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Lower HIV reservoir size in individuals who maintain higher CD4+ T cells counts prior to antiretroviral therapy initiation: the Strategic Timing of Antiretroviral Treatment (START) HIV reservoir study

Title
Lower HIV reservoir size in individuals who maintain higher CD4+ T cells counts prior to antiretroviral therapy initiation: the Strategic Timing of Antiretroviral Treatment (START) HIV reservoir study
Presenter
Edwina Wright
Authors
T. Rasmussen (1,2), S.K Ahuja (3), L. Kuwanda (4), M.J Vjecha (5), F. Hudson (6,7), L. Lal (8), A. Rhodes (9), S. Palmer (10), P. Auberson-Munderi (11), H. Mugerwa (12), R. Wood (13), S. Badal-Faesen (14), S. Pillay (15), R. Mngqibisa (15), A. LaRosa (16), J. Hildago (17), K. Petoumenos (4), C.Y Chiu (9), J. Lutaakome (18,7), J. Kitonsa (18,7), E. Kabaswaga (12), P. Pala (18,7), C. Ganoza (19), K. Fisher (10), C. Chang (4,20,21,22), S.R Lewin (22,1), E. Wright * (21,8,9,22)
Institutions
(1) Peter Doherty Institute, University of Melbourne, Department of Infectious Diseases, Melbourne, Australia, (2) Aarhus University Hospital, Department of Infectious Diseases, Aarhus, Denmark, (3) University of Texas Health Science Center, San Antonio, United States, (4) The Kirby Institute, University of New South Wales, Sydney, Australia, (5) Institute for Clinical Research, Inc.,Veterans Affairs Medical Center, Washington DC, United States, (6) MRC Clinical Trials Unit at UCL, London UK Uganda Virus Research Institute/MRC, London, United Kingdom, (7) LSHTM Uganda Research Unit, HIV Intervention Programme, Entebbe, Uganda, (8) Burnet Institute, Melbourne, Australia, (9) Peter Doherty Institute, University of Melbourne, Melbourne, Australia, (10) Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, Australia, (11) UNAIDS, HIV Prevention, Geneva, Switzerland, (12) Joint Clinical Research Centre, Entebbe, Uganda, (13) The Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa, (14) Clinical HIV Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa, (15) Enhancing Care Foundation, Department of Research and Post-graduate Support, Durban University of Technology, Durban, South Africa, (16) Asociación Civil Impacta Salud y Educación, Lima, Peru, (17) Via Libre, Lima, Peru, (18) Uganda Virus Research Institute/MRC, Entebbe, Uganda, (19) Universidad Peruana Cayetano Heredia, Lima, Peru, (20) Centre for the AIDS Programme of Research in South Africa, Durban, South Africa, (21) Central Clinical School, Monash University, Infectious Diseases, Melbourne, Australia, (22) Alfred Hospital, Melbourne, Australia

BACKGROUND: HIV cure strategies may be enhanced by identifying factors that determine the frequency of latently infected CD4+ T cells on antiretroviral therapy (ART). We investigated the role of the CD4+ T cell count in people initiating ART with > 500 CD4 cells/mm3 for HIV persistence on ART.
METHODS: In this study nested within START, we enrolled people with HIV (PWH) who were randomised to commence immediate ART at enrolment with CD4+ T cell counts of either 500-599, 600-799 or '¥800 cells/mm3. Samples for HIV reservoir analyses were collected after 36-44 months on ART. 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 were quantified We measured T cell expression of HLA-DR, programmed death-1 (PD-1) and phosphorylated signal transducer and activator of transcription-5 (pSTAT5). Virological and immunological measures were compared across CD4+ strata and analysed for associations with clinical characteristics at ART initiation.
RESULTS: A total of 146 study participants were enrolled, 36 in the 500-599, 60 in the 600-799 and 50 in the '¥800 CD4+ T cell strata. Of these, 59 (40%) were males, 87 (60%) were females, 124 (89%) were Black and 20 (13.7%) were Hispanic. Following 36-44 months of ART, total HIV DNA, plasma HIV RNA and HLA-DR expression was significantly lower in PWH with CD4+ T cell count '¥800 cells/mm3 at ART initiation compared to 600-799 or 500-599 cells/mm3. Expression of pSTAT5 did not differ across CD4+ strata but was highly correlated with lower levels of HIV DNA and CA-US HIV RNA. Virological measures were significantly lower in females compared to males.
CONCLUSIONS: We report that commencing ART with a CD4+ T cell count '¥800 cells/mm3 compared to 600-799 or 500-599 cells/mm3 was associated with a significantly lower level of total HIV DNA, plasma HIV RNA and T cell activation after 36-44 months of suppressive ART. Our study revealed considerable differences between women and men in measures of HIV persistence and that pSTAT5 is associated with a reduced frequency of latently infected cells.