| Autor: |
Côrtes FH; Laboratório de Aids e Imunologia Molecular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil., de Paula HHS; Laboratório de Aids e Imunologia Molecular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil., Bello G; Laboratório de Aids e Imunologia Molecular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil., Ribeiro-Alves M; Laboratório de Pesquisa Clínica em DST/Aids, Instituto Nacional de Infectologia Evandro Chagas, FIOCRUZ, Rio de Janeiro, Brazil., de Azevedo SSD; Laboratório de Aids e Imunologia Molecular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil., Caetano DG; Laboratório de Aids e Imunologia Molecular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil., Teixeira SLM; Laboratório de Aids e Imunologia Molecular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil., Hoagland B; Laboratório de Pesquisa Clínica em DST/Aids, Instituto Nacional de Infectologia Evandro Chagas, FIOCRUZ, Rio de Janeiro, Brazil., Grinsztejn B; Laboratório de Pesquisa Clínica em DST/Aids, Instituto Nacional de Infectologia Evandro Chagas, FIOCRUZ, Rio de Janeiro, Brazil., Veloso VG; Laboratório de Pesquisa Clínica em DST/Aids, Instituto Nacional de Infectologia Evandro Chagas, FIOCRUZ, Rio de Janeiro, Brazil., Guimarães ML; Laboratório de Aids e Imunologia Molecular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil., Morgado MG; Laboratório de Aids e Imunologia Molecular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil. |
| Abstrakt: |
Elite controllers (ECs) are rare individuals able to naturally control HIV-1 replication below the detection limit of viral load (VL) commercial assays. It is unclear, however, whether ECs might be considered a natural model of a functional cure because some studies have noted CD4 + T cell depletion and disease progression associated with abnormally high levels of immune activation and/or inflammation in this group. Here, we propose the use of immunological parameters to identify HIV-1 ECs that could represent the best model of a functional cure. We compared plasma levels of six inflammatory biomarkers (IP-10, IL-18, sCD163, sCD14, CRP, and IL-6) and percentages of activated CD8 + T cells (CD38 + HLA-DR + ) between 15 ECs [8 with persistent undetectable viremia (persistent elite controllers) and 7 with occasional viral blips (ebbing elite controllers)], 13 viremic controllers (VCs-plasma VL between 51 and 2,000 RNA copies/mL), and 18 HIV-1 infected patients in combined antiretroviral therapy, with suppressed viremia, and 18 HIV-uninfected controls (HIV-neg). The two groups of ECs presented inflammation and activation profiles similar to HIV-neg individuals, and there was no evidence of CD4 + T cell decline over time. VCs, by contrast, had higher levels of IL-18, IP-10, and CRP and a lower CD4/CD8 ratio than that of HIV-neg ( P < 0.05). Plasma levels of IL-18 and IP-10 correlated positively with CD8 + T cell activation and negatively with both CD4/CD8 and CD4% in HIV-1 controllers. These results suggest that most ECs, defined using stringent criteria in relation to the cutoff level of viremia (≤50 copies/mL) and a minimum follow-up time of >5 years, show no evidence of persistent inflammation or immune activation. This study further suggests that plasmatic levels of IL-18/IP-10 combined with the frequency of CD8 + CD38 + HLA-DR + T cells can be important biomarkers to identify models of a functional cure among HIV-1 ECs. |
