Early Initiation of Antiretroviral Therapy Following In Utero HIV Infection Is Associated With Low Viral Reservoirs but Other Factors Determine Viral Rebound
Por:
Millar, JR, Bengu, N, Vieira, VA, Adland, E, Roider, J, Muenchhoff, M, Fillis, R, Sprenger, K, Ntlantsana, V, Fatti, I, Archary, M, Groll, A, Ismail, N, Garcia-Guerrero, MC, Matthews, PC, Ndung'u, T, Puertas, MC, Martinez-Picado, J and Goulder, P
Publicada:
1 dic 2021
Ahead of Print:
1 may 2021
Resumen:
Background. Early HIV diagnosis allows combination antiretroviral therapy (cART) initiation in the first days of life following in utero (IU) infection. The impact of early cART initiation on infant viral reservoir size in the setting of high-frequency cART nonadherence is unknown.
Methods.Peripheral blood total HIV DNA from 164 early treated (day 0-21 of life) IU HIV-infected South African infants was measured using droplet digital PCR at birth and following suppressive cART. We evaluated the impact of cART initiation timing on HIV reservoir size and decay, and on the risk of subsequent plasma viremia in cART-suppressed infants.
Results.Baseline HIV DNA (median 2.8 log(10) copies/million peripheral blood mononuclear cells, range 0.7-4.8) did not correlate with age at cART initiation (0-21 days) but instead with maternal antenatal cART use. In 98 infants with plasma viral suppression on cART, HIV DNA half-life was 28 days. However, the probability of maintenance of plasma aviremia was low (0.46 at 12 months) and not influenced by HIV DNA load. Unexpectedly, longer time to viral suppression was associated with protection against subsequent viral rebound.
Conclusions.With effective prophylaxis against mother-to-child transmission, cART initiation timing in the first 3 weeks of life is not critical to reservoir size.
Filiaciones:
Millar, JR:
Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa
Univ Oxford, Dept Paediat, Oxford, England
Bengu, N:
Umkhuseli Innovat & Res Management, Pietermaritzburg, South Africa
Vieira, VA:
Univ Oxford, Dept Paediat, Oxford, England
Adland, E:
Univ Oxford, Dept Paediat, Oxford, England
Roider, J:
Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa
Univ Oxford, Dept Paediat, Oxford, England
Africa Hlth Res Inst, Durban, South Africa
German Ctr Infect Res, Munich, Germany
Ludwig Maximilians Univ Munchen, Dept Infect Dis, Munich, Germany
Muenchhoff, M:
German Ctr Infect Res, Munich, Germany
Ludwig Maximilians Univ Munchen, Fac Med, Natl Reference Ctr Retroviruses, Max von Pettenkofer Inst, Munich, Germany
Fillis, R:
Umkhuseli Innovat & Res Management, Pietermaritzburg, South Africa
Sprenger, K:
Umkhuseli Innovat & Res Management, Pietermaritzburg, South Africa
Ntlantsana, V:
Univ KwaZulu Natal, Sch Clin Med, Durban, South Africa
Fatti, I:
Umkhuseli Innovat & Res Management, Pietermaritzburg, South Africa
Archary, M:
Univ KwaZulu Natal, King Edward VIII Hosp, Dept Paediat, Durban, South Africa
Groll, A:
Tech Univ Dortmund, Dept Stat, Dortmund, Germany
Ismail, N:
Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa
:
irsiCaixa AIDS Res Inst, Badalona, Spain
Matthews, PC:
Univ Oxford, Nuffield Dept Med, Oxford, England
Oxford Univ Hosp NHS Fdn Trust, Dept Microbiol & Infect Dis, Oxford, England
John Radcliffe Hosp, Oxford Biomed Res Ctr, Oxford, England
Ndung'u, T:
Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa
Africa Hlth Res Inst, Durban, South Africa
Ragon Inst Massachusetts Gen Hosp MIT & Harvard, Cambridge, MA USA
Max Planck Inst Infect Biol, Berlin, Germany
UCL, Div Infect & Immun, London, England
:
irsiCaixa AIDS Res Inst, Badalona, Spain
:
irsiCaixa AIDS Res Inst, Badalona, Spain
Univ Vic, Cent Univ Catalonia, Vic, Spain
Catalan Inst Res & Adv Studies, Barcelona, Spain
Germans Trias & Pujol Res Inst, Badalona, Spain
Goulder, P:
Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa
Univ Oxford, Dept Paediat, Oxford, England
Ragon Inst Massachusetts Gen Hosp MIT & Harvard, Cambridge, MA USA
Green Published, hybrid
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