Salvage therapy with abacavir and other reverse transcriptase inhibitors for human immunodeficiency-associated encephalopathy.
BACKGROUND
HIV-associated encephalopathy (HIV-AE) is a severe neurologic condition that affects HIV-infected children. The potential benefit of antiretroviral (ARV) agents with good cerebrospinal fluid (CSF) penetration remains to be defined. Abacavir (ABC) achieves good CSF concentrations and studies of high-dose ABC showed benefit in adults with HIV dementia. The present study evaluated the safety and virologic, immunologic and neuropsychological responses of an ARV regimen including high-dose ABC in children with HIV-AE.


METHODS
Children between 3 months and 18 years old and abacavir-naive with HIV-AE and virologic failure were eligible.


RESULTS
: Seventeen children (16 ARV-experienced) were enrolled and 14 children completed 48 weeks of therapy. The overall tolerability was good; 2 children had a possible hypersensitivity reaction. At week 48, 53% and 59% of the children achieved HIV RNA levels below the limit of quantitation in plasma and CSF, respectively. The median (25%-75% range) change of HIV RNA from baseline to week 48 was -2.29 (-0.81 to -2.47) log10 copies/mL in plasma and -0.94 (0 to -1.13) log10 copies/mL in CSF. The mean increases in CD4 (+/-standard error of mean) cell count and CD4% were 427 (+/-169) cells/mm and 8% (+/-2), respectively. Concentrations of soluble tumor necrosis factor receptor II were reduced in plasma and CSF. Children less than 6 years of age demonstrated significant neuropsychological improvement at week 48.


CONCLUSIONS
In the present study with a limited number of children, highly active ARV therapy including high-dose ABC showed a safety profile similar to standard dose ABC and provided clinical, immunologic and virologic response in children with HIV-AE at week 48. Children less than 6 years of age also demonstrated significant neuropsychological improvement.
Saavedra-Lozano
Jesús
J
UT Southwestern Medical Center, Dallas, TX, USA. jsaavedra.hflr@salud.madrid.org
Ramos
José T
JT
Sanz
Francisco
F
Navarro
M Luisa
ML
de José
M I
MI
Martín-Fontelos
P
P
Mellado
María J
MJ
Leal
Juan A León
JA
Rodriguez
Cecilia
C
Luque
Isabel
I
Madison
Samuel J
SJ
Irlbeck
David
D
Lanier
E Randall
ER
Ramilo
Octavio
O
D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000276:immunology / Q000523:psychology / Q000821:virology; D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D002648:Child; D002675:Child, Preschool; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D004342:Drug Hypersensitivity; D005260:Female; D006678:HIV / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood / Q000134:cerebrospinal fluid; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016879:Salvage Therapy; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D012367:RNA, Viral; D047889:Receptors, Tumor Necrosis Factor, Type II; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir