Reduced markers of HIV persistence and restricted HIV-specific immune responses after early antiretroviral therapy in children
ABSTRACT Understanding the extent to which early antiretroviral therapy (ART) can limit the establishment and persistence of the HIV reservoir is an important step to designing interventions aimed at achieving HIV cure. We measured the markers of HIV persistence and HIV-specific immunity in early treated children.
This is a cross-sectional study that enrolled 15 children older than 2 years of age who initiated ART before 6 months of age and had sustained viral suppression. Quantification of total and integrated HIV DNA, and 2-LTR circles in CD4 T cells, fourth generation HIV enzyme immunoassay, and CD4 and CD8 T-cell responses to gag/env peptides by intracellular cytokine staining of CD4 and CD8 T cells were performed.
The median current age was 6.3 years and age at ART initiation was 17 weeks. The median duration of viral suppression was 6 years, and all had HIV RNA less than 50 copies/ml. The median CD4 was 44%. The median total HIV DNA was 132 copies/10 CD4 T cells (range 11-1804) and integrated HIV DNA was 17 copies/10 CD4 T cells (range 0-516), and no one had detectable 2-LTR circles. Nine of the 15 children (60%) had undetectable or extremely low integrated HIV DNA (<20 copies/10 CD4 T cells). All except one (93%) had undetectable HIV-specific CD4/CD8 cell responses and seven (47%) had nonreactive enzyme immunoassay.
Early ART resulted in very low levels of markers of HIV persistence and undetectable HIV-specific immune responses in the majority of HIV-infected children who started ART before 6 months of age.
- AIDS (London, England) 04/2014; 28(7):1069-70. DOI:10.1097/QAD.0000000000000179 · 6.56 Impact Factor
- The Journal of Infectious Diseases 05/2014; 210(10). DOI:10.1093/infdis/jiu298 · 5.78 Impact Factor
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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 mu g 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.Clinical Infectious Diseases 06/2014; 59(7). DOI:10.1093/cid/ciu432 · 9.42 Impact Factor