THE JOURNAL OF INFECTIOUS DISEASES

Dhummakupt A, Siems LV, Singh D, Chen YH, Anderson T, Collinson-Streng A, Zhang H, Patel P, Agwu A and Persaud D.

The Journal of Infectious Diseases. 2018:jiy461-jiy461

DOI: 10.1093/infdis/jiy461

Abstract

Background:

High-level expression of the Fcγ receptor, CD32hi, on CD4+ T cells was associated with enhanced HIV infection of the latent reservoir in one study of adults on antiretroviral therapy. We tested the hypothesis that CD32 was the preferential marker of the latentHIV reservoir in virally suppressed, perinatally, HIV-infected adolescents.

Methods:

The frequency of CD32hi CD4+ T cells was determined by flow cytometry (N=5) and the inducible HIV reservoir in both CD32hi and CD32- CD4+ T cells was quantified (N=4) with a quantitative viral outgrowth assay. Viral outgrowth was measured by the standard p24 ELISA and an ultrasensitive p24 assay (Simoa) with lower limits of quantitation.

Results:

We found a 59.55-fold enrichment in the absolute number of infectious cells in the CD32- population compared to CD32hi cells. Exponential HIV replication occurred exclusively in CD32- CD4+ T cells (mean change=17.46 pg/mL, p=0.038). Induced provirus in CD32hi CD4+ T cells replicated to substantially lower levels, that did not increase significantly over time (mean change=0.026 pg/mL, p=0.234), and were only detected by Simoa.

Conclusions:

Our data suggests that the latent HIV reservoir resides mainly in CD32- CD4+ T cells in virally suppressed, perinatally, HIV-infected adolescents, which has implications for reservoir elimination strategies.