Salvage therapy with abacavir and other reverse transcriptase inhibitors for human immunodeficiency-associated encephalopathy.

Abstract

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.

• Authors: Jesús Saavedra-Lozano, José T Ramos, Francisco Sanz, M Luisa Navarro, M I de José, P Martín-Fontelos, María J Mellado, Juan A León Leal, Cecilia Rodriguez, Isabel Luque, Samuel J Madison, David Irlbeck, E Randall Lanier, Octavio Ramilo
• Journal: The Pediatric infectious disease journal (Pediatr Infect Dis J) Vol. 25 Issue 12 Pg. 1142-52 (Dec 2006) ISSN: 0891-3668 [Print] United States
• PMID: 17133160 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• Dideoxynucleosides
• RNA, Viral
• Receptors, Tumor Necrosis Factor, Type II
• Reverse Transcriptase Inhibitors
• abacavir

Topics

• AIDS Dementia Complex (drug therapy, immunology, psychology, virology)
• Adolescent
• Anti-HIV Agents (administration & dosage, adverse effects, therapeutic use)
• Antiretroviral Therapy, Highly Active
• CD4 Lymphocyte Count
• CD4-CD8 Ratio
• Child
• Child, Preschool
• Dideoxynucleosides (administration & dosage, adverse effects, therapeutic use)
• Drug Hypersensitivity
• Female
• HIV (genetics)
• Humans
• Infant
• Male
• Pilot Projects
• RNA, Viral (blood, cerebrospinal fluid)
• Receptors, Tumor Necrosis Factor, Type II (blood, cerebrospinal fluid)
• Reverse Transcriptase Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Salvage Therapy