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Clin Infect Dis. 2014 Oct;59(7):1012-9. doi: 10.1093/cid/ciu432. Epub 2014 Jun 9.

Early initiation of combination antiretroviral therapy in HIV-1-infected newborns can achieve sustained virologic suppression with low frequency of CD4+ T cells carrying HIV in peripheral blood.

Author information

1
Department of Pediatrics, Hospital for Sick Children, University of Toronto.
2
Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ontario, Canada.
3
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
4
Department of Pediatrics, CHU Sainte-Justine.
5
Centre de recherche du CHU Sainte-Justine, Department of Microbiology, Infectiology and Immunology, and Department of Pediatrics, Université de Montréal, Quebec.
6
Department of Immunology and Medicine, University of Toronto, and Keenan Centre for Biomedical Research of St Michael's Hospital, Toronto.
7
Institute of Medical Sciences, Department of Medicine, University of Toronto, Ontario.
8
Department of Medicine, BC Centre for Excellence in HIV/AIDS, University of British Columbia, Vancouver.
9
National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Ottawa, Ontario, Canada.

Abstract

BACKGROUND:

A human immunodeficiency virus type 1 (HIV-1)-infected infant started on combination antiretroviral therapy (cART) at 30 hours of life was recently reported to have no detectable plasma viremia after discontinuing cART. The current study investigated the impact of early cART initiation on measures of HIV-1 reservoir size in HIV-1-infected children with sustained virologic suppression.

METHODS:

Children born to HIV-1-infected mothers and started on cART within 72 hours of birth at 3 Canadian centers were assessed. HIV serology, HIV-1-specific cell-mediated immune responses, plasma viremia, cell-associated HIV-1 DNA and RNA, presence of replication-competent HIV-1, and HLA genotype were determined for HIV-1-infected children with sustained virologic suppression.

RESULTS:

Of 136 cART-treated children, 12 were vertically infected (8.8%). In the 4 who achieved sustained virologic suppression, HIV serology, HIV-1-specific cell-mediated immune responses (Gag, Nef), and ultrasensitive viral load were negative. HIV-1 DNA was not detected in enriched CD4(+) T cells of the 4 children (<2.6 copies/10(6) CD4(+) T cells), whereas HIV-1 RNA was detected (19.5-130 copies/1.5 µg RNA). No virion-associated HIV-1 RNA was detected following mitogenic stimulation of peripheral blood CD4(+) T cells (5.4-8.0 million CD4(+) T cells) in these 4 children, but replication competent virus was detected by quantitative co-culture involving a higher number of cells in 1 of 2 children tested (0.1 infectious units/10(6) CD4(+) T cells).

CONCLUSIONS:

In perinatally HIV-1-infected newborns, initiation of cART within 72 hours of birth may significantly reduce the size of the HIV-1 reservoirs. Cessation of cART may be necessary to determine whether functional HIV cure can be achieved in such children.

KEYWORDS:

HIV; child; combination antiretroviral therapy; eradication; proviral DNA

PMID:
24917662
PMCID:
PMC4184383
DOI:
10.1093/cid/ciu432
[Indexed for MEDLINE]
Free PMC Article

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