HIV type 1 (HIV-1) proviral reservoirs decay continuously under sustained virologic control in HIV-1-infected children who received early treatment
Program in Molecular Medicine; Department of Pediatrics; Center for Clinical and Translational Science; Program in Bioinformatics and Integrative Biology
Immunology of Infectious Disease | Immunoprophylaxis and Therapy | Infectious Disease | Pediatrics | Virus Diseases
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.
continuous HIV-1 decay, early antiretroviral therapy, prolonged viral suppression, proviral reservoirs, reduced HIV reservoirs
DOI of Published Version
J Infect Dis. 2014 Nov 15;210(10):1529-38. doi: 10.1093/infdis/jiu297. Epub 2014 May 21. Link to article on publisher's site
The Journal of infectious diseases
Luzuriaga K, Tabak B, Garber M, Chen YH, Ziemniak C, McManus MM, Murray D, Strain M, Richman D, Chun T, Cunningham CK, Persaud D. (2014). HIV type 1 (HIV-1) proviral reservoirs decay continuously under sustained virologic control in HIV-1-infected children who received early treatment. Program in Bioinformatics and Integrative Biology Publications. https://doi.org/10.1093/infdis/jiu297. Retrieved from https://escholarship.umassmed.edu/bioinformatics_pubs/89