TUAB0206LB - Oral Abstract
Impact of early initiation of combination antiretroviral therapy on measures of virus in peripheral blood of vertically HIV-1-infected children
Presented by Jason Brophy (Canada).
J. Brophy1, T.-W. Chun2, L. Samson1, F. Kakkar3, H. Soudeyns3, M. Ostrowski4, S. Mujib5, J. Kim6, P. Sandstrom6, R. Harrigan7, S. Read8, A. Bitnun8
1Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Canada, 2National Institute of Allergy & Infectious Diseases, National Institutes of Health, Bethesda, United States, 3Centre Hospitalier Universitaire - Ste-Justine, Universite de Montreal, Montreal, Canada, 4University of Toronto, Department of Immunology and Medicine, Toronto, Canada, 5University of Toronto, Institute of Medical Sciences, Department of Medicine, Toronto, Canada, 6Public Health Agency of Canada, National HIV & Retrovirology Laboratories, Toronto, Canada, 7University of British Columbia, British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada, 8The Hospital for Sick Children, University of Toronto, Toronto, Canada
combination antiretroviral therapy (cART) as HIV-post exposure prophylaxis is routinely
administered to newborns at high risk for HIV infection in our clinical centres.
We investigated measures of HIV-1 reservoir size in peripheral blood of
HIV-1-infected children with sustained virologic suppression (SVS) following
initiation of cART within 72 hours of birth.
records of children born to HIV-1-infected mothers started on cART within 72
hours of birth were reviewed. Those with HIV-1 infection and SVS underwent further
investigation, including HIV-1 serology, HIV-1-specific cell-mediated
responses, HLA genotyping, ultra-sensitive viral load (VL), and measurement of cell-associated
HIV-1 DNA and RNA and replication-competent HIV in peripheral blood. SVS was defined by the absence of detectable
virus in standard VL assay subsequent to achieving an undetectable VL (< 50
copies/mL) for the first time.
newborns initiated cART within 48 hours of birth (ZDV/3TC/nevirapine [n=56];
ZDV/3TC/nelfinavir [n=73]; ZDV/3TC/lopinavir/r [n=7]). Twelve of 136 were
vertically infected (8.8%). In 6 of 12, no consistent suppression of VL was
achieved due to poor adherence. Two children achieved and maintained an
undetectable VL for 2-3 years, but experienced virologic rebound subsequent to
poor adherence. In the four children with SVS, HIV serology, HIV-specific
cell-mediated immune responses (Nef,
Gag) and ultrasensitive VL were
negative. Proviral DNA was not found in enriched CD4+ T-cells
(< 2.6 copies/mg DNA), whereas HIV
RNA was detected in all four children (19.5-130 copies/1.5 mg RNA). No virion-associated HIV
RNA was detected following mitogenic stimulation (5.4-8.0 million CD4+
T-cells) in these four children, but replication competent virus was detected
by quantitative co-culture involving a higher number of cells in one (0.1
infectious units/million CD4+ T-cells). HLA
B*58 and HLA-B sequence variations associated with better HIV control were
found in 3 of the 4 children.
Conclusions: Absence of detectable HIV-1
DNA and absence or low levels of replication-competent virus in peripheral
blood in a subgroup of HIV-1 infected children initiated on cART within 72
hours of birth suggests that early cART could significantly reduce HIV
reservoir size. Cessation of cART may be necessary to determine whether
functional HIV cure can be achieved in such children.
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