Central nervous system immune activation characterizes primary human immunodeficiency virus 1 infection even in participants with minimal cerebrospinal fluid viral burden

Abstract

Background: Central nervous system (CNS) human immunodeficiency virus (HIV) infection and immune activation lead to brain injury and neurological impairment. Although HIV enters the nervous system soon after transmission, the magnitude of infection and immunoactivation within the CNS during primary HIV infection (PHI) has not been characterized.

Methods: This cross-sectional study analyzed cerebrospinal fluid (CSF) and blood from 96 participants with PHI and compared them with samples from neuroasymptomatic participants with chronic infection and ≥ 200 or < 200 blood CD4 T cells/μL, and with samples from HIV-seronegative participants with respect to CSF and plasma HIV RNA, CSF to serum albumin ratio, and CSF white blood cell counts (WBC), neopterin levels, and concentrations of chemokines CXCL10 and CCL2.

Results: The PHI participants (median 77 days post transmission) had CSF HIV RNA, WBC, neopterin, and CXCL10 concentrations similar to the chronic infection participants but uniquely high albumin ratios. 18 participants had ≤ 100 copies/mL CSF HIV RNA, which was associated with low CSF to plasma HIV ratios and levels of CSF inflammation lower than in other PHI participants but higher than in HIV-seronegative controls.

Conclusions: Prominent CNS infection and immune activation is evident during the first months after HIV transmission, though a proportion of PHI patients demonstrate relatively reduced CSF HIV RNA and inflammation during this early period.

Figure 1.

Human immunodeficiency virus (HIV) RNA levels in the blood and cerebrospinal fluid (CSF) compartments and their relationship in each HIV-infected group (A–C); simple linear regression between HIV RNA levels in each compartment and number of days posttransmission (D, E); and univariate Spearman correlation between CSF and plasma HIV RNA levels in primary HIV infection (PHI) participants (F). Upper plots indicate median (middle line), interquartile range (extent of boxes), and 10–90% range (whiskers). Means are denoted by ‘+.’ In D and E regression lines (solid) and 95% confidence intervals (dotted) are indicated. Significant differences between PHI participants and other groups are shown.

Figure 2.

Comparison of levels of immune and inflammatory markers within the cerebrospinal fluis (CSF) in 4 groups of participants: HIV-uninfected (HIV-), primary HIV infection (PHI), chronic infection with CD4 counts ≥200 cells/μL (CHI CD4 ≥200), and chronic infection with CD4 counts <200 cells/μL (CHI CD4 <200). Upper plots indicate median (middle line), interquartile range (extent of boxes), and 10%–90% range (whiskers). Means are denoted with the ‘+.’ Significant differences between PHI participants and other groups are shown. On lower plots, simple linear regression between each CSF marker and days post transmission of sampling are shown with regression lines (solid) and 95% confidence intervals (dotted).

Figure 3.

Comparisons between laboratory parameters in primary human immunodeficiency virus (HIV) infection (PHI) participants with minimal (≤100 copies/mL) cerebrospinal fluid (CSF) HIV RNA (denoted CSF VL≤ 100) and other PHI participants (denoted CSF VL >100). On scatter plots, bars indicate medians. Nonparametric statistical comparisons are shown.