CSF HIV-1 RNA viral load in patients with HIV infection

THESES

CSF HIV-1 RNA viral load in patients with HIV infection (Abstract)^*. Thesis, São Paulo, 2004

Paulo Pereira Christo

^{Correspondence}

Significant progress in the approach to AIDS has been made over the last few years, including a better understanding of the mechanisms of viral replication and disease progression and immunological mechanisms, as well as the introduction of new antiretroviral (ARV) drugs. The quantification of HIV-1 in plasma (viral load) has revolutioned the understanding of viral dynamics in the infected organism and is the best predictive marker of disease progression. A more rational indication of therapy has also been implemented and patient follow-up is becoming the most important tool for monitoring the response to ARV therapy. In contrast, HIV-1 viral load in cerebrospinal fluid (CSF) plays a less known role. Evidence indicates that the brain serves as a reservoir for the virus, which is not controlled by systemic parameters, a fact rendering the measurement of HIV-1 RNA levels in CSF potentially important for the evolution and eradication of the virus from the human body.

The objective of the present study was to determine the viral load in CSF (CVL) and in plasma (PVL) of HIV-1-infected patients with and without neurological manifestations, as well as to correlate the viral load of these two compartments. In addition, CVL was correlated with the time since diagnosis of the infection, presence and type of neurological disease, use of ARV therapy, immunity measured on the basis of CD4+ T lymphocyte count, and CSF cell and protein content.

Ninety-seven patients hospitalized at a reference hospital for infectious diseases with a suspicion of a neurological disorder were prospectively studied. Neurological diseases were ruled out in 23 patients after work-up. Ninety-eight CSF and 82 plasma samples were collected for the quantification of HIV-1 RNA by the NASBA method. Concomitant and valid CSF and plasma samples were available for 70 patients.

The detection rate of HIV-1 RNA was 78.1% in plasma and 55.6% in CSF, with the detection rate in CSF being higher in patients with neurological disease (63.4%), in patients with a CD4 count lower than 200 cells/mm³ (64.4%), in patients not undergoing ARV therapy (82.5%), and in patients with detectable plasma viral load (71.4%). The median CVL of the population studied as a whole or divided into groups of patients with and without neurological disease and with different types of disorders was lower than the median PVL, except for patients with neurocryptococcosis. The ratio between median PVL and CVL showed that PVL was approximately 73 times higher than CVL. However, CVL was higher than in plasma in 11 (16%) of the 70 patients. CVL was correlated with PVL in the total population studied, while no correlation between the two compartments (CSF and plasma) was observed in certain groups of patients, including those with a CD4 count higher than 200 cells/mm³, those not undergoing ARV therapy and those showing a protein content lower than 45. Analysis of the correlation between CVL and the variables studied showed a correlation between the amount of HIV-1 RNA in CSF and the presence of neurological disease and cellularity. A negative correlation was observed between CVL and the time since diagnosis of the infection and CD4+ T lymphocyte count.

In conclusion, CVL was generally lower than PVL and was associated with the presence of neurological diseases and CSF cell count, and a lack of correlation between the two compartments (CSF and plasma) was observed in certain groups of patients, suggesting the existence of compartmentalization of HIV-1 in CSF.

Key words: CSF, HIV, AIDS, viral load.

*

Carga viral do HIV-1 no líquido cefalorraqueano em pacientes portadores do HIV (Resumo). Tese de Doutorado, Universidade de São Paulo (Área: Ciências/Neurologia). Orientador: José Antonio Livramento.

Publication Dates

• Publication in this collection
  05 July 2005
• Date of issue
  June 2005