Publications & Reports

Antiretroviral initiation at >/=800 CD4+ cells/mm3 associated with lower HIV reservoir size.

Rasmussen TA, Ahuja SK, Kuwanda L, Vjecha MJ, Hudson F, Lal L, Rhodes A, Chang J, Palmer S, Auberson-Munderi P, Mugerwa H, Wood R, Badal-Faesen S, Pillay S, Mngqibisa R, LaRosa A, Hildago J, Petoumenos K, Chiu C, Lutaakome J, Kitonsa J, Kabaswaga E, Pala P, Ganoza C, Fisher K, Chang C, Lewin SR, Wright EJ
Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.

Abstract

BACKGROUND: Identifying factors that determine the frequency of latently infected CD4+ T-cells on antiretroviral therapy (ART) may inform strategies for 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 (START) Study, we enrolled people with HIV (PWH) who initiated ART with CD4+ T-cell counts of 500-599, 600-799 or >/=800 cells/mm 3. After 36-44 months on ART, we quantified levels of total HIV-DNA, cell-associated unspliced HIV-RNA (CA-US HIV-RNA) and 2-long terminal repeat HIV-DNA in CD4+ T-cells and measured plasma HIV-RNA by single-copy assay. We measured T-cell expression of HLA-DR, programmed death-1, 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/mm 3 at ART initiation compared to 600-799 or 500-599 cells/mm 3. 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/mm 3 [median (IQR): 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.. CONCLUSION: Initiating ART with a CD4+ count >/=800 cells/mm 3 compared to 600-799 or 500-599 cells/mm 3 was associated with achieving a substantially smaller HIV reservoir on ART.

Link to publisher’s web site

Publication

  • Journal: Clinical Infectious Diseases
  • Published: 09/04/2022
  • Volume: 75
  • Issue: 10
  • Pagination: 1781-1791

Author