Publication Abstract Display
Type: Poster
Title: Frequent intrasubtype HIV dual infection in treated chronically infected individuals.
Authors: Wagner G, Chaillon A, Caballero G, Franklin D, Kosakovsky Pond S, Heaton R, Richman D, Smith D
Date: 02-13-2017
Abstract:Background: HIV dual infection (DI) has been increasingly described among global cohorts followed from primary infection. Investigations into DI have relied mostly on extraction of viral RNA from the blood plasma of infected individuals. However, in the era of antiretroviral therapy (ART) estimates of DI have not been assessed. We hypothesized that characterizing HIV DNA populations from peripheral blood mononuclear cells (PBMC) using deep sequencing would identify instances of DI and determine its rate among chronically infected individuals on ART. Method: Participants of the CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) cohort were selected who had > 4 years between follow-up visits and were receiving ART (N=47). Deep sequencing (454 FLX Titanium, Roche) was performed on PBMC-derived HIV DNA populations using four PCR-amplified coding regions (env C2-V3, gag p24, pol RT, and pol PR). Participants were categorized as DI when (i) phylogenetic reconstruction demonstrated divergent viral populations in a background of epidemiologically unlinked viral sequences, and (ii) divergent clustering persisted over time. Results: Deep sequencing generated 4.9 million viral sequences from 96 PBMC samples from 47 participants, with a median number of 8,121 sequences per coding region per sample (IQR: 4049 – 14,647 sequences). Twelve out of 47 individuals had phylogenetic evidence of DI confirmed across longitudinal timepoints, resulting in a total proportion of DI of 25.5% (95% CI: 15.3% – 39.5%). Despite ART, 15 participants had detectable plasma viral load >500 copies/mL or >2.70 log10 copies/mL; viremia was not associated with DI (p = 0.73, Fisher’s exact). Conclusions: In a U.S. cohort of chronically infected individuals receiving ART, one quarter had DI. Detectable plasma viral load was not associated with DI. Although clinically inapparent, DI is likely to be present more frequently than previously estimated.

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