High levels of genetically intact HIV in HLA-DR+ memory T cells indicates their value for reservoir studies

AIDS. 2020 Apr 1;34(5):659-668. doi: 10.1097/QAD.0000000000002465.


Objective: The contribution of HLA-DR+ memory CD4 T cells to the HIV reservoir during prolonged antiretroviral therapy is unclear as these cells are commonly excluded when assessing for replication-competent HIV. To address this issue, we examined the distribution of genetically intact HIV DNA within HLA-DR- and HLA-DR+ memory CD4 T cells and the RNA transcriptional profile of these cells during antiretroviral therapy.

Design/methods: Full-length DNA sequencing was used to examine the HIV DNA landscape within HLA-DR+ and HLA-DR- memory CD4 T cells. RNA quantification and sequencing was used to interrogate the relationship between HLA-DR status and HIV RNA transcription.

Results: HLA-DR+ CD4 T cells contained a high frequency of genetically intact HIV genomes, contributing over half of the genetically intact viral sequences to the reservoir. Expansions of genetically identical sequences were identified in all T-cell subsets, indicating that cellular proliferation maintains genetically intact and defective viral DNA during therapy. Intracellular HIV RNA levels in HLA-DR+ and HLA-DR- T cells were not statistically different by either long terminal repeat quantitative PCR quantification or single-genome RNA sequencing of the p6-RT region.

Conclusion: The high proportion of intact viral DNA sequences in the proliferative HLA-DR+ subset suggests they are critical in maintaining HIV infection during effective therapy. As such, these cells should be included in any immune intervention targeting HIV during effective therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage*
  • CD4-Positive T-Lymphocytes / immunology
  • DNA, Viral
  • Female
  • HIV Infections / drug therapy*
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification*
  • HLA-DR Antigens / analysis*
  • HLA-DR Antigens / genetics
  • Humans
  • Immunologic Memory
  • Male
  • Sequence Analysis, DNA
  • Sequence Analysis, RNA


  • Anti-HIV Agents
  • DNA, Viral
  • HLA-DR Antigens