Reply to Seligman

Abstract

TO THE EDITOR—We appreciate the suggestions made by Dr Seligman in relation to our work on cerebrospinal fluid (CSF) viral escape. As noted, the detection of low-level viremia in blood samples from patients receiving successful suppressive therapy may result from occasional nonadherence. Because of the limited penetration of some antiretroviral drugs into the central nervous system (CNS), adherence may potentially be even more crucial in the treatment of HIV-1 in the CNS. However, we would argue that the detection of low-level viral load in CSF is indeed of potential importance. Because of limitations in accessibility, residual virus in CSF during suppressive antiretroviral therapy is, if at all present, less well characterized than in blood. However, viral load in the CSF compartment during antiretroviral therapy is usually substantially lower than that in blood in neurologically asymptomatic patients [1, 2]. Previously, detection of selective viral escape in the CSF compartment was rare. Even in patients with systemic treatment failure, the level of HIV-1 RNA is frequently substantially lower in the CSF compartment [2]. However, we fully agree that compartmentalized viral resistance in the CNS remains an important factor to investigate. As suggested by Dr. Seligman, we are currently studying this issue. To increase the sensitivity of the analysis, ultra-centrifugation of CSF samples is implemented for improved HIV-1 RNA yield, followed by polymerase chain reaction amplification, sequencing, and genotypic resistance testing. Using these analyses, we hope to further characterize selective viral resistance as a possible factor in relation to the CSF viral escape found in 10% of patients included in the present study [3].