Detectable viral load in cerebrospinal fluid is associated with neurological symptoms in patients receiving HIV treatment who have an undetectable viral load in their blood, French investigators report in the March 1st edition of Clinical Infectious Diseases.
All eleven patients in the study also had a low nadir CD4 cell count, “suggesting a longer duration of viral replication, a lower immune status, and, therefore, a higher risk for the presence of HIV in the central nervous system.”
HIV can penetrate both the central and peripheral nervous systems leading to a range of acute and chronic neurological problems.
Several studies have shown that HIV treatment that reduces viral load in cerebrospinal fluid (CSF) also reduces the risk of neurological disorders.
However, research suggests that a small number of patients may still experience mild cogitative impairment, despite taking HIV treatment and having an undetectable viral load (below 50 copies/ml) in their blood.
A team of French investigators hypothesised that this could be because HIV was still detectable in CSF (above 200 copies/ml).
They therefore analysed the records of eleven patients taking antiretroviral therapy who presented with neurological symptoms between 2004 and early 2009.
All had been taking a stable HIV treatment combination for at least six months and had had an undetectable plasma viral load for at least three months. Furthermore, all eleven had both blood and CSF viral load measurements taken at the time of their presentation with neurological symptoms. Anti- HIV drug levels were also monitored in CSF, and samples of such fluid was also tested for resistance to antiretroviral drugs.
The study sample included seven men and four women who had a median age of 50 years. They had a long history of HIV infection, the median duration being 15 years.
At the time neurological symptoms developed, the median CD4 cell count was 432 cells/mm3 and the patients had been taking their current antiretroviral regimens for a median of 13 months.
Median nadir CD4 cell count was very low at 55 cells/mm3. Consistent with this, eight patients had been diagnosed with an AIDS-defining illness.
Symptoms of neurological disease ranged from mild headache to coma.
CSF abnormalities were detected in most of the patients. All but one individual had elevated protein levels in their CSF, and eight had elevated white blood and lymphocyte counts.
Despite having an undetectable blood viral load, all the patients had evidence of HIV replication in their CSF, where median viral load was 880 cells/mm3.
Resistance test results on CSF samples were available for eight patients. Five patients had evidence of resistance in their CSF. In two patients, the resistance profile was similar to that detected in the blood between two and six years earlier.
In five of the patients, the HIV present in their CSF was not sensitive to any of the antiretroviral drugs which they were taking. The investigators note that two patients were taking boosted protease inhibitor monotherapy, and that neither of these individuals had adequate drug levels in their CSF.
HIV treatment was modified for ten patients. Drug levels were monitored in seven patients, and all had concentrations within the therapeutic range. The drugs with the highest concentration in CSF were indinavir (Crixivan), nevirapine (Viramune), abacavir (Ziagen) maraviroc (Celsentri) and 3TC (lamivudine, Epivir).
The neurological complaints improved in all eleven patients. Viral load in the CSF of nine patients was monitored a median of six weeks after their antiretroviral therapy was modified. All had an undetectable CSF viral load at this time.
“Physicians should be aware of the possibility of acute HIV-associated central nervous system disorders even in the presence of minor neurological complaints that should prompt a CSF evaluation with the determination of viral replication and genotypic resistance testing”, recommend the investigators.
Canestri A et al. Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy. Clin Infect Dis 50: 773-78, 2010.