14 Set No Evidence of Ongoing Replication in Tissue Compartments During Combination Antiretroviral Therapy

Giorgio Bozzi

Sources of HIV-1 persistence during cART remains uncertain and the contribution of active cycles of HIV replication in tissue compartments is unknown. We studied HIV populations in blood and anatomic compartments from early treated individuals.
We studied samples from 3 patients suppressed for 8-16 years who underwent autopsy for primary effusion lymphoma (n=1) or routine colonoscopy (n=2). HIV-1 from autopsy was quantified (RT-PCR), and sequenced (pro-pol, 1200 nt) from tissue and blood using single genome sequencing (SGS). Sequences (n=263, from autopsy; n=293 from colonoscopy) were aligned and subjected to phylogenetic and compartmentalization analyses.
HIV DNA was detected in most tissues at autopsy (median 1.8, range 1-75/106 cells). Sequences from spleen, lymph node, gut, effusion cells, kidney, lung, testes were obtained after autopsy and compared to peripheral blood lymphocytes (PBL).
Patient sequences showed limited genetic diversity in tissues and PBL (average pairwise distance 0.3–0.6%). HIV populations were well-mixed in tissues and non-divergent from PBL-derived HIV-1, with no evidence of compartmentalization. Identical hypermutants in PBL and tissues demonstrated distribution and trafficking of clonally expanded cells. In the colonoscopy set, analysis of HIV from ileum, colon, and PBL revealed no evidence of ongoing replication and no divergence from pretherapy (12-16 years prior) plasma RNA.
No evidence of ongoing replication was detected in tissues compared to peripheral blood in individuals undergoing cART, suggesting that cART blocks HIV replication.