20th International AIDS Conference - Melbourne, Australia

Abstract

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

Background: Triple 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.
Methods: Health 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.
Results: 136 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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