Using HIV RNA expression inhibitors as an additive therapy might reduce atypical inflammation and restore immune function in HIV-infected individuals on combination anti retroviral therapy (cART), reveals a team of researchers from the Boston University School of Medicine (BUSM).
Immune activation and inflammation persist in the majority of treated HIV-infected individuals and is associated with excess risk of mortality and morbidity.
‘HIV infected individuals have increased risk of developing non-AIDS complications. Use of HIV RNA expression inhibitors might reduce atypical inflammation and restore immune function in HIV-infected individuals on combination anti retroviral therapy (cART)’
HIV-1-infected individuals have excess risk of developing non-AIDS complications such as cardiovascular atherosclerosis, neurocognitive dysfunctions, non-AIDS cancers, osteoporosis, and renal disorders.
Systemic chronic immune activation has been postulated to lead to these non-AIDS complications.Despite long-term viral suppression by cART, it has remained unclear how chronic inflammation is induced in HIV-infected individuals.
In this study, BUSM researchers identified a mechanism of HIV-1-induced chronic immune activation and T cell dysfunction.
In studies performed with primary human macrophages and T cells, they found that persistent infection of macrophages with HIV-1 and expression of intron-containing HIV-1 RNA alone even in the absence of infectious virus production lead to induction of type I interferon (IFN-I)-dependent pro-inflammatory responses and immune exhaustion of co-cultured T cells.
They believe that these findings might provide an explanation for the observed chronic inflammation-associated morbidities in HIV-infected individuals who are on cART.
"We hope our study will broaden knowledge of host-HIV interactions and might help to reduce inflammation-associa.ted disorders caused by chronic viral infections," said Rahm Gummuluru, PhD, corresponding author and associate professor of microbiology.
These findings appear online in the journal Nature Communications.