Patients with untreated HIV infection were found to have consistently decreased cerebrospinal fluid (CSF) HIV RNA viral loads compared with plasma HIV RNA throughout different phases of the disease , except among those with HIV-associated dementia (HAD). These findings, from a cross-sectional study, were published in Clinical Infectious Diseases.

In a cross-sectional multicenter study, researchers analyzed data obtained from 8 centers on patients who were evaluated for untreated HIV infection between 1982 and 2017. The researchers assessed patients’ serum samples for HIV RNA viral load at various stages of the disease and then compared the results.

Among a total of 1018 patients included in the study, the median age was 38 (IQR, 32-47) years and 76% were men. In addition, the median CD4 and CD8 counts were 164 (IQR, 37-390) and 715 (IQR, 450-1095) cells/mL, respectively, the median plasma HIV RNA viral load was 4.92 (IQR, 4.33-5.54) log10 copies/mL, and the median CSF HIV RNA viral load was 3.80 (IQR, 2.86-4.59) log10 copies/mL.


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Compared with plasma HIV RNA, the researchers found that CSF HIV RNA viral loads were decreased by a median of 1.03 log10 copies/mL among most patients (87%). Of note, CSF HIV RNA viral loads that were greater than or equal to plasma HIV RNA were observed in 13% of patients. Patients whose CSF HIV RNA viral loads were greater than their plasma HIV RNA viral loads were classified as CSF discordant.

Among patients with HAD, the median CSF HIV RNA viral load was 4.73 (IQR, 3.84-5.31) log10 copies/mL. The researchers noted that CSF HIV RNA viral loads were most increased (median, 5.35; IQR, 4.91-5.76 log10 copies/mL) among patients who were neuroasymptomatic with a CD4 count of less than 50 cells/mL.

Among patients with central nervous system infections, those with progressive multifocal leukoencephalopathy had significantly  CSF HIV RNA viral loads compared with those with either cryptococcal meningitis (P <.01) or cytomegalovirus encephalitis (P <.05).

The researchers found that the median concentration of CSF neopterin was most increased among patients with HAD (63.5; IQR, 33.0-120 nmol/L). They also noted that patients with CSF discordance had significantly increased median concentrations of CSF neopterin vs those without CSF discordance (33.4 vs 17.8 nmol/L; P <.001). In regard to serum neopterin, median concentrations were most increased among patients with central nervous system infections (32.6; IQR, 16.5-212.1 nmol/L).

Overall, the researchers found that CSF HIV RNA viral loads were most significantly correlated with concentrations of CSF neopterin (r, 0.49; P <.01) and plasma HIV RNA viral loads (r, 0.44; P <.01). Among patients who were neuroasymptomatic, CSF HIV RNA viral loads were significantly correlated with concentrations of CSF neopterin (r, 0.43; P <.01), CSF leukocyte counts (r, 0.42; P <.01), and plasma HIV RNA viral loads(r, 0.35; P <.01). Of patients with HAD, CSF HIV RNA viral loads were significantly correlated with CSF neopterin (r, 0.24; P <.05) and CSF leokocyte counts (r, 0.21; P <.05). Of patients with central nervous system infections, only the albumin ratio was found to be significantly correlated with CSF HIV RNA viral loads (r, 0.47; P <.01).

This study was limited by its retrospective design, extensive follow-up duration, and its use of different polymerase chain reaction testing methods.

According to the researchers, “[the] characterization of CSF findings in different phases of [HIV] infection can be valuable in the clinical management of patients, and the results from this large study contributes to previous knowledge of CSF characteristics among those with untreated HIV infection when evaluating neurologic symptoms.

Disclosure: Some author(s) declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.

Reference

Ulfhammer G, Edén A, Antinori A, et al. Cerebrospinal fluid viral load across the spectrum of untreated HIV-1 infection: a cross-sectional multi-center study. Clin Infect Dis. 2021;ciab943. doi:10.1093/cid/ciab943