Cerebrospinal fluid response to structured treatment interruption after virological failure

Objective Structured antiretroviral treatment interruption (STI) has been a dvocated as a therapeutic strategy for HIV-1 infection. We report initial o bservations of cerebrospinal fluid (CSF) HIV-1 infection in five patients u ndergoing serial lumbar punctures (LPs) during STI undertaken following vir ological failure. Design and methods In this prospective observational study we quantified HI V-1 RNA concentrations and assessed both phenotypic drug susceptibility pro files and genotypic antiviral drug resistance mutations in CSF and plasma d uring the period of treatment interruption. CSF white blood cells were also counted, and patients' neurological status monitored. Results In four of the patients, CSF HIV-1 concentration increased more rap idly than that of the plasma, with consequent reduction in the ratio betwee n plasma and CSF viral loads (pVL :cVL). Three individuals developed robust , though asymptomatic CSF lymphocytic pleocytosis. In all patients the pred ominant HIV-1 quasispecies shifted simultaneously in CSF and plasma from a drug-resistant to a more drug-susceptible phenotype with identical and simu ltaneous changes in genotypes associated with drug resistance. Conclusions STI may be accompanied by previously unrecognized changes in ti ssue viral exposures and lymphocyte traffic. Hence, despite 'virological fa ilure' as evidenced by persistent plasma viremia, ongoing antiretroviral tr eatment prior to its interruption appeared to suppress CSF HIV-1 infection (indeed more effectively than that of plasma) and restrain lymphocyte traff ic into the CSF. Simultaneous change of resistance mutations in CSF and pla sma was likely due to re-emergence and overgrowth of pre-existing strains w ith ready exchange of virus between these two compartments, either facilita ted by or provoking a local CSF lymphocytosis. (C) 2001 Lippincott Williams & Wilkins.