Cerebrospinal fluid soluble CD30 elevation despite suppressive antiretroviral therapy in individuals living with HIV-1

Abstract

Objectives: The aim of this study was to assess soluble CD30 (sCD30), a protein that colocalises with HIV-1 RNA and DNA in lymphoid cells and tissues, in cerebrospinal fluid (CSF) as a marker of HIV-1 infection in the central nervous system (CNS).

Methods: This was a cross-sectional study using archived samples from two clinical cohorts. Soluble CD30 concentrations were measured in paired CSF and plasma from untreated viraemic individuals (n=52), individuals on suppressive antiretroviral therapy (ART) (n=33), HIV-1 controllers (n=10), participants with CSF HIV-1 'escape' (n=11) and controls without HIV-1 infection (n=16). Nonparametric tests were used to compare levels across groups and evaluate correlations with HIV-1 RNA, CSF neurofilament light chain protein (NFL) and neopterin.

Results: Compared with controls (median 30 ng/mL, interquartile range [IRQ] 23-50), plasma sCD30 levels were elevated in viraemic participants (75 ng/mL, 52-116; P<0.001), but not in those on suppressive ART (38 ng/mL, 32-62). In contrast, CSF sCD30 levels were elevated in ART-suppressed individuals (34 ng/mL, 19-46; P=0.001) and in those with CSF 'escape' (33 ng/mL, 27-40; P=0.004) compared with controls (18 ng/mL, 11-23), but not in untreated viraemic individuals. No association was observed between CSF sCD30 and plasma HIV-1 RNA, concurrent or nadir CD4+ T cell count, duration of infection or plasma sCD30. CSF sCD30 correlated with CSF NFL (r=0.34, P=0.001).

Conclusions: In contrast to plasma, sCD30 levels are elevated in the CSF of individuals with HIV-1 infection who are on suppressive ART. Elevated levels of sCD30 in the CSF may be an indicator of persistent CNS HIV-1 infection, although the mechanism underlying this elevation warrants further investigation.

Keywords: CD30; HIV-1; central nervous system (CNS); cerebrospinal fluid (CSF); reservoir.

Supplemental Figure 1.

Sample gating strategy for surface CD30 measurement.

Figure 1.

(a) Plasma sCD30 in HIV-uninfected, untreated viraemic, ART-suppressed, CSF ‘escape’ and controller subgroups. (b) CSF sCD30 in HIV-uninfected, untreated viraemic, ART-suppressed, CSF ‘escape’ and controller subgroups. I indicates statistically significant comparison between group of interest and HIV-1 uninfected subgroup. II indicates statistically significant comparison between group of interest and viraemic subgroup. ART: antiretroviral therapy; CSF: cerebrospinal fluid

Figure 2.

(a) Plasma sCD30 within viraemic individuals, stratified by CD4+ T lymphocyte count at the time of sampling. (b) CSF sCD30 within viraemic individuals, stratified by CD4+ T lymphocyte count at the time of sampling. (c) Plasma sCD30 in individuals with quantifiable plasma HIV-1 RNA (≥40 copies/mL) compared with unquantifiable plasma HIV-1 RNA (<40 copies/mL). (d) CSF sCD30 in individuals with quantifiable CSF HIV-1 RNA compared with unquantifiable CSF HIV-1 RNA. CSF: cerebrospinal fluid.

Figure 3.

(a) CSF sCD30 correlates with CSF WBC in the ART-suppressed subgroup. (b) CSF sCD30 correlates with age-adjusted CSF NFL in the ART-suppressed subgroup. (c) CSF sCD30 correlates with CSF HIV-1 RNA in individuals with CSF HIV-1 ‘escape’. (d) CSF:plasma albumin ratio in HIV-uninfected, untreated viraemic and ART-suppressed individuals. (e) sCD30 index in HIV-uninfected, untreated viraemic and ART-suppressed individuals. Note: r and P values represent nonparametric calculations; lines represent best-fit linear regression. ART: antiretroviral therapy; CSF: cerebrospinal fluid; NFL: neurofilament light chain protein.