Proviral Quasispecies Diversity Is Not Associated With Virologic Breakthrough or CD4 + T Cell Loss in HIV-1 Elite Controllers.

Elite controllers (EC) are able to control HIV-1 replication to extremely low levels (<50 HIV-1 RNA copies/mL) in the absence of antiretroviral therapy. However, some EC experience CD4 ⁺ T cell loss and/or lose their ability to control HIV-1 over the course of infection. High levels of HIV-1 env proviral diversity, activated T cells and proinflammatory cytokines were pointed out as relevant biomarkers for detection of EC at risk of virologic/immunologic progression. The aim of this study was to assess the importance of proviral diversity as a prognostic marker of virologic and/or immunologic progression in EC. To this end, we analyzed plasma viremia, total HIV DNA levels, T cells dynamics, and activation/inflammatory biomarkers in EC with low (EC _LD = 4) and high (EC _HD = 6) HIV-1 env diversity. None of EC _LD and EC _HD subjects displayed evidence of immunologic progression (decrease in absolute and percentage of CD4 ⁺ T cells) and only one EC _HD subject presented virologic progression (≥2 consecutive viral loads measurements above the detection limit) 2-5 years after determination of proviral env diversity. Despite differences in proviral genetic diversity, the EC _LD and EC _HD subgroups displayed comparable levels of total cell-associated HIV DNA, activated CD8 ⁺ T (CD38 ⁺ HLA-DR ⁺ ) cells and plasmatic inflammatory biomarkers (IP-10, IL-18, RANTES, PDGF-AA, and CTACK). These results indicate that the genetic diversity of the HIV-1 proviral reservoir is not a surrogate marker of residual viral replication, immune activation or inflammation, nor an accurate biomarker for the prediction of virologic breakthrough or CD4 ⁺ T cells loss in EC.