Evaluation of human immunodeficiency virus (HIV) type 1 RNA levels in cerebrospinal fluid and viral resistance to zidovudine in children with HIV encephalopathy.
The amount of human immunodeficiency virus (HIV) type 1 RNA and the presence of a codon 215 mutation indicative of zidovudine resistance were evaluated in cerebrospinal fluid (CSF) and plasma obtained from HIV-1-infected children. The level of HIV-1 RNA in CSF was highest in children with severe encephalopathy (n = 25; median, 430 copies/mL; range, 0-2.2 x 10(5) copies/mL) followed by the moderately encephalopathic (n = 7; median, 330; range, 0-1130) and nonencephalopathic groups (n = 9; median, 0; range, 0-566) (P = .007). There was no correlation between CSF and plasma HIV-1 RNA levels. Five of 7 children with the codon 215 mutation in CSF had a progression of encephalopathy, while all 8 children with wild type codon 215 had improved or stable disease during zidovudine treatment (P = .007). These findings suggest that increased viral replication and emergence of drug-resistant HIV-1 variants within the central nervous system may play a role in progression of HIV encephalopathy.
Sei
S
S
Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1928, USA.
Stewart
S K
SK
Farley
M
M
Mueller
B U
BU
Lane
J R
JR
Robb
M L
ML
Brouwers
P
P
Pizzo
P A
PA
D015526:AIDS Dementia Complex / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000821:virology*; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D004352:Drug Resistance, Microbial / Q000235:genetics*; D005500:Follow-Up Studies; D015751:Genes, pol; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development* / Q000472:pathogenicity; D006801:Humans; D007223:Infant; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis*; D015215:Zidovudine / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D012367:RNA, Viral; D015215:Zidovudine