HIV attacks the immune system by killing CD4+ T-cells, eventually making infected individuals vulnerable to opportunistic infections. Antiretroviral therapy (ART) prevents the destruction of the immune system by inhibiting the viral enzymes and preventing the spread of HIV to new cells. However, T-cells infected prior to initiating ART undergo massive proliferation despite treatment, creating a renewable source of infected cells during treatment. Although daughter cells can sometimes generate virus particles, ART prevents those particles from infecting new cells in the blood. It has been suggested that ART has poor penetration into lymph nodes and therefore, viral replication may persist in this compartment during treatment. In this study, we used the Cell Associated HIV RNA and DNA Single Genome Sequencing (CARD-SGS) assay to determine the fraction of infected cells that express HIV RNA and their levels of expression in single PBMCs and in single cells isolated from lymph nodes in two ART-treated donors (5 and 11 years suppressed on ART). We also compared the HIV genetics in the two compartments to determine if viral evolution (due to on-going replication) occurred in the lymph node, making this population divergent from that in the blood. We found the HIV RNA and DNA populations in the lymph nodes and PBMCs to be genetically the same (p=0.7 for a difference) and we found no difference in the fraction of infected cells that express HIV RNA (27% vs. 24%) or in the levels of HIV RNA expression in single cells isolated from both compartments (median of 1 RNA molecule per expressing cell). Our results show that new HIV variants did not emerge in the lymph node during ART nor are there more cells in the lymph node expressing HIV RNA or expressing higher levels of HIV RNA than those in PBMCs. We conclude that on-going viral replication in the lymph node during ART did not likely occur in these two individuals.

Identical HIV populations and levels of proviral expression in lymph nodes and PBMCs in individuals on antiretroviral therapy

253rd National Meeting (2017)

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