Suppression of human immunodeficiency virus replication in human brain tissue by nucleoside reverse transcriptase inhibitors.
Human immunodeficiency virus (HIV) infection of the brain is associated pathologically with neuronal damage and loss. Clinically cognitive impairments can develop, which in some can be improved by highly active antiretroviral therapy (HAART), whereas in others, the infection persists despite treatment. The efficacy of antiretrovirals to treat cognitive impairments may be related to their ability to suppress viral replication in the brain and also to prevent neurodegeneration. To investigate this question, the authors assessed the ability of stavudine (300 nM), zidovudine (2 nM), and abacavir (300 nM) to suppress viral replication in human brain tissue aggregates infected with HIV-1 SF162. Aggregates were cultured for 4 weeks and exposed to nucleoside reverse transcriptase inhibitors (NRTIs) either 24 h prior, simultaneously, or 24 h post infection. Viral replication was assessed by p24 enzyme-linked immunosorbent assay (ELISA) in culture medium. The authors observed a statistically significant reduction in the rate of viral replication for stavudine added 24 h prior to infection univariate analysis of variance ([UANOVA], t = 2.55, df = 17, P =.021). Decreased viral replication observed with zidovudine and abacavir was not statistically significant.
Kandanearatchi
Apsara
A
Section of Experimental Neuropathologyand Psychiatry, Institute of Psychiatry, King's College London, London, United Kingdom. spkaaak@iop.kcl.ac.uk
Vyakarnam
Annapurna
A
Landau
Sabine
S
Everall
Ian Paul
IP
D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000821:virology; D023241:Antiretroviral Therapy, Highly Active; D001921:Brain / Q000821:virology; D015224:Dideoxynucleosides / Q000494:pharmacology; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D066298:In Vitro Techniques; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D018119:Stavudine / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology; D000099227:Abacavir
D015224:Dideoxynucleosides; D018894:Reverse Transcriptase Inhibitors; D018119:Stavudine; D015215:Zidovudine; D000099227:Abacavir