CD8 lymphocytes mitigate HIV-1 persistence in lymph node follicular helper T cells during hyperacute-treated infection

Finding a cure for HIV means finding out where it hides in the body, especially in people taking antiretroviral therapy (ART) to suppress HIV replication. Although the worldwide deployment of ART has altered the HIV epidemic landscape by changing HIV infection from a death sentence to a manageable condition by lifelong treatment.  Most often, there is a rapid rebound of HIV replication evidenced by high viral loads, whenever therapy is stopped. This makes finding an HIV cure a high global health priority. Germinal center in lymph nodes are sites where HIV can live and replicate due to the absence of special immune cells termed cytotoxic T cells, that eliminate infected T cells. This publication contains reports from detailed studies of HIV and immune cells in native lymph node tissues obtained from 36 persons living with HIV (PLWH) who started taking antiretroviral therapy either a few days after HIV detection (early treated) or much later on in infection (Late treated). 13 HIV uninfected persons and 15 PLWH not taking ART were also included in the study as controls. The study results showed that HIV RNA and protein persists even in the lymph nodes obtained from early treated persons. Only 10% of the early treated persons had no detectable residual virus in the lymph nodes. The other 90% had varying amounts of virus. The major hiding spots for the virus were identified as CD4 T follicular helper cells that express a special receptor termed CXCR3. The study results also revealed that having higher numbers of HIV-specific cytotoxic T cells was associated with lower antigen burden, suggesting that these responses may contribute to HIV suppression in lymph nodes during therapy. These findings will make it easier to design specific, targeted treatments to eradicate HIV from sanctuary sites like the lymph nodes.