HIV type 1 (HIV-1) proviral reservoirs decay continuously under sustained virologic control in HIV-1-infected children who received early treatment.
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.
Program in Molecular Medicine Department of Pediatrics Center for Clinical and Translational Science, University of Massachusetts Medical School, Worcester.
Katherine
K
Luzuriaga
Program in Molecular Medicine Bioinformatics and Integrative Biology.
Barbara
B
Tabak
Program in Molecular Medicine Bioinformatics and Integrative Biology.
Manuel
M
Garber
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore.
Ya Hui
YH
Chen
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore.
Carrie
C
Ziemniak
Program in Molecular Medicine Department of Pediatrics.
Margaret M
MM
McManus
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
Danielle
D
Murray
University of California San Diego, La Jolla Veterans Affairs San Diego Healthcare System, California.
Matthew C
MC
Strain
University of California San Diego, La Jolla Veterans Affairs San Diego Healthcare System, California.
Douglas D
DD
Richman
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
Tae-Wook
TW
Chun
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
Coleen K
CK
Cunningham
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore.
Deborah
D
Persaud
D000293:Adolescent; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D011533:Proviruses / Q000302:isolation & purification*; D055502:Secondary Prevention; D016896:Treatment Outcome; D019562:Viral Load
D044966:Anti-Retroviral Agents
continuous HIV-1 decay; early antiretroviral therapy; prolonged viral suppression; proviral reservoirs; reduced HIV reservoirs