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. 2018 Mar 13;217(7):1024-1032.
doi: 10.1093/infdis/jix662.

Anti-Human Immunodeficiency Virus Antibodies in the Cerebrospinal Fluid: Evidence of Early Treatment Impact on Central Nervous System Reservoir?

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Anti-Human Immunodeficiency Virus Antibodies in the Cerebrospinal Fluid: Evidence of Early Treatment Impact on Central Nervous System Reservoir?

Peter D Burbelo et al. J Infect Dis. .
Free PMC article

Abstract

Background: Despite effective antiretroviral therapy (ART), human immunodeficiency virus (HIV) likely persists in the central nervous system (CNS) in treated individuals. We examined anti-HIV antibodies in cerebrospinal fluid (CSF) and blood as markers of persistence.

Methods: Human immunodeficiency virus antibodies were measured in paired CSF and serum before and after long-term treatment of chronic (n = 10) and early infection (n = 12), along with untreated early infection (n = 10).

Results: Treatment of chronic infection resulted in small reductions of anti-HIV antibodies in CSF and serum despite >10 years of suppressive ART. In untreated early infection, anti-HIV antibodies emerged in blood by day 30, whereas CSF antibodies reached similar levels 2 weeks later. Compared with long-term treatment of chronic infection, early ART initiation reduced CSF antibodies by 43-fold (P > .0001) and blood antibodies by 7-fold (P = .0003). Two individuals receiving pre-exposure prophylaxis and then ART early after infection failed to develop antibodies in CSF or blood, whereas CSF antibodies were markedly reduced in the Berlin patient.

Conclusions: To the extent that differential CSF and blood antibodies indicate HIV persistence, these data suggest a relative delay in establishment of the CNS compared with the systemic HIV reservoir that provides an opportunity for early treatment to have a greater impact on the magnitude of long-term CNS infection.

Figures

Figure 1.
Figure 1.
Serum and cerebrospinal fluid (CSF) human immunodeficiency virus (HIV) antibody levels in patients with chronic HIV infection before and after long-term treatment. Antibody measurements were made in (A) serum and (B) CSF samples taken from before and after long-term treatment of subjects with chronic HIV infection and uninfected controls. The y axis reflects the antibody levels in light units determined by luciferase immunoprecipitation systems. The total HIV antibody levels were derived from the sum of antibody values against 7 antigens. The geometric mean antibody levels and 95% confidence interval are shown for each group. The geometric mean level in the chronic HIV-infected participants after treatment was further used as reference for Figure 2. The black dotted line is the cutoff value, based on the uninfected controls, for determining seropositivity of the combined antibody total for serum and CSF. Wilcoxon rank statistical analysis was used to statistically evaluate differences between the paired before and after treatment samples. Abbreviations: ART, antiretroviral therapy.
Figure 2.
Figure 2.
Serum and cerebrospinal fluid (CSF) antibody levels in untreated and treated early human immunodeficiency virus (HIV) infection. Untreated subjects with early HIV infection were evaluated for (A) serum and (B) CSF antibodies in paired cross-sectional and longitudinal samples. Similarly, treated subjects with early HIV infection were evaluated for (C) serum and (D) CSF antibodies in paired cross-sectional and longitudinal samples. Each colored dot reflects an individual subject. An open circle reflects the absence of antiretroviral therapy at that time point. The black dotted line is the cutoff value for determining seropositivity and is based on the uninfected controls of the combined antibody total for serum and CSF. As a reference, the blue dotted line represents the geometric mean antibody levels found in the corresponding serum and CSF of the treated chronically infected subjects. The serum and CSF antibody values for the Berlin patient (red solid dot) are also shown. Abbreviations: LU, light units.

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