Molecular analysis of cerebrospinal fluid: potential for the study of HIV-1 infection of the central nervous system

The molecular analysis of cerebrospinal fluid (CSF) provides an inestimable tool for the study of HIV infection of the central nervous system (CNS). C urrent nucleic acid amplification techniques enable the measurement of CSF HIV-1 RNA levels which can be predictive of HIV-associated neurological dam age. CSF HIV-1 RNA levels do not necessarily correlate with the correspondi ng plasma levels, thus supporting the possibility of an intrathecal virus p roduction, i.e., from brain macrophages. However, in early stages of HIV in fection, as well as during some opportunistic CNS diseases, CNS or CSF infi ltrating lymphocytes might be the main source of CSF virus. A drastic decre ase in CSF viral load is usually observed along with a decrease in plasma l evels in patients receiving highly active antiretroviral therapy (HAART), w ith durable suppression of CSF viral load over months. However, during the first weeks of therapy, the dynamics of response may differ in the CSF as c ompared to plasma, again suggesting that virus replication may be compartme ntalised in the CSF. A number of mechanisms are likely to be involved in th e response to therapy in CSF, including among the others the trafficking of cell populations supporting viral replication between blood, CNS and CSF, and the role of the anatomical brain barriers in limiting the access of ant iretroviral drugs into the CSF. A potential risk associated with compartmen talisation of HIV infection is of an incomplete suppression of virus replic ation in the CSF, thus creating the ground for local development of anti-HI V drug resistance. In order to assess this occurrence, long-term studies of viral load and genotypic analyses on paired CSF and plasma will be necessa ry and these will also help elucidate the complex interrelationship between viral replication in these compartments.