The Latent Human Immunodeficiency Virus (HIV) Reservoir Resides Primarily in CD32-CD4+ T Cells in Perinatally HIV-Infected Adolescents With Long-Term Virologic Suppression

Citation: Dhummakupt A, Siems LV, Singh D, Chen YH, Anderson T, Collinson-Streng A, Zhang H, Patel P, Agwu A, Persaud D. The Latent Human Immunodeficiency Virus (HIV) Reservoir Resides Primarily in CD32-CD4+ T Cells in Perinatally HIV-Infected Adolescents With Long-Term Virologic Suppression. J Infect Dis. 2019 Jan 1;219(1):80-88. doi: 10.1093/infdis/jiy461. PMID: 30053296; PMCID: PMC6284548

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https://www.ncbi.nlm.nih.gov/pubmed/30053296

BACKGROUND:
High-level expression of the Fcγ receptor, CD32hi, on CD4+ T cells was associated with enhanced human immunodeficiency virus (HIV) infection of the latent reservoir in a study of adults receiving antiretroviral therapy. We tested the hypothesis that CD32 was the preferential marker of the latent HIV reservoir in virally suppressed, perinatally HIV-infected adolescents.

METHODS:
The frequency of CD32hiCD4+ 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 enzyme-linked immunosorbent assay and an ultrasensitive p24 assay (Simoa; Quanterix) 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 with CD32hi cells. Exponential HIV replication occurred exclusively in CD32-CD4+ T cells (mean change, 17.46 pg/mL; P = .04). Induced provirus in CD32hiCD4+ T cells replicated to substantially lower levels, which did not increase significantly over time (mean change, 0.026 pg/mL; P = .23) and were detected only with the Simoa assay.

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.

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