Impact of Biological Sex on Immune Activation and Frequency of the Latent HIV Reservoir During Suppressive Antiretroviral Therapy

抑制性抗逆转录病毒治疗期间生物性别对免疫激活和潜伏 HIV 病毒库频率的影响

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作者:Shane D Falcinelli, Bonnie E Shook-Sa, Morgan G Dewey, Sumati Sridhar, Jenna Read, Jennifer Kirchherr, Katherine S James, Brigitte Allard, Simon Ghofrani, Erin Stuelke, Caroline Baker, Nadia R Roan, Joseph J Eron, JoAnn D Kuruc, Catalina Ramirez, Cynthia Gay, Katie R Mollan, David M Margolis, Adaora

Background

Persistent HIV infection of long-lived resting CD4 T cells, despite antiretroviral therapy (ART), remains a barrier to HIV cure. Women have a more robust type 1 interferon response during HIV infection relative to men, contributing to lower initial plasma viremia. As lower viremia during acute infection is associated with reduced frequency of latent HIV infection, we hypothesized that women on ART would have a lower frequency of latent HIV compared to men.

Conclusions

Differences in HIV reservoir frequency and immune activation appear to be small across sexes during long-term suppressive therapy.

Methods

ART-suppressed, HIV seropositive women (n = 22) were matched 1:1 to 22 of 39 ART-suppressed men. We also compared the 22 women to all 39 men, adjusting for age and race as covariates. We measured the frequency of latent HIV using the quantitative viral outgrowth assay, the intact proviral DNA assay, and total HIV gag DNA. We also performed activation/exhaustion immunophenotyping on peripheral blood mononuclear cells and quantified interferon-stimulated gene (ISG) expression in CD4 T cells.

Results

We did not observe evident sex differences in the frequency of persistent HIV in resting CD4 T cells. Immunophenotyping and CD4 T-cell ISG expression analysis revealed marginal differences across the sexes. Conclusions: Differences in HIV reservoir frequency and immune activation appear to be small across sexes during long-term suppressive therapy.

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