While combined antiretroviral therapy (ART) can reduce plasma viral loads to undetectable levels, the degree to which virus is eliminated from other anatomical sites remains unclear. The high frequency of comorbidities in ART+HIV+ patients suggests that persistence of virus may contribute to tissue pathologies. The goal of this study was to identify subjects with undetectable plasma and CSF viral load at death, assay a panel of their autopsy tissues for HIV, and assess tissue histopathology to discover the extent of residual anatomical HIV levels during cART and the potential relationship to tissue injury.
The National Neurological AIDS Bank (NNAB) and AIDS and Cancer Specimen Resource (ACSR) autopsy cohort was screened to identify 20 HIV+/ART-treated participants who had undetectable plasma and CSF viral loads at autopsy. Extensive medical histories were compiled for each participant. Detailed histopathological findings were noted in multisite autopsy specimens (n=212, including up to 6 brain and 6 lymphoid tissues per subject). All tissues were assayed for the presence of HIV DNA using quantitative and digital drop PCR. A subset of tissues was evaluated for HIV RNA using RNAscope in situ hybridization assay.
The median patient age and length of HIV infection was 46.5 years and 12 years, respectively. Fifteen of the 20 patients developed cancer. Abnormal histological findings in the spleen, lung, lymph node and liver were identified in 90% of the participants. Aorta and kidney were abnormal in 50 and 60% of the participants, respectively. 75% of participants demonstrated a degree of atherosclerosis and all brain tissues analyzed demonstrated slight to severe pathology. Overall, 66% of the tissues studied contained HIV DNA copies >200/million cell equivalents. Selected RNAscope studies localized HIV to macrophages within cancer tissues (See Figure). In HIV RNA positive brain tissue, infiltrating macrophages surrounded HIV+ cells.
This study confirms the presence of HIV within diverse anatomical tissues in virally suppressed ART+ patients. Persistent virus replication in tissues could promote inflammatory diseases, including cancer, atherosclerosis and other organ-associated diseases. These ACSR/NNAB cohorts, along with others of their kind, are highly valuable resources for future studies of HIV reservoirs and persistence.