Abstract
BackgroundThe neurofilament is a major structural component of myelinated axons. Increased cerebrospinal fluid (CSF) concentrations of the light chain of the neurofilament protein (NFL) can serve as a sensitive indicator of central nervous system (CNS) injury. To assess whether interrupting antiretroviral treatment of HIV infection might have a deleterious effect on the CNS, we measured NFL levels in HIV-infected subjects interrupting therapy.We identified subjects who had CSF HIV RNA concentrations below 50 copies/mL at the time combination antiretroviral therapy was interrupted, and for whom CSF samples were available before and after the interruption.ResultsA total of 8 subjects were studied. The median (range) CSF NFL level at baseline was <125 (<125–220) ng/L (normal <250 ng/L). All 8 subjects exhibited an increase in CSF and plasma HIV RNA after stopping therapy, accompanied by intrathecal immunoactivation as evidenced by CSF lymphocytic pleocytosis (7/8 patients) and increased CSF neopterin concentration (5/6 patients). Three subjects showed a consistent increase in CSF NFL, rising from <125 ng/L to a maximum of 880 (at day 148), 1,010 (day 58) and 10,930 ng/L (day 101). None exhibited new neurological symptoms or signs, or experienced functional deterioration during the period off treatment; of 5 who underwent brief quantitative neurological testing, none showed worsening performance.ConclusionThese findings suggest that resurgence of active HIV replication may result in measurable, albeit subclinical, CNS injury. Further studies are needed to define the frequency and pathobiological importance of the increase in CSF NFL.
Highlights
The neurofilament is a major structural component of myelinated axons
Three subjects showed a consistent increase in cerebrospinal fluid (CSF) neurofilament protein (NFL), rising from
None exhibited new neurological symptoms or signs, or experienced functional deterioration during the period off treatment; of 5 who underwent brief quantitative neurological testing, none showed worsening performance. These findings suggest that resurgence of active HIV replication may result in measurable, albeit subclinical, central nervous system (CNS) injury
Summary
The neurofilament is a major structural component of myelinated axons. Increased cerebrospinal fluid (CSF) concentrations of the light chain of the neurofilament protein (NFL) can serve as a sensitive indicator of central nervous system (CNS) injury. To assess whether interrupting antiretroviral treatment of HIV infection might have a deleterious effect on the CNS, we measured NFL levels in HIV-infected subjects interrupting therapy. Effective in suppressing infection, current ART regimens do not eradicate HIV, and prolonged treatment may be complicated by development of drug resistance and an array of side effects [3]. Structured (or strategic) treatment interruption (STI) was initially studied as a means of enhancing HIV-specific immunity via an autovaccination phenomena or reducing the levels of drug resistant HIV, its potential therapeutic utility is being studied primarily as a way to maintain the immunologic and clinical benefit of therapy while reducing drug-toxicity and drugcosts [4]. Despite continued concerns over the safety of interrupting therapy, a large proportion of subjects in clinical practice interrupt therapy for reasons related to drug toxicity, treatment fatigue and/or drug costs
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