Peripheral blood lymphocyte proviral DNA predicts neurocognitive impairment in clade C HIV

Vurayai Ruhanya,Graeme Brendon Jacobs,Richard Helmuth Glashoff,Soraya Seedat,John A Joska,George Nyandoro,Susan Engelbrecht,Robert H Paul

doi:10.1007/s13365-020-00882-9

Abstract

It is not known if proviral DNA in the periphery corresponds to cognitive status in clade C as it does in clade B and recombinant forms. A cross-sectional study was conducted on participants investigated for HIV-associated neurocognitive impairment in South Africa. HIV-1 proviral DNA was quantified using a PCR assay targeting a highly conserved HIV-1 LTR-gag region. Fifty-four (36.7%) participants were cognitively impaired and 93 (63.3%) were not impaired. Forty-three (79.6%) of the cognitively impaired participants were female and 11 (20.4%) were male. There was no significant age difference between cognitively impaired and unimpaired participants (p = 0.42). HIV-1 DNA in cognitively impaired PLWH was significantly higher than in cognitively normal individuals (p = .016). Considering impaired participants, lymphocyte HIV-1 DNA was significantly higher in males than females (p = 0.02). There was a modest positive correlation between lymphocyte HIV-1 DNA and global deficit scores (GDS) r = 0.176; p = 0.03). The two measures of viral load, lymphocyte HIV-1 DNA copies/million and plasma RNA copies/ml, were positively correlated (r = 0.39; p < .001). After adjusting for other covariates, age, sex, treatment status, and the interactions between impairment and treatment, the multivariate regression showed association between proviral load and neurocognitive impairment; omega effect size was 0.04, p value = 0.010. The burden of HIV-1 peripheral blood lymphocyte proviral DNA corresponds to neurocognitive impairment among individuals infected with clade C disease. Therefore, therapeutic strategies to reduce the HIV-1 proviral DNA reservoir in lymphocytes may improve neurocognitive outcomes in PLWH.

Highlights

HIV-1-associated neurocognitive disorders (HAND) remain an important clinical concern
HIV RNA has been detected in CSF within 8 days of infection, and immune activation is associated with neuropathogenesis (Hellmuth et al 2015; Valcour et al 2012)
This study demonstrated a significant correspondence between peripheral blood lymphocyte HIV-1 DNA load and neurocognitive impairment in adults with HIV-1 subtype C infection

Summary

Introduction

HIV-1-associated neurocognitive disorders (HAND) remain an important clinical concern. HAND affects 40–70% of HIV-1-infected patients (Williams et al 2014; Yusuf et al 2017), despite immune reconstitution and viral suppression because of combination antiretroviral therapy (cART). HIV RNA has been detected in CSF within 8 days of infection, and immune activation is associated with neuropathogenesis (Hellmuth et al 2015; Valcour et al 2012). Residual viremia and HIV-1 DNA reservoirs in the periphery are linked to activation-induced neuronal damage (Cysique et al 2015; Valcour et al 2012) as well as chronic immune activation from macrophages, glial cells, and astrocytes (Hong and Banks 2015)

Objectives

Methods

Results

Conclusion