Neurocognitive Trajectories After 72 Weeks of First-Line Anti-retroviral Therapy in Vietnamese Adults With HIV-HCV Co-infection.

Robert H Paul,Nguyen Tat Thanh,Glen M Chew,Nguyen Van Vinh Chau,Thomas A Premeaux,Thuy Le,Joseph A D Mcbride,Cecilia M Shikuma,Vo Trieu Ly,Lishomwa C Ndhlovu,Andrew C Belden,Jacob D Bolzenius,Dominic C Chow

doi:10.3389/fneur.2021.602263

Abstract

Background: Long-term neurocognitive outcomes following first-line suppressive anti-retroviral therapy (ART) remain uncertain for individuals with HIV and hepatitis C (HCV) co-infection. The study examined neurocognitive performance before and after 72 weeks of ART using repeated multivariate analyses and latent trajectory models.Methods: One hundred and sixty adults with chronic, untreated HIV infection (n = 80 with HCV co-infection and n = 80 HIV mono-infected) and 80 demographically similar healthy controls were recruited from the Hospital for Tropical Diseases in Ho Chi Minh City and the surrounding community, respectively. Neurocognitive measures (adapted for use in Vietnam) and liver enzyme tests were compared across groups at baseline. Repeated multivariate and group-based trajectory analyses (GBTA) examined neurocognitive subgroup profiles of the co-infected individuals after 72 weeks of de novo efavirenz- (n = 41) or raltegravir-based (n = 39) ART.Results: Baseline analyses revealed worse motor function in HIV-HCV co-infected individuals compared to both comparison groups. Longitudinal analyses revealed improved neurocognitive performance by week 48 for most participants regardless of treatment arm. GBTA identified a subgroup (35% of HIV-HCV sample) with persistent motor impairment despite otherwise successful ART. Higher HIV viral load and lower CD4+ T cell count at baseline predicted persistent motor dysfunction. Liver indices and ART regimen did not predict neurocognitive outcomes in HIV-HCV co-infected individuals.Conclusions: Most HIV-HCV co-infected individuals achieve normative neurocognitive performance after 48 weeks of de novo suppressive ART. However, individuals with more severe HIV disease prior to ART exhibited motor impairment at baseline and 72 weeks after otherwise successful treatment. Interventions aimed at improving motor symptoms at the time of HIV treatment onset may improve long-term clinical outcomes in HIV-HCV co-infected adults.

Highlights

As of 2016, 2.3 million cases of HIV-HCV co-infection were reported globally (1)
As expected, coinfected individuals randomized to the raltegravir-based vs. efavirenz-based treatment arms did not differ on baseline levels of plasma HCV RNA, HIV RNA, CD4+ T cell count, AFP, ALT, AST, or Fibroscan, but did differ on hepatotoxicity
Additional analyses using RM-ANOVA with FDR showed no significant difference between treatment arm over time on depression scores or CD4+ T cell count

Summary

Introduction

As of 2016, 2.3 million cases of HIV-HCV co-infection were reported globally (1). HIV-HCV co-infection disproportionately affects individuals residing in resource-limited settings, where access to direct acting anti-viral treatment for HCV is less readily available (2–5). Despite long-term use of anti-retroviral therapy (ART) HIVHCV co-infected adults report increased use of medical services and level of disability, as well as a greater burden of chronic health complications compared to individuals with HIV monoinfection (8, 9). Fabiani et al (18) reported a significant association between global neurocognitive status and plasma levels of HCV-RNA in co-infected individuals who were receiving suppressive ART. These results suggest that HIV treatment alone does not prevent the development of neurocognitive complications, but longitudinal studies are needed to tease apart neurocognitive profiles of HIV presenting with or without comorbid HCV. The study examined neurocognitive performance before and after 72 weeks of ART using repeated multivariate analyses and latent trajectory models

Methods

Results

Discussion

Conclusion