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.
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Citation: 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
continuous HIV-1 decay, early antiretroviral therapy, prolonged viral suppression, proviral reservoirs, reduced HIV reservoirs
Luzuriaga, Katherine; Tabak, Barbara; Garber, Manuel; Chen, Ya Hui; Ziemniak, Carrie; McManus, Margaret M.; Murray, Danielle; Strain, Matthew; Richman, Douglas; Chun, Tae-Wook; Cunningham, Coleen K.; and Persaud, Deborah, "HIV type 1 (HIV-1) proviral reservoirs decay continuously under sustained virologic control in HIV-1-infected children who received early treatment" (2014). Program in Bioinformatics and Integrative Biology Publications and Presentations. Paper 89.