Portal de Periódicos da CAPES

Neurological efficacy of stavudine, zidovudine, and lamivudine

1998; Elsevier BV; Volume: 352; Issue: 9125 Linguagem: Inglês

10.1016/s0140-6736(05)60498-9

1474-547X

Bruce J. Brew,

HIV/AIDS drug development and treatment

Norbert Foudraine and colleagues (May 23, p 1547)1Foudraine NA Hetelmans RMW Lange JA et al.Cerebrospinal fluid HIV-1 RNA and drug concentrations after treatment with lamivudine plus zidovudine or stavudine.Lancet. 1998; 351: 1547-1551Summary Full Text Full Text PDF PubMed Scopus (152) Google Scholar report on cerebrospinal-fluid (CSF) HIV-1 RNA and drug concentrations after treatment with lamivudine plus zidovudine or stavudine. Importantly, none of the patients studied had AIDS dementia complex. The importance of HIV-1 RNA in the CSF in such patients is unknown, in contradistinction to its strong relation to the severity of AIDS dementia complex when that disorder is present.2Brew BJ Pemberton L Cunningham P Law M Levels of HIV-1 RNA correlate with AIDS dementia.J Infect Dis. 1997; 175: 963-966Crossref PubMed Scopus (201) Google Scholar Intuitively, one might be tempted to think that the CSF HIV-1 RNA reflects subclinical brain disease, but there are four potential sources of CSF HIV-1 RNA: a leak from the plasma through a disturbed blood-brain barrier; spill over from productive brain infection; shedding from productive infection of the meningeal compartment (meningeal macrophages); or shedding of HIV-1 from trafficking of activated productively infected T cells through the central-nervous system. Although in the report from Foudraine and co-workers it seems unlikely that a disturbed blood-brain barrier could account for the CSF HIV-1 RNA, because of the lack of correlation between the CSF and plasma compartments, there is still the possibility that the CSF HIV-1 RNA in these non-demented patients is derived from the meningeal macrophage compartment, not the brain. Currently, the best prognostic marker for AIDS dementia complex is CSF β32 microglobulin: substantially raised concentrations carry a 17–fold increase in risk.3Brew BJ Dunbar N Pemberton L Kaldor J Cerebrospinal fluid concentrations of β2 microglobulin and neopterin predict the development of AIDS dementia complex.J Infect Dis. 1996; 174: 294-298Crossref PubMed Scopus (101) Google Scholar Thus, whether CSF HIV-1 RNA concentrations predict the development of AIDS dementia complex remains to be proven. A preliminary answer to this issue would be to assess if the patients in the study by Foudraine had raised concentrations of CSF β32 microglobulin and if the concentrations dropped with therapy. As the investigators state, prospective data on the role of CSF HIV-1 RNA in patients without AIDS dementia complex are urgently needed.