Format

Send to

Choose Destination
J Infect Dis. 2014 Nov 15;210(10):1529-38. doi: 10.1093/infdis/jiu297. Epub 2014 May 21.

HIV type 1 (HIV-1) proviral reservoirs decay continuously under sustained virologic control in HIV-1-infected children who received early treatment.

Author information

1
Program in Molecular Medicine Department of Pediatrics Center for Clinical and Translational Science, University of Massachusetts Medical School, Worcester.
2
Program in Molecular Medicine Bioinformatics and Integrative Biology.
3
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore.
4
Program in Molecular Medicine Department of Pediatrics.
5
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
6
University of California San Diego, La Jolla Veterans Affairs San Diego Healthcare System, California.
7
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.

Abstract

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.

KEYWORDS:

continuous HIV-1 decay; early antiretroviral therapy; prolonged viral suppression; proviral reservoirs; reduced HIV reservoirs

PMID:
24850788
PMCID:
PMC4215073
DOI:
10.1093/infdis/jiu297
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center