Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure
Por:
Casado, C, Galvez, C, Pernas, M, Tarancon-Diez, L, Rodriguez, C, Sanchez-Merino, V, Vera, M, Olivares, I, De Pablo-Bernal, R, Merino-Mansilla, A, Del Romero, J, Lorenzo-Redondo, R, Ruiz-Mateos, E, Salgado, M, Martinez-Picado, J and Lopez-Galindez, C
Publicada:
5 feb 2020
Resumen:
Elite controllers (EC) represent a small subset of HIV-1-infected people that spontaneously control viral replication. However, natural virological suppression and absence of immune dysfunction are not always long-term sustained. We define exceptional EC (EEC) as HIV-1 subjects who maintain the EC characteristics without disease progression for more than 25 years. We analyzed three EEC, diagnosed between 1988 and 1992, who never showed signs of clinical disease progression in absence of any antiretroviral treatment. A comprehensive clinical, virological, and immunological study was performed. The individuals simultaneously exhibited >= 3 described host protective alleles, low levels of total HIV-1 DNA (<20 copies/10(6) CD4(+) T-cells) without evidence of replication-competent viruses (<0.025 IUPM), consistent with high levels of defective genomes, strong cellular HIV-1-specific immune response, and a high poly-functionality index (>0.50). Inflammation levels of EEC were similar to HIV-1 negative donors. Remarkably, they showed an exceptional lack of viral evolution and 8-fold lower genetic diversity (<0.01s/n) in env gene than other EC. We postulate that these EEC represent cases of spontaneous functional HIV-1 cure. A non-functional and non-genetically evolving viral reservoir along with an HIV-1-specific immune response seems to be key for the spontaneous functional cure.
Filiaciones:
Casado, C:
Inst Salud Carlos III, Ctr Nacl Microbiol, Lab Referencia & Invest Retrovirus, Virol Mol, Madrid, Spain
:
AIDS Res Inst IrsiCaixa, Badalona, Spain
Univ Autonoma Barcelona, Cerdanyola Del Valles, Spain
Pernas, M:
Inst Salud Carlos III, Ctr Nacl Microbiol, Lab Referencia & Invest Retrovirus, Virol Mol, Madrid, Spain
Tarancon-Diez, L:
Univ Seville, Virgen Rocio Univ Hosp, Inst Biomed Seville IBiS, Clin Unit Infect Dis Microbiol & Prevent Med,CSIC, Seville, Spain
Rodriguez, C:
Hosp Clin San Carlos IdISSC, Ctr Sanitario Sandoval, Madrid, Spain
Sanchez-Merino, V:
Inst Salud Carlos III, Ctr Nacl Microbiol, Lab Referencia & Invest Retrovirus, AIDS Immunopathol Unit, Madrid, Spain
Vera, M:
Hosp Clin San Carlos IdISSC, Ctr Sanitario Sandoval, Madrid, Spain
Olivares, I:
Inst Salud Carlos III, Ctr Nacl Microbiol, Lab Referencia & Invest Retrovirus, Virol Mol, Madrid, Spain
De Pablo-Bernal, R:
Univ Seville, Virgen Rocio Univ Hosp, Inst Biomed Seville IBiS, Clin Unit Infect Dis Microbiol & Prevent Med,CSIC, Seville, Spain
Merino-Mansilla, A:
Inst Salud Carlos III, Ctr Nacl Microbiol, Lab Referencia & Invest Retrovirus, AIDS Immunopathol Unit, Madrid, Spain
Del Romero, J:
Hosp Clin San Carlos IdISSC, Ctr Sanitario Sandoval, Madrid, Spain
Lorenzo-Redondo, R:
Northwestern Univ, Div Infect Dis, Feinberg Sch Med, Chicago, IL 60011 USA
Ruiz-Mateos, E:
Univ Seville, Virgen Rocio Univ Hosp, Inst Biomed Seville IBiS, Clin Unit Infect Dis Microbiol & Prevent Med,CSIC, Seville, Spain
:
AIDS Res Inst IrsiCaixa, Badalona, Spain
:
AIDS Res Inst IrsiCaixa, Badalona, Spain
Univ Vic, Cent Univ Catalonia UVic UCC, Vic, Spain
Catalan Inst Res & Adv Studies ICREA, Barcelona, Spain
Lopez-Galindez, C:
Inst Salud Carlos III, Ctr Nacl Microbiol, Lab Referencia & Invest Retrovirus, Virol Mol, Madrid, Spain
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