after exposure to HIV, are relatively resistant to virus killing, and are able to produce lots of new virus. Most currently available treatments target HIV during its infection of T cells, but if the virus also infects and accumulates in large amounts in macrophages, additional drugs may be required."
To test the idea that macrophages might harbor significant amounts of virus, Martin and colleagues infected macaque monkeys with SHIV virus. This laboratory-generated hybrid of HIV and the monkey version of the virus wiped out most of the animals' CD4+ T cells with remarkable speed. Still, they produced high levels of virus, suggesting it had taken root in a another cell type. Analyzing lymph node and spleen tissue from the monkeys showed that 95 percent of the virus-producing cells were macrophages. Only 1 or 2 percent were T cells. "If we want to completely eliminate the virus, we need to attack it everywhere it lives, not just in the T cells," Martin says. "Our studies suggest we need new classes of antiretroviral agents that can target HIV during infections of tissue macrophages. They potentially could eliminate this reservoir of virus and obviously complement currently available drugs."