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.