TY - JOUR
T1 - HIV Type 1 (HIV-1) Proviral reservoirs decay continuously under sustained Virologic control in HIV-1-infected children who received early treatment
AU - Luzuriaga, Katherine
AU - Tabak, Barbara
AU - Garber, Manuel
AU - Chen, Ya Hui
AU - Ziemniak, Carrie
AU - McManus, Margaret M.
AU - Murray, Danielle
AU - Strain, Matthew C.
AU - Richman, Douglas D.
AU - Chun, Tae Wook
AU - Cunningham, Coleen K.
AU - Persaud, Deborah
N1 - Publisher Copyright:
© 2014 © The Author 2014.
PY - 2014/11/15
Y1 - 2014/11/15
N2 - Background.Early initiation of combination antiretroviral therapy (cART) to human immunodeficiency virus type 1 (HIV-1)-infected infants controls HIV-1 replication and reduces mortality. Methods.Plasma viremia (lower limit of detection, <2 copies/mL), T-cell activation, HIV-1-specific immune responses, and the persistence of cells carrying replication-competent virus were quantified during long-term effective combination antiretroviral therapy (cART) in 4 perinatally HIV-1-infected youth who received treatment early (the ET group) and 4 who received treatment late (the LT group). Decay in peripheral blood mononuclear cell (PBMC) proviral DNA levels was also measured over time in the ET youth. Results.Plasma viremia was not detected in any ET youth but was detected in all LT youth (median, 8 copies/mL; P =. 03). PBMC proviral load was significantly lower in ET youth (median, 7 copies per million PBMCs) than in LT youth (median, 181 copies; P =. 03). Replication-competent virus was recovered from all LT youth but only 1 ET youth. Decay in proviral DNA was noted in all 4 ET youth in association with limited T-cell activation and with absent to minimal HIV-1-specific immune responses. Conclusions.Initiation of early effective cART during infancy significantly limits circulating levels of proviral and replication-competent HIV-1 and promotes continuous decay of viral reservoirs. Continued cART with reduction in HIV-1 reservoirs over time may facilitate HIV-1 eradication strategies.
AB - Background.Early initiation of combination antiretroviral therapy (cART) to human immunodeficiency virus type 1 (HIV-1)-infected infants controls HIV-1 replication and reduces mortality. Methods.Plasma viremia (lower limit of detection, <2 copies/mL), T-cell activation, HIV-1-specific immune responses, and the persistence of cells carrying replication-competent virus were quantified during long-term effective combination antiretroviral therapy (cART) in 4 perinatally HIV-1-infected youth who received treatment early (the ET group) and 4 who received treatment late (the LT group). Decay in peripheral blood mononuclear cell (PBMC) proviral DNA levels was also measured over time in the ET youth. Results.Plasma viremia was not detected in any ET youth but was detected in all LT youth (median, 8 copies/mL; P =. 03). PBMC proviral load was significantly lower in ET youth (median, 7 copies per million PBMCs) than in LT youth (median, 181 copies; P =. 03). Replication-competent virus was recovered from all LT youth but only 1 ET youth. Decay in proviral DNA was noted in all 4 ET youth in association with limited T-cell activation and with absent to minimal HIV-1-specific immune responses. Conclusions.Initiation of early effective cART during infancy significantly limits circulating levels of proviral and replication-competent HIV-1 and promotes continuous decay of viral reservoirs. Continued cART with reduction in HIV-1 reservoirs over time may facilitate HIV-1 eradication strategies.
KW - continuous HIV-1 decay
KW - early antiretroviral therapy
KW - prolonged viral suppression
KW - proviral reservoirs
KW - reduced HIV reservoirs
UR - http://www.scopus.com/inward/record.url?scp=84911005930&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84911005930&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiu297
DO - 10.1093/infdis/jiu297
M3 - Article
C2 - 24850788
AN - SCOPUS:84911005930
SN - 0022-1899
VL - 210
SP - 1529
EP - 1538
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 10
ER -