Antiretroviral Initiation at ≥800 CD4+ Cells/mm3Associated with Lower Human Immunodeficiency Virus Reservoir Size

Thomas A. Rasmussen, Sunil K. Ahuja, Locadiah Kuwanda, Michael J. Vjecha, Fleur Hudson, Luxshimi Lal, Ajantha Rhodes, Judy Chang, Sarah Palmer, Paula Auberson-Munderi, Henry Mugerwa, Robin Wood, Sharlaa Badal-Faesen, Sandy Pillay, Rosie Mngqibisa, Alberto Larosa, Jose Hildago, Kathy Petoumenos, Chris Chiu, Joseph LutaakomeJonathan Kitonsa, Esther Kabaswaga, Pietro Pala, Carmela Ganoza, Katie Fisher, Christina Chang, Sharon R. Lewin, Edwina J. Wright

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Identifying factors that determine the frequency of latently infected CD4+T cells on antiretroviral therapy (ART) may inform strategies for human immunodeficiency virus (HIV) cure. We investigated the role of CD4+ count at ART initiation for HIV persistence on ART. Methods: Among participants of the Strategic Timing of Antiretroviral Treatment Study, we enrolled people with HIV (PWH) who initiated ART with CD4+T-cell counts of 500-599, 600-799, or≥800 cells/mm3. After 36-44 months on ART, the levels of total HIV-DNA, cell-associated unspliced HIV-RNA (CA-US HIV-RNA), and two-long terminal repeat HIV-DNA in CD4+T cells were quantified and plasma HIV-RNA was measured by single-copy assay. We measured T-cell expression of Human Leucocyte Antigen-DR Isotype (HLA-DR), programmed death-1, and phosphorylated signal transducer and activator of transcription-5 (pSTAT5). Virological and immunological measures were compared across CD4+strata. Results: We enrolled 146 PWH, 36 in the 500-599, 60 in the 600-799, and 50 in the≥800 CD4 strata. After 36-44 months of ART, total HIV-DNA, plasma HIV-RNA, and HLA-DR expression were significantly lower in PWH with CD4+T-cell count≥800 cells/mm3 at ART initiation compared with 600-799 or 500-599 cells/mm3. The median level of HIV-DNA after 36-44 months of ART was lower by 75% in participants initiating ART with≥800 vs 500-599 cells/mm3 (median [interquartile range]: 16.3 [7.0-117.6] vs 68.4 [13.7-213.1] copies/million cells, respectively). Higher pSTAT5 expression significantly correlated with lower levels of HIV-DNA and CA-US HIV-RNA. Virological measures were significantly lower in females. Conclusions: Initiating ART with a CD4+count≥800 cells/mm3 compared with 600-799 or 500-599 cells/mm3 was associated with achieving a substantially smaller HIV reservoir on ART.

Original languageEnglish (US)
Pages (from-to)1781-1791
Number of pages11
JournalClinical Infectious Diseases
Volume75
Issue number10
DOIs
StatePublished - Nov 15 2022
Externally publishedYes

Keywords

  • HIV
  • HIV cure
  • HIV reservoir
  • antiretroviral therapy

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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