HIV Persistence During Antiretroviral Therapy Caused by Cellular Proliferation

Cellular proliferation predominantly drives HIV persistence on antiretroviral therapy, according to a new study.

Reducing the HIV reservoir—a group of cells that are infected with HIV but are not actively producing new HIV—has proven to be one of the biggest challenges for researchers searching for a cure for the virus. Although adherence to antiretroviral therapy (ART) lowers the rate of HIV proliferation and can result in viral suppression, some infected cells still proliferate and can persist for decades despite treatment.

According to a new study, cellular proliferation generates the majority of infected cells during ART, suggesting that reducing proliferation can decrease the size of the HIV reservoir and work toward a cure. The study provides an answer to the longstanding question facing HIV researchers: Does HIV survive through replication from infected cells that evade treatment or through proliferation from cells that have HIV genes from earlier infection?

“There is debate whether infection remains due to HIV replication within a small population of cells or persistence of memory CD4+ cells with HIV integrated into human chromosomal DNA,” wrote the researchers. “If the latter mechanism predominates, prolonged cellular lifespan and/or cellular proliferation may sustain stable numbers of infected cells.”

When the HIV virus infects a cell, it inserts its DNA into the human chromosome, creating a unique genetic signature. Thus, the researchers assumed that cells arising from viral replication would have unique sequences, whereas those generated from cellular proliferation would have equivalent sequences and thus be part of clonal populations. Using ecologic tools, the researchers studied the abundance of clonal HIV by applying methods to integration site and replication-competent HIV sequence data.

Continue reading on The American Journal of Managed Care.