Extremely low viral reservoir in treated chronically HIV-1-infected individuals

EBioMedicine. 2020 Jul:57:102830. doi: 10.1016/j.ebiom.2020.102830. Epub 2020 Jun 21.


Background: Small viral reservoirs are found predominantly in HIV-1 controllers and individuals treated during acute/early HIV-1 infection. However, other HIV+ individuals could naturally also harbour low viral reservoirs.

Methods: We screened 451 HIV-1-infected treated-individuals with suppressed plasma viremia for at least 3 years and stored cryopreserved peripheral blood mononuclear cells (PBMCs). Total HIV-DNA was analysed in PBMCs with ddPCR. Individuals with <50 HIV-DNA copies/106 PBMCs constitute the 'Low Viral Reservoir Treated' cohort (LoViReT). Longitudinal samples were obtained from 12 chronically treated LoViReT and compared to 13 controls (>50 HIV-DNA copies/106 PBMCs) to analyse total HIV-DNA, T-cell and NK-cell populations, HIV-1 specific antibodies, and plasma inflammation markers.

Findings: We found that 9.3% of the individuals screened had <50 HIV-DNA copies/106 PBMCs. At least 66% initiated cART during the chronic phase of HIV-1 infection (cp-LoViReT). Cp-LoViReT harboured lower levels of HIV-DNA before cART and after treatment introduction the decays were greater compared to controls. They displayed a marked decline in quantity and avidity in HIV-specific antibodies after initiation of cART. Cp-LoViReT had fewer CD8+ TTM and TEMRA in the absence of cART, and higher CD8+ TN after 18 months on therapy.

Interpretation: Treated chronically HIV-1-infected LoViReT represent a new phenotype of individuals characterized by an intrinsically reduced viral reservoir, less impaired CD8+ T-cell compartment before cART, and low circulating HIV-1 antigens despite being treated in the chronic phase of infection. The identification of this unique group of individuals is of great interest for the design of future eradication studies.

Funding: MSD Spain.

Keywords: HIV latency; HIV reservoir; HIV-specific antibodies; immunophenotyping; total HIV-DNA.

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / adverse effects
  • CD4-Positive T-Lymphocytes / virology
  • Disease Reservoirs / virology*
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects
  • HIV-1 / pathogenicity
  • Humans
  • Leukocytes, Mononuclear / virology
  • Male
  • Spain / epidemiology
  • Viral Load / drug effects
  • Viremia / blood
  • Viremia / drug therapy*
  • Viremia / virology


  • Anti-HIV Agents