Recovery of replication-competent virus from CD4 T cell reservoirs and change in coreceptor use in human immunodeficiency virus type 1-infected children responding to highly active antiretroviral therapy.
Highly active antiretroviral therapy (HAART) suppresses plasma viremia in most patients with human immunodeficiency virus (HIV) infection. Prospective study of HIV-infected children (n=27) shows that, in 8 of 12 who responded to HAART (>/=0.5 log reduction in plasma HIV RNA), HAART restricted the number of coreceptors used by the predominant HIV isolate (mean number of coreceptors used at baseline was 4, vs. 1 coreceptor used at 6 months after treatment). This decrease was most striking in 6 of 8 children whose HIV coreceptor tropism changed from X4-tropic at baseline to R5-tropic. In 6 of 10 children tested, with plasma HIV RNA levels of <50 copies/mL, R5-tropic virus was isolated from CD4 T cell reservoirs. All the responding children had a significant increase in naive CD4 T cells (P<.05). These results show that persistent HIV T cell reservoirs are present in children and that HAART may influence the number and type of coreceptors used by the predominant virus isolate.
Equils
O
O
Division of Pediatric Infectious Diseases, Cedars-Sinai Medical Center, UCLA Children's Hospital, UCLA AIDS Institute, Los Angeles, California 90095, USA.
Garratty
E
E
Wei
L S
LS
Plaeger
S
S
Tapia
M
M
Deville
J
J
Krogstad
P
P
Sim
M S
MS
Nielsen
K
K
Bryson
Y J
YJ
D000293:Adolescent; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002454:Cell Differentiation; D002648:Child; D018920:Coculture Techniques; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D019888:Nelfinavir / Q000008:administration & dosage / Q000627:therapeutic use; D011446:Prospective Studies; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use; D018119:Stavudine / Q000008:administration & dosage / Q000627:therapeutic use; D019562:Viral Load; D014779:Virus Replication; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use
D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D018119:Stavudine; D019888:Nelfinavir; D019438:Ritonavir