Antiretroviral Initiation at ≥800 CD4+ Cells/mm3 Associated With Lower Human Immunodeficiency Virus Reservoir Size

Autor: 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 Lutaakome, Jonathan Kitonsa, Esther Kabaswaga, Pietro Pala, Carmela Ganoza, Katie Fisher, Christina Chang, Sharon R Lewin, Edwina J Wright
Rok vydání: 2022
Předmět:
Zdroj: Rasmussen, T A, Ahuja, S K, Kuwanda, L, Vjecha, M J, 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, S R & Wright, E J 2022, ' Antiretroviral Initiation at ≥800 CD4+ Cells/mm3 Associated With Lower Human Immunodeficiency Virus Reservoir Size ', Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, vol. 75, no. 10, pp. 1781-1791 . https://doi.org/10.1093/cid/ciac249
ISSN: 1537-6591
1058-4838
Popis: 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.
Databáze: OpenAIRE
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