The latent human immunodeficiency virus (HIV) reservoir resides primarily in CD32 ^- CD4 ⁺ T Cells in Perinatally HIV-Infected Adolescents with Long-Term Virologic Suppression

Background High-level expression of the Fc3 receptor, CD32 hi, 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 CD32 hi CD4 ⁺ T cells was determined by flow cytometry (N = 5) and the inducible HIV reservoir in both CD32 hi 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 CD32 hi cells. Exponential HIV replication occurred exclusively in CD32 ^- CD4 ⁺ T cells (mean change, 17.46 pg/mL; P =.04). Induced provirus in CD32 hi CD4 ⁺ 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.