This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Highly active antiretroviral therapy (HAART) for HIV-1 infection has significantly improved the lifespan and quality of life of HIV-infected children and adults. However, even when replication of the virus is halted by HAART, there are reservoirs where the virus hides and will begin to replicate once drug-therapy is stopped. Additionally, drug-resistant virus from continued replication threatens the longevity of HIV therapy. A significant portion of patients continue to have replication despite therapy that keeps the virus suppressed in the blood. The location or locations in the body where this replication persists is unknown. One possibility is that the replication persists in the specific lung cells, called macrophages. Macrophages are less susceptible to some of the HIV-drugs because the cells do not convert the drug to the active form or the cells require a much higher concentration of the drug to stop replication. Additionally, it is difficult to get enough of the drug to the lung macrophages. In order to determine if lung macrophages are both a reservoir and a site of persistent replication of HIV-1 infection, we are collecting lung macrophages by induced sputum yearly and extra blood at clinical visits to compare the virus in the blood cells to the virus in the lung cells in 20 children on HAART. Through detailed genetic analyses, we will be able to determine if the lung cells are a reservoir of HIV-injection and if lung macrophages are a site of persistent replication. If replication continues in the lung macrophages when suppressed in the blood, then future studies will be proposed to evaluate the activity of different anti-HIV drug regimens in the lung macrophages.
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